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Introduction: The number of young adults with eating disorders or subthreshold eating disorders has increased recently. Although disordered eating behaviors persist once they appear, there have been relatively few studies on factors that might cause disordered eating behaviors. The purpose of this study was to investigate how the eating attitudes of young adults change over time and the risk factors that increase disordered eating behaviors. Methods: A total of 1,141 college students, 639 males and 502 females, participated. We investigated changes in eating attitudes (using EAT-26 and BITE), depressive symptoms (using BDI-II), and stress coping (using CISS, which has three subscales) between 2 time points: at college entrance and in the fourth year of college. We divided the students into three groups (clinical, subthreshold, and healthy) based on EAT-26 scores and compared their BDI-II and CISS scores. Next, we identified students who developed disordered eating behaviors, both clinical and subthreshold, during their time at college (exacerbated students) and compared depressive symptoms and stress coping styles between exacerbated students and healthy students (unchanged students). Results: The students in the subthreshold group (both males and females) scored significantly higher on the BDI-II and emotion-oriented coping (CISS-E) than the students in the healthy group at college entrance. Additionally, the exacerbated students (both males and females) scored significantly higher on the CISS-E in the fourth year than unchanged students. The female exacerbated students scored significantly higher on the BDI-II than female unchanged students at both time points. Conclusions: Our results show that depressive symptoms and nonadaptive stress coping are associated with an increased risk of disordered eating behaviors. This study suggests that early intervention may be necessary for both the clinical and subthreshold groups. The key to early intervention may be to manage not only eating behaviors but also depressive symptoms and stress coping.

Cell labeling technologies, including the Cre/loxP system, are powerful tools in developmental biology. Although the conventional Cre/loxP system has been extensively used to label the expression of specific genes, it is less frequently used for labeling protein-protein interactions owing to technical difficulties. In the present study, we generated a new Gal4-dependent transgenic reporter mouse line that expressed Cre recombinase and a near-infrared fluorescent protein, miRFP670. To examine whether this newly generated transgenic mouse line is applicable in labeling of protein-protein interaction, we used a previously reported transgenic mouse lines that express Notch1 receptor with its intracellular domain replaced with a yeast transcription factor, Gal4. Upon the binding of this artificial Notch1 receptor and endogenous Notch1 ligands, Gal4 would be cleaved from the cell membrane to induce expression of Cre recombinase and miRFP670. Indeed, we observed miRFP670 signal in the mouse embryos (embryonic day 14.5). In addition, we examined whether our Cre recombinase was functional by using another transgenic mouse line that express dsRed after Cre-mediated recombination. We observed dsRed signal in small intestine epithelial cells where Notch1 signal was suggested to be involved in the crypt stem cell maintenance, suggesting that our Cre recombinase was functional. As our newly generated mouse line required only the functioning of Gal4, it could be useful for labeling several types of molecular activities in vivo.

To assess the time trend of diagnostic accuracy of pre- and post-eradicationA series 100 of conventional endoscopic image sets taken from subjects undergoing gastric cancer screening at a polyclinic were evaluated by 5 experienced assessors. Each assessor independently examined endoscopic findings according to the Kyoto classification and then determined theThe overall diagnostic accuracy ofDiagnostic accuracy of

BACKGROUND AND AIM The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan. METHODS We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. RESULTS Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P

Background Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined. Methods The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects. Results For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%). Conclusions The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.

Background Health care workers (HCWs) are at high risk of contracting blood-borne infections including hepatitis B virus (HBV) infection. In Japan, all HCWs are required to receive HB vaccination before beginning work. This study aimed to investigate the dynamics of the HB surface antibody (anti-HBs) titer after a three-dose HB vaccination in HCWs and to determine effective scheduling of HB vaccination for non-responders. Methods Subjects included 832 medical and dental students who had received a three-dose HB vaccination (Bimmugen® 0.5 ml/vial). Anti-HBs was measured three times (before the third dose and 1 and 5 months after the third dose) using the CLIA method. The cut-off value of anti-HBs acquisition was 10 mIU/mL. After booster doses (three maximum) were administered to non-responders, the anti-HBs titers were measured again. Results Out of 832 students, 491 were analyzed, of which 58.9% (289) were male. Anti-HBs-positive rates before the third dose and 1 and 5 months later were 47.9%, 95.9%, and 89.0%, respectively. The relationship between the antibody titer at one month (x) and 5 months (y) was estimated by log10y = log10x − 0.134 (P Conclusion Anti-HBs titer decreases by an average of 20% within 4 months between the 1st and 5th month after the third dose. Therefore, anti-HBs titer should be measured periodically after completing the three-dose vaccination. Additionally, results suggested that booster doses are effective if administered with the same schedule as primary vaccination.

