Search

Background: Bismuth quadruple therapy is currently consensus recommendation for first-line Helicobacter pylori ( H . pylori ) treatment; however, the optimal duration is unknown. We compared the efficacy of 10-day bismuth quadruple therapy with that of 14-day bismuth quadruple therapy for first-line eradication., Methods: For our multicentre, parallel randomised, open-label, and non-inferiority study, we recruited H. pylori treatment-naïve patients from one medical centre and one teaching hospital in Taiwan. Patients were randomly assigned (1:1) to receive 10-day (PBMT-10) or 14-day (PBMT-14) bismuth quadruple therapy. The primary outcome was the eradication rate as determined by intention-to-treat (ITT) and per-protocol (PP) analyses. The eradication rates between the two groups were compared using a one-sided α value of 0.025 and a non-inferiority margin of 7%. The secondary outcomes were the rate of adverse effects. The trial is registered with ClincialTrials.gov (NCT04527055)., Findings: From August 3, 2020 to April 28, 2023, 313  H. pylori treatment-naïve patients (PBMT-10 = 157; PBMT-14 = 156) were enrolled. 35 patients were excluded from PP analyses. The eradication rates (95% CI) for PBMT-10 and PBMT-14 were respectively 92.4% (88.2%-96.5%) and 92.9% (88.9%-97.0%) by ITT analyses, and 97.9% (95.5%-100.0%) and 99.3% (97.8%-100.0%) by PP analyses. The eradication rates for PBMT-10 were non-inferior to those for PBMT-14 (absolute difference [lower boundary of the one-sided 97.5% CI] -0.6% [-6.7%], P NI  = 0.020 in ITT analyses, -1.4% [-5.8%], P NI  = 0.007 in PP analyses). The rates of overall adverse effects (54.1% versus 57.1%, P  = 0.604) were similar between the two groups; nevertheless, the rates of dizziness (18.5% versus 34.0%, P  = 0.003) and vomiting (4.5% versus 12.8%, P  = 0.008) were lower in PBMT-10 than in PBMT-14., Interpretation: The 10-day bismuth quadruple therapy was non-inferior to the 14-day therapy as a first-line treatment for eradicating H. pylori infection and had no different rates of overall adverse effects, but less serious adverse events in terms of dizziness and vomiting., Funding: The National Science and Technology Council and Ministry of Health and Welfare, Taiwan., Competing Interests: All authors declare no potential conflicts, including financial, professional, or personal, that are relevant to the manuscript., (© 2024 The Author(s).)

Background: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure., Materials and Methods: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure., Results: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027)., Conclusions: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure., (© 2023 John Wiley & Sons Ltd.)

Objective: Common bile duct (CBD) stones caused diseases are life-threatening. Because CBD stones locate in the distal part of the CBD and have relatively small sizes, detecting CBD stones from CT scans is a challenging issue in the medical domain., Methods and Procedures: We propose a deep learning based weakly-supervised method called multiple field-of-view based attention driven network (MFADNet) to detect CBD stones from CT scans based on image-level labels. Three dominant modules including a multiple field-of-view encoder, an attention driven decoder and a classification network are collaborated in the network. The encoder learns the feature of multi-scale contextual information while the decoder with the classification network is applied to locate the CBD stones based on spatial-channel attentions. To drive the learning of the whole network in a weakly-supervised and end-to-end trainable manner, four losses including the foreground loss, background loss, consistency loss and classification loss are proposed., Results: Compared with state-of-the-art weakly-supervised methods in the experiments, the proposed method can accurately classify and locate CBD stones based on the quantitative and qualitative results., Conclusion: We propose a novel multiple field-of-view based attention driven network for a new medical application of CBD stone detection from CT scans while only image-levels are required to reduce the burdens of labeling and help physicians automatically diagnose CBD stones. The source code is available at https://github.com/nchucvml/MFADNet after acceptance., Clinical Impact: Our deep learning method can help physicians localize relatively small CBD stones for effectively diagnosing CBD stone caused diseases., (This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.)

