Effect of Instruction on Preventing Delayed Bleeding after Colorectal Polypectomy and Endoscopic Mucosal Resection.

BACKGROUND: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. METHODS: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. RESULTS: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. CONCLUSION: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.

Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer.

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12-122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134-9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.

Phosphorylated STAT3 expression linked to SOCS3 methylation is associated with proliferative ability of gastric mucosa in patients with early gastric cancer.

Gastric cancers (GCs) may develop in the gastric mucosa after elimination of Helicobacter pylori (H. pylori) using eradication therapy. Cytokine signaling is a key mechanism underlying GC development and progression, and STAT3 signaling may serve a central role in gastritis-associated tumorigenesis. In the present study, suppressor of cytokine signaling 3 (SOCS3) methylation was examined, as an activator of phosphorylated (p-)STAT3 expression in the non-neoplastic gastric mucosa (non-NGM) of patients with early GC. The methylation status of the SOCS3 gene promoter was analyzed using methylation-specific PCR in the non-NGM of patients with or without early GC. Expression levels of p-STAT3 and Ki67 were investigated immunohistochemically in non-NGM with early GC before and after H. pylori eradication. In non-NGM, SOCS3 promoter methylation was detected in 17/51 patients (33.3%) with early GC. In those patients, the non-NGM labeling indices of both Ki67 and p-STAT3 were significantly higher compared with that in patients with early GC without SOCS3 methylation. A significant correlation between Ki67 and p-STAT3 expression levels was demonstrated in the non-NGM of patients with early GC. In patients with early GC without SOCS3 methylation, the labeling indices of both Ki67 and p-STAT3 in non-NGM were significantly reduced after H. pylori eradication, whereas no such change was observed in patients with early GC with SOCS3 methylation. SOCS3 methylation is associated with continuous p-STAT3 overexpression and enhanced epithelial cell proliferation in non-NGM of patients with early GC.

Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin.

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues.

Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of Reg family gene expression in a colitis model and focused on the regulation of Reg IIIß and IIIγ, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the Reg family and cytokines (IL-6, IL-17, and IL-22) was evaluated by real-time RT-PCR, and Reg IIIß/γ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among Reg family genes, Reg IIIß and IIIγ were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated cytokines (IL-6, IL-17, and IL-22) was also significantly increased in those tissues, being significantly correlated with that of Reg IIIß/γ. STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.

DNA methylation silencing of microRNA gene methylator in the precancerous background mucosa with and without gastric cancer: Analysis of the effects of H. pylori eradication and long-term aspirin use.

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.

Molecular alterations and PD-L1 expression in non-ampullary duodenal adenocarcinoma: Associations among clinicopathological, immunophenotypic and molecular features.

Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare. Little is known about its clinicopathological and molecular features or its management. Herein we retrospectively analyzed the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG island methylator phenotype (CIMP), and immunostaining including mucin phenotype and PD-L1 expression. The incidence of MSI, KRAS/BRAF/GNAS mutations and CIMP was 51.6%, 34.4%/3.1%/6.5% and 28.1%, respectively. PD-L1 expression was seen in 34.4% of patients. No significant associations between clinicopathological features and KRAS/BRAF/GNAS genetic mutations or CIMP were found. Histologically non-well-differentiated-type NADCs and those in the 1st portion of the duodenum were significantly associated with later stages (stages III-IV) (P = 0.006 and P = 0.003, respectively). Gastric-phenotype NADCs were frequently observed in the 1st portion and in late-stage patients; their cancer cells more frequently expressed PD-L1. Histologically, the non-well-differentiated type was an independent predictor of PD-L1 expression in cancer cells (OR 25.05, P = 0.04) and immune cells (OR 44.14, P = 0.02). Only late-stage disease (HR 12.23, P = 0.01) was a prognostic factor for worse overall survival in a Cox proportional hazards regression model. Our observation of high proportions of MSI and PD-L1 expression may prompt the consideration of immune checkpoint inhibitors as a new treatment option for NADCs.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

Duodenal low-grade inflammation and expression of tight junction proteins in functional dyspepsia.