Summary: Fear extinction is a component of cognitive flexibility that is relevant for important psychiatric diseases, but its molecular mechanism is still largely elusive. We established mice lacking the kinesin-4 motor KIF21B as a model for fear extinction defects. Postsynaptic NMDAR-dependent long-term depression (LTD) is specifically impaired in knockouts. NMDAR-mediated LTD-causing stimuli induce dynamic association of KIF21B with the Rac1GEF subunit engulfment and cell motility protein 1 (ELMO1), leading to ELMO1 translocation out of dendritic spines and its sequestration in endosomes. This process may essentially terminate transient activation of Rac1, shrink spines, facilitate AMPAR endocytosis, and reduce postsynaptic strength, thereby forming a mechanistic link to LTD expression. Antagonizing ELMO1/Dock Rac1GEF activity by the administration of 4-[3′-(2″-chlorophenyl)-2′-propen-1′-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP) significantly reverses the knockout phenotype. Therefore, we propose that KIF21B-mediated Rac1 inactivation is a key molecular event in NMDAR-dependent LTD expression underlying cognitive flexibility in fear extinction. : Morikawa et al. establish a mouse model lacking NMDAR-mediated cognitive flexibility by deleting the Kif21b kinesin gene. The mouse is impaired in terminating a Rac1 activity cycle by ELMO1 sequestration for LTD expression and treatable by the Rac1GEF inhibitor CPYPP. These findings have implications for further study of cognitive flexibility. Keywords: kinesin, KIF21B, ELMO1, cognitive flexibility, fear extinction, synaptic plasticity, LTD, NMDAR-mediated LTD, Rac1 activity cycle, CPYPP

Background and Aim: Reddish depressed lesions (RDLs) frequently observed in patients following Helicobacter pylori eradication are indistinguishable from gastric cancer. We examined the clinical and histological feature of RDLs and its relevant endoscopic diagnosis including magnifying narrow-band imaging (M-NBI). Methods: We enrolled 301 consecutive patients with H. pylori eradication who underwent endoscopy using white light imaging (WLI). We examined the prevalence and host factors contributing to the presence of RDLs. Next, we used M-NBI in 90 patients (104 RDLs), and compared the diagnostic efficacy between M-NBI and WLI groups using propensity-score matching analysis. Results: In 301 patients after eradication, 117 (39%) showed RDLs. Male, open-type atrophy, and gastric cancer history were risk factors for RDLs. A gastric biopsy was needed in 83 (71%) during WLI observation and only 2 were diagnosed with adenocarcinoma. In M-NBI group, a biopsy was performed in 21 (20%), and 9 were diagnosed with adenocarcinoma. A biopsy was required in fewer patients, and the positive predictive value of a biopsy was statistically higher in M-NBI than in the WLI group (p < 0.01). Conclusions: RDLs are frequently observed in high-risk patients for gastric cancer after eradication. M-NBI demonstrated significantly superior diagnostic efficacy with respect to RDL.

Backgrounds and Aims The Japan NBI Expert Team (JNET) classification is the first universal narrow-band imaging magnifying endoscopic classification of colorectal tumors. Considering each type in this classification, the diagnostic ability of Type 2B is the weakest. Generally, clinical behavior is believed to be different in each gross type of colorectal tumor. We evaluated the differences in the diagnostic performance of JNET classification for each gross type (polypoid and superficial) and examined whether the diagnostic performance of Type 2B could be improved by subtyping. Methods We analyzed 2933 consecutive cases of colorectal lesions, including 136 hyperplastic polyps/sessile serrated polyps, 1926 low-grade dysplasias (LGDs), 571 high-grade dysplasias (HGDs), and 300 submucosal (SM) carcinomas. We classified lesions as polypoid and superficial type and compared the diagnostic performance of the classification system in each type. Additionally, we subtyped Type 2B into 2B-low and 2B-high based on the level of irregularity in surface and vessel patterns, and we evaluated the relationship between the subtypes and histology, as analyzed separately for polypoid and superficial types. We also estimated interobserver and intraobserver variability. Results The diagnostic performance of JNET classification did not differ significantly between polypoid and superficial lesions. Ninety-nine percent of Type 2B-low lesions were LGDs, HGDs, or superficial submucosal invasive (SM-s) carcinomas. In contrast, 60% of Type 2B-high lesions were deep submucosal invasive (SM-d) carcinomas. The results were not different between each gross type. Interobserver and intraobserver agreements for Type 2B subtyping were good, with kappa values of .743 and .786, respectively. Conclusions Type 2B subtyping may be useful for identifying lesions that are appropriate for endoscopic resection. JNET classification and Type 2B sub classification are useful criteria, regardless of gross type.

