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Objective A high plasma level of remnant-like particle cholesterol (RLP-C), which is equivalent to triglyceride-rich lipoprotein remnant, is an important coronary risk marker. RLP-C level is high, independent of other plasma lipids, in patients with chronic kidney disease (CKD) undergoing hemodialysis. The effect of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on plasma levels of RLP-C in patients with diabetes mellitus and CKD under hemodialysis was studied. Methods Teneligliptin 20 mg/day was administered to 15 patients with diabetes and CKD undergoing hemodialysis for 12 weeks. Ten patients with diabetes and CKD undergoing hemodialysis were allocated to the control group. Blood was sampled following a 12-h fast. Fasting plasma glucose (FPG), C-peptide, triglyceride, low-density lipoprotein (LDL)-cholesterol (C), high-density lipoprotein (HDL)-C, RLP-C, apolipoprotein (apo) B, oxidized LDL, lipoprotein lipase, and glycated hemoglobin (HbA1c) were measured. Results HbA1c decreased in the teneligliptin group but significantly increased in the control group. FPG and RLP-C significantly decreased in the teneligliptin group. Plasma lipoprotein-related parameters except RLP-C were not affected by teneligliptin treatment. Conclusion Teneligliptin treatment significantly reduced plasma levels of RLP-C, FPG, and HbA1c in patients with diabetes with CKD who are undergoing hemodialysis.

Background and study aims Positive horizontal margins in resected specimens are sometimes encountered after endoscopic submucosal dissection (ESD) for early gastric cancers, and appropriate treatment strategies for these cases are not established. The aim of this study was to evaluate current empirical treatments for patients with positive horizontal or indeterminable margins after ESD. Patients and methods We performed a multicenter survey and data from 14 hospitals were collected. The pooled proportions of positive horizontal or indeterminable margins and those of patients followed up without early intervention were calculated using a logistic-normal random-effects model. For calculating pooled estimates, subgroup analyses of high- and non-high-volume centers were conducted. Results A total of 11,796 ESD cases were enrolled and 229 patients (2 %) had positive horizontal or indeterminable margins. Ninety-eight cases were treated within 30 days of ESD and 131 cases were followed up without early treatments. Pooled estimates of positive margins in high- and non-high-volume centers were 1 % (95 % CI: 1 % – 2 %) and 2 % (95 % CI: 1 % – 4 %), respectively, and were not heterogeneous (P = 0.191). The proportion of patients followed up without early intervention ranged from 30 % to 100 %. The pooled estimate was 68 % (95 % CI: 50 % – 83 %). The pooled estimates of high- and non-high-volume centers were 65 % (95 % CI: 38 % – 85 %) and 72 % (95 % CI: 44 % – 89 %), respectively, and were not heterogeneous (P = 0.692). Conclusion There was insufficient consensus regarding treatment strategies used for early gastric cancer with positive horizontal or indeterminable margins after ESD. Further studies are required to establish a consensus.

Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of unrelated bone marrow transplantation due to aplastic anemia associated with DC. The patient died of uncontrollable refractory intestinal bleeding. Three cases of DC with life-threatening hemorrhaging after transplantation have been reported; however, the bleeding origin could not be determined. Our case is the only patient in which a gastrointestinal bleeding point, jejunal multiple angioectasia, was determined.

Background and Aim: Toll-like receptor (TLR) 2 and TLR4 are cell surface signaling receptors that are involved in the recognition of and host response to Helicobacter pylori. Our aim was to investigate the association between TLR gene polymorphisms and susceptibility of Japanese subjects to 4 H. pylori-related gastrointestinal diseases. Methodology: A total of 100 patients with histologically diagnosed gastric cancer, 105 patients with gastric ulcer, 102 with atrophic gastritis, 72 with duodenal ulcer and 428 healthy controls were recruited. A TaqMan assay was used to genotype 7 single nucleotide polymorphisms (SNPs) in TLR2 and 6 SNPs in TLR4. Results: There was a tendency for TLR4 rs10759932 TC/CC genotypes to be associated with a decreased risk of gastric cancer (p = 0.059); however, this did not reach statistical significance. No significant associations were found between polymorphisms in TLR2 or TLR4 and the risks for gastric cancer, gastric ulcer, duodenal ulcer, or atrophic gastritis. Conclusion: The 13 SNPs inTLR2 and TLR4 examined in this study may not be linked with the development of H. pylori-related gastrointestinal diseases. Further studies with larger numbers of subjects are necessary to verify the present findings.

