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Objective: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research., Design: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM., Results: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence., Conclusion: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist., Competing Interests: Competing interests: No conflicts of interest are declared by MD-R, SS, HE-S, MB, NU, HT, LGC, DL, EL, AR, J-YF, LM, JB, EJK, EME-O. PM is a member of advisory board/lecturer of Aboca, Alfasigma, Allergosan, Bayer, Biocodex, Menarini advisory boards/lectures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Gastric cancer (GC) is the third cause of cancer mortality worldwide. A screening strategy that combines an upper gastrointestinal endoscopy (UGIE) with a screening colonoscopy may be cost-effective in intermediate-risk regions. This study aimed to evaluate the intention to adhere to combined endoscopic screening and assess knowledge of GC symptoms, risk factors, and barriers to screening., Methods: Cross-sectional study enrolling individuals eligible for CRC screening in northern Portugal, where a populational fecal occult blood test (FOBT) program is implemented. The validated PERCEPT-PREVENT tool was applied across three groups: (a) not yet invited to CRC screening, (b) FOBT-positive referred to colonoscopy, and (c) primary colonoscopy screening., Results: A high acceptance rate was observed for combined endoscopic screening (94%; n = 264) [not yet invited to CRC screening 98% (n = 90) vs. FOBT-positive referred to colonoscopy 90% (n = 103) vs. primary colonoscopy 97% (n = 71); p = 0.017], with the vast majority reporting intention to adhere in the setting of full reimbursement (97%; n = 255). Most respondents were unaware of any possible GC symptom (76%; n = 213), risk factor (73%; n = 205), and UGIE-related complication (85%; n = 237). Regular follow-up with the primary care physician (Odds Ratio (OR) 27.59, 95% confidence interval (CI) 2.99-254.57), lower perceived negative health consequences of UGIE (OR 1.40, 95% CI 1.13-1.74), and lower perceived financial burden (OR 2.46, 95% CI 1.04-5.85) were the only factors independently associated with a higher intention to undergo combined screening., Conclusions: Willingness to undergo combined endoscopic screening was notably high and positively impacted by lower perceived barriers. Additional efforts should be undertaken to improve levels of digestive health literacy., (© 2024 John Wiley & Sons Ltd.)

Introduction: The incidence of local recurrence following gastric endoscopic submucosal dissection (ESD) remains a clinical concern. We aimed to evaluate the impact of narrow safety margin (< 1 mm) on the recurrence rate., Methods: A retrospective cohort study was conducted across two centers. Cases of R0-ESD with subsequent recurrence were compared to matched controls in a 1:2 ratio in a case-cohort analysis., Results: Over a median period of 25 months (IQR 14-43), a recurrence rate of 3% (95%CI 1.7-4.3) was observed, predominantly (13/21) following R0 resections with favourable histology. Endoscopic retreatment was feasible in 18 of 21 recurrences. The proportion of R0-cases where the safety margin in both horizontal (HM) and vertical (VM) margin exceeded 1 mm was similarly distributed in the recurrence and non-recurrence group, representing nearly 20% of cases. However, cases with HM less than 1 mm, despite VM greater than 1 mm, nearly doubled in the recurrence group (7.7% vs . 3.9%), and tripled when both margins were under 1 mm (23.1% vs . 7.7%). Despite this trend, statistical significance was not achieved ( p  = 0.05). In the overall cohort, the only independent risk factor significantly associated with local recurrence was the presence of residual tumor at the HM (HM1) or not assessable HM (HMx) (OR 16.5 (95%CI 4.4-61.7), and OR 11.7 (95%CI 1.1-124.1), respectively)., Conclusions: While not common or typically challenging to manage, recurrence post-ESD warrants attention and justifies rigorous post-procedural surveillance, especially in patients with HM1, HMx, and probably also in those with R0 resections but narrow safety margin.

Background: Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients., Methods: This case-cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan-Meier and Cox proportional hazards model analyses., Results: MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03-5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07-8.95, p = 0.037)., Conclusions: This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care., (© 2024. The Author(s).)

