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ObjectiveThe best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.DesignInternational multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed.Results30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%–90%).ConclusionManagement of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, noninterventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Objective: The adherence to Helicobacter pylori eradication treatment is a cornerstone for achieving an adequate treatment efficacy. The objective of the study was to determine which factors could influence on the compliance of treatments. Materials and Methods: Systematic prospective non- interventional registry (Hp- EuReg) of the clinical practice of European gastroenterologists. Compliance was adequate: >90% drug intake. Data collected until September 2021 at AEG-REDCap e- CRFand was subject to quality control. Modified intention-to-treat (mITT) analyses were performed. The multivariate analysis evaluated the factors associated with the effectiveness of the treatments and the compliance. Results: Of the 38, 698 records, 646 (1.7%) did not have adequate compliance. There was a higher non- compliance rate in patients prescribed with longer therapies (10-, 14-days), rescue treatment, with uninvestigated/functional dyspepsia, and reporting adverse events. Non- adherence was lower in first- line as compared to rescue treatment (1.5% vs. 2.2% ; p

Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The gene expression profiles of 107 treatment‐naïve, intestinal type, gastroesophageal adenocarcinomas were assessed by the Illumina‐HTv4.0 beadchip. Differential gene expression (limma), unsupervised subgroup assignment (mclust) and pathway analysis (gage) were undertaken in R statistical computing and results were related to demographic and clinical parameters. Unsupervised assignment of the gene expression profiles revealed three distinct molecular subgroups, which were not associated with anatomical location, tumor stage or grade (p > 0.05). Group 1 was enriched for pathways involved in cell turnover, Group 2 was enriched for metabolic processes and Group 3 for immune‐response pathways. Patients in group 1 showed the worst overall survival (p = 0.019). Key genes for the three subtypes were confirmed by immunohistochemistry. The newly defined intrinsic subtypes were analyzed in four independent datasets of gastric and esophageal adenocarcinomas with transcriptomic data available (RNAseq data: OCCAMS cohort, n = 158; gene expression arrays: Belfast, n = 63; Singapore, n = 191; Asian Cancer Research Group, n = 300). The subgroups were represented in the independent cohorts and pooled analysis confirmed the prognostic effect of the new subtypes. In conclusion, adenocarcinomas at the GEJ comprise three distinct molecular phenotypes which do not reflect anatomical location but rather inform our understanding of the key pathways expressed., What's new? Adenocarcinomas that arise at the junction between the esophagus and the stomach are currently classified based on location. Here, the authors looked at patterns of gene expression of these cancers. They found that gastro‐esophageal junction adenocarcinomas can be sorted into three biological subtypes, independent of location, based on gene expression. Group 1 cancers have boosted stomach‐specific genes that combat the effects of acid reflux. Group 2 tumors express genes characteristic to the intestinal tract, and the genes active in Group 3 relate to inflammation. The differences in biological pathway expression means that these differences could be used to improve treatment.

Introduction: Antibiotic resistance is the major factor affecting our ability to cure Helicobacter pylori infection. Quadruple therapy is currently recommended ; however, triple therapy with two antibiotics may be sufficient in those patients without clarithromycin resistance. Aims & Methods: To evaluate the effectiveness of the treatments according to the clarithromycin H. pylori resistance in Europe. International multicenter prospective non-interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection. Infected adult patients diagnosed with culture registered at AEG-REDCap e- CRF from 2013 to 2019. Per-protocol (PP) analysis was performed based on the presence or absence of clarithromycin bacterial resistance. Results: Overall, 5, 036 patients were included: 1, 747 (35%) were resistant and 3, 289 (65%) sensitive to clarithromycin. The overall eradication rate was higher in clarithromycin-susceptible patients (91% vs. 84% ; p< 0.001). Triple therapy with a PPI, clarithromycin and amoxicillin achieved over 90% eradication rates in clarithromycin- susceptible patients. However, in those with clarithromycin- resistance, optimal effectiveness was only achieved when treated with quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth. Conclusion: Classic triple therapy with a PPI, clarithromycin and amoxicillin achieves optimal results (>90%) in patients susceptible to clarithromycin. However, when clarithromycin resistance is unknown, quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth may be a better treatment option.