Background and Aims: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material., Methods: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material., Results: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm 2 and 10.74 mm 2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] μg vs .70 [interquartile range, .27-1.24] μg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001)., Conclusions: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Goal: Diagnosing the corpus-predominant gastritis index (CGI) which is an early precancerous lesion in the stomach has been shown its effectiveness in identifying high gastric cancer risk patients for preventive healthcare. However, invasive biopsies and time-consuming pathological analysis are required for the CGI diagnosis. Methods: We propose a novel gastric section correlation network (GSCNet) for the CGI diagnosis from endoscopic images of three dominant gastric sections, the antrum, body and cardia. The proposed network consists of two dominant modules including the scaling feature fusion module and section correlation module. The front one aims to extract scaling fusion features which can effectively represent the mucosa under variant viewing angles and scale changes for each gastric section. The latter one aims to apply the medical prior knowledge with three section correlation losses to model the correlations of different gastric sections for the CGI diagnosis. Results: The proposed method outperforms competing deep learning methods and achieves high testing accuracy, sensitivity, and specificity of 0.957, 0.938 and 0.962, respectively. Conclusions: The proposed method is the first method to identify high gastric cancer risk patients with CGI from endoscopic images without invasive biopsies and time-consuming pathological analysis., (© 2023 The Authors.)

Background: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer., Methods: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not., Results: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status., Conclusion: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055)., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Background/aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses., Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed., Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568)., Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Background: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients., Methods: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively., Results: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor., Conclusions: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015)., (© 2022. The Author(s).)

Background: Helicobacter pylori infection is the leading cause of peptic ulcer and chronic gastritis and may initiate gastric carcinogenesis following the Correa cascade. Another lineage of metaplasia, spasmolytic peptide-expressing metaplasia (SPEM) has recently been found to be an alternative precursor to gastric cancer. To date, few reports have investigated gastric precancerous lesions among children with H. pylori infection. This study aimed to evaluate the histopathological pattern of H. pylori atrophic gastritis in children and the extent of precancerous lesions., Materials and Methods: This study enrolled pediatric patients with H. pylori infection from 1998 to 2019. During esophagogastroduodenoscopy examinations, biopsy fragments were collected from the gastric antrum and corpus for rapid urease test, culture, and histology evaluation. The presence and degree of chronic inflammation, activity of gastritis, H. pylori density, atrophy, and intestinal metaplasia (IM) were assessed according to the modified Updated Sydney System. Trefoil factor 2 (TFF2) immunohistochemistry was also performed to assess SPEM in the gastric tissues collected from each case using rabbit anti-human TFF2 antibodies., Results: A total of 92 children with H. pylori infection and adequate gastric mucosa biopsies were enrolled. Esophagogastroduodenoscopy showed that 39 (42.4%) had duodenal ulcers, 11 (12.0%) had gastric ulcers, 41 (44.6%) had gastritis, and 1 (1.1%) had negative findings. Mild-to-moderate IM was identified in 4 patients (4.3%). SPEM was found in 8 patients (8.7%) with a significantly higher incidence among female patients (15.8% vs. 8.7%, p = .031). Gastric glandular atrophy presented in 28 patients (30.4%), and high-grade atrophy was more common in female patients (3.2% vs. 1.9%, p = .031)., Conclusions: The prevalence rates of atrophic gastritis in the children with H. pylori infection were 30.4% for gastric glandular atrophy, 4.3% for IM and 8.7% for SPEM. SPEM and high-grade atrophy were more common in female patients., (© 2022 John Wiley & Sons Ltd.)

Background: Helicobacter pylori infection is a major cause of peptic ulcers and gastric cancer. This study aimed to compare the eradication rate and essential costs of culture-based and empiric therapy strategies in treating pediatric H. pylori infection., Methods: We retrospectively enrolled patients aged <18 years with a diagnosis of H. pylori infection who received esophagogastroduodenoscopy at two medical centers in southern Taiwan from 1998 to 2018. Patients with positive cultures and minimum inhibitory concentration test results were allocated to a culture-based strategy, and those with negative cultures or without culture as an empiric therapy strategy. We collected demographic data and eradication rates, and calculated the total essential costs of treating a hypothetical cohort of 1,000 pediatric patients based on the two strategies., Results: Ninety-six patients were enrolled, of whom 55 received a culture-based strategy and 41 received an empiric therapy strategy. The eradication rates with the first treatment were 89.1 and 75.6% in the culture-based and empiric therapy strategy, respectively. There were no significant differences in age, sex, and endoscopic diagnosis between the two strategies. For every 10% increase in those receiving a culture-based strategy, the total cost would have been reduced by US$466 in a hypothetical cohort of 1,000 patients. For every 10% increase in successful eradication rate, the total cost was reduced by US$24,058 with a culture-based strategy and by US$20,241 with an empiric therapy strategy., Conclusions: A culture-based strategy was more cost effective than an empiric therapy strategy in treating pediatric H. pylori -infected patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hung, Chen, Ku, Sheu and Yang.)

