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We herein report a very unusual case of small bowel obstruction caused by phytobezoar in a 69-year-old woman who consumed a large amount of bracken. The patient presented with nausea and vomiting. Computed tomography revealed an air-filled foreign body in the jejunum that had likely caused the small bowel obstruction. A fibrous foreign body diagnosed as a phytobezoar was detected using double-balloon enteroscopy. The obstruction was successfully resolved by crushing the phytobezoar repeatedly using a snare. Small bowel obstructions caused by phytobezoars are often treated with surgical interventions. However, endoscopic fragmentation using a snare is a minimally invasive treatment alternative.

Existing options for attaching facial and somato prostheses, such as skin adhesives, are problematic because of microbial colonization and skin irritation. This study aims to evaluate the suitability of adhesive polyurethane gel sheets containing cetylpyridinium chloride (CPC)-montmorillonite (Mont) for prosthesis fastening.Adhesive gel sheets were fabricated as mixtures of base resin (99.6 wt% polyol) and hardening agent at a ratio of 3:1 with 0 (control), 2, 5, 10, or 15 wt% CPC-Mont. The controlled release of CPC, antimicrobial activity, in vitro skin irritation, and adhesive force against silicone and human skin at different blending ratios were determined. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA), analysis of covariance (ANCOVA), Tukey's test, or single regression analysis, as appropriate.The amount of CPC released increased with the CPC-Mont blending ratio and was linearly proportional to the surface occupation area ratio of CPC-Mont. The samples with5 wt% CPC-Mont exhibited antimicrobial activity against Staphylococcus aureus at an exposure time of 0 d, and samples with2 wt% CPC-Mont exhibited antimicrobial activity against Candida albicans at an exposure time of 1 d. All samples were classified as non-irritant based on an in vitro skin irritation test. The adhesive force on the silicone material and human skin decreased with increasing CPC-Mont blending ratio.Samples with 5 wt% CPC-Mont are potential candidates as antimicrobial adhesive polyurethane gel sheets for fastening facial and somato prostheses.

Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear.This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings.Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD.Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

The typical macroscopic appearance of gastrointestinal follicular lymphoma (FL) are multiple white granules or small white polyps, called multiple lymphomatous polyposis type, and subsequent mass lesions with or without ulceration; however, an ulcer type with a stricture is extremely rare. We report a case of a 79-year-old male with severe jejunal stricture due to FL with an uncommon chromosomal translocation t(2;18)(p12;q21). The patient was treated with jejunectomy subsequent rituximab monotherapy with a favorable response. The presence of the stricture made its endoscopic diagnosis confusing; however, it was certainly accompanied by the distinctive white granules on the surface of the tumor as seen in typical FL. With the possibility of an FL with stricture in mind, it is important to collect subtle endoscopic findings of the surrounding mucosa carefully, in order to arrive at an accurate endoscopic diagnosis and eventually to the proper therapeutic option.

No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality. We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores. We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin

To assess the usefulness of linked color imaging (LCI), a recently developed image-enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE).Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non-Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter- and intra-observer agreements were analyzed among endoscopists.WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non-Exs or endoscopists with no experience with EoE patients. Inter-observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively;LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with "moderate" to "substantial" consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.

Eosinophilic gastroenteritis (EGE) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes and presents with a variety of gastrointestinal manifestations. Important diagnostic evidence for EGE can be provided by endoscopy; however, the specific small-bowel capsule endoscopic (SBCE) findings remain unknown. We herein report the SBCE findings of three cases of EGE as well as those of the previous cases. The most common findings in patients with EGE were multiple erythema and erosions with surrounding redness on SBCE; these findings should be considered for the diagnostic evaluation for EGE.

Objects Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. Methods A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010 to 2012 and received at least 1 follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. Results Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles: 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since 2 esophageal adenocarcinoma cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16%-2.44%) in 232 patient-years and 0.31% (-0.13%-1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from esophageal adenocarcinoma. Conclusion This is the largest prospective follow-up study with endoscopy to investigate the incidence of esophageal adenocarcinoma in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs. 1.2%/year).

The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully. We screened initial EGC and adjacent non-cancerous mucosa ESD-resected specimens for somatic variants of 409 cancer-related genes, assessing their mutational burden (MB) to predict molecular markers for metachronous post-ESD development. We compared variants between ten patients diagnosed with MGC more than 3 years after ESD and ten age-matched patients who did not have MGC developments after successful HP eradication. We found no significant background differences between the two groups. In adjacent non-cancerous mucosa, the MB tended to be higher in the patients with metachronous developments than in the others. Somatic genomic alterations of RECQL4, JAK3, ARID1A, and MAGI1 genes were significantly associated with MGC development. The criteria including both the MB and their variants, which had potential significant values for predicting MGC. In conclusion, combined of assessing specific somatic variants and MB may be useful for predicting MGC development. This study included a limited number of subjects; however, our novel findings may encourage further exploration of the significance of the molecular features of EGC that predict MGC development, thereby promoting focused follow-up strategies and helping elucidate the mechanisms.