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis., Competing Interests: Competing interests: DSB has served as speaker for Abbott, AstraZeneca, Alfasigma, Biocodex, Pfizer, Reckitt Benckiser, Takeda, KRKA, PRO.MED.CS Praha and Dr Reddy’s Laboratories. LGC has served as speaker for Takeda and EMS. FDM has served as consultant for Biohit Healthcare. MD-R has served as consultant for Roche and Medtronic. DD has served as consultant for Reckits, Dr Reddy’s, Zentiva, AbbVie, Terapia and Takeda. EME-O is Editor of Gut. EJK is member of the Editorial Board of Gut. MLe has served as research consultant for Eiken Chemical. MLi has served as speaker for Abbott, AstraZeneca, Alfasigma, Biocodex, KRKA and PRO.MED.CS Praha. TM-B received research grants from: AstraZeneca, BMS, Biohit and Fujirebio; and has been involved in congresses and educational supported by AAA, AstraZeneca, MSD, BMS, Viatris and Pierre Fabre. FM has served as consultant for Phathom and Biocodex. ES has served as speaker for AbbVie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots and Unifarco; has served as consultant for AbbVie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas, Takeda and Unifarco; and has received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco and Zeta Farmaceutici. NS has served as speaker for Astellas and consultant for Bristol-Myers Squibb. KS has served as consultant for Fuji Film Co. NU has served as speaker for lectures for: Olympus Co, Fuji Film Co, Boston Scientific Japan, Daiichi-Sankyo Co, Takeda Pharmaceutical Co, EA Pharma Co, Otsuka Pharmaceutical Co, AstraZeneca Co, Miyarisan Pharmaceutical Co and AI Medical Service Co., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Endoscopic screening for gastric cancer (GC) is not recommended in low-intermediate incidence countries. Artificial intelligence (AI) has high accuracy in GC detection and might increase the cost-effectiveness of screening strategies. We aimed to assess the cost-effectiveness of AI for GC detection in settings with different GC incidence and different accuracies of AI systems., Methods: Cost-effectiveness analysis (using Markov model) comparing different screening strategies (no screening versus single esophagogastroduodenoscopy (EGD) at 50 years versus stand-alone EGD every 5/10 years versus combined EGD and screening colonoscopy once or twice per decade in Netherlands, Italy and Portugal) with variable AI accuracy settings. The primary outcome was the incremental cost-effectiveness ratio of the different strategies versus no screening. Deterministic and probabilistic sensitivity analyses were conducted., Results: Without AI, one single EGD at 50 years (Netherlands, Italy, Portugal), EGD combined with screening colonoscopy once per decade (Italy and Portugal) and EGD combined with screening colonoscopy twice per decade (Portugal) are cost-effective when compared with no screening. If AI increases the accuracy of EGD by at least 1% in comparison to the accuracy of white-light endoscopy accuracy (89%), combined screening twice per decade also becomes cost-effective in Italy. If AI accuracy reaches at least 96%, combined screening once per decade is also cost-effective in the Netherlands., Discussion: In European countries, AI-assisted EGD may improve the cost-effectiveness of GC screening with combined EGD and screening colonoscopy. The actual effect of AI on cost-effectiveness may vary dependent on the accuracy and costs of the AI system., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease., Design: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared., Results: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen., Conclusion: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surveillance after gastric endoscopic submucosal dissection (ESD) is recommended for all patients owing to the persistent risk of metachronous gastric lesions (MGLs). We developed and validated a prediction score to estimate MGL risk after ESD for early neoplastic gastric lesions, to define an individualized and cost-saving approach., Methods: Clinical predictors and a risk score were derived from meta-analysis data. A retrospective, single-center, cohort study including patients with ≥ 3 years of standardized surveillance after ESD was conducted for score validation. Predictive accuracy of the score by the area under the receiver operating characteristic curve (AUC) was assessed and cumulative probabilities of MGL were estimated., Results: The risk score (0-9 points) included six clinical predictors (scored 0-3): positive family history of gastric cancer, older age, male sex, corpus intestinal metaplasia, synchronous gastric lesions, and persistent Helicobacter pylori infection (FAMISH). The study population included 263 patients. The MGL rate was 16 %. The score diagnostic accuracy for predicting MGL at 3 years' follow-up, measured by the AUC, was 0.704 (95 %CI 0.603-0.806). At 3 years and a cutoff < 2, the score achieved maximal sensitivity and negative predictive value; 15 % of patients could be assigned to a low-risk group, in which the progression to MGL was significantly lower than for the high-risk group ( P  = 0.04)., Conclusion: The FAMISH score might be a useful tool to accurately identify patients with low-to-intermediate risk for MGL at 3 years of follow-up who could have surveillance intervals extended to reduce the burden of care., Competing Interests: M. Dinis-Ribeiro has been a consultant for Roche (2022) and Medtronic (2021). A. Rei, R. Ortigão, M. Pais, L.P. Afonso, P. Pimentel-Nunes, and D. Libânio, declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objectives: The management of individuals with gastric intestinal metaplasia (GIM) includes biopsies for its staging and to diagnose Helicobacter pylori (Hp ). Advanced-stage GIM can be estimated by endoscopy through EGGIM, and a new device permits the real-time assessment of ammonia for the identification of Hp infection. The aim of this study was to assess the simultaneous use of EGGIM and real-time assessment of ammonia to avoid biopsies and reduce the burden of care in clinical practice., Methods: A multicentre study involving 101 consecutively enrolled patients [52% male; 65(18-85) years]. During endoscopy, gastric juice was aspirated and analysed; EGGIM was determined in real-time. Targeted biopsies were performed and histopathological assessment was used as gold standard., Results: Advanced-stage GIM were detected in 14.9% of patients and Hp infection in 18.8%. EGGIM showed for advanced-stage GIM a sensitivity, specificity and NPV of 86.7%, 84.9% and 97.3%, whilst real-time assessment of ammonia, 83.3%, 78.2% and 95.4%, respectively. Gastric juice was insufficient in 5 (5.0%). Overall, 64 (67%) patients were correctly diagnosed by EGGIM and real-time assessment of ammonia. If the 47 (49%) patients negative to both assessments would have avoided biopsies, only 4 (4.2%) would have been missed: two with advanced-stage GIM and two with Hp infection., Conclusion: The combination of endoscopic assessment and real-time analysis of Hp allows the exclusion of advanced-stage GIM or Hp infection without the need of biopsies in a significant proportion of individuals. This may allow in specific situations to abstain from biopsies reducing the burden of care., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture., Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO., Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level., Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO., Funding: German Research Foundation (DFG)., Competing Interests: Declaration of interests MDR reports consulting fees from Roche Diagnostics and Medtronic; leadership or fiduciary role in the European Society of Gastrointestinal Endoscopy (ESGE) and World Endoscopy Organization (WEO). All other authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastric cancer (GC) screening is arguable in most Western countries. Liquid biopsies are a great promise to answer the unmet need for less invasive diagnostic biomarkers in GC. Thus, we aimed at systematically reviewing the current knowledge on liquid biopsy-based biomarkers in GC screening. A systematic search on PubMed/MEDLINE and Scopus databases was performed on published articles reporting the use of non-blood specimen (saliva, gastric juice [GJ], urine and stool) on GC diagnosis. 3208 records were retrieved by June 2022. After removal of duplicate records, 2379 abstracts were screened, and 84 full texts included in this systematic review. More than 90% of studies were reported on Asian populations. Overall, 9 studies explored stool-, 12 saliva-, and 29 urine-derived biomarkers for GC detection. Additionally, 37 studies, representing the majority, analyzed GJ, focusing on nucleic acid molecules. Several miRNAs and lncRNA molecules have been associated with GC risk, particularly miR-21 (area under the curve [AUC] = 0.97, 95% CI: 0.94-1.00). Considering salivary biomarkers, the best described model in validation sets included the soybean agglutinin and Vicia villosa agglutinin lectins (AUC = 0.89, 95% CI: 0.80-0.99). Most studies in urine carried out metabolomic approaches, with two discriminatory models presenting AUC values superior to 0.97. This systematic review emphasizes the potential role of non-blood-based biomarkers, although further validation, particularly in Western countries, is mandatory, namely for non-invasive screening and/or monitoring, as well as the use of GJ as a tool to enhance upper gastrointestinal endoscopy accuracy., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence., Methods: Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search., Results: Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 - 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 - 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 - 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 - 0.31%; EGC 0.08%, 95% CI 0.04 - 0.13%) and PG (GC 0.10%, 95% CI 0.05 - 0.16%; EGC 0.10%, 95% CI 0.04 - 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better., Discussion: Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.