It is clinically important to diagnose drug-induced gastric lesions correctly. Recently, the use of proton pump inhibitors (PPI) has increased worldwide. The histological features induced by PPI have been reported; however, few reports have described endoscopic findings induced by PPI. Therefore, we aimed to clarify the characteristic endoscopic features in PPI users and associated pathogenic factors.We prospectively registered 1007 consecutive participants (70 PPI users and 937 nonusers) who underwent endoscopic examination for cancer screening in three hospitals/clinics. Clinical data and endoscopic findings were recorded in the registration forms. We compared the endoscopic features between the two groups and evaluated contributing factors via univariate and multivariate analyses.Multiple white elevated lesions (MWEL) and cobblestone-like mucosa (CLM) were more commonly observed in PPI users compared with nonusers (p .01). Foveolar hyperplastic polyps were also frequently observed in PPI users but were not statistically significantly different (p = .06). MWEL and CLM were more frequently observed in older patients than in younger patients. MWEL was more frequently observed in female patients than in male patients; however, CLM was predominantly observed in male patients.MWEL and CLM are characteristic endoscopic features in PPI users. A gender-associated difference was noted in terms of the frequency of these lesions.

Backgrounds and Aims: The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system. Methods: We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated. Results: Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (Conclusion: The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.

The serological risk prediction system combines the pepsinogen test and anti-Helicobacter pylori (H. pylori) antibody determination. In this system, chronic atrophic gastritis (CAG) is diagnosed using the pepsinogen test. Patients who are H. pylori negative and pepsinogen negative are classified into group A, are assumed to be H. pylori uninfected, and are at an extremely low risk for gastric cancer. However, gastric cancers are detected in this group. The aim of this study is to clarify the clinicopathological status of group A patients with gastric cancer. A total of 109 gastric cancer patients classified as group A were enrolled in a multicenter study. Group A patients were divided into two subgroups: group AN (H. pylori uninfected) and group AP (H. pylori infected). They were compared to 183 H. pylori-infected gastric cancer patients who were not in group A. Of the 109 patients, only 7 were classified as group AN; the other 102 were classified as group AP. The clinicopathological features of group AP included older age, predominantly differentiated type cancer, endoscopically visualized CAG, and pepsinogen (PG) I/II ratio lower than that of group AN. In group AN, the depressed type was dominant, and the PG I/II ratio was higher than in those gastric cancer patients who were infected with H. pylori. Patients in group AP had CAG, and their gastric cancers were similar to those of H. pylori-eradicated patients. Concerning the recent ABC classification system, advanced decision criteria should be proposed to decrease the false-negative evaluation of gastric cancer risk.

Reddish depressed lesions (RDLs) frequently observed in patients following Helicobacter pylori eradication are indistinguishable from gastric cancer. We examined the clinical and histological feature of RDLs and its relevant endoscopic diagnosis including magnifying narrow-band imaging (M-NBI).We enrolled 301 consecutive patients with H. pylori eradication who underwent endoscopy using white light imaging (WLI). We examined the prevalence and host factors contributing to the presence of RDLs. Next, we used M-NBI in 90 patients (104 RDLs), and compared the diagnostic efficacy between M-NBI and WLI groups using propensity-score matching analysis.In 301 patients after eradication, 117 (39%) showed RDLs. Male, open-type atrophy, and gastric cancer history were risk factors for RDLs. A gastric biopsy was needed in 83 (71%) during WLI observation and only 2 were diagnosed with adenocarcinoma. In M-NBI group, a biopsy was performed in 21 (20%), and 9 were diagnosed with adenocarcinoma. A biopsy was required in fewer patients, and the positive predictive value of a biopsy was statistically higher in M-NBI than in the WLI group (p0.01).RDLs are frequently observed in high-risk patients for gastric cancer after eradication. M-NBI demonstrated significantly superior diagnostic efficacy with respect to RDL.

Background The aim of this study was to examine the necessity of early intervention for students with potential bulimia by investigating how the eating attitudes of college students change and examining the relation between bulimic symptoms and depressive symptoms or the ability to cope with stress. Methods The study participants were students who entered Hiroshima University in 2014. This study was conducted at two time points: Time-1 in 2014 and Time-2 in 2017. The Eating Attitudes Test-26 (EAT-26), Bulimic Inventory Test, Edinburgh (BITE), Beck Depression Inventory-II (BDI-II), and Coping Inventory for Stressful Situations (CISS) were administered at Times 1 and 2, and the responses were compared between the time points. Next, we compared the BDI-II scores of the BITE improved and worsened groups. In addition, we divided the participants into a clinical group, subthreshold group, and healthy group based on the BITE score at Time-1to compared their depressive symptoms and the ability to cope with stress. Results Significantly higher BITE and BDI-II scores were recorded for both males and females at Time-2 than at Time-1. The BDI-II score at Time-1 was significantly higher in the BITE worsened group than in the BITE improved group. The BDI-II scores at Time-1 were significantly higher for both males and females in the subthreshold group than in the healthy group. Furthermore, significantly higher CISS-T and CISS-E scores were recorded at Time-1 for females in the subthreshold group than for females in the healthy group. Conclusions Based on these results, intervention for students the subthreshold group is important, and the key to intervention may be to address not only eating behaviors but also depressive symptoms and stress coping. Trial registration UMIN000029474 Registered 9 October, 2017 (retrospectively).

