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BACKGROUND: Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. METHODS: In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. RESULTS: While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. CONCLUSION: Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication. [ABSTRACT FROM AUTHOR]

Objectives: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC., Methods: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE., Results: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003)., Conclusion: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists., (© 2024 Japan Gastroenterological Endoscopy Society.)

Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective The impact of Helicobacter pylori infection on gastric endoscopic findings in non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGIDs) remains unclear. This study investigated the influence of H. pylori infection on the prevalence and distribution of gastric lesions. Methods The details of 75 patients diagnosed with non-EoE EGIDs were retrospectively reviewed. Of the 56 patients with a definitive diagnosis according to the Japanese criteria (any GI tract; ≥20 eosinophils/high-power field), 25 patients with pathologic gastric eosinophil infiltration (gastric EI; ≥30 eosinophils/high-power field) were investigated in detail. The prevalence and distribution of gastric endoscopy findings were assessed according to the gastric mucosal atrophy status, an indicator of H. pylori infection. Results Erythema (76%) was the most common finding in the gastric EI-positive group, followed by erosions (36%), ulcers (28%), ulcer scars (28%), and edema (24%). None of these lesions differed significantly in frequency between the patients with and without gastric atrophy. When erosions, ulcers, and ulcer scars were unified, they were slightly more common in the gastric bodies of patients with gastric atrophy than those without gastric atrophy; however, no preferential site was found in those without gastric atrophy. We identified six patients with active gastric ulcers, and half had large, deep ulcers with marginal swelling/irregularity. Conclusion Gastric endoscopy findings in non-EoE EGIDs with gastric EI were evenly observed in the stomach, with no specific trend in frequency or distribution depending on atrophic gastritis, an indicator of H. pylori infection. Gastric ulcers in patients with non-EoE EGIDs should be considered in the differential diagnosis of idiopathic peptic ulcers.

Background and Aim: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM., Methods: This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients., Results: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM., Conclusions: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk., Methods: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study., Results: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001)., Conclusions: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c-SRC, which are tumor-promoting genes. The FAXC/ANXA2/c-SRC complex forms in the mitochondria. FAXC enhances SRC-dependent ANXA2 phosphorylation at tyrosine-24, and the C-terminal amino acid residues (351-375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial-mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: Blue light imaging (BLI) and linked color imaging (LCI) are superior to conventional white light imaging for detecting esophageal squamous cell carcinoma (ESCC). Hence, we compared their diagnostic performances in ESCC screening., Methods: This open-labeled, randomized controlled trial was performed at seven hospitals. Patients with a high risk of ESCC were randomly assigned to the BLI group (BLI followed by LCI) and LCI group (LCI followed by BLI). The primary end-point was the detection rate of ESCC in the primary mode. The main secondary end-point was its miss rate in the primary mode., Results: In total, 699 patients were enrolled. The detection rate of ESCC did not significantly differ between the BLI and LCI groups (4.0% [14/351] vs. 4.9% [17/348]; P = 0.565); however, the number of patients with ESCC tended to be smaller in the BLI group (19 vs. 30). Notably, the miss rate of ESCC was lower in the BLI group (26.3% [5/19] vs. 63.3% [19/30]; P = 0.012) and LCI detected no ESCCs missed by BLI. The sensitivity was higher in BLI (75.0% vs. 47.6%; P = 0.042); on the other hand, the positive predictive value in BLI tended to be lower (28.8% vs. 45.5%; P = 0.092)., Conclusions: The detection rates of ESCC did not significantly differ between BLI and LCI. Although BLI may have the potential to be advantageous over LCI for the diagnosis of ESCC, it is still unclear whether BLI is superior to LCI, and a further large-scale study is needed., Trial Registration: Japan Registry of Clinical Trials (jRCT1022190018-1)., (© 2023 Japan Gastroenterological Endoscopy Society.)

Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs., Methods: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study., Results: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737)., Conclusion: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated., (© 2023. Japanese Society of Gastroenterology.)

Purpose: Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years., Methods: We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan-Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno's C-statistics., Results: During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7% and 99.2%, respectively. No significant differences in OS were found among curability categories. The Cox proportional hazards model revealed the geriatric nutritional risk index (GNRI) and the Charlson comorbidity index (CCI) to be predictors of 3-year survival. We established a final model (EGC-2 model) expressed by GNRI - (2.2×CCI) with a cutoff value of 96. The overall survival rate was significantly lower in the model value < 96 group than in the model value ≥ 96 group (P < 0.001)., Conclusions: The prediction model using GNRI and CCI will be useful to support decision-making for the treatment of EGC in elderly patients aged ≥ 85 years., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area., Methods: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment., Results: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years)., Conclusions: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs., (© 2023. Japanese Society of Gastroenterology.)