INTRODUCTION : Metachronous gastric lesions (MGL) are a significant concern after both endoscopic and surgical resection for early gastric cancer. Identification of risk factors for MGL could help to individualize surveillance schedules and potentially reduce the burden of care, but data are inconclusive. We aimed to identify risk factors for MGL and compare the incidence after endoscopic resection (ER) and subtotal gastrectomy. METHODS : We conducted a systematic review by searching PubMed, ISI, and Scopus, and performed meta-analysis. RESULTS : 52 studies were included. Pooled cumulative MGL incidence after ER was 9.3 % (95 % confidence interval [CI] 7.7 % to 11.0 %), significantly higher than after subtotal gastrectomy (1.2 %, 95 %CI 0.5 % to 2.2 %). After adjusting for mean follow-up, predicted MGL at 5 years was 9.5 % after ER and 0.7 % after subtotal gastrectomy. Older age (mean difference 1.08 years, 95 %CI 0.21 to 1.96), male sex (odds ratio [OR] 1.43, 95 %CI 1.22 to 1.66), family history of gastric cancer (OR 1.88, 95 %CI 1.03 to 3.41), synchronous lesions (OR 1.72, 95 %CI 1.30 to 2.28), severe gastric mucosal atrophy (OR 2.77, 95 %CI 1.22 to 6.29), intestinal metaplasia in corpus (OR 3.15, 95 %CI 1.67 to 5.96), persistent Helicobacter pylori infection (OR 2.08, 95 %CI 1.60 to 2.72), and lower pepsinogen I/II ratio (mean difference -0.54, 95 %CI -0.86 to -0.22) were significantly associated with MGL after ER. Index lesion characteristics were not significantly associated with MGL. ER treatment was possible in 83.2 % of 914 MGLs (95 %CI 72.2 to 91.9 %). CONCLUSION : Follow-up schedules should be different after ER and subtotal gastrectomy, and individualized further based on diverse risk factors., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The cumulative lifetime risk of gastric cancer (GC) in patients with Lynch syndrome (LS) is reported to be 8%. There is limited evidence on specific risk factors for GC and no agreement among guidelines on gastric endoscopic surveillance schedule in LS patients., Aims and Methods: We conducted a retrospective cohort study to identify risk factors for gastric precancerous conditions (chronic atrophic gastritis and intestinal metaplasia) and GC in patients with LS and a case-control study to compare the prevalence of these conditions with a control group., Results: We included 385 LS patients (40.5% male, mean age 49.0 years). During a median follow-up period of 48 months (interquartile range, 24-84 months), precancerous conditions were identified in 110 patients (34%) and the prevalence of advanced stages of atrophic gastritis was 3% for OLGA III/IV and 0.6% OLGIM III/IV. Family history of GC was significantly associated with OLGA III/IV ( P = 0.020). Among LS patients, 10 patients (2.6%) were diagnosed with GC (incidence rate of 5/1000 persons-year). Older age and OLGA III/IV were identified as risk factors for GC ( P < 0.001). When compared with controls, patients with LS had significantly higher rates of Hp infection ( P = 0.035) and lower OLGA and OLGIM stages ( P < 0.001 and P = 0.026, respectively)., Conclusion: In our cohort, the incidence of GC and advanced stages of atrophic gastritis was low. Older age and OLGA III/IV were associated with a higher risk of GC. Identification of risk factors for GC in LS patients can help tailoring endoscopic surveillance., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND : Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. METHODS : Data on 41 138 gastric cancers diagnosed in 2007-2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007-2011 vs. 2012-2016 were compared. RESULTS : Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. CONCLUSIONS : This is the first study comparing trends (2007-2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This study aimed to build convolutional neural network (CNN) models capable of classifying upper endoscopy images, to determine the stage of infection in the development of a gastric cancer. Two different problems were covered. A first one with a smaller number of categorical classes and a lower degree of detail. A second one, consisting of a larger number of classes, corresponding to each stage of precancerous conditions in the Correa's cascade. Three public datasets were used to build the dataset that served as input for the classification tasks. The CNN models built for this study are capable of identifying the stage of precancerous conditions/lesions in the moment of an upper endoscopy. A model based on the DenseNet169 architecture achieved an average accuracy of 0.72 in discriminating among the different stages of infection. The trade-off between detail in the definition of lesion classes and classification performance has been explored. Results from the application of Grad CAMs to the trained models show that the proposed CNN architectures base their classification output on the extraction of physiologically relevant image features. Clinical relevance- This research could improve the accuracy of upper endoscopy exams, which have margin for improvement, by assisting doctors when analysing the lesions seen in patient's images.

Endoscopic resection for early gastric cancer is recommended when the risk of lymph node metastasis is negligible and should be performed through submucosal dissection due to well-established short- and long-term results. To overcome technical difficulties and decrease adverse events some techniques have been studied. This review outlines current strategies for improving patient selection and highlights innovative techniques that help minimize adverse events. Moreover, we discuss how to improve management after curative and noncurative resections., (© 2022 Wiley Periodicals LLC.)