Background and Aim Gastric cancer develops due to atrophic gastritis induced by Helicobacter pylori (H. pylori) infection. Serum levels of pepsinogen (PG) are known to be excellent markers for evaluating the degree of atrophic gastritis. We investigated whether chronic gastritis could be diagnosed by evaluating serum PG levels. Methods A total of 4483 patients (average age, 49.7 years; 2879 men) were included in this study. Fasting serum samples were collected and anti-H. pylori antibody and PG levels were evaluated. We evaluated the endoscopic atrophy grade or histological extent of gastritis, and calculated the diagnostic capability of this serum marker. Results A total of 4483 patients, were diagnosed as being positive (4160) or negative (323) for H. pylori-induced gastritis. In patients with H. pylori-induced gastritis, the PG II levels were higher and the PG I/II ratios were lower than among those without H. pylori gastritis. A cut-off values of (i) PG I/II ≤ 5; (ii) PG II ≥ 10 or PG I/II ≤ 5; (iii) PG II ≥ 12 or PG I/II ≤ 4.5 showed high sensitivity and accuracy (over 90%) for diagnosing H. pylori-induced gastritis. Moreover, in a mass screening of healthy subjects, a cut-off value of PG I/II ≤ 4.5 might be better for diagnosing the presence of gastritis because of a sensitivity and specificity > 80%. Conclusions The presence of H. pylori-induced gastritis can be evaluated using serum PG levels.

Background Helicobacter pylori infection produces progressive mucosal damage that may eventually result in gastric cancer. We studied the changes that occurred in the presence and severity of atrophic gastritis and the prevalence of H. pylori infection that occurred coincident with improvements in economic and hygienic conditions in Japan since World War II. Materials and Methods The prevalence of H. pylori infection and histologic grades of gastric damage were retrospectively evaluated using gastric biopsy specimens obtained over a 40-year period. Gastric atrophy and intestinal metaplasia were scored using the updated Sydney classification system. Results The prevalence of H. pylori and severity of atrophy were examined in 1381 patients including 289 patients examined in the 1970s (158 men; mean age, 44.9 years), 787 in the 1990s (430 men; 44.2 years), and 305 in the 2010s (163 men; 53.2 years). Overall, the prevalence of H. pylori infection decreased significantly from 74.7% (1970s) to 53% (1990s) and 35.1% (2010s) (p

Background The incidence of gastric cancer after successful Helicobacter pylori eradication has been increasing. We previously reported that epithelium with low-grade atypia (ELA) appeared on the surface of gastric cancer after H. pylori eradication. Here, we investigate the clinical and biological characteristics of such ELA. Methods We studied 27 cases of gastric cancer detected after successful H. pylori eradication therapy. We examined the prevalence of ELA among these cases and its significance for endoscopic discovery after H. pylori eradication. We additionally investigated the mucus, p53 and Ki67 expressions in ELA. Results Epithelium with low-grade atypia that continuous with the gastric tumor was detected in 22 of 27 cases (81%), a significantly greater percentage than that for controls (p

Background and Objective Colorectal endoscopic submucosal dissection (ESD) is technically challenging. Our aim was to identify predictors of incomplete resection and perforation in colorectal ESD. Design Retrospective study. Setting Academic Japanese endoscopy unit. Patients and Main Outcome Measurements A total of 267 consecutive cases of colorectal tumors treated by ESD from May 2010 to February 2013 were analyzed. Predictors of incomplete resection and perforation, including lesion size, growth type, pathological diagnosis, use of hemostatic forceps, degree of fibrosis, history of biopsy, history of local endoscopic treatment, and endoscopic operability. Results The incomplete resection rate was 4.1%. The perforation rate was 5.6%. Univariate analysis identified severe fibrosis ( P = .032), submucosal (SM) deep (>1000 μm) invasion ( P = .033) and poor endoscopic operability ( P = .030) as predictors of incomplete resection, and severe fibrosis ( P = .038), postendoscopic treatment ( P = .016), and poor endoscopic operability ( P = .012) as predictors of perforation. Multivariate analysis identified poor endoscopic operability and SM deep invasion as independent predictors of incomplete resection, and poor endoscopic operability and severe fibrosis as independent predictors of perforation. There was no adjustment of P values for multiple testing. Limitation A single-center study by a single colonoscopist. All statistical results should be taken as descriptive only. Conclusions Poor endoscopic operability and SM deep invasion were significant independent predictors of incomplete resections. Poor endoscopic operability and severe fibrosis were significant independent predictors of perforation. These features may provide helpful information when planning colorectal ESD.

Background.Recently, endoscopic submucosal dissection (ESD) has become a standard treatment method for early gastric cancer and concurrent stomach preservation. However, metachronous recurrences have become a major problem. We evaluated the incidence and clinicopathologic features of and examined the risk factors for metachronous gastric tumors.Methods.A total of 357 patients who underwent ESD for gastric tumors (245 early gastric cancers and 112 adenomas) and were followed up for more than 12 months without recurrence within the first 12 months were enrolled. We investigated the incidence and clinicopathologic features of metachronous tumors after ESD. We also analyzed the potential risk factors for metachronous tumors using the Kaplan-Meier method and Cox’s proportional hazards model.Results.The annual incidence of metachronous tumors after ESD was 2.4%. The median period until discovery after initial ESD was 26.0 months, and the median observation period was 52.6 months. Male patients developed metachronous tumors more frequently (P=0.04), and the hazard ratio of female to male patients was 0.36 (95% confidence interval: 0.11–0.89).Conclusions.Patients with a previous history of gastric tumors have a high risk of subsequent gastric tumor development and male patients should be carefully followed up after ESD for gastric tumor.

