Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg).

BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Empirical rescue treatment of Helicobacter pylori infection in third and subsequent lines: 8-year experience in 2144 patients from the European Registry on H. pylori management (Hp-EuReg).

OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

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, non-interventional 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.

Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg).

BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: 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. DESIGN: 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. 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. RESULTS: 30 394 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%). CONCLUSION: Management 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.

Adverse Event Profile During the Treatment of Helicobacter pylori: A Real-World Experience of 22,000 Patients From the European Registry on H. pylori Management (Hp-EuReg).

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. DISCUSSION: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance.

Quality in diagnostic upper gastrointestinal endoscopy for the detection and surveillance of gastric cancer precursor lesions: Position paper of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre calidad de la endoscopia digestiva alta para la detección y vigilancia de las lesiones precursoras de cáncer gástrico.

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.

Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre cribado de cáncer gástrico en poblaciones con baja incidencia.

This positioning document, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Endoscopia Digestiva and the Sociedad Española de Anatomía Patológica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.

Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients.

BACKGROUND & AIMS: Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry. METHODS: We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily. RESULTS: Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0). CONCLUSIONS: In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

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® ; 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 (<80%) results.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain.

INTRODUCTION: Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS: Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS: One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION: Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

Prospective, study comparing the accuracy of two different stool antigen tests (Premier Platinum HpSA and novel ImmunoCard STAT! rapid test) for the diagnosis of Helicobacter pylori infection.

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.

Small intestinal bacterial overgrowth is common after gastrectomy but with little impact on nutritional status. / El sobrecrecimiento bacteriano de intestino delgado es una entidad frecuente tras gastrectomía, pero con escasa relevancia en el estado nutricional.

BACKGROUND: Available evidence assessing the impact of small intestinal bacterial overgrowth (SIBO) following gastrectomy is limited. OBJECTIVES: To evaluate the prevalence of SIBO after gastrectomy and its association with malnutrition. To describe the antibiotic treatment required to correct it and if nutritional status improves. MATERIAL AND METHODS: A prospective cohort study was performed at the Agencia Sanitaria Costa del Sol (Costa del Sol Health Agency) from 2012 to 2015. A hydrogen-methane breath test with oral glucose overload was performed. Demographic variables and nutritional parameters were collected at baseline and one month after effective treatment of SIBO. The antibiotic regimens and the number of treatment lines used were assessed. RESULTS: Sixty gastrectomy patients were analysed, 58.3% of which were male. A sub-analysis of the curve was performed at 45min to minimise possible false positives, and SIBO was identified in 61.6% of cases. SIBO patients tended to have a lower BMI, although this trend was not statistically significant. After treatment with rifaximin, 94.6% of patients were still positive for SIBO, which fell to 85.7% after metronidazole. The rate of total antibiotic treatment failure was 67.6%. No statistically significant changes were found in nutritional parameters after treatment. CONCLUSIONS: SIBO was identified in 61.6% of patients after gastrectomy. No correlation was found with any malnutrition parameter. Rifaximin and metronidazole were found to be largely ineffective in eradicating SIBO. When treatment was effective, the impact on malnutrition was negligible and may have been associated with other factors.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

OBJECTIVE: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. BACKGROUND: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. METHODS: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. RESULTS: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. CONCLUSIONS: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.

Management of antiplatelet and anticoagulant therapy for endoscopic procedures: Introduction to novel oral anticoagulants.

The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.