Search

Change in mucosal microbiome is associated with various types of cancer in digestive tract. We hypothesized that microbial communities in the esophageal endoscopic wash fluids reflects resident flora in esophageal mucosa that is associated with esophageal carcinoma (EC) risk and/or directly correlates microbiome derived from EC tumor tissue. Studying microbial communities in esophageal endoscopic wash samples would be therefore useful to predict the incidence or risk of EC. We examined microbial communities of the endoscopic wash samples from 45 primary EC and 20 respective non-EC controls using 16S rRNA V3-V4 amplicon sequencing. The result was also compared with microbial communities in matched endoscopic biopsies from EC and non-cancerous esophageal mucosa. Compared with non-EC controls, 6 discriminative bacterial genera were detected in EC patients. Among them, relative abundance ratio of Prevotella and Shuttlewarthia, as well as decrease of genus Prevotella presented good prognostic performance to discriminate EC from controls (area under curve, 0.86, 0.82, respectively). Multivariate analysis showed occurrence of EC was an independent factor associated with decrease of this bacteria. Abundance of genus Prevotella in the esophageal endoscopic wash samples was significantly correlated with the abundance of this bacteria in the matched endoscopic biopsies from non-cancerous esophageal mucosa but not in the EC tissues. Our findings suggest that microbiome composition in the esophageal endoscopic wash samples reflects resident flora in the esophagus and significantly correlates with the incidence of EC., (© 2024. The Author(s).)

Background and Aims: Early gastric cancers (EGCs) after Helicobacter pylori (H. pylori) eradication often appear as reddish depressed lesions (RDLs); the same features are also appeared in benign stomachs after eradication. We compared clinic-pathological and endoscopic features of benign and neoplastic RDLs after H. pylori eradication., Methods: 228 neoplastic RDLs after H. pylori eradication were studied. All lesions were divided into neoplastic RDLs (differentiated carcinoma or adenoma, n=114) and benign RDLs (n=114) according to the histology. Clinical and pathological characteristics were compared in neoplastic and benign groups. Endoscopic diagnostic yields using the white light (WL) endoscopy, chromoendoscopy (CE) using indigo carmine dye and the magnifying endoscopy with narrow-band imaging (ME-NBI) were also evaluated in relation to the pathological diagnosis., Results: Size of neoplastic RDLs was larger than that of benign RDLs (p<0.01). Sensitivity, specificity and accuracy for predicting pathological types of RDLs was 70.1%, 52.6% and 61.4% for the WL, 65.8%, 63.1% and 65.4% for the CE, while the ME-NBI scored better with the 88.6%, 88.6%, 99.1% and 93.9% of sensitivity, specificity and accuracy. The accuracy of the ME-NBI was 99.9% (113/114) in the benign RDLs and 89.4% (101/114) for the neoplastic RDLs. Undiagnosed neoplastic RDLs using the ME-NBI were associated with more differentiated tumors such as adenoma and well-differentiated adenocarcinoma (tub1) and the presence of an unclear demarcation line., Conclusions: ME-NBI is useful to diagnose RDLs after H. pylori eradiation, while some of neoplastic lesions are difficult to diagnose using the ME-NBI.

Helicobacter pylori induces DNA methylation in gastric mucosa, which links to gastric cancer (GC) risk. In contrast, CpG island methylator phenotype (CIMP) is defined as high levels of cancer-specific methylation and provides distinct molecular and clinicopathological features of GC. The association between those two types of methylation in GC remains unclear. We examined DNA methylation of well-validated H. pylori infection associated genes in GC and its adjacent mucosa and investigated its association with CIMP, various molecular subtypes and clinical features. We studied 50 candidate loci in 24 gastric samples to identify H. pylori infection associated genes. Identified loci were further examined in 624 gastric tissue from 217 primary GC, 217 adjacent mucosa, and 190 mucosae from cancer-free subjects. We identified five genes (IGF2, SLC16A2, SOX11, P2RX7, and MYOD1) as hypermethylated in H. pylori infected gastric mucosa. In non-neoplastic mucosa, methylation of H. pylori infection associated genes was higher in patients with GC than those without. In primary GC tissues, higher methylation of H. pylori infection associated genes correlated with CIMP-positive and its related features, such as MLH1 methylated cases. On the other hand, GC with lower methylation of these genes presented aggressive clinicopathological features including undifferentiated histopathology, advanced stage at diagnosis. H. pylori infection associated DNA methylation is correlated with CIMP, specific molecular and clinicopathological features in GC, supporting its utility as promising biomarker in this tumor type., (© 2023 Wiley Periodicals LLC.)