The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system.We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated.Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (3 U/mL) of the Hp-Ab improved the discrimination of group A with CAG by 8%.The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.

Background and Aim: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is clinically useful in diagnosing gastric cancer and determining treatment options; however, there is a learning curve. Accurate FICE-based diagnosis requires training and experience. In addition, objectivity is necessary. Thus, a software program that can identify gastric cancer quantitatively was developed. Methods: A bag-of-features framework with densely sampled scale-invariant feature transform descriptors to magnifying endoscopy images of 46 mucosal gastric cancers was applied. Computer-based findings were compared with histologic findings. The probability of gastric cancer was calculated by means of logistic regression, and sensitivity and specificity of the system were determined. Results: The average probability was 0.78 0.25 for the images of cancer and 0.31 0.25 for the images of noncancer tissue, with a significant difference between the two groups. An optimal cut-off point of 0.59 was determined on the basis of the receiver operating characteristic curves. The computer-aided diagnosis system yielded a detection accuracy of 85.9% (79/92), sensitivity for a diagnosis of cancer of 84.8% (39/46), and specificity of 87.0% (40/46). Conclusion: Further development of this system will allow for quantitative evaluation of mucosal gastric cancers on magnifying gastrointestinal endoscopy images obtained with FICE.

Background Endoscopic detection of superficial squamous epithelial lesions of the pharynx has increased. Objective To clarify the association between macroscopic and histologic characteristics of intraepithelial pharyngeal neoplasias, and to evaluate the effectiveness of endoscopic submucosal dissection (ESD) for their treatment. Design Retrospective analysis of the features of high-grade dysplasia or carcinoma in situ (HGD/CIS) versus low-grade dysplasia (LGD) and of ESD-based outcomes. Setting Endoscopy department at a university hospital. Patients Fifty-one patients with 66 lesions treated by ESD from November 2007 to March 2011. Results Primary hypopharyngeal lesions were significantly more frequent in HGD/CIS than in LGD (54.1% vs 20.7%, P = .011), and oropharyngeal lesions were significantly less frequent in HGD/CIS (45.9% vs 79.3%, P = .011). HGD/CIS lesions were significantly larger than LGD lesions (median 8 mm vs 4 mm, P Limitations Retrospective design and single-center study. Conclusions HGD/CIS and LGD differ in various clinical features. ESD appears to be an effective treatment for pharyngeal intraepithelial neoplasias.

Background: Bile acid and Helicobacter pylori (H. pylori) are important toxic factors for gastric mucosal injury. We examined the role of bile acid in promoting histologic gastritis and gastric carcinoma in Japanese patients. Methods: A total of 767 patients (452 men, mean age 51.1 years) were studied. Gastric juice was collected by gastro-endoscopic examination, and the bile acid concentration was examined by enzymatic method. The grade of histologic gastritis was evaluated by gastric biopsies, and the relationship between the bile acid concentration and the gastritis score was examined. The occurrence of gastric cancer was examined by a retrospective cohort study. CDX2/CINC1 expression in RGM-1 cells was evaluated by real-time PCR. Results: In H. pylori–positive patients, we found significant positive correlation between the bile acid concentration and the grades of atrophy/intestinal metaplasia (P < 0.01). However, we found significant negative associations between the bile acid concentrations and the histologic scores of mononuclear cell/neutrophil infiltrations (P < 0.01). Patients with a high concentration of bile acid developed gastric cancer more frequently than those with a low concentration (P < 0.05). Cholic acid treatment significantly increased CDX2 expression in RGM-1 cells. CINC1 expression in RGM-1 cell was significantly induced by coculture with H. pylori, and the induction was reduced by glycochenodeoxycholic acid treatment. Conclusion: The bile acid in gastric juice contributes to the progression of histologic atrophy and intestinal metaplasia without inflammatory cell infiltration, followed by carcinogenesis in H. pylori–positive patients. Impact: Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration. Cancer Epidemiol Biomarkers Prev; 21(11); 2101–7. ©2012 AACR.