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

Background: Gastric dysbiosis has been hinted as a potential cause of gastric cancer. However, changes in microbiome throughout the major stages of gastric carcinogenesis remain mostly unknown., Objective: To describe gastric microbiome at different stages, analysing for the first time dysbiosis specifically in patients with early gastric cancer (EGC)., Methods: Cross-sectional study including patients ( n  = 77) with endoscopically and histologically confirmed normal stomachs (controls; n  = 25), advanced atrophic gastritis with intestinal metaplasia (IM; n  = 18) and EGC ( n  = 34). Endoscopic biopsies from antrum and corpus ( n  = 154) were analyzed. Next-generation sequencing was performed characterizing microbial communities down to the species level based on full-length 16SrRNA gene profiling., Results: Significant differences were found in the microbiome profile between the groups. Firmicutes were more frequent ( p  = .012) and Proteobacteria were less frequent ( p  = .04) both in the IM and EGC when comparing to controls. Relative frequency of Helicobacter pylori , when present, was much higher in the controls (83%) when comparing to the other groups (IM 1%, EGC 27%; p  = .006), being the dominant bacteria only in the controls. Dysbiosis was present already and more significantly at the IM stage, with two bacteria progressively increasing from controls to IM then to cancer: Gemella from 1.48 to 3.9% ( p  = .014); and Streptococcus from 19.3 to 33.7% ( p  = .04), being the EGC dominant bacteria., Conclusions: Our results confirm Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis. Gemella but particularly Streptococcus is significantly increased in patients with EGC. Specific modulation of these bacteria may change gastric cancer risk.

Gastric cancer is a common cause of death worldwide and its early detection is crucial to improve its prognosis. Its incidence varies throughout countries, and screening has been found to be cost-effective at least in high-incidence regions. Identification of individuals harbouring preneoplastic lesions and their surveillance or of those with early gastric cancer are extremely important processes and endoscopy play a key role for this purpose. Unfortunately, also quality and accuracy for endoscopic detection varies among centres and endoscopists. Recent studies about Artificial Intelligence applied to endoscopic imaging show that these technologies perform very well and could be extremely useful for endoscopists to achieve the accuracy needed for gastric cancer screening. Nonetheless, as its introduction in this field is very recent, most studies are carried out offline and its results in clinical practice need to be further validated namely by incorporating all the components/dimensions of endoscopy from pre to post-assessment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The cyclooxygenase-2 (COX-2)/prostaglandin E 2 (PGE 2 ) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 ( PTGS2 ), ATP binding cassette subfamily C member 4 ( ABCC4 ), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD ), and solute carrier organic anion transporter family member 2A1 ( SLCO2A1 ) PGE 2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY ® iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14-7.74, p = 0.027; 95% CI: 1.22-15.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67-26.48, p < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE 2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.

Background: Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established., Aims: The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages., Methods: Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples., Results: We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2-14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs., Conclusion: We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients' surveillance., (© 2021 S. Karger AG, Basel.)

BACKGROUND : Image-enhanced endoscopy (IEE) improves the accuracy of endoscopic diagnosis. We aimed to assess the value of IEE for gastric preneoplastic conditions and neoplastic lesions. METHODS : Medline and Embase were searched until December 2018. Studies allowing calculation of diagnostic measures were included. Risk of bias and applicability were assessed using QUADAS-2. Subgroup analysis was performed to explore heterogeneity. RESULTS : 44 studies met the inclusion criteria. For gastric intestinal metaplasia (GIM), narrow-band imaging (NBI) obtained a pooled sensitivity and specificity of 0.79 (95 %CI 0.72-0.85) and 0.91 (95 %CI 0.88-0.94) on per-patient basis; on per-biopsy basis, it was 0.84 (95 %CI 0.81-0.86) and 0.95 (95 %CI 0.94-0.96), respectively. Tubulovillous pattern was the most accurate marker to detect GIM and it was effectively assessed without high magnification. For dysplasia, NBI showed a pooled sensitivity and specificity of 0.87 (95 %CI 0.84-0.89) and 0.97 (95 %CI 0.97-0.98) on per-biopsy basis. The use of magnification improved the performance of NBI to characterize early gastric cancer (EGC), especially when the vessel plus surface (VS) classification was applied. Regarding other technologies, trimodal imaging also obtained a high accuracy for dysplasia (sensitivity 0.93 [95 %CI 0.85-0.98], specificity 0.98 [95 %CI 0.92-1.00]). For atrophic gastritis, no specific pattern was noted and none of the technologies reached good diagnostic yield. CONCLUSION : NBI is highly accurate for GIM and dysplasia. The presence of tubulovillous pattern and the VS classification seem to be useful to detect GIM and characterize EGC, respectively. These features should be used in current practice and to standardize endoscopic criteria for other technologies., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E 2 , a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved in its synthesis and exportation, respectively, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), responsible for its inactivation. Even though there are distinct molecular signatures across ethnic populations, most published studies focus on Asian populations. Our main aim was to explore the genetic expression of the aforementioned molecules in a Caucasian population. 94 "Normal" and 89 tumoral formalin-fixed paraffin-embedded (FFPE) samples from GC patients were used to assess the mRNA expression of PTGS2 , ABCC4 , hydroxyprostaglandin dehydrogenase 15-(NAD) ( HPGD) , SLCO2A1 by Real-Time PCR. We found an upregulation for the PTGS2 gene mean factor of 2.51 and a downregulation for the HPGD and SLCO2A1 genes (mean factor of 0.10 and 0.37, respectively) in tumorous mucosa in a gender-independent manner. In females, we observed an ABCC4 downregulation and a PTGS2 mRNA upregulation compared to males in tumoral mucosa (mean factor of 0.61 and 1.64, respectively). We reported dysregulation of the inflammation triggered PGE 2 pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients.