Helicobacter pylori causes gastrointestinal diseases, the manifestations of diseases are more serious in adults than in children. Lewis antigen expressions on the gastric epithelium serves as receptors targeted by H. pylori . Moreover, the MAPK signaling pathway involves glycoprotein synthesis of Lewis antigens. We aimed to investigate whether differences in H. pylori -induced MAPK responses mediate gastric Lewis antigens expression and colonization density differently in children and adults. We used human stomach fetal epithelium (HSFE) and SV40-immortalized human normal gastric epithelial (GES-1) cell lines to mimic primary gastric epithelium of children and adults, respectively. H. pylori colonization intensity and Lewis antigens were significantly higher in GES-1 than in HSFE cells, whereas IL-8 and IL-6 levels were significantly higher in HSFE than in GES-1 cells after infection. c-Jun N-terminal kinase (JNK) siRNA and inhibitor (SP600125) experiments showed that Lewis antigen expression and H. pylori colonization were reduced in GES-1 cells but increased in HSFE cells. Furthermore, p-p38 intensity was significantly higher in the superficial epithelium of the children than in the adults with/without H. pylori infection. The overexpression of p38 in GES-1 cells downregulated H. pylori -induced JNK activity mimicking H. pylori infection in children. In conclusion, a higher p38 expression in gastric epithelium counteracting JNK activity in children may contribute to lower Lewis antigen expression and colonization density than in adults after H. pylori infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Lu and Sheu.)

Background: The current guideline recommends patients who meet high probability criteria for choledocholithiasis to receive endoscopic retrograde cholangiopancreatography (ERCP). However, adverse events can occur during ERCP. Our goal is to determine whether endoscopic ultrasound (EUS) before ERCP can avoid unnecessary ERCP complications, especially in patients with a negative CT scan., Methods: A total of 604 patients with high probability of choledocholithiasis were screened and 104 patients were prospectively enrolled. Patients with malignant biliary obstruction, altered GI anatomy, and choledocholithiasis on CT scan were excluded. Among them, 44 patients received EUS first, and ERCP if choledocholithiasis present (EUS-first group). The other 60 patients received ERCP directly (ERCP-first group). The baseline characteristics, presence of choledocholithiasis, and complications were compared between groups. All patients were followed for 3 months to determine the difference in recurrent biliary event rate. Cost-effectiveness was compared between the two strategies., Results: There was no marked difference in age, sex, laboratory data, presenting with pancreatitis, and risk factors for choledocholithiasis. Overall, 51 patients (49.0%) had choledocholithiasis, which did not justify the risk of direct ERCP. In the EUS-first group, 27 (61.4%) ERCP procedures were prevented. The overall complication rate was significantly lower in the EUS-first group compared to the ERCP-fist group (6.8% vs. 21.7%, P = 0.04). The number-needed-to-treat to avoid one unnecessary adverse event was 6.71. After a 3-month follow-up, the cumulative recurrence biliary event rates were similar (13.6% vs. 15.0%, P = 0.803). EUS-first strategy was more cost-effective than the ERCP-first strategy (mean cost 2322.89$ vs. 3175.63$, P = 0.002)., Conclusions: In high-probability choledocholithiasis patients with a negative CT, the EUS-first strategy is cost-effective, which can prevent unnecessary ERCP procedures and their complications., (© 2022. The Author(s).)

In this study, we aimed to analyze whether serum prealbumin and transferrin have a higher sensitivity than albumin for detecting malnutrition and predicting survival in esophageal cancer patients. A total of 212 patients were prospectively enrolled. Serum albumin, prealbumin, and transferrin were analyzed by enzyme-linked immunosorbent assays. The association of nutritional markers with survival was analyzed. We found that malnutrition was presented in 44.5% of the patients, while 56.6% were unaware of their body weight change. The area under the curve for diagnosing malnutrition was largest for prealbumin, followed by transferrin and albumin, with optimal breakpoints of 21 mg/dL, 206 mg/dL, and 4.3 g/dL, respectively, for diagnosing malnutrition. The diagnostic sensitivity for malnutrition was 34.1-63.4% with a single marker and this increased to 80.5% with all 3 markers. In patients with normal albuminemia (≥ 4.3 g/dL), a low level of prealbumin and/or transferrin predicted malnutrition and poor prognosis. Multivariate Cox regression analysis confirmed that a low level of the nutritional marker was an independent poor prognostic factor. In conclusion, serum prealbumin and transferrin outperformed albumin in identifying esophageal cancer patients with malnutrition and poor prognosis. Checking all three markers will help with the early diagnosis of malnutrition and enable timely intervention.