Gastrin is a growth factor for the gastric epithelial cells. However, it is unknown how gastric receptor (GR) expression is regulated in the gastric mucosa. We studied GR expression using a newly raised antibody and investigated the relationship between GR expression and gastritis. Gastric receptor expression in 63 human gastric mucosa was studied. Helicobacter pylori infection and histological gastritis status were evaluated in gastric biopsy samples. In gastric ulcer cases, additional biopsy specimens were taken from injured mucosa. Fasting sera were collected and serum gastrin level evaluated. MKN-28 cells were cultured at various pH conditions, and the change in GR expression was determined. Gastric receptor expression was detected in the foveolar epithelium of the gastric mucosa, and its expression was stronger in patients infected with H. pylori. In particular, higher expression was detected in regenerating injured mucosa. There was no association between gastritis score/serum gastrin level and GR expression in H. pylori-positive cases. In MKN-28 cells, GR protein expression was lower in neutral conditions than in acidic or alkaline conditions. Gastric mucosal injury with H. pylori infection destroys the pH barrier on the foveolar epithelium and may induce GR expression through pH changes.

Background and Aims The Japan NBI Expert Team (JNET) was established in 2011 and has proposed a universal narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors. The aim of this study was to evaluate the clinical usefulness of the JNET classification for colorectal lesions. Methods We analyzed 2933 colorectal lesions, which were diagnosed by NBI magnifying observation before endoscopic treatment or surgery. The colorectal lesions consisted of 136 hyperplastic polyps/sessile serrated polyps (HPs/SSPs), 1926 low-grade dysplasia (LGD), 571 high-grade dysplasia (HGD), 87 superficial submucosal invasive (SM-s) carcinomas, and 213 deep submucosal invasive (SM-d) carcinomas. We evaluated the relationship between the JNET classification and the histologic findings of these lesions. Results The sensitivity, specificity, positive and negative predictive values, and accuracy of Type 1 lesions for the diagnosis of HP/SSP were, respectively, 87.5%, 99.9%, 97.5%, 99.4%, and 99.3%; of Type 2A lesions for the diagnosis of LGD were 74.3%, 92.7%, 98.3%, 38.7%, and 77.1%; of Type 2B lesions for the diagnosis of HGD/SM-s carcinoma were 61.9%, 82.8%, 50.9%, 88.2%, and 78.1%; for Type 3 lesions for the diagnosis of SM-d carcinoma were 55.4%, 99.8%, 95.2%, 96.6%, and 96.6%, respectively. Conclusions Types 1, 2A, and 3 of the JNET classification were very reliable indicators for HP/SSP, LGD, and SM-d carcinoma, respectively. However, the specificity and positive predictive value of Type 2B were relatively lower than those of others. Therefore, an additional examination such as pit pattern diagnosis using chromoagents is necessary for accurate diagnosis of Type 2B lesions.

Background and Aim: Serum screening systems are beneficial for gastric cancer mass surveys; however, the marker for diffuse type gastric cancer (DGC) is not defined. We attempted to define the high-risk group for DGC by using serum markers of anti-Helicobacter pylori antibody and pepsinogens (PG). Methods: Forty-two patients in the early stage of DGC and 511 controls were enrolled. Fasting serum samples were collected, and anti-H. pylori antibody and PG were evaluated. The risk for DGC was calculated. Results: The prevalence of DGC was higher in H. pylori-positive patients (odds ratio [OR] = 4.3 in men, 9.6 in women). DGC prevalence was significantly higher in the PG1+ group in women (OR = 10.7); however, it was lower in the PG3+ group in both men and women. Patients with PG II ≥ 30 revealed a significantly higher risk for DGC. By combining factors, higher OR (OR = 12.5 in men, 42.7 in women) were obtained when we defined the risk group as H. pylori-positive, PG-negative, and having PG II ≥ 30. Conclusion: The risk group for DGC can be defined by evaluating ordinary serum gastritis markers.

Background and Aims: The true prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) is unknown. We attempt to clarify the prevalence and clinicopathologic features of HpNGC in Japanese. Methods: Helicobacter pylori infection was detected by antibody titer and microscopic observation. In addition, we confirmed the lack of endoscopic atrophy and histologic gastritis. In these cases, we added urea breath test or rapid urease test to confirm the absence of H. pylori. The mucus phenotype of gastric cancer tissue was also evaluated by immunohistochemistry. Results: We screened 3161 gastric cancer cases from 1996 to 2010, and 21 cases were regarded as H. pylori negative. Clinically, patients with HpNGC were younger than patients with H. pylori-positive gastric cancer (controls), and revealed a lack of male dominancy. Histologically, diffuse type was frequently found. All patients examined were pepsinogen negative. Among HpNGC cases with endoscopic resection, the depressed macroscopic appearance was dominant. The prevalence of HpNGC was calculated as 0.66% (95% confidence interval = 0.41–1.01). The mucus phenotype of HpNGC was similar to that of the controls. Conclusion: The prevalence of HpNGC is very low and its pathological characteristics are different from common gastric cancer.