A 47-year-old man presented with dysgeusia, anorexia, and diarrhea. An endoscopic evaluation showed widespread gastrointestinal nodular inflammation and polyps. The pathological findings were consistent with Cronkhite-Canada Syndrome (CCS). Prednisolone therapy resulted in clinical improvement. However, CCS relapse complicated with gastric obstruction was observed during drug tapering. Although his symptoms disappeared after the reintroduction of steroids, he developed membranous nephritis. Additional cyclosporine A (CyA) treatment dramatically improved his proteinuria and residual gastrointestinal polyposis. The clinical symptoms resolved with steroid treatment, while CyA was effective for both CCS lesions and membranous nephropathy. CyA might therefore be a potential treatment option for CCS associated with membranous nephropathy.

Purpose The mechanical properties, antimicrobial activity, and biocompatibility of a novel antimicrobial tissue conditioner containing cetylpyridinium chloride with montmorillonite (CPC-Mont) were evaluated. Methods To examine the mechanical properties of the novel material, hardness, consistency, and penetration tests were conducted. Antimicrobial activity against Candida albicans (C. albicans) and Staphylococcus aureus (S. aureus) was evaluated. Cell viabilities of fibroblasts and epithelial cells using eluates from materials were measured to evaluate cytotoxicity. In addition, to assess tissue response, animal experiments were conducted. Results The hardness test results were similar to those of other commercially available materials. The novel tissue conditioner showed good antimicrobial activity against C. albicans and S. aureus compared with other materials. This effect was sustained for a week for C. albicans. In the case of S. aureus, microbial growth was suppressed for up to 3 weeks. Cell viability of the novel material for the eluate at 1 day was significantly less than those of other material for both cells. However, the cell viability at 7 days showed no significant difference. Animal experiments demonstrated that inflammatory responses around materials were not observed on the oral mucosa as other material. Conclusion Within the limitations of this in vitro and in vivo study, the results suggest that the newly developed tissue conditioner containing CPC-Mont has not only excellent antimicrobial properties, but also the same mechanical properties and biocompatibility as tissue conditioners on the market.

Objective Esophageal eosinophilia (EE), a histological hallmark of eosinophilic esophagitis, is classified into two endoscopic phenotypes: localized and diffuse EE. Our aim was to determine the prevalence of EE localized in the lower esophagus and to describe its clinical features in comparison with diffuse EE. Methods Data from 81 consecutive patients with EE were retrospectively investigated. EE was histologically defined as ≥15 eosinophils per high-power field. Based on the endoscopic appearance with a histological assessment, EE was classified as either diffuse or localized type. We compared the clinical features, including the medical treatment and natural course, between the two types. Results Of the 81 patients, 52 (64.2%) had diffuse EE, and 29 (35.8%) had localized EE. Among men patients, localized EE was significantly more common than diffuse EE. In localized EE, dysphagia and food impaction were less prevalent, and the presence of rings was significantly less common than in diffuse EE. Acid-suppressive therapy was administered to only 3 of the 29 patients with localized EE. In asymptomatic patients, especially those with localized EE, endoscopic abnormalities did not worsen but rather improved in some findings, such as with regard to furrows or exudate, during the natural course of three years without medical treatment. Conclusion Localized EE has a strong predilection for men patients and accounted for more than one third of all cases of EE. This condition appears to be less symptomatic and necessitates milder medical treatment than diffuse EE and might not worsen progressively.

Intramural esophageal dissection (IED), like esophageal perforation, is a rare complication of eosinophilic esophagitis (EoE). A 44-year-old woman who had experienced EoE for 8 years complained of food impaction, severe neck pain, and odynophagia as well as consulted the emergency unit. She was diagnosed with IED with mediastinal emphysema by enhanced computed tomography. After admission, she was treated conservatively with noninvasive treatment, including fasting, intravenous feeding, and antibiotics. Only nine cases of IED with EoE have been previously reported. All were male, and our patient was the first female patient from Asia. Urgent endoscopy was conducted in eight cases, of which three were worse after endoscopy, and in one case, total esophagectomy was conducted due to subsequent esophageal perforation. We did not perform urgent endoscopy on our patient because of a potentially increased risk of esophageal perforation through the procedure. When patients with EoE complain of severe retrosternal pain, odynophagia, or dysphagia, IED should be considered in addition to food impaction.

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.