Background: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects., Methods: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors., Results: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT., Conclusion: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Background/aims: Endoscopic ultrasonography (EUS)-guided tissue acquisition requires a long learning curve. We aimed to compare the skill maturation curves between fine needle aspiration (FNA) and biopsy (FNB) for tissue acquisition., Methods: The initial 60 procedures performed by the trainee endosonographer (30 FNA vs. 30 FNB) were consecutively enrolled. The difference in procedure performance was compared between the two groups. Learning curves were assessed. Twenty additional cases were subsequently enrolled to assess the consistency of performance in the FNB group., Results: The FNB group acquired larger tissue samples (2.35 vs. 0.70 mm2; p<0.001) with lower blood content (p=0.001) and higher tissue quality (p=0.017) compared with the FNA group. In addition, the FNB group required less needle pass to establish a diagnosis (2.43 vs. 2.97; p=0.006). A threshold diagnostic sensitivity of ≥80% was achieved after performing 10 FNB procedures. The number of needle passes significantly decreased after conducting 20 FNB procedures (1.80 vs. 2.70; p=0.041). The diagnostic sensitivity and number of needle passes remained the same in the subsequent FNB procedures. By contrast, this skill maturation phenomenon was not observed after performing 30 FNA procedures., Conclusion: In EUS-guided tissue acquisition, the FNB needle was more efficient and thus shortened the learning curve of EUS-guided tissue acquisition in trainee endosonographers.

In this paper, we propose a novel deep ensemble feature (DEF) network to classify gastric sections from endoscopic images. Different from recent deep ensemble learning methods, which need to train deep features and classifiers individually to obtain fused classification results, the proposed method can simultaneously learn the deep ensemble feature from arbitrary number of convolutional neural networks (CNNs) and the decision classifier in an end-to-end trainable manner. It comprises two sub networks, the ensemble feature network and the decision network. The former sub network learns the deep ensemble feature from multiple CNNs to represent endoscopic images. The latter sub network learns to obtain the classification labels by using the deep ensemble feature. Both sub networks are optimized based on the proposed ensemble feature loss and the decision loss which guide the learning of deep features and decisions. As shown in the experimental results, the proposed method outperforms the state-of-the-art deep learning, ensemble learning, and deep ensemble learning methods.

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B 12 is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B 12 supplementation and intramuscular administration of vitamin B 12 are equally effective in the treatment of vitamin B 12 deficiency., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2019. Published by Elsevier B.V.)

Objective: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC)., Methods: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed., Results: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori ., Conclusion: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori . Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC., Competing Interests: Competing interests: J-ML reports receiving lecture fees from Takeda Pharmaceuticals (Taiwan) and Abbott Laboratories. PM reports receiving advisory and lecture fees from Bayer, Mayoly Spindler and Nordmark. DYG is a consultant for RedHill Biopharma and Phathom Pharmaceuticals regarding novel H. pylori therapies and has received research support for culture of Helicobacter pylori., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection., Methods: We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive 13 C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy., Results: The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025)., Conclusion: Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.

Background: This study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome., Methods: We retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival., Results: Patients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3)., Conclusion: Large primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted., Competing Interests: The authors have declared that no competing interests exist.