Introduction: Antibiotic resistance is the major factor affecting our ability to cure Helicobacter pylori infection. Understanding the different H. pylori antibiotic resistances could be the key to improve treatment effectiveness. Aims & Methods: To evaluate the H. pylori antibiotic resistance both prior and after one or several eradication treatments, in order to provide the most appropriate recommendations for the eradication of H. pylori. International multicenter prospective non-interventional European Regis-try on H. pylori Management (Hp- EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection by European gastroenterologists. Infected adult patients diagnosed with culture and with a result of the antibiotic resistance test registered at AEG- REDCap e-CRF from 2013 to 2019. Per-protocol (PP) analysis was performed. The antibiotic bacterial resistances were described by treatment line. Results: A total of 32, 447 patients were included, and culture was performed in 3, 474 (11%). In naïve patients, 21% reported single clarithromycin resistance, and 11% dual (clarithromycin and metronidazole) resistance. Antibiotic resistance increased markedly from the first treatment, reaching over 37% dual resistance in second-line treatment. Conclusion: In Europe, culture testing to determine antibiotic resistance against H. pylori is scarce. H. pylori single clarithromycin resistance remains high (>15%) in all treatment lines, and greater than 20% in naïve patients. Dual or triple resistances are frequent and increase remarkably after the first treatment failure. Resistance to amoxicillin or tetracycline is exceptional.

BACKGROUND: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. OBJECTIVE: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. METHODS: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociacion Espanola de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. RESULTS: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e. three capsules every 6 hours for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n=1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n=375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n=236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. CONCLUSIONS: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile.

Introduction: Bacterial antibiotic resistance changes over time based on multiple factors. It is essential to study these trends to apply preventive strategies to help reducing such resistances.Aims & Methods: To conduct a time-trend analysis of the antibiotic resistance to H. pylori infection in the European Registry on H. pylori (Hp-EuReg). International multicenter prospective non- interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection by European gastroenterologists. All infected adult patients diagnosed with culture and with a result of the antibiotic resistance test were registered at AEG-REDCap e-CRF from 2013 to 2019.Results: A total of 32, 447 patients were included, and culture was performed in 3, 474 (11%), where 2, 483 näive patients were included for analysis. Resistance to at least one antibiotic was described in 57% of the patients. Resistance to metronidazole (27%) was most frequent, whereas resistance to tetracycline and amoxicillin was below 1%. Clarithromycin resistance remained above 15% throughout the studied years. A significant decrease in the metronidazole resistance rate was observed between 2013 (38%) and 2018 (21%).Conclusion: In naïve patients, resistance to clarithromycin remained above 15% in the period 2013-2019. A progressive decrease in metronidazole resistance was observed. No increasing or decreasing trend was observed in the bacterial resistance to other antibiotics.

Background Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. Aim To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). Methods A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. Results One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera(R); n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. Conclusion In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (

Introduction: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.Aims & Methods: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap up to April 2020. Variables included: demographics, previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention-to-treat (mITT) and per-protocol (PP) analyses were performed and data were subject to quality review to ensure information reliability.Results: In total 36, 319 patients from 29 European countries were evaluated and 24, 882 (70%) first-line empirical H. pylori treatments were included for analysis. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (40%), followed by concomitant treatment (19%) and bismuth quadruple (Pylera®) (10%) achieving 83%, 91% and 95% mITT eradication rate, respectively. Over 90% effectiveness was obtained only with 10 and 14-day bismuth quadruple or 14-day concomitant treatment (Table). Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates.Conclusion: Management of H. pylori infection by European gastroenterologists is heterogeneous. Only quadruple therapies lasting at least ten days are able to achieve over 90% eradication rates.

The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P< 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P

Background Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA. Methods Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways. Findings We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P Interpretation The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.