Objectives: To assess the value of endoscopic grading of gastric intestinal metaplasia (EGGIM), operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric neoplasia (EGN) and to investigate other factors possibly associated with its development., Design: Single centre, case-control study including 187 patients with EGN treated endoscopically and 187 age-matched and sex-matched control subjects. Individuals were classified according to EGGIM, OLGA and OLGIM systems. EGN risk according to gastritis stages and other clinical parameters was further evaluated., Results: More patients with EGN had EGGIM of ≥5 than control subjects (68.6% vs 13.3%, p<0.001). OLGA and OLGIM stages III/IV were more prevalent in patients with EGN than in control subjects (68% vs 11%, p<0.001, and 61% vs 3%, p<0.001, respectively). The three systems were the only parameters significantly related to the risk of EGN in multivariate analysis: for EGGIM 1-4 (adjusted OR (AOR) 12.9, 95% CI 1.4 to 118.6) and EGGIM 5-10 (AOR 21.2, 95% CI 5.0 to 90.2); for OLGA I/II (AOR 5.0, 95% CI 0.56 to 44.5) and OLGA III/IV (AOR 11.1, 95% CI 3.7 to 33.1); for OLGIM I/II (AOR 11.5, 95% CI 4.1 to 32.3) and OLGIM III/IV (AOR 16.0, 95% CI 7.6 to 33.4)., Conclusion: This study confirms the role of histological assessment as an independent risk factor for gastric cancer (GC), but it is the first study to show that an endoscopic classification of gastric intestinal metaplasia is highly associated with that outcome. After further prospective validation, this classification may be appropriate for GC risk stratification and may simplify every day practice by reducing the need for biopsies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Regional lymph node metastasis is an important prognostic factor for patients with gastric cancer. Occult tumour cells (OTCs), including either micrometastases (MMs) or isolated tumour cells (ITCs), may be a key factor in the development of cancer recurrence in pN0 patients., Aims: We aimed to determine the frequency and prognostic significance for disease recurrence of OTCs., Materials and Methods: This retrospective cohort study included all consecutive patients with pN0 gastric adenocarcinoma between January 2000 and December 2011 (n = 73). Immunohistochemistry using the pan-cytokeratin antibody AE1/AE3 was used to detect OTCs in 1257 isolated lymph nodes., Results: OTCs were identified in 30 patients (41%), including 20 cases with MMs (27%) and 10 cases with ITCs (14%). Disease recurrence and cancer-related death were observed in 24 (33%) and 20 patients (27%), respectively, and both were significantly associated with the detection of OTCs. A significant difference was also observed for the mean survival time between patients with OTCs and those without OTCs [100 vs 158 months (p = 0.015)]. The presence of OTCs was statistically significantly associated with the Lauren classification, tumour size and lymphatic permeation. Multivariate analyses revealed that only age, T stage and the presence of ITCs in lymph nodes were independent factors for recurrence. The presence of ITCs increased the risk for recurrence by 11.1-fold., Conclusions: In a significant proportion of patients diagnosed as stage pN0, OTCs may be identified in lymph nodes if carefully searched for, which can negatively affect their prognosis. The presence of ITCs was found to be an independent factor for recurrence and after proper validation should be considered during lymph node assessment for prognosis definition.

Introduction and Aim: hereditary diffuse gastric cancer (HDGC) can be caused by a CDH1 mutation. It often presents as multiple foci of signet ring cell carcinoma (SRCC) that is rarely detected by gastroscopy. Prophylactic total gastrectomy is recommended at a young age. The aim of this study was to determine the adequacy of gastroscopy according to the Cambridge protocol in patients with a CDH1 mutation., Methods: patients with a CDH1 mutation admitted to our department between September 2016 and October 2018 were evaluated. All patients underwent a baseline gastroscopy according to the Cambridge protocol, followed by a recommended total gastrectomy. Endoscopic findings, the number of biopsies and histological evaluation of biopsy samples were registered. Postoperative histopathological assessment was compared with endoscopic findings in patients that underwent a total gastrectomy (n = 13)., Results: twenty-five patients were included and 35 gastroscopies performed. On these, 996 gastric biopsies were performed, which included 952 random and 44 targeted. Only three patients had SRCC foci in random biopsies and one also had SRCC lesions in two targeted biopsies. In our cohort, 332 random and 22 targeted biopsies were needed to identify a single SRCC focus. Total gastrectomy was performed in 13 patients and SRCC foci were identified in 12 surgical specimens, the remaining specimen had a precursor lesion of HDGC., Discussion: gastroscopy has a poor sensitivity to detect SRCC. Even with Cambridge protocol, gastroscopy has a very limited role in the surveillance of patients with a CDH1 mutation and prophylactic total gastrectomy is the most advisable option. Nevertheless, endoscopic protocols should be optimized to favor targeted biopsies over a high number of random biopsies.

Competing Interests: None

Competing Interests: None

Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low- and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.

Objective: Endoscopic submucosal dissection (ESD) is now established as the first option to manage early gastric neoplasms, but its efficacy may vary according to diverse factors. We aimed to systematically identify risk factors for poor short-term outcomes of gastric ESD with the purpose to improve patients' selection and management., Methods: Three online databases (MEDLINE, ISI Web of Knowledge and Scopus) were searched (last search on June 2018) for poor outcomes of gastric ESD (deep submucosal invasion, piecemeal/incomplete resection, noncurative resection and local recurrence)., Results: One hundred five studies were included referring to 52.126 ESDs. Undifferentiated histology and upper location (vs lower) were associated with submucosal invasion [odds ratio (OR) = 2.42 [95% confidence interval (CI), 1.62-3.61] and OR = 3.20 (1.04-9.86), respectively] and deep submucosal invasion [OR = 2.98 (2.02-4.39) and OR = 2.35 (1.45-3.81), respectively]. Lesion size greater than 30 mm and ulceration were associated with piecemeal resection [OR = 2.78 (1.17-6.60) and OR = 2.76 (1.23, 6.20), respectively]. Lesion size greater than 30 mm, ulceration, upper location and fibrosis were risk factors for incomplete resection [OR = 3.83 (2.68-5.49), OR = 4.06 (1.62-10.16), OR = 3.71 (2.49-5.54) and OR = 4.46 (1.66-11.96), respectively]. A noncurative resection was more often observed for lesions located in the upper third of the stomach [OR = 1.49 (1.24-1.79)], depressed morphology [OR = 1.49 (1.04-2.12)] and those outside standard criteria [OR = 3.56 (2.31-5.48)]. Older age was significantly linked with local recurrence rates [OR = 3.08 (1.13-5.02)]., Conclusion: Several risk factors influence poor efficacy short-term outcomes of gastric ESD that may be used to inform both patients and health providers about the expected efficacy.