This study investigated the compositional differences in fecal microbiota between children with and without H. pylori infection and tested whether probiotics-containing yogurt and bacterial eradication improve H. pylori -related dysbiosis. Ten H. pylori -infected children and 10 controls ingested probiotics-containing yogurt for 4 weeks. Ten-day triple therapy plus yogurt was given to the infected children on the 4th week. Fecal samples were collected at enrollment, after yogurt ingestion, and 4 weeks after successful H. pylori eradication for cytokines and microbiota analysis using ELISA and metagenomic sequencing of the V4 region of the 16S rRNA gene, respectively. The results showed H. pylori -infected children had significantly higher levels of fecal TGF-β1 than those who were not infected. Eight of 295 significantly altered OTUs in the H. pylori -infected children were identified. Among them, the abundance of F. prausnitzii was significantly lower in the H. pylori -infected children, and then increased after yogurt ingestion and successful bacterial eradication. We further confirmed probiotics promoted F. prausnitzii growth in vitro and in ex vivo using real-time PCR. Moreover, F. prausnitzii supernatant significantly ameliorated lipopolysaccharide-induced IL-8 in HT-29 cells. In conclusions, Probiotics-containing yogurt ingestion and H. pylori eradication can restore the decrease of fecal F. prausnitzii in H. pylori -infected children.

Background: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy., Methods: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4 th -28th day after the first bleeding episode., Results: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01)., Conclusions: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Objective: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO)., Design: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs)., Results: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively., Conclusion: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms., Trial Registration Number: NCT02388724., Competing Interests: Competing interests: MC received speaker honorarium from Xian Janssen, AstraZeneca China, Ipsen Tianjin, Takeda China and CMS China. CFC is an employee of Takeda Development Center Asia, and stock shareholder in Air Liquide and Abbott Laboratories. NF is an employee of Takeda Pharmaceutical Company, and WZ is a former employee of Takeda Pharmaceutical Company. K-L G received fees for participating in an advisory committee or review panel and speaking and chairing for Takeda Pharmaceutical Company. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Since the use of dexlansoprazole in Asian subjects with gastroesophageal reflux disease (GERD) has not been adequately characterized, this study was conducted to evaluate the efficacy and safety of dexlansoprazole modified-release in Asian subjects with non-erosive reflux disease (NERD) and erosive esophagitis (EE)., Methods: In this phase 4, open-label, non-randomized, uncontrolled, multicenter, multi-country study sponsored by Takeda, subjects aged ≥ 20 years with persistent typical GERD symptoms for at least 6 months underwent endoscopy. Based on endoscopic findings, they were assigned to either dexlansoprazole modified-release 30 mg once-daily for 4 weeks (NERD group) or dexlansoprazole modified-release 60 mg once-daily for 8 weeks (EE group). The primary endpoint was the percentage of days that subjects did not experience any 24hour heartburn or acid regurgitation., Results: Of the 445 subjects screened from Hong Kong, South Korea, and Taiwan, 208 were enrolled in the NERD group (mean age: 53.6 years, male: 34.6%) and 88 in the EE group (mean age: 51.7 years, male: 55.7%). Over the treatment period, the median percentage of days that subjects did not experience any 24-hour heartburn or acid regurgitation was 26.9% and 65.5% in the NERD and EE groups, respectively; for nighttime heartburn or acid regurgitation the proportions were 59.3% and 83.3%, respectively. The treatment was well tolerated with low incidence of treatment-related adverse events in NERD and EE groups (6.7% and 5.7%, respectively)., Conclusions: In Asian patients with GERD, treatment with dexlansoprazole modified-release indicates a favorable efficacy and safety profile in relieving heartburn and acid regurgitation symptoms.

Background: Helicobacter pylori infection is known to alter growth-related hormones and affect growth in young children. However, it is still unknown whether maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and whether this can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development., Methods: In this prospective cohort study, we recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined as > 12 U/ml of anti-H. pylori IgG in maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. The growth of the included neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth., Results: Of the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p = 0.04) and lower cord blood levels of IGF-1 (< 35 ng/ml, 70.0% vs. 40.7%, p = 0.02) and IGFBP-3 (< 1120 ng/ml, 100.0% vs. 76.3%, p = 0.02) compared with the seronegative women. No significant impacts on birth weight, childhood growth and cognitive development were found to be correlated with maternal H. pylori seropositivity during pregnancy., Conclusions: Maternal H. pylori infection during pregnancy was more likely to lead to the development of GH, but was not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for mothers with H. pylori infection.