BACKGROUND: Duodenal changes in functional dyspepsia (FD) might be related to the development of symptoms. However, relationships among low-grade inflammation, Helicobacter pylori infection, and protein expression by tight junctions (TJs) in the duodenum are unclear. We therefore aimed to determine whether duodenal inflammation and genes associated with TJ proteins are associated with FD. METHODS: We evaluated inflammatory cell infiltration of the duodenum, H pylori infection, and genes associated with TJ proteins in duodenal biopsy specimens from 35 patients with FD according to the Rome III diagnostic questionnaire and from 31 asymptomatic controls without structural diseases. We immunohistochemically detected eosinophils and mast cells and counted them. The expression of claudins, occludin, and zonula occludens (ZO)-1 mRNA was evaluated using quantitative RT-PCR. Infection with H pylori was determined by measuring serum antibodies, rapid urease or urea breath tests, and endoscopic findings. RESULTS: Sex, age, and H pyloriinfection rates did not differ between patients with FD and controls. The numbers of eosinophils and mast cells were significantly increased in patients with FD compared with controls and were significantly correlated. Inflammatory cell counts in the duodenum were not associated with H pylori infection status. Claudin-3 mRNA expression was increased in the patients with FD. CONCLUSIONS: Subtle inflammation identified in the duodenum of patients with FD might be associated with the onset and persistence of dyspeptic symptoms.

Colonic M1 macrophage is associated with the prolongation of gastrointestinal motility and obesity in mice treated with vancomycin.

Gut microbiota plays a pivotal role in not only the gastrointestinal (GI) immune system but also GI motility and metabolism. Antibiotic treatments are likely to affect the gut flora and GI immune system, subsequently disturbing GI motility and body metabolism. In the present study, we investigated antibiotic­induced alterations of body metabolism and GI motility in association with the macrophage profile in the colon. Specific pathogen­free (SPF) mice (ICR; 6 weeks old; female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 5 weeks, and subsequent changes in pathophysiology were observed. The expression of CD80 and CD163 was examined by immunohistochemistry and the expression of cytokines in colonic tissues was evaluated by reverse transcription­quantitative polymerase chain reaction. The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. In the vancomycin­treated SPF mice, significant increases in body weight, cecum weight and GITT were observed compared with the controls. The number of CD80­positive M1 macrophages and the expression of interferon­Î³ and interleukin­12 were significantly increased, whereas, the numbers of CD163­positive M2 macrophages in the mucosal and muscular layers were decreased in the colon of vancomycin­treated mice. GITT was positively correlated with the number of CD80­positive M1 macrophages in the colonic mucosa; however, was negatively correlated with the number of CD163­positive M2 macrophages in the mucosal and muscular layers. Therefore, it was suggested that antibiotic treatment affects body metabolism and GI motility, accompanied by alterations in macrophage polarization and cytokine profiles in the colon.

Objective image analysis of non-magnifying image-enhanced endoscopy for diagnosis of small depressed early gastric cancers.

Background Gastric cancers (GC) after H. pylori eradication are difficult to diagnose even by magnifying narrow-band imaging (NBI) or blue laser imaging (BLI) endoscopy. Little is known with regard to non-magnifying (NM)-NBI/BLI for early GC so we examined the efficacy of NM-NBI/BLI for early GC diagnosis. Methods We retrospectively analyzed the images of 29 small (≤ 1 cm) intramucosal GC that had been treated with endoscopic submucosal dissection and 137 benign depressed lesions (BDLs). The brightness and shape of the GCs and BDLs by NM-NBI/BLI were assessed with ImageJ software. Results The NBI/BLI-index, which indicates the brightness of NBI/BLI for visualization, was significantly higher in GC than BDLs in both the H. pylori -infected ( P  = 0.009) and -eradicated group ( P  < 0.0001), indicating that GC exhibited brighter colors than the normal surrounding mucosa. The C-index, which refers to the circularity of the lesion, was also significantly higher in GC than BDLs in both H. pylori -infected ( P  = 0.006) and -eradicated cases ( P  = 0.004). Based on receiver-operating characteristic curve analysis, cutoff values for the NBI/BLI- and C-indices for GC were 1.04 and 0.58 in the H. pylori -infected cases, and 0.98 and 0.64 in the H. pylori -eradicated cases. With the reference value of the NBI/BLI-index set at ≥ 0.69 with the C-index at ≥ 0.21 in the H. pylori -infected and the NBI/BLI-index at ≥ 0.80 with the C-index at ≥ 0.32 in the H. pylori -eradicated cases, both the sensitivity and negative predictive value for early GC were 100 %. A high NBI/BLI-index tended to be associated with a wide length of the intervening part histologically in the H. pylori -eradicated cases ( P  = 0.09). Conclusions The small depressed-type early GC had brighter color and rounder shape compared to BDLs in both H. pylori -infected and -eradicated cases. The NBI/BLI- and C-indices calculated by the image analysis may facilitate identification of small depressed-type GC.