Background and study aims Esophageal endoscopic submucosal dissection (ESD) has a higher complication rate than gastric ESD. Scissor-type devices, including the stag beetle (SB) knife, are reportedly safer and have shorter procedure times than tip devices. To clarify the characteristics of the SB knife, we compared the treatment outcomes of esophageal ESD with a tip-type knife to those with an SB knife combination. Patients and methods Between January 2016 and March 2023, clinical data from 197 lesions in 178 patients who underwent esophageal ESD were analyzed retrospectively. Every lesion was assigned to either the tip-type group or the SB group based on the devices with which the submucosa was initially dissected. We compared procedure time and complications and analyzed the risk of muscular exposure using multivariate analysis. Results Procedure time was not significantly different between the tip-type and SB groups (60.3±42.2 min vs. 58.8±29.1 min). The variation in procedure time was significant according to F test P =0.002). Incidence of muscular exposure was significantly lower in the SB group than in the tip-type group (24.5% vs. 11.1%, P =0.016). These differences were significant in resected specimens larger than 21 mm. Procedure time over 60 minutes (odds ratio [OR] 2.5, 95% confidence interval [CI]: 1.15-5.42, P =0.02) was a risk factor for muscular exposure, and submucosal dissection with an SB knife was a safety factor (OR 0.4, 95% CI: 0.18-0.89, P =0.02). Conclusions Performing esophageal ESD with an SB knife is a safe procedure with less variation in procedure time and less muscule exposure., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Competing Interests: The authors declare that they have no conflict of interest.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of myofibroblasts with inflammatory blood cell infiltration. It commonly occurs in the lungs and rarely in the esophagus. We herein report a valuable case of IMT originating in the esophagus. A 60-year-old Japanese woman with dysphagia had a large subepithelial lesion in the cervical esophagus, which was 15 cm in length. Surgical resection was performed to confirm the pathological diagnosis and improve the symptoms. The postoperative diagnosis was IMT composed of multiple nodules. There was no recurrence or metastasis within one year after surgery.

Background/aim: The combination of atezolizumab plus bevacizumab (Atz/Bev) has become widely used as a first-line therapy for advanced hepatocellular carcinoma (HCC). However, for post-Atz/Bev therapy, evidence on the outcomes of molecular targeted agents, such as lenvatinib, is limited. The present study aimed to assess the clinical effectiveness of lenvatinib on advanced HCC in patients who had previously undergone Atz/Bev treatment., Patients and Methods: Twenty patients with HCC, who received lenvatinib after Atz/Bev treatment, were enrolled in the study. In particular, we examined the impact of adverse events (AEs), such as anorexia and general fatigue. During the treatment, lenvatinib dosages were adjusted or temporarily discontinued in response to AEs. Treatment outcomes were retrospectively evaluated., Results: The objective response rate (ORR) and disease control rate (DCR) for lenvatinib treatment were 25.0% and 95.0%, respectively, according to the Response Evaluation Criteria in Solid Tumors. The median progression-free survival (PFS) was 6.0 months, and the median overall survival (OS) was 10.5 months. Eleven patients experienced anorexia or fatigue, leading to a reduction in the dose of lenvatinib but not to a significant difference in the time to drug discontinuation. Importantly, there were no significant differences between the 11 anorexia/fatigue-suffering patients and the nine other patients with regard to PFS and OS., Conclusion: Lenvatinib can be efficacious and safe for treating advanced HCC patients previously treated with Atz/Bev, and AEs such as anorexia and general fatigue can be effectively managed without losing lenvatinib's therapeutic benefits., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.

Molecular mechanisms of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remain unclear in Japanese patients. Japanese EACs frequently have underlying short length BE: short-segment BE (SSBE), for which, neoplastic potential remains unclear. We performed comprehensive methylation profiling of EAC and BE in Japanese patients, mostly comprised with SSBE. Using three different groups of biopsies obtained from non-neoplastic BE from patients without cancer (n = 50; N group), with EAC (n = 27; ADJ group) and EAC (n = 22; T group), methylation statuses of nine candidate genes (N33, DPYS, SLC16A12, CDH13, IGF2, MLF1, MYOD1, PRDM5, and P2RX7) were examined by the bisulfite pyrosequencing. Reduced representation bisulfite sequencing was performed to characterize the genome-wide methylation status in 32 samples (12 from N, 12 ADJ, and 8 from T groups). In the candidate approach, methylation levels of N33, DPYS, and SLC16A12 were higher in ADJ and T groups compared to that in N group. The ADJ group was an independent factor for higher DNA methylation in non-neoplastic BE. The genome-wide approach demonstrated an increase of hypermethylation from ADJ to T groups relative to N group near the transcription start sites. Among gene groups hypermethylated in ADJ and T groups (n = 645) and T group alone (n = 1438), 1/4 and 1/3 were overlapped with downregulated genes in the microarray data set, respectively. Accelerated DNA methylation is observed in EAC and underlying BE in Japanese patients, mostly comprised with SSBE, highlighting the potential impact of methylation in early carcinogenesis., (© 2023 Wiley Periodicals LLC.)