Background: Antimicrobial resistance of Helicobacter pylori reduces the eradication rate. This study aimed to investigate changes in antimicrobial susceptibility of H pylori isolated from children in Taiwan in the past two decades., Methods: This study enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a national tertiary referring hospital from 1998 to 2018. H pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E test. The antibiotic resistance rates and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018., Results: A total of 70 Helicobacter pylori isolates (29 from 1998 to 2008 and 41 from 2009 to 2018) were identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n = 31), gastric ulcers (n = 9), and gastritis (n = 30). The overall antimicrobial resistance rates of clarithromycin and metronidazole were 22.9% and 21.4%, respectively. The dual resistance rate of clarithromycin and metronidazole was 10%. Resistance rates of levofloxacin and amoxicillin were 8.3% and 2.9%, respectively. None of the isolates were resistant to tetracycline. Compared with the isolates from 1998 to 2008, those from 2009 to 2018 had higher MICs and resistance rates of clarithromycin (26.8% vs 17.2%, P = 0.35) and metronidazole (26.8% vs 13.8%, P = 0.19), but not levofloxacin (9.8% vs 5.3%, P = 1.0) or coresistance to clarithromycin and metronidazole (12.2% vs 6.9%, P = 0.69)., Conclusions: The antimicrobial resistance rates of pediatric H pylori isolates to clarithromycin and metronidazole increased during the past decade. The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H pylori eradication rates., (© 2019 John Wiley & Sons Ltd.)

Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen., Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells' stemness properties in vitro and in vivo ., Results: The authors' data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo ., Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient's clinical outcomes in the future., Competing Interests: Conflict of interest statement: The authors declare no conflicts of interest in preparing this article., (© The Author(s), 2019.)

Background: The long-term outcomes of post-colonoscopy colorectal cancer have varied in previous studies. Our nationwide cohort analysis estimated expected years of life lost to adjust for lead time bias., Aim: We recalculated the long-term outcomes for post-colonoscopy and detected colorectal cancer., Methods: Patients with colorectal cancer registered in the Taiwan Cancer Registry between 2002 and 2009 were enrolled. The detected group included 22,169 cases of colorectal cancer confirmed within 6 months after a colonoscopy. The post-colonoscopy group included 1653 cancer patients who received a colonoscopy 6-60 months before diagnosis. Patients were followed up until 2011. We simulated age-, sex-, and calendar year-matched referents from life tables in the Taiwan National Vital Statistics using a Monte Carlo method. The life expectancy and expected years of life lost of the cancer patients were obtained from extrapolation of the logit transformation of the survival ratio between the cancer cohorts and the referent groups., Results: Post-colonoscopy colorectal cancer had shorter life expectancies than detected cancer (stages 2-4: 13.6 vs. 16.1 years; 8.7 vs. 12.6 years; 2.1 vs. 4.1 years, p < 0.001). The loss-of-life expectancy did not show this trend after adjusting for lead time bias. Post-colonoscopy colorectal cancer was found at an older age, more often proximal, and was associated with previous endoscopic polypectomy procedures (p < 0.001)., Conclusions: Post-colonoscopy colorectal cancer leads to a shorter life expectancy, which appears partially explained by the presence of lead time bias. Quality assurance for colonoscopy and close surveillance for high risk groups would reduce post-colonoscopy colorectal cancer.

Aims/introduction: Helicobacter pylori infection is associated with insulin resistance and glycemia in non-diabetes. However, the relationship between H. pylori infection and glycemia in diabetes remains inconclusive. Therefore, we explored the effect of H. pylori infection status and its eradication on glycemic control and antidiabetic therapy in type 2 diabetes patients., Materials and Methods: A total of 549 diabetes patients were recruited for sequential two-step approach (immunoglobulin G [IgG] serology followed by 13 C-urea breath test [UBT]) to discriminate "active" (IgG+ and UBT+) from "non-active" (UBT- or IgG-) H. pylori infection, and "past" (IgG+ but UBT-) from "never/remote" (IgG-) infection. The differences in hemoglobin A1c (A1C) and antidiabetic regimens between groups were compared. In the "active" infection group, the differences in A1C changes between participants with and without 10-day eradication therapy were compared after 3 months., Results: Despite no between-group difference in A1C, the "active" infection group (n = 208) had significantly more prescriptions of oral antidiabetic drug classes (2.1 ± 1.1 vs 1.8 ± 1.1, P = 0.004) and higher percentages of sulfonylurea use (67.3% vs 50.4%, P < 0.001) than the "non-active" infection group (n = 341). There were no differences in A1C and oral antidiabetic drug classes between "past" (n = 111) and "never/remote" infection groups (n = 230). Compared with the non-eradication group (n = 99), the eradication group (n = 98) had significant within-group (-0.17 ± 0.80%, P = 0.036) and between-group (-0.23 ± 0.10%, P = 0.024) improvements in A1C., Conclusions: Diabetes patients with active H. pylori infection need higher glycemic treatment intensity to achieve comparable glycemia. Furthermore, H. pylori eradication decreases A1C, and thus improves glycemic control., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background and Aims: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication., Methods: We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication., Results: GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P < 0.01) than controls. The tissue miR-21, 155, and 223 in antrum were higher in cases with SPEM than in those without SPEM (P <= 0.05). There was similar SPEM reversibility after H pylori eradication between GCF subjects and controls (72% vs 69%, P = 0.852). In the SPEM regressed cases, tissue miR-21, 155, and 223 decreased after H pylori eradication (P < 0.05)., Conclusion: The H pylori-infected GCF subjects were prone to have SPEM with higher tissues miR-21, 155, and 223 expressions. H pylori eradication can result in a 70% SPEM regression, accompanied by a decline in miR-21, 155, and 233 expression levels., (© 2019 John Wiley & Sons Ltd.)