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)., (© 2021 Japan Gastroenterological Endoscopy Society.)

In this study, a 76-year-old man initially diagnosed with branch-duct pancreatic intraductal papillary mucinous tumor is presented. During follow-up, stenosis was discovered in the main pancreatic duct of the tail. A nodular lesion was found in the pancreatic duct consistent with the stenosis. Distal pancreatectomy was performed since it was suspected to be malignant. Histopathology revealed polymorphic mononuclear cells proliferated with osteoclast-like giant cells in the nodule. The patient was finally diagnosed with anaplastic pancreatic cancer with osteoclast-like giant cells, a relatively rare tumor. It is reported herein with a review of the literature.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2 high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G 0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274 low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274 low cells, and that BEX2 knockdown decreased the tumorigenicity and G 0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G 0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.

Background: Accumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC)., Methods: PDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined., Results: Suppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis., Conclusions: CD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and study aims  We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods  We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results  A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P  < 0.0001). Conclusions  Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

Gastric arteriovenous malformation (AVM) is an uncommon cause of upper gastrointestinal bleeding, and the endoscopic findings are unclear. We herein describe a case of gastric AVM in a 28-year-old man. Esophagogastroduodenoscopy showed a Dieulafoy lesion surrounded by a red mucosa with a sharp margin, which implied blood vessel malformation. Computed tomography angiography and conventional angiography revealed aggregated vessels on the greater curvature. Partial gastrectomy was performed, with no recurrent bleeding postoperatively. The histopathological diagnosis was AVM. We conclude that gastric AVM should be considered in the differential diagnosis of patients who present with a Dieulafoy lesion surrounded by a red mucosa.

We selected appropriate indices for color rendition and determined their recommended values for ultra-high-definition television (UHDTV) production using white LED lighting. Since the spectral sensitivities of UHDTV cameras can be designed to approximate the ideal spectral sensitivities of UHDTV colorimetry, they have more accurate color reproduction than HDTV cameras, and thus the color-rendering properties of the lighting are critical. Comparing images taken under white LEDs with conventional color rendering indices (R a , R 9-14 ) and recently proposed methods for evaluating color rendition of CQS, TM-30, Q a , and SSI, we found the combination of R a and R 9 appropriate. For white LED lighting, R a ≥ 90 and R 9 ≥ 80 are recommended for UHDTV production.

Background: Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients., Methods: A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test., Results: The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females., Conclusions: Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms.

Background: The relative contribution of gastric acid secretion and Helicobacter pylori infection to low-dose aspirin-induced gastropathy remains to be clarified. This is partly because the capability of the infection to modify gastric acid secretion complicates the interaction. The aim of this study was to estimate the association of aspirin-induced mucosal injury, as well as H. pylori infection, with gastric acid output., Methods: A total of 186 male outpatients, comprising 60 aspirin takers, on 100 mg of enteric-coated aspirin daily and 126 non-aspirin takers were prospectively enrolled in this study. Gastrin-stimulated acid output was estimated by the endoscopic gastrin test. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score. Multiple logistic regression analyses were used to adjust for potential confounders., Results: The gastric acid secretion level, with an odds ratio (OR) (95% confidence interval [CI]) of 10.5 (3.0-36.9) and aspirin administration, with an OR (95% CI) of 7.4 (3.0-18.3) were independently associated with gastric mucosal injury, and the co-existence of both factors greatly elevated the risk of mucosal injury, with an OR (95% CI) of 77.0 (13.5-440.0). H. pylori infection, itself, did not show any significant effect on the aspirin-induced mucosal injury after adjusting for gastric acid secretion., Conclusions: This study has demonstrated that aspirin-induced gastropathy is directly associated with gastric acid secretion. In addition, it also suggested that the gastric acid secretion level modulates the association between H. pylori infection and aspirin-induced gastropathy.