The following are some common features of ulcerative colitis (UC) and Crohn's disease (CD) on transabdominal ultrasonography (TUS). UC, which consists primarily of mucosal inflammation, is seen on TUS as wall thickening with preserved layer structure continuing from the rectum in the active phase of UC. Inflammation confined to the mucosa is seen as thickening of the mucosal/submucosal layers. When the inflammation becomes severe, the echogenicity of the submucosal layer decreases and the layer structure becomes indistinct. CD, which consists primarily of discontinuous transmural inflammation, shows more pronounced hypoechoic wall thickening than UC at the transmural inflammation. On TUS, the layer structure becomes indistinct and gradually disappears due to the depth of the myriad inflammation during the active phase of CD. It is important to evaluate the changes in wall thickening and layer structure when diagnosing UC and CD with TUS. In addition, diagnostic techniques such as color Doppler and contrast-enhanced ultrasonography, which can be used to assess blood flow, and elastography, which can be used to evaluate stiffness, are also used. Thus, TUS is a noninvasive and convenient modality that shows promise as a useful examination for diagnosis of UC and CD., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

In inflammatory bowel disease, including Crohn's disease and ulcerative colitis, an excessive immune response due primarily to T-cell lymphocytes causes inflammation in the gastrointestinal tract. Lesions in Crohn's disease can occur anywhere in the gastrointestinal tract, i.e., from the oral cavity to the anus. Endoscopically, aphthoid lesions/ulcers believed to be initial lesions progress to discrete ulcers, which coalesce to form a longitudinal array and progress to longitudinal ulcers with a cobblestone appearance, which is a typical endoscopic finding. Before long, complications such as strictures, fistulas, and abscesses form. Lesions in ulcerative colitis generally extend continuously from the rectum and diffusely from a portion of the colon to the entire colon. Endoscopically, lack of vascular pattern, fine granular mucosa, erythema, aphthae, and small yellowish spots are seen in mild cases; coarse mucosa, erosions, small ulcers, bleeding (contact bleeding), and adhesion of mucous, bloody, and purulent discharge in moderate cases; and widespread ulcers and marked spontaneous bleeding in severe cases., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Background/aim: Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp., Patients/methods: 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated., Results: Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86)., Conclusion: LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tahara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

(1) Background: This study aimed to investigate clinical outcomes for cabozantinib in clinical practice in patients with advanced hepatocellular carcinoma (HCC) previously treated with atezolizumab plus bevacizumab (Atz/Bev), with a focus on whether patients met criteria of Child-Pugh Class A and Eastern Cooperative Oncology Group performance status (ECOG-PS) score 0/1 at baseline. (2) Methods: Eleven patients (57.9%) met the criteria of both Child-Pugh class A and ECOG-PS score 0/1 (CP-A+PS-0/1 group) and eight patients (42.1%) did not (Non-CP-A+PS-0/1 group); efficacy and safety were retrospectively evaluated. (3) Results: Disease control rate was significantly higher in the CP-A+PS-0/1 group (81.1%) than in the non-CP-A+PS-0/1 group (12.5%). Median progression-free survival, overall survival and duration of cabozantinib treatment were significantly longer in the CP-A+PS-0/1 group (3.9 months, 13.4 months, and 8.3 months, respectively) than in the Non-CP-A+PS-0/1 group (1.2 months, 1.7 months, and 0.8 months, respectively). Median daily dose of cabozantinib was significantly higher in the CP-A+PS-0/1 group (22.9 mg/day) than in the non-CP-A+PS-0/1 group (16.9 mg/day). (4) Conclusions: Cabozantinib in patients previously treated with Atz/Bev has potential therapeutic efficacy and safety if patients have good liver function (Child-Pugh A) and are in good general condition (ECOG-PS 0/1).

Background: Anisakiasis is a parasitic disease caused by the consumption of raw or undercooked fish that is infected with Anisakis third-stage larvae. In countries, such as Japan, Italy, and Spain, where people have a custom of eating raw or marinated fish, anisakiasis is a common infection. Although anisakiasis has been reported in the gastrointestinal tract in several countries, reports of anisakiasis accompanied by cancer are rare., Case Presentation: We present the rare case of a 40-year-old male patient with anisakiasis coexisting with mucosal gastric cancer. Submucosal gastric cancer was suspected on gastric endoscopy and endoscopic ultrasonography. After laparoscopic distal gastrectomy, granulomatous inflammation with Anisakis larvae in the submucosa was pathologically revealed beneath mucosal tubular adenocarcinoma. Histological and immunohistochemical investigation showed cancer cells as intestinal absorptive-type cells that did not produce mucin., Conclusion: Anisakis larvae could have invaded the cancer cells selectively because of the lack of mucin in the cancerous epithelium. Anisakiasis coexisting with cancer is considered reasonable rather than coincidental. In cancer with anisakiasis, preoperative diagnosis may be difficult because anisakiasis leads to morphological changes in the cancer., Competing Interests: The ethical approval and documentation for a case report was waived with approval of the Institutional Review Board at Fujita Health University.The authors declare that they have no conflict of interests.