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective., Competing Interests: M. Leja has shares in and receives a salary from the Digestive Diseases Centre GASTRO, SIA (from approximately 2000 to present); his department receives research support with a special offer for reagents (including for pepsinogen detection) from Eiken Chemical (2013 to present); he is a Board member of the Latvian Association of Gastroenterology (from approximately 2000 to present), F. Megraud’s department has received a grant from Allergan (2014 to February 2019). J. E. van Hooft has received lecture fees from Medtronic (2014 – 2015) and consultancy fees from Boston Scientific (2014 – 2016); her department has received research grants from Cook Medical (2014 – 2018) and Abbott (2014 – 2017). B. Annibale, M. Areia, R. Barros, F. Carneiro, M. Dinis-Ribeiro, J.-M. Dumonceau, G. Esposito, J.-F. Fléjou, M. Garrido, I. Kikuste, E. J. Kuipers, D. Libânio, R. Marcos-Pinto, T. Matysiak-Budnik, and P. Pimentel-Nunes have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background & Study Aims: Gastric intestinal metaplasia (GIM) is the most common precursor of gastric cancer. Our aim is to determine if presenting symptoms predict gastric cancer precursor lesions in a high-risk population., Patient and Methods: Consecutive unique patients evaluated by endoscopy for upper gastrointestinal symptoms at the Los Angeles County Hospital between 2010 and 2014 were evaluated. Presenting symptoms were classified as low- or high-risk depending on the procedure indication as coded using the Clinical Outcomes Research Initiative (CORI) system. Endoscopy and histology results were used to classify findings as benign, GIM, high-risk GIM, or malignant. The primary outcome was the proportion of patients with premalignant or malignant gastric findings who had high-risk clinical indications for endoscopy relative to those with benign results., Results: A total of 3699 patients underwent endoscopy to evaluate upper gastrointestinal symptoms. There were 373 (10.1%) patients with GIM of which 278 had high-risk GIM. One hundred and sixty (4.3%) patients were diagnosed with gastric cancer. High-risk indications for upper endoscopy predicted gastric cancer (OR 1.8 [95% CI 1.3-2.6]) but not GIM (OR 1.0 [0.8-1.3]) or high-risk GIM (OR 0.9 [0.7-1.2]). Hispanic or Asian patients and patients >50 years old were more likely to have GIM, high-risk GIM, and cancer., Conclusions: Performance of upper endoscopy for high-risk indications is inadequate to detect GIM and marginal for malignancy. At risk patients should undergo upper endoscopy for both low- and high-risk symptoms. Screening certain populations deserve additional study and may, in fact, be cost-effective., (© 2018 John Wiley & Sons Ltd.)

Background: There are no prospective studies comparing endoscopic submucosal dissection (ESD) and gastrectomy, especially evaluating patient-reported outcomes. Our aim was to compare the safety and impact on quality of life (QoL) of ESD and gastrectomy in patients with early gastric neoplasia., Methods: This prospective study included consecutive patients presenting with early gastric neoplasia in a tertiary center from January 2015 to August 2016. Data collection included curative resection, adverse events (AEs), and patient-reported outcomes (questionnaires: EORTC QLQ-C30, EORTC STO-22, EQ-5D-5 L, and Assessment of Survivor Concerns) before and after interventions (after 1 month, 3 - 6 months, and 1 year)., Results: 254 patients with early lesions were included: 153 managed by ESD and 101 by gastrectomy, the former being significantly older and with less advanced lesions. Mean procedural time and length of stay were significantly higher in the surgery group (164 vs . 72 minutes and 16.3 vs . 3.5 days; P  < 0.001). Complete resection was higher in the surgical group (99 % vs . 90 %; P  = 0.02); ESD was curative in 79 % of patients. Severe AEs and surgical re-intervention were significantly more frequent in the gastrectomy group (21.8 % vs. 7.8 % and 11 % vs . 1 %, respectively). Endoscopic treatment was associated with a positive impact on global health-related QoL at 1 year (net difference + 9.9; P  = 0.006), role function and symptom scales (fatigue, pain, appetite, eating restrictions, dysphagia, and body image). Concerns about recurrence did not differ between the groups., Conclusions: In patients with early gastric neoplasia, ESD is safer and is associated with a positive impact on health-related QoL when compared with gastrectomy, without increasing fear of recurrence and new lesions., Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas., Aim: The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer., Participants and Methods: A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI≤70 ng/ml and PGI/PGII≤3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]., Results: Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were 'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6]. Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58% (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups was over 24 months., Conclusion: The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.