Helicobacter pylori infection is the major cause for mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancers. On the other hand, gastric cancers are known to arise from gastric mucosal atrophy. We here report a case of signet ring cell gastric cancer that developed after radiation therapy for MALT lymphoma in H. pylori-uninfected patient whose stomach did not show gastric mucosal atrophy. A 58-year-old female was referred to our hospital for treatment of gastric MALT lymphoma. This patient was not infected with H. pylori, and upper gastrointestinal endoscopy revealed that she did not have gastric mucosal atrophy but had submucosal tumor-like MALT lymphoma lesion in the anterior wall of the upper gastric body. Since conventional eradication therapy was ineffective, her whole stomach was irradiated as a second-line therapy. The MALT lymphoma lesion turned into complete remission state after the therapy. The patient was followed every 6 months by upper gastrointestinal endoscopy for 4 years as complete remission until a newly developed decolorized depressed lesion was detected in the greater curvature of the proximal antrum, a completely different location from the MALT lymphoma lesion. A biopsy specimen from the lesion contained signet ring cell carcinoma, and she was successfully treated by endoscopic submucosal dissection. No signs of recurrence have been detected so far. The radiation therapy for MALT lymphoma might be associated with the occurrence of this signet ring cell gastric cancer, and since MALT lymphoma is indolent in nature, this case suggests that careful consideration is required when choosing the second-line therapy for MALT lymphoma patients.

Objective: In Orientals, deficient aldehyde dehydrogenase 2 (ALDH2) is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). The local metabolism of carcinogenic acetaldehyde in the upper gastrointestinal tract could be involved in the association, but the underlying mechanism has not been fully elucidated. Since an anacidic stomach can promote bacteria-catalyzed local acetaldehyde production, the gastric acid level could also affect acetaldehyde metabolism. This study investigated whether ALDH2-related susceptibility to ESCC differs depending on the gastric secretion level., Material and Methods: Sixty-two patients with ESCC and sex- and age-matched normal controls were enrolled in this study. ALDH2 polymorphism was analyzed by polymerase chain-restriction fragment length polymorphism, and those with an inactive allele (ALDH2-1/2-2 or ALDH2-2/2-2) were defined as ALDH2 deficient. Gastrin-stimulated acid output was assessed by endoscopic gastrin test and hypochlorhydria was defined as 0.6 mEq/10 min or lower. Multiple logistic regression analyses were used to adjust for other potential confounders., Results: ALDH2 deficiency or hypochlorhydria was more prevalent in ESCC compared with controls and both showed increased independent associations with ESCC in multivariate analysis. Stratified analysis by the gastric acid secretion level revealed that the associations between the ALDH2 genotype and ESCC differed according to the individual gastric acid secretion levels and that ALDH2 deficiency was a significant risk factor for ESCC exclusively in individuals with hypochlorhydria with an odds ratio (95% confidence interval): 5.0 (1.2-21.2)., Conclusion: Microbial production of carcinogen acetaldehyde in the presence of gastric hypochlorhydria is most probably involved in the mechanism of ALDH2-related susceptibility to ESCC.

Neutron diffraction data for T(6) porcine insulin were collected to 2.1 A resolution from a single crystal partly deuterated by exchange of mother liquor. A maximum-likelihood structure refinement was undertaken using the neutron data and the structure was refined to a residual of 0.179. The hydrogen-bonding network of the central core of the hexamer was observed and the charge balance between positively charged Zn ions and their surrounding structure was interpreted by considering the protonation and/or deprotonation states and interactions of HisB10, water and GluB13. The observed double conformation of GluB13 was essential to interpreting the charge balance and could be compared with the structure of a dried crystal of T(6) human insulin at 100 K. Differences in the dynamic behaviour of the water molecules coordinating the upper and lower Zn ions were observed and interpreted. The hydrogen bonds in the insulin molecules, as well as those involving HisB10 and GluB13, are discussed. The hydrogen/deuterium (H/D) exchange ratios of the amide H atoms of T(6) porcine insulin in crystals were obtained and showed that regions highly protected from H/D exchange are concentrated in the centre of a helical region of the B chains. From the viewpoint of soaking time versus H/D-exchange ratios, the amide H atoms can be classified into three categories.