Background: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC., Methods: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects., Results: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria ( Actinomyces , Streptococcus , Veillonella , Lactobacillus ) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control., Conclusions: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Pancreatic ductal adenocarcinoma (PDAC) can be treated with surgery, chemotherapy, and radiotherapy. Despite medical progress in each field in recent years, it is still insufficient for managing PDAC, and at present, the only curative treatment is surgery. A typical pancreatic cancer is relatively easy to diagnose with imaging. However, it is often not recommended for surgical treatment at the time of diagnosis due to metastatic spread beyond the pancreas. Even if it is operable, it often recurs during postoperative follow-up. In the case of PDAC with a diameter of 10 mm or less, the 5-year survival rate is as good as 80% or more, and the best index for curative treatment is tumor size. The early detection of pancreatic cancer with a diameter of less than 10 mm or carcinoma in situ is critical. Here, we provide an overview of the current status of diagnostic imaging features and genetic tests for the accurate diagnosis of early-stage PDAC.

Objectives: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years., Methods: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients., Results: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001)., Conclusion: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC., (© 2022 Japan Gastroenterological Endoscopy Society.)

Background and Aim: In colorectal endoscopic submucosal dissection (ESD), post-ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure., Methods: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses., Results: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264-8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317-28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053-6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090-13.61, P = 0.036) were independent risk factors for PECS., Conclusions: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology., Methods: Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE-L*a*b* color space were calculated in the original and enhanced images., Results: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36)., Conclusion: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Endoscopy is widely applied in the examination of gastric cancer. However, extensive knowledge and experience are required, owing to the need to examine the lesion while manipulating the endoscope. Various diagnostic support techniques have been reported for this examination. In our previous study, segmentation of invasive areas of gastric cancer was performed directly from endoscopic images and the detection sensitivity per case was 0.98. This method has challenges of false positives and computational costs because segmentation was applied to all healthy images that were captured during the examination. In this study, we propose a cascaded deep learning model to perform categorization of endoscopic images and identification of the invasive region to solve the above challenges. Endoscopic images are first classified as normal, showing early gastric cancer and showing advanced gastric cancer using a convolutional neural network. Segmentation on the extent of gastric cancer invasion is performed for the images classified as showing cancer using two separate U-Net models. In an experiment, 1208 endoscopic images collected from healthy subjects, 533 images collected from patients with early stage gastric cancer, and 637 images from patients with advanced gastric cancer were used for evaluation. The sensitivity and specificity of the proposed approach in the detection of gastric cancer via image classification were 97.0% and 99.4%, respectively. Furthermore, both detection sensitivity and specificity reached 100% in a case-based evaluation. The extent of invasion was also identified at an acceptable level, suggesting that the proposed method may be considered useful for the classification of endoscopic images and identification of the extent of cancer invasion.

Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents. Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis. The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06-4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19-8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47-11.80, P.007) were significant risk factors after discharge. Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Small intestinal tumors (adenoma and adenocarcinoma, SIT) are rare, and their microRNA (miRNA) expression profiles have not been established. Previously, we reported a relationship between miRNA expression profiles and the development, growth, morphology, and anticancer drug resistance of colorectal tumors. Here, we demonstrate that the miRNA expression profile of SIT is significantly different from those of tumors of the colon. We compared the onco-related miRNA expression profiles of SIT and colorectal tumors and found them to be different from each other. The expressions of miR-143 and miR-145 were frequently downregulated in SIT and colorectal tumors but not in sessile serrated adenoma/polyp tumors. The profiles of SIT and colorectal carcinomas of miR-7, miR-21, and miR-34a were considerably different. Upregulation of miR-31 expression was not found in any SIT cases. Our data suggested that miR-143 and miR-145 might act as anti-oncomirs common to adenocarcinoma of the small intestine, similar to those of colorectal adenoma and other cancers. However, the expression profiles of the other miRNAs of SIT were significantly different from those of colorectal tumors. These findings contribute useful insights into the tumor development and diagnosis of SIT.

There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Aim: The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml., Patients and Methods: Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3 rd - or later-line therapy. The median AFP level was 2259 ng/ml., Results: The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline., Conclusion: In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3 rd - or later-line therapy. Additional studies are needed to confirm the efficacy and safety of RAM as 2 nd -line treatment after Atz/Bev in Child-Pugh A patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN., (© 2022. Japanese Society of Gastroenterology.)