Sex differences in associations among metabolic syndrome, obesity, related biomarkers, and colorectal adenomatous polyp risk in a Japanese population.

To investigate sex differences in the associations among metabolic syndrome, obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a cross-sectional, multicenter study was conducted on 489 consecutive individuals who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of adiponectin and leptin, as well as homeostatic model assessment of insulin resistance were also evaluated. The presence and number of adenomatous polyps, including advanced adenoma, were higher in men than in women. Metabolic syndrome was a risk factor for adenomatous polyps in both sexes. Large waist circumference was an independent risk factor for adenomatous polyps in men, and high BMI and large waist circumference were risk factors for adenomatous polyps in women. Interestingly, low BMI was associated with large adenomatous polyps (≥10 mm) and advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp development only in women. In contrast, the highest quartile of leptin concentration had a 3.67-fold increased adenomatous polyp risk compared with the lowest quartile only in men. These results indicate that regarding colorectal pathogenesis, sex differences were identified in obesity but not in metabolic syndrome. Visceral obesity and a high serum leptin level may be risk factors for colorectal adenomatous polyp development in Japanese men.

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis.

The risk of gastric cancer (GC) remains in precancerous conditions, including atrophic mucosa and intestinal mucosa (IM), even after H. pylori treatment. To define the molecular changes following H. pylori eradication, molecular alterations in the gastric mucosa with and without GC were evaluated in a long-term follow-up study. A total of 232 biopsy specimens from 78 consecutive patients, including atrophic gastritis patients with follow-up ≥3 y after successful H. pylori eradication (AG group), patients who developed early GC after successful eradication (≥3 y) (GC group), and patients with H. pylori-positive atrophic gastritis (Hp group), were analyzed. H. pylori eradication was associated with significant reductions of methylation of several genes/loci in atrophic mucosa (non-IM), but not in IM. In contrast, the incidence of CpG island methylator phenotype (CIMP) in IM was significantly higher in the GC group than in the AG group. miR-124a-3 methylation and miR-34c methylation were more frequently identified in IM, with very few in non-IM mucosa among the three groups. H. pylori eradication can reverse methylation only in non-IM mucosa. CIMP in IM may have potential as a surrogate maker of GC development, and methylation of miR-124a-3 and miR-34c is a molecular event in IM that may not be associated with GC development.

Rectal Foreign Body of Eggplant Treated Successfully by Endoscopic Transanal Removal.

Transanal rectal foreign body implies that a foreign body has been inserted transanally due to sexual orientation or other reasons and cannot be removed. Such cases require emergency measures because foreign bodies often present difficulties in manual removal or endoscopic removal and may even require surgery when peritonitis due to gastrointestinal perforation occurs. We report a patient in our hospital who had a rectal foreign body inserted into the deep part of the proctosigmoid that could be removed endoscopically. A 66-year-old man visited our hospital because of an eggplant which had been inserted into his rectum by his friend and could not be removed. Since plain abdominal computed tomography showed a foreign body thought to be an eggplant in the proctosigmoid, the foreign body was captured and removed with a snare under lower gastrointestinal endoscope guidance.

Filaggrin and tight junction proteins are crucial for IL-13-mediated esophageal barrier dysfunction.

Eosinophilic esophagitis (EoE) is an allergy-mediated disease that is accompanied by IL-13 overexpression and an impaired esophageal barrier. Filaggrin (FLG) and tight junction (TJ) proteins are considered to contribute to epithelial barrier function. However, their functional involvement in EoE has not been elucidated. Here, we aimed to determine the IL-13-mediated barrier dysfunction and expression of TJ-related proteins in EoE and to characterize interactions among TJ-related proteins involved in the barrier function of the esophageal epithelium. Biopsy specimens from EoE patients were analyzed. Primary human esophageal epithelial cells (HEECs) were cultured using an air-liquid interface (ALI) system. The permeability of TJs was assayed by biotinylation. Transepithelial electrical resistance (TEER) was measured after stimulation with IL-13 and after siRNA silencing of FLG expression. FLG and TJ genes and proteins were assessed by quantitative RT-PCR, Western blot analysis, and immunofluorescent staining. The biotinylation reagent diffused through the paracellular spaces of whole stratified epithelial layers in EoE biopsy samples. The TEER decreased in ALI-cultured HEECs after IL-13 stimulation. Although the protein level of FLG decreased, that of the TJ proteins increased in the mucosa of EoE biopsy samples and in ALI-cultured HEECs after IL-13 stimulation. IL-13 altered the staining patterns of TJ proteins and the epithelial morphology. FLG siRNA transfection significantly decreased TEER. The IL-13-mediated reduced esophageal barrier is associated with the altered expression pattern but not with the levels of TJ-associated proteins. A deficiency of FLG altered the stratified epithelial barrier. NEW & NOTEWORTHY Esophageal permeability to small molecules was increased in patients with eosinophilic esophagitis (EoE) and could be induced by IL-13 in our unique air-liquid interface-cultured primary multilayer human esophageal epithelial cells in vitro. A deficiency of filaggrin disrupted the esophageal stratified epithelial barrier. The decreased esophageal barrier in EoE was associated with the altered staining pattern of tight junction proteins, although the levels of the proteins themselves do not appear to be changed.