BACKGROUND Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P

OBJECTIVES The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. METHODS In this multicenter observation study, GC and non-GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura-Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. RESULTS Overall, 115 GC and 265 non-GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5-5.3]), high EGGIM score (OR 1.8 [1.0-3.1]) and opened-type Kimura-Takemoto (OR 2.5 [1.4-4.5]) had significant associations with GC risk. In the Kyoto classification, opened-type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image-enhanced endoscopy, and map-like redness in the corpus were independent high-risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). CONCLUSIONS The OLGIM stage III/IV, high EGGIM score and open-typed Kimura-Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).

Background: Obesity and metabolic syndrome are considered the risk factors of colorectal adenoma (CRA) and colorectal cancer (CRC). Chemerin is a novel adipocytokine associated with the development of gastric cancer, esophageal cancer, hepatocellular carcinoma, and CRC. However, the relationship between chemerin levels and CRA remains unclear. Objective: This study is aimed at investigating the ­association between serum chemerin levels and the development of CRA. Methods: We conducted a total colonoscopy-based cross-sectional case-control study of 80 male patients with CRA and 80 male age-matched control individuals without CRA, according to their endoscopic findings. Serum chemerin concentrations were measured using a sandwich enzyme-linked immunosorbent assay kit, and the OR of CRA was calculated via logistic regression analysis. Results: The mean serum chemerin level of the CRA group was significantly higher than that of the control group (7.9 ± 0.41 vs. 5.16 ± 0.34 ng/mL, p < 0.001). Serum chemerin level was positively correlated to the development of CRA (r = 0.34). Multivariate logistic regression analysis revealed that a high chemerin level was independently associated with the development of CRA (OR 2.82, 95% CI 1.39–5.72). Conclusions: Our findings indicated that increased serum chemerin levels are positively associated with the presence of CRA in men. Chemerin may play an important role in the development of CRA.

Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon benign disorder leading to esophageal strictures. The etiology remains unknown; however, anti-fungal treatments or endoscopic balloon dilation can improve early esophageal strictures and these rarely require surgical treatment. We report a case of a 46-year-old male with a 6 cm-long esophageal stricture due to EIPD, which did not improve following treatment with an anti-fungal agent, eventually causing aspiration pneumonia. Therefore, we performed a thoraco-laparoscopic esophagectomy, and his symptoms were improved after surgery. This case suggests that a surgical treatment should be considered in patients with extensive, severe strictures attributable to EIPD.

General population-based cohort studies provide solid evidence on mass Helicobacter pylori (HP) eradication effects. Self-reported questionnaires are occasionally used in such studies to ascertain the HP eradication history. However, reports on the reliability of these questionnaires are lacking. This general population-based cohort study included 899 individuals with HP infection at the baseline survey who were reported to have eradicated it at the 5-year follow-up survey. Of these, the medical records of 280 patients were available for investigation, and the HP eradication status of 93 individuals was ascertained. Their medical records were reviewed, and the reliability of the self-reported questionnaire responses was assessed. Of the 91 individuals who successfully eradicated HP based on the medical records, 90 (98.9%) answered the self-reported questionnaire correctly, with an unweighted kappa value of 0.661 (p

OBJECTS Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB. METHODS Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents. RESULTS Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P

To evaluate the in vitro antimicrobial effect of low- and high-viscosity experimental mouthrinses containing cetylpyridinium chloride (CPC) and 4-isopropyl-3-methylphenol (IPMP) on Streptococcus pneumoniae, Klebsiella pneumoniae, Porphyromonas gingivalis, Streptococcus mutans, and Candida albicans.Low- and high-viscosity experimental mouthrinses containing 0.05% CPC and 0.1% IPMP were fabricated. Non-viscous mouthrinses containing either CPC- or IPMP were used as controls. The antimicrobial activity (sterilization or exposure time) of mouthrinses was evaluated based on the bactericidal criterion of10¹ viable cells in 0.1 mL of culture medium.The sterilization time of the low-viscosity experimental mouthrinse was shorter than that of the high-viscosity mouthrinse. However, whereas a 10-minute exposure to the low-viscosity mouthrinse resulted in no viable cells of C. albicans, neither the CPC- or IPMP mouthrinses had an antimicrobial effect for the same exposure time. These findings show that the low-viscosity experimental mouthrinse containing anodal CPC and neutral IPMP exhibited superior antimicrobial effects against pneumonia- and oral infection-related bacteria compared with the control mouthrinses.In Japan, the oral care with the low-viscosity experimental mouthrinse containing CPC and IPMP as alternatives to those based on chlorhexidine are available for preventing the development of pneumonia- and oral infection-related bacteria.