Background and Aim: Serrated adenomas (SAs), recently subdivided into traditional SAs (TSAs) and sessile SAs (SSAs), are recognized as a distinct form of neoplasia of the colorectum. One of the characteristics of SAs is hypermaturation of the gland epithelium due to the low extent of cell loss by apoptosis. Mutations of mitochondrial DNA (mtDNA) are closely associated with abnormality in apoptosis. We therefore examined mtDNA mutations in colorectal lesions including hyperplastic polyps (HPs), SSAs, TSAs, and carcinomas. Methods: Examined were 25 HPs, 32 SSAs, 19 TSAs, and 138 carcinomas. The D310 region of the mtDNAs was examined by microsatellite assay. Results: mtDNA mutations were detected in none of 25 (0%) HPs, one of 32 (3%) SSAs, six of 19 (32%) TSAs, and eleven of 133 (8%) carcinomas (five of the 138 carcinomas were not informative). The frequency of mtDNA mutations in the TSAs was significantly higher than that in the HPs, SSAs, and carcinomas (P = 0.004, P = 0.008, and P = 0.009, respectively). The frequency of mtDNA mutations in carcinomas was not significantly higher than that in HPs and SSAs (P = 0.14 and P = 0.28, respectively). Conclusion: Our data suggest that mtDNA mutations may play an important role in the development of TSAs and could be used as a genetic marker to aid in the diagnosis of colorectal lesions.

Background and Aim: In the treatment of superficial esophageal tumors (SET), en bloc histologically-complete resection reduces the risk of local recurrence. Endoscopic oblique aspiration mucosectomy (EOAM) and endoscopic submucosal dissection (ESD) have been applied to resect SET. The aim of this study was to retrospectively determine whether ESD is more advantageous than EOAM for SET. Methods: In the present study, there was a total of 122 patients in whom 162 SET were resected endoscopically at Hiroshima University Hospital. EOAM (83 lesions/63 patients) or ESD (79 lesions/59 patients) was performed. En bloc histologically-complete resection rates, operation time, complications, and the local recurrence rate were studied. Results: In SET > 20 mm, the en bloc histologically-complete resection rate was significantly higher with ESD than with EOAM (94% vs 42%, P 15 mm should be treated with ESD to reduce local recurrence. In lesions ≤15 mm, EOAM might be preferable, especially in high-risk patients.

Few reports have described the cancer prevalence of peptic ulcer patients with long-term follow-up studies. We have conducted a long-term retrospective cohort study of Japanese peptic ulcer patients and evaluated the risk factors for the occurrence of gastric cancer (GCa). A total of 136 patients diagnosed with peptic ulcers from 1975 to 1983 were enrolled. These 136 cases [102 males and 34 females; 69 gastric ulcer (GU) and 67 duodenal ulcer (DU) patients at the time of enrolment; mean follow-up period of 14.4 years (range 1–30 years)] after being matched with a tumour registry database in Hiroshima prefecture were surveyed for GCa. We investigated Helicobacter pylori duodenal ulcer promoter gene A (dupA) using paraffin-embedded gastric biopsy specimens in 56 cases. Gastric acid secretion and basal acid output (BAO) in 40 cases, and maximal acid output in 68 cases, had been measured at first diagnosis of peptic ulcers. GCa was detected in 24 patients (17 with GU, 7 with DU) during the follow-up. The prevalence of GCa was significantly higher in GU patients than in DU patients (log-rank test PdupA-positive H. pylori was detected not only in DU patients (9/20) but also in GU patients (9/36). Gastric acid output was significantly larger in quantity in patients with dupA-positive H. pylori than in those with dupA-negative H. pylori (PdupA-positive H. pylori and a high BAO level (log-rank test PdupA-positive H. pylori were negatively associated with GCa.

Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure. We aimed to retrospectively assess the relationship between the outcome of ESD for colorectal tumors and the degree of fibrosis.We examined 203 consecutive patients with colorectal tumors larger than 20 mm in diameter who had undergone ESD at our hospital from November 2002 to June 2009. During ESD, the degree of submucosal fibrosis was classified into three types (F0-2). The relationship between the degree of fibrosis and the lesion characteristics and those between the outcome of ESD and the degree of fibrosis were analyzed.In the cases of granular laterally spreading tumors, the incidence of F2 fibrosis in nodular mixed-type tumors was significantly higher than that in homogenous-type tumors. An increase in the experience of the operators caused significant improvements in the rates of complete en bloc resection (p = 0.022) and perforation (p = 0.03) in the cases of lesions with F0-1 fibrosis. By contrast, operator experience did not cause any significant improvements in the rates of complete en bloc resection and perforation in the cases of lesions with F2 fibrosis.Experienced operators could safely perform complete en bloc resection in the cases of lesions with F0-1 fibrosis. However, in the cases of lesions with F2 fibrosis, the rate of complete en bloc resection was low and the perforation rate was high even when ESD was performed by an experienced operator.