Aim: For patients with bowel obstruction, intestinal decompression by a long tube is recommended. We assessed the usefulness of a new technique for insertion of a long tube with a guidewire placed by transnasal ultrathin endoscopy., Methods: Nineteen patients who had been diagnosed as suffering from bowel obstruction underwent long-tube insertion with the ropeway technique using a guidewire placed by transnasal endoscopy. Thirty-three patients who had undergone conventional insertion of a long tube were included as controls. The success rate of intubation of the small bowel and the time required for the procedure were compared between the subjects and controls., Results: The success rate of intubation was 94.7% (18/19) in subjects and 84.8% (28/33) in controls (P = 0.53). The time required for insertion in the subjects and controls was 24.1 +/- 8.1 min and 48.7 +/- 25.3 min, respectively, with a statistically significant difference (P < 0.001). No complications relevant to the procedure were encountered in either of the groups., Conclusion: Long-tube insertion facilitated by transnasal endoscopy reduces the time required for insertion in comparison with the conventional technique without endoscopy. Endoscopy-assisted long-tube insertion with the ropeway method is a safe and useful procedure for decompression in patients with bowel obstruction.

Background: It is often difficult to insert a long intestinal tube in the small bowel of patients with bowel obstruction, and it often results in long procedure time and severe patient distress., Objective: To assess the usefulness of the ropeway method by using a guidewire placed with the assistance of transnasal ultrathin endoscopy in long-tube insertion for patients with bowel obstruction., Design: Prospective, randomized, controlled, single-center study., Patients and Interventions: Thirty-four consecutive patients with bowel obstruction requiring decompression participated in the study and were randomized to the insertion of a long tube with the ropeway method (ILTR) group (ie, insertion along an endoscopically placed guidewire that was passed through only the distal 4 cm of the tube) or insertion by a conventional method group (C group)., Main Outcome Measurements: The time required for the procedure (main), success rate, x-ray exposure time, and intensity of patient distress measured with a visual analog scale of 1 to 5 (better to worse)., Results: The mean (+/- standard deviation) duration of the procedure in the successful cases in the ILTR group and the C group was 16.1 +/- 5.6 minutes and 26.4 +/- 13.8 minutes, respectively (P = .010). The success rate was 100% in the ILTR group and 88% in the C group (P = .48). The mean (+/- standard deviation) x-ray exposure time and intensity of patient distress were, respectively, 16.4 +/- 8.7 minutes and 33.2 +/- 12.3 minutes (P < .001) and 2.6 +/- 0.7 and 3.7 +/- 1.2 (P = .016)., Limitations: Single-center study and small sample size to evaluate overall safety., Conclusions: Long-tube insertion for bowel obstruction with the ropeway method facilitated by transnasal ultrathin endoscopy was superior to conventional fluoroscopic placement with regard to overall procedure success, time required, and patient comfort.

Background: Clinical demand for total colonoscopy (TCS) is increasing. Improvement of the cecal intubation rate and shortening of the examination time would expand the capacity for TCS., Objective: To assess the efficacy of a transparent hood attached to the tip of a colonoscope for cecal intubation in TCS., Design: Prospective, randomized, controlled study., Setting: Single tertiary-referral center., Interventions: TCS., Main Outcome Measurements: Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps., Methods: Patients who were to undergo screening and/or surveillance TCS for colorectal cancer were invited to participate in the study. Cecal intubation time and rate, complications, patient discomfort, and detection rate of colonic polyps were evaluated., Results: A total of 592 patients enrolled in this study were randomly allocated to the hood group and no-hood group. The mean (SD) cecal intubation time in the hood group and the no-hood group was 10.2 +/- 12.5 minutes and 13.4 +/- 15.8 minutes, respectively (P = .0241). The effect of its use was more prominent in the expert endoscopists group compared with those with moderate experience. The cecal intubation rate and the detection rate of small polyps in the 2 groups were similar. The grade of patient discomfort was significantly lower in the hood group. No complications were encountered with the use of the hood., Conclusions: Use of a transparent hood on the tip of a colonoscope shortened the time required for cecal intubation and decreased patient discomfort; such use was more effective among experts in shortening the examination time.

To observe the ionized status of the amino acid residues in proteins at different pH (protein pH titration in the crystalline state) by neutron diffraction, hen egg-white lysozyme was crystallized over a wide pH range (2.5-8.0). Crystallization phase diagrams at pH 2.5, 6.0 and 7.5 were determined. At pH < 4.5 the border between the metastable region and the nucleation region shifted to the left (lower precipitant concentration) in the phase diagram, and at pH > 4.5 the border shifted to the right (higher precipitant concentration). The qualities of these crystals were characterized using the Wilson plot method. The qualities of all crystals at different pH were more or less equivalent (B-factor values within 25-40). It is expected that neutron diffraction analysis of these crystals of different pH provides equivalent data in quality for discussions of protein pH titration in the crystalline state of hen egg-white lysozyme.