The purpose of this study was to clarify the usage and understanding of denture adhesives among 1,825 denture wearers, aged 40 years and older in Japan, using a web-based survey. The NTTCom Online survey (a closed investigation) was conducted over a period of 4 days using a 13-item questionnaire about denture adhesives. Results showed that 67.1% of the respondents were satisfied with their dentures; 81.5% of respondents knew about denture adhesive, but only 347 (19.0%) had used the product. Products used by the 347 denture wearers included cream type (79.7%), cushion type (16.2%), and powder type (3.2%). The most common reason for the selection of a particular type was "Saw the product" (59.9%), followed by "Saw an advertisement" (19.3%), and "Explanation at a dental clinic" (8.4%). The response of "Ill-fitting denture" significantly affected the response of "Use of denture adhesives" (chi-square test; P < 0.001). Moreover, the sensitivity (0.56) was lower than the specificity (0.75). These findings show that denture adhesives were not always necessary for those with ill-fitting dentures.

Circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) are elevated in patients with inflammatory bowel disease. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis (GMA). We investigated the effect of CA beads on sICAM-1 and sVCAM-1 plasma concentrations in vitro. Because GM adsorption to CA beads increased with a rise in the incubation temperature in our previous study, peripheral blood was incubated with and without CA beads at 5, 25, 37, or 43 °C and plasma sICAM-1 and sVCAM-1 was measured. The sICAM-1 and sVCAM-1 concentrations in samples incubated with CA beads were significantly lower than those without CA beads at all four temperatures. However, no significant differences were observed both sICAM-1 and sVCAM-1 plasma levels at the four different temperatures after incubation with CA beads. These results suggest that independent of incubation temperature, sICAM-1 and sVCAM-1 are likely to adsorb CA beads. These molecules may be a new index for predicting the therapeutic effects of GMA.

// Yasushi Takahashi 1 , Kaname Uno 1 , Katsunori Iijima 2 , Yasuhiko Abe 3 , Tomoyuki Koike 1 , Naoki Asano 1 , Kiyotaka Asanuma 1 and Tooru Shimosegawa 1 1 Division of Gastroenterology, Tohoku University, Miyagi, Japan 2 Department of Gastroenterology, Akita University, Miyagi, Japan 3 Department of The Second Internal Medicine, Yamagata University, Miyagi, Japan Correspondence to: Kaname Uno, email: kaname@wa2.so-net.ne.jp Keywords: gastric cancer; helicobacter pylori eradication; mucosal barrier dysfunction; epithelial-mesenchymal transition Received: October 26, 2017 Accepted: February 24, 2018 Published: April 06, 2018 ABSTRACT Gastric cancer (GC) after eradication for Helicobacter pylori ( H.pylori ) increases, but its carcinogenesis is not elucidated. It is mainly found in acid non-secretion areas (ANA), as mucosal regeneration in acid secretory areas (AA) after eradication changes the acidity and bile toxicity of gastric juice. We aimed to clarify the role of barrier dysfunction of ANA by the stimulation of pH3 bile acid cocktail (ABC) during carcinogenesis. We collected 18 patients after curative endoscopic resection for GC, identified later than 24 months after eradication, and took biopsies by Congo-red chromoendoscopy to distinguish AA and ANA (UMIN00018967). The mucosal barrier function was investigated using a mini-Ussing chamber system and molecular biological methods. The reduction in mucosal impedance in ANA after stimulation was significantly larger than that in AA, 79.6% vs. 87.9%, respectively. The decrease of zonula occludens-1 (ZO-1) and let -7a and the increase of snail in ANA were significant compared to those in AA. In an in vitro study, the restoration of ZO-1 and let -7a as well as the induction of snail were observed after stimulation. High mobility group A2 (HMGA2)-snail activation, MTT proliferation, and cellular infiltration capacity were significantly increased in AGS transfected with let -7a inhibitor, and vice versa . Accordingly, using a mini-Ussing chamber system for human biopsy specimens followed by an in vitro study, we demonstrated for the first time that the exposure of acidic bile salts to ANA might cause serious barrier dysfunction through the let -7 a reduction, promoting epithelial-mesenchymal transition during inflammation-associated carcinogenesis even after eradication.

Background/Aims: Obesity and insulin resistance are associated with an increased risk of colorectal adenoma (CRA). Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis through its amplification of insulin secretion in response to oral nutrients; however, its role in human CRA remains unknown. We investigated oral glucose-mediated GLP-1 secretion in patients with adenoma. Methods: We performed a case-control study of 15 nondiabetic patients with pathologically diagnosed CRA and 10 age-matched healthy controls without adenoma. Plasma concentrations of active GLP-1 were measured during a 75 g oral glucose tolerance test. Results: Mean waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) values, the total areas under the curve (AUC) of glucose and insulin were significantly higher in patients with CRA than in controls. The total AUC of GLP-1 (p = 0.01) was lower in patients with CRA than in controls. Moreover, the total AUC of GLP-1 showed a negative correlation with WC, total AUC of glucose, and HOMA-IR. Multiple linear regression analyses revealed that the total AUC of GLP-1 was independently correlated with the number and maximum size of CRAs. Conclusion: GLP-1 could actively participate in the development of CRA in humans, particularly in patients with metabolic syndrome.