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Recently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated.We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS).Among 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%).Overall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.

Evaluation of chronic constipation is important, although it is often difficult to satisfactorily treat due to the complex interplay of factors. This study aimed to determine whether the volume of intraluminal contents and lateral diameter of the colon measured from computed tomography (CT) images were correlated with the symptoms of chronic constipation and stool consistency. Consecutive patients who underwent the Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) questionnaires and simple abdominal CT were selected retrospectively. The intestinal tract diameter at each site was measured, and the amounts of stool and gas in the intestinal tract were evaluated at five levels. Of the 149 study participants, 54 were males and 95 were females and their mean age was 72.1 years. In the right hemi-colon, CSS5 (Time) correlated significantly with gas volume (p < 0.01). In the left hemi-colon, stool volume correlated significantly with CSS2 (Difficulty), CSS3 (Completeness), CSS5 (Time) and CSS total (p < 0.05). The BSFS negatively correlated with gas volume and diameter in the right hemi-colon and with gas volume in the rectum (p < 0.05). CT findings including stool volume, gas volume and diameter correlated with some constipation symptoms and stool consistency. These findings may be useful in evaluating and treating constipation.

Bile acids are strongly associated with the pathogenesis of functional gastrointestinal diseases. In recent years, blue laser imaging (BLI) endoscopy has emerged as a novel image-enhanced endoscopic method, which illustrates bile as a reddish hue. The present study investigated the factors that affect the area of bile in duodenal bulbs using BLI. For this purpose, patients (356 cases) who underwent upper endoscopy with BLI between April, 2017 and December, 2019, and completed patient background and symptom questionnaires [Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) and Frequency Scale for Symptoms of gastroesophageal reflux disease (FSSG)], were retrospectively investigated. Each BLI bile score was calculated as a percentage of bile area in a field of view in the duodenal bulb using a KS400 image analysis system, and the association with abdominal symptoms was examined using multiple regression analysis. The patient characteristics included the following: Age (in years), 69.9±11.3; male/female ratio, 146/210; body mass index, 23.0±3.8; reflux esophagitis (M/A/B/C), 143/19/3/3; atrophic gastritis (C-0/C1-3/O1-3), 132/100/124; proton pump inhibitor potassium competitive acid blocker/aspirin/ursodeoxycholic acid/gall bladder stones/cholecystectomy, 105/27/18/43/18; BLI bile score, 7.10 (±14.34); CSS score, 3.55 (±3.80); BSFS score, 3.91 (±1.02); and FSSG score, 4.80 (±5.76). Correlation coefficients (P0.05) for the BLI bile score were found for cholecystectomy (Rho=0.137) and aspirin use (Rho=0.118). In multiple regression analysis, independent predictors of the BLI bile score were cholecystectomy [standardized partial regression coefficient (β)=0.169, P=0.001] and the BSFS score (β=0.107, P=0.042). On the whole, the present study demonstrates that the duodenal bile area in BLI upper endoscopy is associated with cholecystectomy and fecal characteristics.

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Background With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE). Methods Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21–39 points was comparable to white light, and E*) and L* a* b* color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system. Results The mean age of patients was 67.1 years (range: 27–89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was “moderate” for LA grade M and “substantial” for erosive RE. The LCI intra-rater reliability was “moderate–substantial” for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE (P Conclusion LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.

Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics.From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

There is limited evidence on the association between tooth loss and hearing impairment (HI). The present cross-sectional study investigated the association between tooth loss and the prevalence of HI in 1004 Japanese adults aged 36 to 84 years.HI was defined as present when pure-tone average was25 dB at a frequency of 0.5, 1, 2, and 4 kHz in the better hearing ear. Visual oral examinations were performed. Adjustments were made for age, sex, smoking status, leisure-time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income.Of 1004 study subjects, the prevalence of HI was 24.8% (n = 249). Compared with having 28 teeth, having22 teeth, but not having 26 to28 or 22 to26 teeth, was associated with an increased prevalence of HI; the multivariate adjusted ORs (95% CI) of having 26 to28, 22 to26, and22 teeth were 1.41 (0.85-2.38), 1.51 (0.90-2.57), and 1.96 (1.18-3.30), respectively (p for trend = 0.01).The results suggest that tooth loss may be associated with an increased prevalence of HI.

Salivary hemoglobin (Hb) for screening of periodontitis is approved under the pharmaceutical affairs law of Japan. Two reagents are commercially available for the modified fecal occult blood test: Saliva Hemo Plus and OC-AUTO S Latex Reagent. We simultaneously measured split specimens from 561 samples by using these two methods and compared the differences and agreement between both methods. Moreover, saliva samples were collected from 10 subjects at five time points during the day for analysis of circadian variations and fluctuation. The Pearson's correlation coefficient for these two reagents was 0.794. The Bland-Altman plot of differences in salivary Hb levels measured by the two reagents indicated that the difference included fixed errors (0.55 μg/mL). On analysis of circadian variations, no statistically significant differences were observed using the Friedman test. However, fixed errors were observed between wake-up time and before dinner and before lunch and before dinner, and no random errors were observed by Bland-Altman analysis. In conclusion, the salivary Hb levels measured using OC-AUTO S Latex Reagent were lower than those measured using Saliva Hemo Plus, along with a tendency for higher levels in the morning. Thus, when performing salivary tests these observations must be considered.