A proton-pump inhibitor (PPI), clarithromycin-based, triple therapy has been the recommended treatment for Helicobacter pylori eradication for the past 15 years. Due to a steady increase in H. pylori ...resistance to clarithromycin, this triple clarithromycin-based treatment has become progressively less efficacious. Several approaches are available to address this situation: one is to test for clarithromycin resistance so that this triple clarithromycin-based regimen is given only to those who will benefit; a second is to prescribe the drugs sequentially, beginning with amoxicillin and a PPI followed by clarithromycin and metronidazole, again with a PPI or the four drugs prescribed concomitantly; a third alternative is to use bismuth-based quadruple therapy, PPI plus a standardized three-in-one capsule, bismuth subcitrate potassium, metronidazole, and tetracycline (BMT, sold under licence as Pylera®). The advantages of these different approaches are reviewed, including the relevance of BMT three-in-one capsule in clinical practice.
This article summarizes the main findings concerning
associated with gastric MALT lymphoma (GML). Considered together, GML strains based on their virulence factor profile appear to be less virulent ...than those associated with peptic ulcers or gastric adenocarcinoma. A particular Lewis antigen profile has been identified in GML strains and could represent an alternative adaptive mechanism to escape the host immune response thereby allowing continuous antigenic stimulation of infiltrating lymphocytes.
The progress this year in Helicobacter pylori diagnosis concerned essentially endoscopy and molecular techniques. New endoscopy techniques such as blue laser imaging and magnifying narrow band ...imaging allow the visualization of mucosal aspects representing H. pylori infection, intestinal metaplasia, and even ambiguous early gastric cancer. Several real‐time PCRs have also been used either to quantify H. pylori or to detect mutations associated with clarithromycin resistance in gastric biopsies or applied on gastric juice, stool specimens, or the oral cavity. The presence of H. pylori in free‐living amebae purified from wastewater and drinking water was also determined by PCR and sequencing, as well as culture from a few wastewater samples. Among the noninvasive methods, the urea breath test was used in different conditions, including with a new test meal, which is claimed to avoid the proton‐pump inhibitor washout period before testing. Several articles concerning antibody detection and stool antigen test were also published.
Summary Background Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments ...necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. Methods We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative13 C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov , number NCT00669955. Findings 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of −10% (95% CI 15·1–32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. Interpretation Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori , especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy. Funding Axcan Pharma Inc.
Background
Knowledge of antimicrobial susceptibility, especially to macrolides, has become crucial for the management of Helicobacter pylori infection. Our aim was to evaluate two new PCR kits able ...to detect H. pylori in gastric biopsies as well as the mutations associated with macrolide resistance.
Materials and Methods
Two hundred successive biopsies (received from gastroenterologists all over France) were used. The two new kits tested were Amplidiag H. pylori+ClariR from Mobidiag Espoo, Finland, and RIDA®GENE H. pylori from R‐Biopharm, Darmstadt, Germany. Culture and a validated in‐house real‐time PCR were also performed, and in the case of a positive culture, Etest for clarithromycin was carried out. Discrepancies were solved by looking at the pathologic data.
Results
Culture was positive in 68 cases (34%), and with our in‐house real‐time PCR in these 68 cases plus 5 others (N = 73, 36%). All were also detected by the two new kits. In addition, RIDA®GENE H. pylori detected one more positive also detected by Amplidiag H. pylori+ClariR, and Amplidiag detected two other positives. Of these three additional cases, pathology confirmed the positivity for two. Only one case diagnosed by Amplidiag could be considered as a false positive. With regard to clarithromycin resistance, 22 cases were detected. The corresponding mutations (A2142/43G) were all identified with the three PCRs.
Conclusions
These two new kits which have an excellent sensitivity and specificity are convenient to use, adaptable to different thermocyclers, provide quick results, and deserve to be used in H. pylori diagnosis for a better choice of treatment regimen.
Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers ...allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types.
The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by
tumorsphere assays and
xenografts by limiting dilution assays.
We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres
and tumors
CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH
cells represented a core within the CD44
/CD166
subpopulation that contained the highest frequency of tumorigenic CSCs
The ALDH
cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH
cells, a process that was partially reversed by verapamil treatment.
CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor.
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Medline, PubMed and the Cochrane databases were searched on epidemiology and diagnosis of Helicobacter pylori for the period of April 2011–March 2012. Several studies have shown that the prevalence ...of H. pylori infection is decreasing in adults and children in many countries. Various diagnostic tests are available, and most of them have high sensitivity and specificity. The Maastricht IV/Florence consensus report states that the urea breath test using 13C urea remains the best test to diagnose H. pylori infection. Among the stool antigen tests, the ELISA monoclonal antibody test is recommended. All these tests were used, either as a single diagnostic test or in combination, to investigate H. pylori infection among different populations throughout the world. Of particular interest, current improvements in high‐resolution endoscopic technologies enable increased diagnostic accuracy for the detection of H. pylori infection, but none of these techniques, at present, are specific enough for obtaining a real‐time diagnosis of H. pylori infection.
Abstract Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and ...cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid CSF total tau protein Tau, phospho-tau181 protein pTau181 ), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin IL-1β, IL-6, IL-8, tumor necrosis factor TNF-α) and pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load (magnetic resonance imaging MRI fluid-attenuated inversion recovery FLAIR with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme-linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was associated with a decreased Mini Mental State Examination (MMS) ( p = 0.024), and higher CSF pTau181 ( p = 0.014) and tau ( p = 0.021) levels. A decreased PgI/II ratio (i.e., an increased gastric atrophy) was associated with the infection ( p = 0.005). Homocysteine levels were positively correlated to Fazekas score ( r = 0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels ( r = 0.44; p = 0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-α, p = 0.019) were associated with the infection, but systemic inflammation results were controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio OR, 0.83 0.72–0.97; p = 0.017), plasma IL-1β level (OR, 0.31 0.11–0.87; p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63 0.43–0.93; p = 0.020) were still associated with the infection. AD patients infected by H. pylori tended to be more cognitively impaired. Studies are needed to attest to the impact of H. pylori infection on AD course, especially on cerebrovascular lesions and neuroinflammation.
Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls ...disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.
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