Association between gastrointestinal motility and macrophage/mast cell distribution in mice during the healing stage after DSS­induced colitis.

Irritable bowel syndrome (IBS) frequently occurs after infectious colitis or inflammatory bowel disease in patients with complete remission. This suggests that post­inflammation­associated factors may serve a role in the pathophysiology of IBS; however, the mechanism responsible remains unclear. In the present study, the involvement of macrophages and mast cells in alteration of gastrointestinal (GI) motility was investigated in mice in the remission stage after acute colitis. C57BL/6 mice were administered 2% dextran sulfate sodium in drinking water for 5 days and their intestinal tissues were investigated at intervals for up to 24 weeks. Expression of the mannose receptor (MR) and tryptase was examined by immunohistochemistry, and the GI transit time (GITT) was measured by administration of carmine red solution. A minimal degree of inflammatory cell infiltration persisted in the colon and also the small intestine of mice in remission after colitis and the GITT was significantly shorter. The number of muscularis MR­positive macrophages was significantly increased in the small intestine of mice in remission after colitis and negatively correlated with GITT. Furthermore, results indicated that the number of muscularis tryptase­positive mast cells was significantly increased throughout the intestine of mice during the healing process after colitis and was positively correlated with GITT. The present findings suggested an increased number of macrophages and/or mast cells in the intestinal muscular layer may be associated with the pathophysiology of GI dysmotility after colitis.

[Diagnosis of duplication of the sigmoid colon prior to surgery:a case study].

A 16-year-old woman identified with colonic distention using chest X-rays visited our hospital. Although abdominal computed tomography (CT), colonoscopy, and barium enema study indicated suspected duplication of the sigmoid colon, the exact portion of communication between the normal colon and the duplicated colon could not be determined. The patient was released, but followed up due to the lack of symptoms. After 7 months, she was urgently re-hospitalized due to the complaint of abdominal pain. Her abdominal CT revealed the wall thickness and distention of the duplication as well as voluminous stool containing barium. After the improvement of her symptoms and on the basis of the inflammatory findings, laparoscopic surgery was performed on the patient. Finally, the lesion was diagnosed as tubular- and continuous-type colonic duplication. Duplication of the colon is a relatively rare occurrence in adulthood. Herein, we report a case of duplication of the sigmoid colon diagnosed prior to surgery in an adult.

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95% CI: 0.06-0.41, p = 0.0002), but was less effective in reversing the methylation that occurred in IM. Frequent hypermethylation including that of CDH1 in AM increased in the GC group compared to the AG group, and CDH1 methylation was an independent predictive marker of GC (OR: 8.50, 95% CI: 2.64-25.33, p = 0.0003). In patients with long-term aspirin use, the changes of molecular events in AM but not IM may be an important factor in the reduction of cancer incidence. In addition, methylation of the CDH1 gene in AM may be a surrogate of GC.

Involvement of gut microbiota in the association between gastrointestinal motility and 5­HT expression/M2 macrophage abundance in the gastrointestinal tract.

Serotonin (5­hydroxytryptamine; 5­HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5­HT expression and macrophage abundance in the GI tract was examined. Germ­free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen­free mice and their GI tissues were evaluated 4 weeks later. The expression of 5­HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5­HT­positive endocrine cells and muscularis MR­positive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5­HT­positive cells in the upper GI and muscularis MR­positive macrophages throughout the GI tract. The numbers of 5­HT­positive endocrine cells and muscularis MR­positive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5­HT/muscularis MR­positive macrophage axis in the GI tract.

Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study.

Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored < 80 % accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups. Results A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P < 0.001). Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569).