Background and Aims: Gastric intestinal metaplasia (GIM) is a gastric cancer precursor. Narrow-band imaging (NBI) may improve detection of GIM. We compared detection of GIM with high-definition white-light (HD-WL) endoscopy, NBI, and mapping biopsies in a population with increased gastric cancer risk., Methods: Patients undergoing upper endoscopy had HD-WL examination by 1 endoscopist, followed by an NBI examination by a second endoscopist blinded to HD-WL findings. The location of abnormalities detected by HD-WL and NBI were recorded by a research coordinator, and targeted biopsies of abnormal areas were performed after NBI. Subsequently, 5 mapping biopsies were performed per patient. Biopsy specimens were read by a pathologist blinded to mode of acquisition. The primary outcome was the proportion of patients with GIM., Results: We enrolled 112 patients: 107 (96%) were Hispanic or Asian, and 34 (30%) had GIM. Higher proportions of patients with GIM were detected by NBI (22/34 [65%]) and mapping (26/34 [76%]) versus HD-WL (10/34 [29%]) (P < .005 for both comparisons). GIM was detected by NBI in only 6 patients and only by mapping biopsy in 10 patients; no patient had GIM detected solely by HD-WL. Higher proportions of sites with GIM also were detected with NBI (30/57 [53%]) and mapping biopsies (38/57 [67%]) than HD-WL (16/57 [28%]) (P < .005 for both comparisons). The median number of biopsies per patient with mapping biopsies (5) was significantly higher than with NBI (2) or HD-WL (1)., Conclusions: HD-WL endoscopy is insufficient for detection of GIM in patients at increased risk for gastric cancer. NBI-targeted biopsies plus mapping biopsies should be used. (Clinical trial registration number: NCT02197351.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Gastric polyps include a wide spectrum of lesions with different histology and neoplastic potential. They are found in up to 6% of upper gastrointestinal endoscopy and are usually asymptomatic and incidentally diagnosed, being in the vast majority epithelial gastric polyps. Hyperplastic, fundic gland and adenomas are the most common types of gastric polyps and, although each type may have typical endoscopic appearances, they all must be sampled at the initial endoscopy for histological assessment. Also, the normal appearing gastric mucosa should be sampled to stage atrophic changes, rule out endoscopically non-visible dysplasia and to diagnose Helicobacter pylori. Polyposis syndromes that affect the stomach are rare but should be taken into account. Hamartomatous polyps can be found in Juvenile polyposis, Cowden syndrome and Peutz-Jeghers syndrome. On the other hand, multiple fundic gland polyps are present in the majority of patients with familial adenomatous polyposis. In this study we provide a comprehensive review on the evaluation and management of gastric epithelial polyps, in this way helping physicians to properly handle this type of lesions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Atrophic gastritis (AG) is at increased risk of gastric neoplasia, thus surveillance gastroscopy has been proposed., Aims: To assess cost of detecting gastric neoplasias by surveillance endoscopy according to identified risk factors in Italy., Methods: Post-hoc analysis of a cohort study including 200 AG-patients from Italy followed up for a mean of 7.5 (4-23.4) years was done. Considered risk factors were: age >50years, extensive atrophy, pernicious anaemia, OLGA-OLGIM scores 3-4 at diagnosis. The number of 4-year-surveillance endoscopies needed to be performed to detect one gastric neoplasia (NNS) was calculated., Results: In 19 patients neoplasias (4 gastric cancers, 8 type 1 gastric carcinoids, 7 dysplasias) were detected at the 361 surveillance gastroscopies, corresponding to NNS of 19 and a cost per gastric neoplastic lesion of €2945. By restricting surveillance to pernicious anaemia patients, reduction of NNS and cost per neoplasia to 13.8 and €2139 may be obtained still detecting 74% of neoplasias. By limiting the surveillance to pernicious anaemia patients and OLGA 3-4, 5 (26.3%) neoplasias would have been detected with a corresponding NNS of 5.4 and a cost per lesion of €837., Conclusion: Risk factors may allow an efficient allocation of financial and medical resources for endoscopic surveillance in AG in a low risk country., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Health-related quality of life assessment is increasingly important as it can help both clinical research and care for patients, particularly among oncological patients. Quality of Life Questionnaire - OES18 (esophageal module) and Quality of Life Questionnaire - OG25 (esophagogastric module) are the European Organization for Research and Treatment of Cancer modules for the evaluation of quality of life in patients with esophageal and esophagogastric cancers, respectively. The aim of our study was to translate, to culturally adapt and to perform a pilot testing to create the Portuguese version of both questionnaires., Material and Methods: The European Organization for Research and Treatment of Cancer guidelines were followed for translation, cultural adaptation and pilot testing of Quality of Life Questionnaire - OES18 (esophageal module) and Quality of Life Questionnaire - OG25 (esophagogastric module). The Quality of Life Questionnaire - OG25 (esophagogastric module) went through a process of forward (English → Portuguese) and backward (Portuguese → English) translation, by independent native speaker translators. After review, a preliminary version was created to be pilot tested among Portuguese patients. As a Brazilian version was already available for Quality of Life Questionnaire - OES18 (esophageal module), the questionnaire was simply culturally adapted and pilot tested. Both cancer and non-cancer patients were included., Results: Overall, 30 patients completed the Portuguese version of each questionnaire. Afterwards, a structured interview was conducted to find and report any problematic items. Troublesome items and wording were changed according to the pilot testing results. The final versions were sent to the European Organisation for Research and Treatment of Cancer Quality of Life Group and approved., Conclusion: The Portuguese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - OES18 (esophageal module) and OG25 (esophagogastric module) questionnaires are useful, reliable and valid tools for measuring health-related quality of life in patients with esophageal and esophagogastric cancers, respectively. They can now be used in clinical setting and for scientific purposes.