Background and Aim: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70–90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. Lactobacillus gasseri can suppress both clarithromycin-susceptible and -resistant strains of H. pylori in vitro. The aim of this study was to determine the effect of pretreatment with L. gasseri- containing yogurt on H. pylori eradication. We conducted a randomized, controlled clinical trial in patients with H. pylori infection. Methods: A total of 229 patients were randomized into either a 1-week triple therapy of rabeprazole (10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200 mg bid) or triple therapy plus L. gasseri-containing yogurt. In the yogurt-plus-triple therapy groups, yogurt containing L. gasseri OLL2716 (112 g) was given twice daily for 4 weeks (3 weeks pretreatment and also 1 week during eradication therapy). Clarithromycin resistance was determined by the detection of a mutation in 23S rRNA using nested polymerase chain reaction and the direct sequencing of DNA from pretreatment feces. H. pylori eradication was diagnosed based on the urea breath test and a stool antigen test after 8 weeks of eradication. Results: The status of H. pylori susceptibility to clarithromycin was successively determined in 188 out of 229 samples. The rate of infection with clarithromycin-resistant strains of H. pylori was 27.1%. Overall eradication (intention to treat/per protocol) was 69.3/74.5% for the triple-only group, and 82.6/85.6% for the yogurt-plus-triple group (P = 0.018/P = 0.041). Eradication of primary clarithromycin-resistant strains tended to be higher for yogurt-plus-triple therapy than triple-only therapy (38.5 vs 28.0%, respectively, P = 0.458). Conclusion: This study confirmed that the major cause of treatment failure is resistance to clarithromycin. A 4-week treatment with L. gasseri-containing yogurt improves the efficacy of triple therapy in patients with H. pylori infection.

Aim. The study assessed the usefulness of a recently developed method for respiratory rate (RR) monitoring in patients undergoing endoscopic submucosal dissection (ESD) under deep sedation.Methods. Study subjects comprised 182 consecutive patients with esophageal cancer or gastric cancer undergoing ESD. The usefulness of acoustic RR monitoring was assessed by retrospectively reviewing the patients’ records for age, gender, height, weight, past history, serum creatinine, RR before ESD, and total dose of sedative.Results. Respiratory suppression was present in 37.9% of (69/182) patients. Continuous monitoring of RR led to detection of respiratory suppression in all these patients. RR alone was decreased in 24 patients, whereas both RR and blood oxygen saturation were decreased in 45 patients. Univariate analysis showed female gender, height, weight, and RR before treatment to be significantly associated with respiratory suppression. Multivariate analysis showed RR before treatment to be the only significant independent predictor [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.73–0.95, andP=0.006] of respiratory suppression.Conclusion. In this study, the difference in RR before treatment between patients with and without respiratory suppression was subtle. Therefore, we suggest that acoustic RR monitoring should be considered in patients undergoing ESD under sedation to prevent serious respiratory complications.

To develop probiotics for Helicobacter pylori infection, we screened 203 Latobacillus strains. Lactobacillus gasseri OLL2716 (LG21) was selected as the most effective strain to inhibit the growth of H. pylori by in vitro tests and animal study. We examined the effects of yogurt containing LG21 on H. pylori infection in humans. The intake of yogurt containing LG21 both decreases the number of H. pylori and also reduces mucosal inflammation. LG21 was shown to be effective as a probiotic for H. pylori infection.

Background: Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are important factors in gastric mucosal injury. However, the relationship between H. pylori and NSAID-related gastroduodenal mucosal injury has not been clarified. Aim: To determine the role of H. pylori in NSAID-induced gastric mucosal injury and to examine the effects of H. pylori, indomethacin and sofalcone on gastric epithelial cells in culture, as a useful model to study gastric mucosal injury. In addition, we studied the effect of sofalcone, a gastric mucosal protection agent, on H. pylori and NSAID-induced gastric mucosal injury. Methods: Cytotoxic and noncytotoxic strains of H. pylori were used, each with an inoculum of 107 cfu/mL. The effect on the growth of RGM–1 cells (a rat gastric epithelial cell line) was studied by MTT assay, and levels of prostaglandin E2 in culture supernatants were measured by EIA. Results: Both cytotoxic and noncytotoxic strains of H. pylori tended to induce cell injury in RGM-1 cells at 48 h after inoculation. Indomethacin alone induced gastric epithelial injury in a dose-dependent manner, but did not augment cell injury induced by H. pylori. In addition, sofalcone (10−5 mol/L) showed a suppressive effect on indomethacin-induced gastric epithelial injury. Conclusion: These findings indicate that indomethacin induces gastric mucosal injury regardless of H. pylori infection, and suggests that sofalcone may be a useful drug in the treatment of NSAID-induced mucosal injury.