Background: Migration is at an all-time high worldwide, and despite increased focus on international migrants, there is little evidence about internal migrants' exposures to socioeconomic, occupational, and environmental risk factors in low-and middle-income countries., Objective: The aim of this study was to examine differences in occupational health and access to water, sanitation, and hygiene (WASH) between internal migrants and non-migrants., Methods: A face-to-face survey (n = 937) was conducted in Mandalay, Myanmar. Bivariate and multivariate analysis included traditional social determinants such as education, income, occupation, gender, age, and location in addition to internal migration status., Findings: The majority of internal migrants (23% of the total sample) were labor migrants (67.3%), and while common social determinants (e.g., household income, education, and gender) were not statistically different between migrants and non-migrants, these groups reported different occupational profiles (p < 0.001). Migrants had higher odds of being street vendors (AOR = 2.26; 95% CI 1.33-3.85; p = 0.003) and were less likely to work labor jobs such as in factories or construction (AOR = 0.44; 95% CI 0.19-1.00; p = 0.051) when controlling for age, gender, education, and location. Internal migrants had significantly greater probabilities of experiencing some injuries and illness symptoms, such as cuts, vomiting, coughing, heatstroke, and diarrhea at work (p < 0.001). Compared to non-migrants, migrants' households were approximately three times more likely (AOR = 3.45; 95% CI 2.17-5.62; p < 0.001) to have an unimproved source of drinking water and twice as likely (AOR = 1.98; 95% CI 1.10-3.58; p < 0.05) to have unimproved sanitation facilities in their homes., Conclusions: The results underscore the importance of considering internal migration as an aspect of social determinants analyses, and the need for targeting appropriate WASH interventions to address inequities., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Gallbladder (GB) diseases represent various lesions including gallstones, cholesterol polyps, adenomyomatosis, and GB carcinoma. This review aims to summarize the role of endoscopic ultrasound (EUS) in the diagnosis of GB lesions. EUS provides high-resolution images that can improve the diagnosis of GB polypoid lesions, GB wall thickness, and GB carcinoma staging. Contrast-enhancing agents may be useful for the differential diagnosis of GB lesions, but the evidence of their effectiveness is still limited. Thus, further studies are required in this area to establish its usefulness. EUS combined with fine-needle aspiration has played an increasing role in providing a histological diagnosis of GB tumors in addition to GB wall thickness.

Rationale: API2-MALT1 positive gastric mucosa-associated lymphoid tissue (MALT) lymphomas are considered to have favorable prognosis. We report a case of API2-MALT1 positive gastric MALT lymphoma, treated by endoscopic submucosal dissection (ESD)., Patient Concerns: A 51-year-old man underwent esophagogastroduodenoscopy (EGD) for the annual health checkup examination., Diagnoses: The EGD showed a reddish depressed lesion with small reddish spots in the lower gastric body. There was no endoscopic atrophy in the entire stomach and Helicobacter pylori (H. pylori) serum test was negative. Infiltration of small lymphocytes was shown in the gastric tissues obtained by the endoscopic biopsy. The fluorescence in situ hybridization using the biopsy samples confirmed the presence of genetic translocation of API2-MALT1, suggesting that the lesion is API2-MALT1 positive MALT lymphoma., Interventions: Since endoscopic ultrasound suggested that the lesion was localized within the lamina propria mucosae, we performed ESD to achieve the en bloc resection of the lesion., Outcomes: Conclusive diagnosis of gastric MALT lymphoma was made based on the resected specimen. Lateral and vertical margins were negative. No lymphoma cells were detected using endoscopic biopsy after 5 years., Lessons: Our report suggests that ESD can be considered as alternative treatment for API2-MALT1 positive gastric MALT lymphoma if the lesion was localized within the gastric mucosa., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to clarify the association of MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation status. Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Results: Either rs3735656 or rs10226620, located in the 3'-UTR of MAFK , was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10; p  = 0.0012, and OR, 1.98; p  = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele ( p  = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of p14 ARF and p16 INK4a were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and CDKN2A methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with CDKN2A methylation in a recessive genetic model (OR, 3.58; p  = 0.0071, OR, 4.49; p  = 0.0004, and OR, 3.45; p  = 0.0027, respectively). Conclusions: Our results indicate that carrying the minor allele of the MAFK polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CDKN2A CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.

Introduction: Polyethylene glycol-electrolyte lavage solution plus ascorbic acid (PEG-ELS-Asc) has been recommended for colonoscopy, but little is known about the safety of PEG-ELS-Asc in patients with chronic kidney disease (CKD). The aim of this study was to determine its safety and efficacy in CKD patients., Methods: Blood and urine samples prospectively collected before and after same-day bowel preparation for colonoscopy with the conventional volume of PEG-ELS-Asc, vital signs before and after colonoscopy, and adverse events within 30 days postcolonoscopy were analyzed in consenting patients with CKD. The cleansing level was evaluated with the Boston bowel preparation score (BBPS) from colonoscopic findings., Results: Of 57 patients enrolled, 1 was excluded for refusal. Serum bicarbonate significantly dropped, and blood hemoglobin, serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, and uric acid significantly rose after bowel preparation, although these changes were not clinically important. Only in nondialysis patients did the platelet count and potassium significantly rise, although these changes were not clinically important either. Renal function, such as the urea, creatinine, and estimated glomerular filtration rate, was not significantly altered. An adequate bowel cleansing score, BBPS ≥ 6, was achieved in 94% of patients. The blood pressure and heart rate were not significantly different between before and after colonoscopy in either nondialysis ( n = 32) or dialysis ( n = 19) patients. There were no adverse events associated with bowel preparation and colonoscopy within 30 days postcolonoscopy., Conclusions: The conventional volume of same-day bowel preparation with PEG-ELS-Asc may be safe and effective in CKD patients., Competing Interests: The other authors report conflicts of interest., (Copyright © 2021 Naoki Ohmiya et al.)