Background: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59., Methods: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing., Results: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1-6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001)., Conclusions: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.

Background: A consensus on the management of Helicobacter pylori has been developed. We aimed to assess whether dissemination through continuing medical education (CME) could enhance the adoption of this consensus among clinicians and to explore potential barriers to acceptance., Materials and Methods: Four CME courses were held to disseminate the consensus. Adoption surveys were performed to evaluate participants' behavior in the past and their commitment to adopt the consensus in future clinical practice after CME. The gaps and barriers to adoption were also surveyed., Results: A total of 240 physicians had attended the CME courses and received surveys with the 22 statements/substatements of the consensus. Before CME, adoption was good in six, fair in ten, and poor in six. After CME, 21 statements had either an initial >90% adoption or improvement to good or fair (P < 0.001), but one still had poor even though it showed improvement (P = 0.02). Although commitment was good or fair after CME, there was a >20% gap between "commitment" and "no barrier" to adoption for 11 statements, ten of which had a main barrier of financial incentives. Among the statements with fair or poor commitment after CME, less commitment to adoption and more barriers related to financial incentives were pronounced in clinicians serving in regional/district hospitals or clinics compared to those serving in medical centers., Conclusions: Continuing medical education may improve the adoption of the H. pylori consensus. The financial incentives were shown to be a main barrier to adoption of the consensus and should be improved., (© 2018 John Wiley & Sons Ltd.)

Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits. Limited intrathoracic anastomotic leakage postesophagectomy can be managed with intravenous antibiotics and self-expanding metal stent (SEMS) or jejunal tube. Enteral nutrition in patients receiving preoperative chemotherapy or chemoradiation provides benefits of maintaining weight, decreasing toxicity, and preventing treatment interruption. Tube feeding or SEMS can offer nutrition support in patients with unresectable esophageal cancer, but SEMS is not recommended for those with neoadjuvant chemoradiation before surgery. Enteral immunonutrition may preserve lean body mass and attenuates stress response after esophagectomy. Administration of glutamine may decrease the severity of chemotherapy induced mucositis. Enteral immunonutrition achieves greater nutrition status or maintains immune functions during concurrent chemoradiation.

Background/purpose: The prevalence of Gastroesophageal reflux disease (GERD) is increasing worldwide, including Asia. Although several consensus reports have been published, little is known regarding the adherence of the physicians on the consensus of GERD. We aimed to survey the agreements and adherence of physicians to the Taiwan GERD consensus before and after the continual medical education (CME) courses., Methods: Two-hundred and twenty-seven physicians, including 81 fellows of gastroenterology, 135 qualified gastroenterologists, and 11 non-gastroenterologist attending physicians were invited to the CME course. Their agreements and adherence to the statements before and after the CME course were assessed by the pre-defined questionnaire with the aid of electronic keypads. The adherence rate before and after the CME course were compared by the McNemar test to indicate the changes in their willingness to follow the statements in clinical practice., Results: The rates of agreement of the 227 participating physicians were uniformly greater than 80% for all of the 22 statements. However, the adherence rates were lower than 80% in 16 statements before the CME intervention. The adherence rates were significantly (p < 0.05) increased in 15 of these 16 statements after the CME intervention. The adherence rate can be improved to greater than 80% for those statements with high level of evidence., Conclusion: Although physicians agreed with the statements, the pre-CME survey disclosed limited adherence rates to the statements. The education intervention through the CME courses can improve the adherence of consensus statement, especially for those with higher level of evidence., (Copyright © 2017. Published by Elsevier B.V.)