Objective The objective of this study was to comparatively analyse the gastric fluid (GF) microbiota between patients with functional dyspepsia (FD) and healthy controls (HC), and to assess the effect of probiotics on the microbiota. Design Twenty-four Japanese patients with FD who met the Rome III definition and 21 age-matched and gender-matched HC volunteers were enrolled. The patients with FD had been treated with LG21, a probiotic strain. The GF was sampled after an overnight fast using a nasogastric tube. The bile acids concentration was determined by ELISA. The V3-V4 region of 16S rRNA gene was amplified using bacterial DNA from the GF, and then about 30 000 high-quality amplicons per sample were grouped into operational taxonomic units for analyses. Results The ratio of GF samples in which the bile acids were detectable was significantly greater in the FD than in the HC groups. In the bacterial composition analysis at the phylum level, the GF microbiota had a Bacteroidetes > Proteobacteria abundance and an absence of Acidobacteria in the FD group, in contrast, the GF microbiota had a Bacteroidetes Proteobacteria abundance and the presence of Acidobacteria in the HC group. Probiotic therapy in patients with FD shifted the composition of the GF microbiota to that observed in the HC volunteers. Conclusions Alteration in the GF microbiota was found in patients with FD compared with HC volunteers. Reflux of the small intestinal contents, including bile acid and intestinal bacteria, to the stomach was suggested to induce a bacterial composition change and be involved in the pathophysiology underlying FD. Probiotics appear effective in the treatment of FD through the normalisation of gastric microbiota. Trial registration number UMINCTR 000022026; Results.

In patients with functional upper gastrointestinal disorders such as gastroesophageal reflux disease and functional dyspepsia, the presence of symptoms is thought to occur in the absence of any organic diseases and the mechanisms behind this remain unclear. We therefore examined the relationship between stomach-related biomarker levels and symptoms. Twenty-four outpatients who had taken proton-pump inhibitors every day were enrolled in this study. The subjects consumed yogurt containing 109 colony-forming units of Lactobacillus gasseri OLL2716 (LG21) every day for three months. They underwent four clinical examinations in total. Each examination consisted of answering a questionnaire with a frequency scale for the symptoms of GERD (FSSG), and included measurements of the serum gastrin, ghrelin, and pepsinogens I and II levels. As a result, the FSSG score and the PGI value showed a decrease and an increase, respectively, after LG21 treatment when analyzed without age adjustment. A multiple regression analysis with additional adjustments for gender and age revealed a strong association between the PGI value and the FSSG symptom scores. Therefore either the PGI level itself or the factors regulating the PGI level might be involved in the etiology of these symptoms.

The mechanism by which Helicobacter pylori induces apoptosis remains unclear. In a previous study using biopsy samples, we found a significant correlation between the urease activity of an H. pylori strain and the apoptosis level induced by this strain. Therefore, in this study, we investigated whether urease and/or the ammonia generated by urease can induce apoptosis. Human gastric epithelial cell lines were cocultured with H. pylori , and the levels of apoptosis and ammonia production were measured. The medium was supplemented (or not supplemented) with urea and cytokines. While a large amount of ammonia (>30 mM) accumulated in the coculture containing urease-positive H. pylori and urea, no significant degree of apoptosis occurred. In the presence of tumor necrosis factor alpha (TNF-α), however, a marked acceleration of apoptosis was found in this coculture. Such enhancement of apoptosis was also induced by the addition of 4 to 8 mM ammonia to the cell culture without either H. pylori or urea but containing TNF-α. These results suggested that ammonia accelerates cytokine-induced apoptosis in gastric epithelial cells, while ammonia or urease molecules alone are unable to induce a significant degree of apoptosis.

Summary Background: Sofalcone has been reported to exert anti-ulcer and gastroprotective actions, but its exact mechanism of action remains unknown. In our laboratory, we found that indomethacin-induced gastric ulcers become worse when associated with Helicobacter pylori infection. Methods: We employed the H. pylori-infected gnotobiotic murine model to examine the effect of sofalcone on indomethacin-induced gastric ulcers in the presence of H. pylori infection. In vitro experiments were also done to evaluate the effects of sofalcone on H. pylori growth, adherence of H. pylori to the MKN45 cells (a human gastric epithelial cell line), and these cells' IL-8 production in the presence of H. pylori. Results: We found that sofalcone produced a significant improvement in ulcer size as well as a substantial reduction in the number of H. pylori colonies in H. pylori-infected gnotobiotic mice. In vitro sofalcone has a significant bacteriocidal effect against H. pylori and can also significantly prevent adherence of this bacterium to MKN45 cells, thus remarkably reducing IL-8 production of these cells in response to stimulation by H. pylori. Conclusion: Our results suggest that sofalcone can improve ulcer healing by the mechanisms mentioned above.