Objectives: We determined the efficacy of fecal microbiota transplantation (FMT) and subsequent changes in fecal microbiota and short-chain fatty acid (SCFA) levels in patients with ulcerative colitis (UC), Crohn's disease (CD), and recurrent Clostridioides difficile infection (rCDI)., Methods: A filtered solution of Japanese donor feces was endoscopically administered. The efficacy of FMT was evaluated after 8 weeks using the Mayo score, Crohn's Disease Activity Index (CDAI), and the absence of diarrhea with stool toxin negativity in patients with active UC, CD, and rCDI, respectively. For fecal microbiota analysis, the 16S ribosomal RNA gene was sequenced, and fecal SCFA levels were measured., Results: Clinical response was achieved in 5/20 (25%), 3/4 (75%), and 4/4 (100%) patients with UC, CD, and rCDI, respectively. Clinical remission was achieved in 4/20 (20%) and 1/4 (25%) patients with UC and CD, respectively. Linear discriminant analysis illustrated that UC responders had lower counts of Clostridium cluster XIVa before FMT and higher counts after FMT. Higher Fusicatenibacter saccharivorans counts in donors were significantly correlated with 8-week clinical remission. Patients with CD exhibited lower Blautia , Dorea , and Eubacterium counts before FMT and higher Collinsella , Dorea , and Eubacterium counts after FMT, accompanied by functional profiles predictive of SCFA fermentation and elevated fecal butyrate concentrations. Patients with rCDI displayed significantly lower abundances of Clostridium clusters IV and XIVa before FMT and higher abundances after FMT accompanied by elevated fecal propionate concentrations., Conclusions: FMT exhibited various efficacy against UC, CD, and rCDI by altering the gut microbiota and SCFA production., Competing Interests: Naoki Ohmiya received commercial research fundings from Nippon Kayaku Co. Ltd., EA Pharma Co. Ltd., and Eli Lilly Japan K.K.

Background: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa., Methods: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14 ARF , p16 INK4a , DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/μL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis., Results: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14 ARF , p16 INK4a , DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14 ARF ). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM., Conclusions: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.

Background: CDKN2A hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between CDKN2A methylation status and MIF polymorphisms (rs755622 and rs5844572)., Methods: One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of p14 ARF and p16 INK4a was determined by MSP; MIF genotypes were identified by PCR-SSCP., Results: We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated p14 ARF or p16 INK4a . Carrying the rs755622 C allele indicated a significantly higher risk for p14 ARF methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08-4.32; p = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for p16 INK4a methylation (OR, 2.57; 95% CI, 1.26-5.24; p = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both p14 ARF and p16 INK4a when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22-6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25-6.62; p = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55-262.6; p = 0.0059 and OR, 4.38; 95% CI, 1.12-17.2; p = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46-144.3; p = 0.022)., Conclusions: Taken together, our findings suggest that MIF genotypes associated with inflammation may also be involved in promoting carcinogenesis via CDKN2A hypermethylation in patients diagnosed with UC.

Background and Aim: Needle-based confocal laser endomicroscopy (nCLE) allows for real-time optical biopsies during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Little is known about nCLE imaging of gastrointestinal subepithelial lesions (GI-SEL); therefore, we determined its feasibility., Methods: We carried out EUS, nCLE, and finally FNA in 25 patients with GI-SEL between November 2015 and December 2018. We retrospectively compared nCLE findings with pathological findings of EUS-FNA or surgical specimens. For concordance analysis, two endoscopists independently validated representative nCLE images 5 months or more after examinations., Results: Adequate sample acquisition rate of EUS-FNA was 67% per needle pass and 96% per patient. EUS-FNA was diagnostic in 80% (20/25), suspicious in 4% (1/25), and nondiagnostic in 16% (4/25). nCLE image acquisition rate was 100% and its concordance rate with final pathology was 88% (22/25), which was not significantly different from diagnostic and suspicious EUS-FNA. nCLE could differentiate GI stromal tumors (GISTs) from leiomyoma, in that GISTs were characterized by contrast-enhanced densely populated spindle cell tumors with unenhanced rod-shaped nuclei in 93% of 14 patients, whereas leiomyomas were characterized by narrower spindle cell tumors with fewer and smaller unenhanced nuclei in 100% of three patients. In rectal metastasis from lung adenocarcinoma, some pleomorphic dark nests were observed. At concordance analysis between the two endoscopists' validation results, κ value was 0.560 (P < 0.001), indicating moderate agreement. There were no adverse events associated with nCLE and EUS-FNA., Conclusion: Needle-based confocal laser endomicroscopy can be safe and useful for on-site detection of abnormalities of GI-SEL (UMIN 000013857)., (© 2019 Japan Gastroenterological Endoscopy Society.)