Background/purpose: Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use., Methods: The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding., Results: The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05)., Conclusion: Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083)., (Copyright © 2017. Published by Elsevier B.V.)

Background and Aim: Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long-term outcomes deserve follow-up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5-year longitudinal cohort., Methods: Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding., Results: The proportion of patients with rebleeding during the 3.5-year follow-up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5-fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person-year, P = 0.012, log-rank test)., Conclusions: Patients with Rockall scores ≥6 are at risk of long-term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5-fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls., Methods: A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls., Results: The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11-4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15-0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus., Conclusions: Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection., Trial Registration: ClinicalTrial: NCT02466919 , retrospectively registered may 17, 2015.

Background: This study investigated whether levofloxacin-containing concomitant therapy can effectively eradicate Helicobacter pylori infection in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 797 T2DM patients were screened for anti-H. pylori IgG antibodies, and the presence of H. pylori infection was confirmed by 13 C-urea breath test. We prospectively randomized 114 of these patients to receive either 10 d of levofloxacin-concomitant therapy (n = 55) or sequential therapy (n = 59). Antimicrobial resistance of H. pylori isolates collected from the patients with T2DM (n = 109) and dyspeptic controls without DM (n = 110) was determined using the E-test. This study was approved by our Institutional Review Board (A-BR-103-021)., Results: The H. pylori eradication rates with concomitant therapy were higher than sequential therapy in both intention-to-treat (96.4% versus 81.4%, p = 0.012) and per-protocol (100% versus 85.4%, p = 0.006) analysis. The adverse effects in both groups were similarly mild. In the patients who received sequential therapy, clarithromycin resistance was significantly associated with eradication failure (p = 0.02). There were no significant differences in the antibiotic-resistant rates to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin between the patients with and without T2DM., Conclusions: Ten days of levofloxacin-containing concomitant therapy is an effective and well-tolerated treatment to eradicate H. pylori infection for T2DM patients. Key messages Ten days of levofloxacin-containing concomitant therapy is well tolerated and superior to clarithromycin-containing sequential therapy for first-line H. pylori eradication in patients with type 2 diabetes. Clarithromycin resistance to H. pylori is the main factor associated with eradication failure in clarithromycin-containing sequential therapy in diabetic patients.

Background: Corpus-predominant gastritis index (CGI) is an early histological marker to identify Helicobacter pylori-infected gastric cancer relatives at risk of cancer. This study validated whether CGI is more prevalent in H. pylori-infected nonulcer dyspepsia (NUD) subjects than in duodenal ulcer (DU) controls and whether it is reversible after H. pylori eradication or is correlated with noninvasive biomarkers., Materials and Methods: In this longitudinal cohort study, 573 H. pylori-infected subjects were enrolled, including 349 NUD and 224 DU. Gastric specimens were provided to assess CGI, spasmolyic polypeptide-expressing metaplasia (SPEM), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM). Serum pepsinogen I and II levels were assessed using enzyme-linked immunosorbent assay. CGI subjected were followed up at least 1 year after H. pylori eradication., Results: NUD subjects had higher prevalence rates of CGI (47.0% vs 29.9%, P<.001) and OLGIM stages III-IV (24.1% vs 15.2%, P=.01) than controls. CGI was highly prevalent in NUD subjects after the age of 40, which was 10 years earlier than atrophic gastritis and intestinal metaplasia. NUD subjects with CGI had higher risk of SPEM (OR 2.86, P<.001) and lower serum pepsinogen I/II ratios (P<.001) than those without CGI. Serum pepsinogen I/II ratios <9 could predict CGI modestly (AUROC 0.69, 95% CI: 0.63-0.74). CGI was regressed after eradication (P<.001)., Conclusions: CGI was more prevalent in H. pylori-infected NUD subjects than in controls, was correlated with SPEM, and may serve as a marker earlier than OLGIM to indicate risk of gastric cancer. Moreover, CGI could be regressed after eradication., (© 2017 John Wiley & Sons Ltd.)