Summary Background Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a systemic disorder that predominantly affects the bowels but is also associated with venous thromboembolism (VTE). Aim To provide a quantitative assessment of the association of IBD with venous thromboembolism risk and to explore the possible sources of heterogeneity in the current literature, a meta-analysis of case–control and cohort studies was conducted. Methods Studies were identified by a literature search of the PubMed and Scopus databases (from inception inclusive 31 December 2012) for English language studies. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias. Results Eleven studies met our inclusion criteria. The summary RR for deep venous thromboembolism (DVT) and pulmonary embolism (PE) comparing subjects both with and without IBD was 2.20 (95% CI 1.83–2.65). After adjusting for obesity and smoking, summary relative risks near 2.0 were seen for venous thromboembolism in both UC and CD patients. Conclusion This meta-analysis showed that inflammatory bowel disease is associated with an approximately two-fold increase in the risk of venous thromboembolism.

Churg-Strauss syndrome (CSS) is a systemic vascular disorder characterized by severe bronchial asthma, hypereosinophilia, and allergic rhinitis. Small intestinal ulcers associated with CSS are a relatively rare manifestation that causes gastrointestinal bleeding. Multiple deep ulcers with an irregular shape are characteristic of small intestinal involvement of CSS. Video-capsule-endoscopy (VCE), double-balloon endoscopy (DBE) and Spirus assisted enteroscopy have been developed recently and enabled observation of the small intestine. In this case report, we have described a patient with CSS who had multiple deep ulcers in the jejunum detected by oral DBE. Since severe gastrointestinal (GI) involvement has been identified as an independent factor associated with poor outcome, the careful investigation of GI tract must be needed for CSS patients with GI symptoms. We describe the usefulness of DBE for diagnosis of small intestinal ulcers in patient with CSS.

To evaluate the efficacy of adding irsogladine maleate (IM) to proton-pump inhibitor (PPI) therapy in non-erosive reflux disease (NERD) treatment.One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM (group I) or rabeprazole plus placebo (group P). The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and the short form (SF)-36 quality of life questionnaires after four weeks of treatment. We also assessed whether patients with NERD with minimal changes (grade M) had different responses to the therapies compared with patients who did not have minimal changes (grade N).Group I and group P showed significant improvements in their FSSG scores after the treatment (from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P. Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N (modified Los Angeles classification) (7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041). The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.The addition of IM to rabeprazole significantly improves gastroesophageal reflux disease symptoms and the quality of the lives of patients with NERD grade N.

Cost-Effectiveness Analysis of Radiofrequency Ablation for Barrett's Esophagus With Low-Grade Dysplasia: Results From a Randomized Controlled Trial (SURF) Kai Yi N. Phoa, Wilda Rosmolen, Bas L. Weusten, Raf Bisschops, Erik J. Schoon, Krish Ragunath, Grant Fullarton, Massimiliano di Pietro, Narayanasamy Ravi, Mike Visser, Johan Offerhaus, Cees A. Seldenrijk, Sybren L. Meijer, Fiebo T. Ten Kate, Jan Tijssen, Marcel G. Dijkgraaf, Jacques J. Bergman

To examine the efficacy of Lactobacillus gasseri OLL2716 (LG21) as a probiotic for Helicobacter pylori in humans, 31 subjects infected with the bacterium ingested yogurt containing LG21 daily for an 8 week period. The [(13)C]urea breath test and assays of serum pepsinogens revealed a significant improvement following LG21 treatment. LG21 was thus determined to be effective in both suppressing H. pylori and reducing gastric mucosal inflammation.

Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. An increasing number of malignant mesothelioma cases have been reported in recent years. We report here a very rare case of malignant peritoneal mesothelioma with both umbilical hernia and umbilical metastasis which is also called Sister Mary Joseph’s nodule. We performed laparoscopy which showed specific laparoscopic findings, and the pathological findings of the biopsy specimen led to the diagnosis. This case was associated with umbilical hernia which could be induced by massive ascites. A newly developed abdominal hernia should be noted as a primary symptom of malignant peritoneal mesothelioma, as shown in the present case.