Goals: We determined whether full-spectrum endoscopy (FUSE) improved the visualization rates of blind spots in a single-center case control study., Background: FUSE provides a 210-degree angle of view with a left side-viewing camera in addition to a forward-viewing camera. FUSE can improve the detectability of blind spots in conventional forward-viewing esophagogastroduodenoscopy (EGD), such as the major duodenal papilla (MDP) and the anal side of the pyloric ring., Study: Between April 2016 and May 2017, successful visualization rates of the whole MDP and anal side of the pyloric ring were compared between 103 participants who underwent FUSE and 1045 participants who underwent EGD. Pain and discomfort at insertion and during and after the examination were assessed using a visual analog scale in 38 participants who underwent FUSE with a previous examination history of EGD., Results: The successful visualization rates of MDP and the anal side of the pyloric ring in the FUSE group were significantly higher than those in the conventional EGD group; 83.4% versus 35.1% for MDP (P<0.001) and 86.4% versus 7.1% for the anal side of the pyloric ring (P<0.001), respectively. The visual analog scale were not significantly different between FUSE and previous EGD in a portion of the FUSE group. In addition, the detection rate of the periampullary diverticula was also significantly higher in the FUSE group than that in the conventional EGD group (8.7% vs. 1.6%, P<0.001)., Conclusions: This study provides evidence supporting that FUSE is superior to EGD for precise visualization of blind spots in the duodenum.

The study objective was to examine barriers and facilitators of maternal health services utilization in Myanmar with the highest maternal mortality ratio in Southeast Asia. Data for 258 mothers with children under five were extracted from a community health survey administered between 2016 and 2017 in Mandalay, the largest city in central Myanmar, and analyzed for associations between determinants of maternal health care choices and related outcomes. The study showed that late antenatal care was underutilized (41.7%), and antenatal care attendance was significantly associated with geographical setting, household income, education, and access to transportation ( p ≤ 0.05). Less than one-third of women gave birth at home and 18.5% of them did so without the assistance of traditional birth attendants. Household education level was a significant predictor for home delivery ( p < 0.01). Utilization of postnatal care services was irregular (47.9%-70.9%) and strongly associated with women's places of delivery ( p < 0.01). Efforts geared towards improving maternal health outcomes should focus on supporting traditional birth attendants in their role of facilitating high-quality care and helping women reach traditional health facilities, as well as on maternal health literacy based on culturally appropriate communication., Competing Interests: The authors declare no conflicts of interest.

Predicting Helicobacter pylori (Hp) status by endoscopic finding would be useful in recent clinical condition that the use of proton-pump inhibitors, anti-platelet, and anti-coagulant have become widespread. We aimed to elucidate the diagnostic accuracy of magnifying narrow-band imaging (M-NBI) endoscopy in distinguishing Hp status in patients with or without history of successful Hp eradication and compare this accuracy to the diagnostic accuracy of conventional white light (WL) endoscopy.Two hundred seven endoscopic examinations before and after Hp eradication were performed in prospective 163 patients. Endoscopic images by using the M-NBI and conventional WL were stored electronically and randomly allocated to 2 readers for evaluation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed by reference to Hp status assessed by conventional clinical test.Sensitivity, specificity, PPV, NPV, and accuracy for predicting Hp status for the conventional WL was 72.2%, 75.5%, 72.2%, 75.5%, and 73.9% for the first reader; 86.6%, 57.3%, 64.1%, 82.9%, and 71.0% for the second reader. On the other hand, sensitivity, specificity, PPV, NPV, and accuracy for predicting Hp status for the M-NBI was 96.9%, 93.6%, 93.1%, 97.1%, and 95.2% for the first reader; 92.8%, 93.6%, 92.8%, 93.6%, and 93.2% for the second reader, respectively. The diagnostic accuracy of M-NBI was significantly higher than that of WL (P < .0001 for both readers). Inter-observer agreement of M-NBI (k = 0.83) was also better than that of WL (k = 0.53).M-NBI was capable of distinguishing Hp status before and after eradication therapy.

Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods: LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori -related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori -related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.

Background and study aims  Endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has not been established. Probe-based confocal laser endomicroscopy (pCLE: Cellvizio) provides real-time endomicroscopic analysis. We developed and validated a new pCLE classification of SNADET based on abnormal findings. Patients and methods  pCLE scanning of 20 SNADET lesions including 16 adenomas and four carcinomas was retrospectively evaluated to explore abnormal pCLE findings in relation to histological features. Diagnostic yield of pCLE findings was prospectively evaluated in an additional 20 SNADET lesions including 16 adenomas and four carcinomas. Results  In a retrospective study, we identified four abnormal pCLE findings of SNADETs: (1) dark epithelium, (2) columnar cells irregularly extending to the lumen, (3) distorted crypt structure, and (4) fluorescein leakage. Dark epithelium distinguished neoplastic lesions (adenomas and carcinomas) from non-neoplastic duodenal mucosa with a sensitivity of 90 % and a specificity of 100 %. Distorted crypt structure distinguished carcinomas from adenomas and non-neoplastic duodenal mucosa with a sensitivity of 100% and a specificity of 94 %. In the prospective study, the sensitivity and the specificity of the dark epithelium for the diagnosis of neoplastic lesions (adenomas + carcinomas) was 75% and 100 %. Sensitivity and the specificity of the distorted crypt structure for discrimination of carcinoma from adenoma were 100 % and 94 %, respectively. Conclusions  The pCLE findings correlated with the histopathology of the SNADETs. Dark epithelium and distorted crypt structure were informative pCLE findings to predict presence of neoplasia and cancer in the SNADET, respectively. UMIN-CTR UMIN000013857 TRIAL REGISTRATION: Single-Center, prospective observational trial UMIN000013857 at upload.umin.ac.jp.

Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen ( PSCA ), and the other was a polymorphism (rs4072037) in mucin 1 ( MUC1 ). DNA methylation is associated with gastric cancer and Helicobacter pylori ( H. pylori )-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori , a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori- -related promoter CGI methylation in the nonneoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection ( IGF2, MYOD1 , and SLC16A12 ). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori -positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06-5.29; P = 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41-7.25; P = 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori -related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction., (©2019 American Association for Cancer Research.)

Drug resistance makes treatment difficult in cancers. The present study identifies and analyzes drug resistance-related miRNA in colorectal cancer. We established 4 types of 5-fluorouracil (5-FU)-resistant colon cancer cell lines in vitro and in vivo. We then analyzed the miRNA expression profile by miRNA array in these 4 cell lines, and identified the drug resistance-related miRNAs. We examined the expression levels of the identified miRNA in 112 colorectal tumor samples from the patients. We identified 12 possible miRNAs involved in 5-FU resistance by miRNA arrays. We then examined the relationship between miR-31, which was the most promising among them, and drug resistance. The ectopic expression of mimic miR-31 showed significant 5-FU resistance in the parental DLD-1 cells, while anti-miR-31 caused significant growth inhibition in DLD/F cells; that is, 5-FU-resistant colon cancer cell line DLD-1 under exposure to 5-FU. When we exposed high doses of 5-FU to parent or 5-FU-resistant cells, the expression levels of miR-31 were raised higher than those of controls. Notably, the expression levels of miR-31 were positively correlated with the grade of clinical stages of colorectal tumors. The protein expression levels of factors inhibiting hypoxia-inducible factor 1 were downregulated by transfection of mimic miR-31 into DLD-1 cells. This study provides evidence supporting the association of miR-31 with 5-FU drug resistance and clinical stages of colorectal tumors., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background & Aims: We aimed to establish a comorbidity index for small bowel vascular diseases (SBVD) associated with small bowel bleeding (SBB) and recurrent bleeding., Methods: We performed a retrospective analysis of 404 patients diagnosed with SBB via double-balloon enteroscopy, at 2 hospitals in Japan from June 2003 through July 2016. We collected data on comorbidities, computed Charlson Comorbidity Index and anticoagulation and risk factors in atrial fibrillation (ATRIA) scores, and analyzed associations with SBVD, rebleeding, and overall survival associated with bleeding and/or comorbidities. We used these data to develop a comorbidity index to identify patients at risk for SBVD, rebleeding, and reduced survival time. We validated our findings in a separate, prospective cohort of 88 patients with SBB., Results: We developed a weighted index (the Ohmiya index) that identified patients who developed SBVD with an area under the receiver operating characteristic (AUROC) curve of 0.7758; this value was higher than that of the Charlson index score (0.6828; P < .0001) or ATRIA score (0.6728; P < .0001) alone. Among the 51 patients taking oral anticoagulants, there was no significant difference in AUROCs for the Ohmiya score (0.5254) vs the outcomes registry for better informed treatment score (0.5857; P = .4300). In the retrospective cohort, the Ohmiya index identified patients with SBVD with 68% sensitivity (93/137), 84% specificity (223/267), and 78% accuracy (316/404); in the validation cohort, these values were 63% (22/35), 85% (45/53), and 76% (67/88), respectively. Onset age <50 years and index score <2 identified patients with Meckel's diverticulum and Crohn's disease with 53% accuracy. Onset age ≥50 years and index score <2 identified patients with inflammatory diseases, drug-induced injuries, or tumors with 72% accuracy. An index score ≥2 identified patients with SBVD with 68% accuracy, regardless of age. Among patients with Ohmiya index scores ≥2, 33% had rebleeding; among patients with scores <2, 15% had rebleeding (hazard ratio for score ≥2, 1.729; 95% CI, 1.038-2.882; P = .0355)., Conclusion: We developed an index, based on comorbidities and age of onset of SBB, that identified patients at risk for rebleeding and vascular disease (for example, enteroscopic hemostasis for SBVD, medication for inflammatory diseases, surgery with enteroscopic tattooing for tumors and diverticula). UMIN: 000025693., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)