Intestinal-type gastric adenocarcinoma arises from a multistep process starting with Helicobacter pylori infection followed by gastric atrophy, gastric intestinal metaplasia and dysplasia. Indeed, patients with gastric precancerous conditions or lesions (GPC) are at increased risk to develop gastric cancer even in regions with low incidence. Thus, the identification and surveillance of a high risk subgroup could lead to the diagnosis of cancer at early stage and improve survival. However, both endoscopic and histological accuracy and interobserver agreement in the diagnosis of GPC are still far from optimal. Also, there are conceptual differences between the West and the East in the diagnosis and surveillance of patients. In the former, multiple gastric biopsies are still recommended but Eastern gastroenterologists select patients to surveillance according to the results of endoscopy or serology. In this literature review we describe the cascade of GPC and we highlight the differences between eastern and western clinical practice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Aims: Postprocedural bleeding (PPB) is the most common adverse event associated with endoscopic resection. Several studies have tried to identify risk factors for PPB after gastric EMR and endoscopic submucosal dissection (ESD), with controversial results. This systematic review and meta-analysis aimed to identify significant risk factors for PPB after gastric EMR and ESD., Methods: Three online databases were searched. Pooled odds ratio (OR) was computed for each risk factor using a random-effects model, and heterogeneity was assessed by Cochran's Q test and I(2)., Results: Seventy-four articles were included. Pooled PPB rate was 5.1% (95% confidence interval, 4.5%-5.7%), which did not vary according to different study designs. Male sex (OR, 1.25), cardiopathy (OR, 1.54), antithrombotic drugs (OR, 1.63), cirrhosis (OR, 1.76), chronic kidney disease (OR, 3.38), tumor size > 20 mm (OR, 2.70), resected specimen size > 30 mm (OR, 2.85), localization in the lesser curvature (OR, 1.74), flat/depressed morphology (OR, 1.43), carcinoma histology (OR, 1.46), and ulceration (OR, 1.64) were identified as significant risk factors for PPB, whereas age, hypertension, submucosal invasion, fibrosis, and localization (upper, middle, or lower third) were not. Procedure duration > 60 minutes (OR, 2.05) and the use of histamine-2 receptor antagonists instead of proton pump inhibitors (OR, 2.13) were the procedural factors associated with PPB, whereas endoscopist experience and preprocedural proton pump inhibitors were not. Second-look endoscopy was not associated with decreased PPB (OR, 1.34; 95% confidence interval, .85-2.12)., Conclusions: Risk factors for PPB were identified that can help to guide management after gastric ESD, namely adjusting further management. Second-look endoscopy is not associated with decreased PPB., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Adverse events can occur during and after the endoscopic resection of upper gastrointestinal lesions. Their incidence can be minimized through the adoption of preventive measures and their final outcomes can be optimized through prompt identification and adequate treatment. In this evidence-based review we describe the risk factors for adverse events, preventive measures to avoid them and their management when they occur. Algorithms of action are also provided. Oesophageal strictures can be prevented with corticosteroids (either locally injected or systemically administered) and treated with endoscopic dilatation. Bleeding can be minimized through the adoption of prophylactic coagulation and novel preventive measures are emerging and being evaluated. Bleeding management includes coagulation therapy, clips and haemostatic powders. Perforations can nowadays be successfully treated endoscopically in the majority of the cases and conservative treatment is associated with favourable outcomes although optimal management is unclear., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Esophagogastroduodenoscopy (EGD) is considered a very effective method to identify gastric cancer (GC). However, the existence of missed lesions has been frequently discussed. This systematic review and meta-analysis aimed at assessing the magnitude of missing GC diagnosis with EGD and its predictive factors., Methods: MEDLINE was searched to identify all studies assessing and reporting the proportion of missed GC diagnosis with EGD. Pooled proportion and negative predictive values were computed using the random-effects model and heterogeneity was assessed using the Cochrane Q-test and I., Results: The studies included (n=22) were grouped by study design. The pooled negative predictive value was 99.7% (95% confidence interval 99.6-99.9%). Missed GCs proportion was 9.4% (95% confidence interval 5.7-13.1%), being 10.0% in studies including patients with negative EGD followed over time, 8.3% in studies including patients with GC, and 23.3% in studies evaluating the proportion of missed synchronous lesions. Mainly, missed cancers were located in the gastric body both in Eastern and in Western studies (39 and 47%, respectively). The majority of missed GCs were adenocarcinomas. Younger age (<55 years), female sex, marked gastric atrophy, gastric adenoma or ulcer, and inadequate number of biopsy fragments were reported as predictive factors for diagnostic failure., Conclusion: EGD is a very effective method to rule out GC. However, missing GC with EGD is not uncommon, with one out of 10 cancers being potentially missed. Interestingly, lesions were more often missed in the body and therefore a more rigorous protocol for endoscopy and biopsy should be implemented worldwide.

Background and Aim: Some studies suggest that narrow-band imaging (NBI) can be more accurate at diagnosing gastric intestinal metaplasia and dysplasia than white-light endoscopy (WLE) alone. We aimed to assess the real-time diagnostic validity of high resolution endoscopy with and without NBI in the diagnosis of gastric premalignant conditions and to derive a classification for endoscopic grading of gastric intestinal metaplasia (EGGIM)., Methods: A multicenter prospective study (five centers: Portugal, Italy, Romania, UK, USA) was performed involving the systematic use of high resolution gastroscopes with image registry with and without NBI in a centralized informatics platform (available online). All users used the same NBI classification. Histologic result was considered the diagnostic gold standard., Results: A total of 238 patients and 1123 endoscopic biopsies were included. NBI globally increased diagnostic accuracy by 11 percentage points (NBI 94 % vs. WLE 83 %; P < 0.001) with no difference in the identification of Helicobacter pylori gastritis (73 % vs. 74 %). NBI increased sensitivity for the diagnosis of intestinal metaplasia significantly (87 % vs. 53 %; P < 0.001) and for the diagnosis of dysplasia (92 % vs. 74 %). The added benefit of NBI in terms of diagnostic accuracy was greater in OLGIM III/IV than in OLGIM I/II (25 percentage points vs. 15 percentage points, respectively; P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for EGGIM in the identification of extensive metaplasia was 0.98., Conclusions: In a real-time scenario, NBI demonstrates a high concordance with gastric histology, superior to WLE. Diagnostic accuracy higher than 90 % suggests that routine use of NBI allows targeted instead of random biopsy samples. EGGIM also permits immediate grading of intestinal metaplasia without biopsies and merits further investigation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Early diagnosis of gastric cancer may be achieved through surveillance of patients with extensive gastric intestinal metaplasia (eGIM). However, diagnosis of eGIM generally implies histology. We aimed at determining the accuracy of high-resolution endoscopy with light-narrow band imaging (NBI) to assess the presence of eGIM on a per-patient basis., Material and Methods: Prospective cohort of 60 patients divided into two groups: derivation cohort (n = 25) to evaluate the reliability and validity, and a real-time validation group (n = 35). In the derivation group, six endoscopists with two levels of expertise were asked to estimate the grade of GIM based in endoscopic images (white light endoscopy, light-NBI and amplification/near focus). In the real-time validation set, experienced endoscopists were asked to similarly record their real-time optical diagnosis. Histology was then considered as the gold standard., Results: In the derivation group diagnosis accuracy was 60% with WLE (non-expert 59% vs. 61% experts), increasing to 73% after NBI magnification (non-expert 63% vs. 83% expert, p < 0.05). Moreover, proportion of agreement with histology was 83%, with a correct diagnosis of eGIM in 87% for experienced observers. In the real-time group experts obtained 89% global diagnostic accuracy correctly identifying 91% of the eGIM. The sensitivity, specificity, LR + and LR- of real-time endoscopic diagnosis of eGIM was 0.92 (CI95%:0.67-0.99), 0.96 (0.79-0.99), 21.1 (3.08-144) and 0.09 (0.013-0.57)., Conclusion: For the first time the reliability of high-resolution endoscopy with light-NBI for extension of GIM is described. Our results suggest that more than 90% of individuals at risk could be identified without the need for biopsies, simplifying the current recommendations.