The characteristics of synchronous and subsequent lesions of serrated adenomas (SAs) of the colorectum are still unclear. This study aimed to clarify the characteristics of synchronous and subsequent lesions of SAs compared with tubular adenomas (TAs) of the colorectum. Patients were divided into 2 groups: SA (127 patients) and TA (158 patients). The mean follow-up durations in the SA and TA groups were 39.7 and 42.7 months, respectively. The number and clinical features of the synchronous and subsequent lesions of both groups were examined. In the SA group, 19 (15%) patients had synchronous lesions and 3 (2%) patients had subsequent lesions. In the TA group, 68 (43%) patients had synchronous lesions and 14 (9%) patients had subsequent lesions. The frequencies of patients with synchronous and subsequent lesions in the SA group were significantly lower than those in the TA group (p < 0.0001 and p = 0.02, respectively). The most frequent synchronous lesion was SA (67%) in the SA group and TA (95%) in the TA group. The most subsequent lesion was SA (62%) in the SA group and TA (100%) in the TA group. The histology of the index polyp and synchronous and subsequent lesions tended to be identical. No invasive colorectal carcinomas were observed in either group. Our data suggest that the colonic tumorigenesis potential of patients with SA may differ from that of patients with TA.

Background/Aims: Tyrosine phosphorylation of the EPIYA motif in Helicobacter pylori CagA (CagA-P) plays an important role in toxic reaction. Diffuse-type gastric cancer (DGC) has a poor prognosis. We tried to clarify the expression level of CagA-P in DGC patients. Methods: We enrolled 42 early-stage DGC patients (DGC group; 20 males, 22 females, mean age 58.2 years) and 42 age- and gender-matched atrophic gastritis (AG) patients (AG group) as controls. We evaluated histological and serological gastritis and examined two markers; the serum titer of anti-CagA-P antibody and CagA-P expression in gastric mucosa. Results: In the DGC group, we found significantly higher corpus histological gastritis scores for activity, atrophy, and intestinal metaplasia. The titer of anti-CagA-P antibody and CagA-P expression in the corpus were significantly higher in the DGC group, especially in females (p < 0.05). Sixteen patients (38.1%) in the DGC group showed both positive markers, and the odds ratio for DGC occurrence was 4.00 (95% CI = 1.07–14.91), while that for females was 9.00 (95% CI = 1.29–62.97). Conclusions: CagA-P plays a role in active corpus gastritis, which may link to DGC carcinogenesis. Clinical quantification of CagA-P-related markers may be useful for the evaluation of DGC risk, especially in females.

The aim of this study was to clarify predictive factors for response to eradication therapy in cases of Helicobacter pylori (H. pylori)-positive API2-MALT1-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Sixty-six patients who were examined for H. pylori infection and the presence of the API2-MALT1 chimeric transcript and who underwent H. pylori eradication therapy as first-line therapy, were enrolled in this study. Immunohistochemical markers (p53, Ki-67, and BCL10), microsatellite instability, loss of heterozygosity, serum levels of antibodies (anti-H. pylori and anti-CagA), and markers for gastritis (gastrin and pepsinogens) were examined, and the results were compared between patients whose tumors regressed completely after eradication therapy (responders) and patients whose tumors did not regress (non-responders). Of the 66 patients with localized gastric MALT lymphoma, 47 (71.2%) showed complete remission after eradication therapy. None of the H. pylori-negative (n = 9) and/or API2-MALT1-positive (n = 7) patients responded to antibacterial treatment. Of 44 patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma, 38 (86.4%) showed complete remission after eradication therapy. Titers of antibodies against H. pylori and CagA protein were significantly higher in the responders than in the non-responders (P = 0.0235 and 0.0089, respectively). No significant difference between the groups was observed for the other factors. In conclusion, measurement of titers of serum antibodies to H. pylori and CagA protein may be useful for predicting the response to eradication therapy in patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma.

Background: The Flexible spectral Imaging Color Enhancement (FICE) system estimates the spectrum reflectance from a white-light endoscopic image and reconstitutes a color image from the wavelength, including useful information about the GI tract. The aim of this study was to investigate the usefulness of FICE with a specific wavelength in the assessment of early gastric cancers (EGCs), and the relationship between the FICE visualization and blood vessels. Design: A retrospective study. Setting: Department of Endoscopy, Hiroshima University, Hiroshima, Japan. Patients and Main Outcome Measurements: The study subjects consisted of 100 patients with EGCs (78 differentiated, 22 undifferentiated) who underwent an endoscopic or surgical resection. We analyzed the wavelengths to generate the maximum difference of the spectral reflectance between the normal gastric mucosa and the EGCs. We observed the same visual field first with white-light endoscopy and then with the FICE system. Then, we scored the demarcation of color between the cancer and the normal mucosa of white-light endoscopic observation and FICE observation, each without magnification. We examined the relationship between the score of the FICE image and the section of the vascular space. Results: The wavelength that generated the maximum difference in the tissue was 530 nm. The score of the FICE observation improved in 46 cases (46%), was unchanged in 54 cases (54%), and decreased in no cases (0%). There was a correlation between the score of the FICE images and the section of the vascular spaces. Conclusions: The FICE observation demonstrated that setting the wavelength at 530 nm resulted in an improvement in the visualization of the EGCs. It is thought that the FICE system is noninvasive and may more easily detect EGC without dye during both routine and detailed examinations. (Gastrointest Endosc 2009;69:1052-8.)