Helicobacter pylori eradication for the prevention of gastric cancer

Le cancer gastrique reste la seconde cause de décès par cancer dans le monde. Il existe une relation étroite entre infection à Helicobacter pylori et cancer gastrique. Le but de cette revue est de faire le point sur l’intérêt de l’éradication de Helicobacter pylori dans la prévention du cancer gastrique. La prévention primaire (avant la survenue de lésions prénéoplasiques : atrophie et métaplasie intestinale), la prévention secondaire (en présence de lésions pré-néoplasiques), la prévention tertiaire (après exérèse endoscopique d’un cancer superficiel) sont envisagées. Même si l’effet bénéfique d’une éradication au stade précoce de la cancérogenèse en zone de forte incidence du cancer est bien démontré, les résultats d’études randomisées en cours devraient déterminer l’impact réel d’un tel traitement.Gastric cancer is the second leading cause of cancer-related death worldwide. A clear association between Helicobacter pylori and gastric cancer was established years ago. Our aim is to discuss current evidence of Helicobacter pylori eradication for prevention of gastric cancer. Primary preventive of eradication (before occurrence of pre-malignant gastric lesions: atrophy and intestinal metaplasia), secondary preventive effect (with pre-malignant gastric lesions), tertiary preventive effect (after curative endoscopic resection of early gastric cancer) are discussed. Currently, Helicobacter pylori eradication seems to be indicated at the earliest stage of gastric carcinogenesis; nevertheless the results of ongoing controlled trials should highlight the real impact of such treatment

Devenir des folates au cours de la transformation des végétaux verts (identification des points clés et des mécanismes)

Les folates sont des vitamines hydrosolubles, impliqués dans la limitation d apparition de pathologiestelles que les anomalies de fermeture du tube neural. L homme est dépendant de son alimentation pourcouvrir ses besoins en folates. Les légumes sont une des sources importantes de folates. Dans un mêmetemps, les légumes verts sont principalement consommés à partir de produits transformés, cuits,surgelés ou appertisés. Il est donc important de maitriser les paramètres de la transformation afin depréserver au mieux les teneurs finales en folates. L objectif de ce travail a donc été d identifier l impactdu procédé de transformation (industriel et domestique) sur la perte en folates. Deux procédésindustriels ont été étudiés : la surgélation des épinards et l appertisation des haricots verts, lestraitements domestiques ont consisté en la cuisson de légume dans de l eau à ébullition ou à la vapeur.Les traitements thermiques (blanchiment et cuisson vapeur) n induisent pas de diminutionssignificatives de la concentration en folates. En revanche, des pertes sont observées lorsque les légumessont en contact étroit avec l eau. Cette étude a permis de mettre à jour deux mécanismes de perte, ladiffusion et la dégradation thermique. La diffusion des folates a été étudiée à l échelle du laboratoire, lesconstantes de diffusion des folates ont été déterminées. La diffusion est largement influencée par lamatrice elle-même, plus que par la température ou le pH. La part de la dégradation thermique, etnotamment l oxydation, ne peut être exclue au cours de la diffusion. C est pourquoi des cinétiques dedégradation ont été réalisées à différentes température et différentes teneurs en oxygène, à partir depurées d épinards et de haricots verts ainsi que sur des solutions modèles. L oxygène joue un rôleimportant dans la dégradation chimique, notamment dans les solutions modèle. Les matrices végétalesconstituraient donc une barrière à l oxydation des folates. Les folates sont globalement assez bienconservés au cours du procédé de transformation. Une des pistes de recherche qui prendrait un sens dansla continuité de ce travail serait l étude de l impact des procédés de transformation sur labioaccessibilité des folatesFolates are water-soluble vitamins, involved in the limitation of diseases such as neural tube defects.Man is dependent on his food to cover its folates needs. Fruits and vegetables, particularly greenvegetables are one of the major dietary sources of folates. In the same time, green vegetables are mainlyconsumed as processed products, cooked frozen or canned. It is therefore important to controlprocessing parameters in order to preserve folates content in final products. The aim of this study was toidentify the impact of processing (industrial and domestic) on folates loss. Two industrial processingchains were studied: spinach freezing chain and green beans canning chain, home treatments consistedin vegetables boiling or steaming. Thermal treatments (blanching and steaming) did not induce asignificant decrease in folates concentrations. In contrast, losses were observed when vegetables were inclose contact with the water. This study identifies two mechanisms of losses, leaching and thermaldegradation. Folates diffusion was studied on a laboratory scale, the diffusion constants for folates weredetermined. Diffusion was more influenced by the matrix, than by temperature or pH. Some of thermaldegradation, including oxidation, can not be excluded during leaching experiments. Degradationkinetics were performed at different temperature, with different oxygen contents, from spinach andgreen beans puree as well as model solutions. Oxygen plays an important role in chemical degradation,especially in model solutions. Plant matrix seemed to have protective effect, maybe as a barrier tooxygen. Folates are generally fairly well preserved during processing. One of the perspectives would bethe study of the impact of processing on folates bioaccessibilityAVIGNON-Bib. numérique (840079901) / SudocSudocFranceF

Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p < 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p < 0.001) and arachidonic acids (p < 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p < 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 ± 0.44 to 1.24 ± 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

International audienceBackground: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). Aims: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. Methods: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41 months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. Results: Only 53.5% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the 9 participating centres (27.3% to 70.0%, p= < 0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (47.6% vs 68.5%, p=< 0.0001). Independent predictors of colonoscopic surveillance were male sex, UC IBD subtype, longer disease duration, previous history of CRC, and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 70.7%, 26.6 and 30.0% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. Conclusions: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis

Limited effectiveness with a 10-day bismuth-containing quadruple therapy (Pylera®) in third-line recue treatment for Helicobacter pylori infection. A real-life multicenter study

[EN]To assess the effectiveness, safety, and tolerance of Pylera® as a third-line in clinical practice.This was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori-infected individuals treated with Pylera® and a proton-pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI-clarithromycin-amoxicillin as first-line and to levofloxacinamoxicillin-PPI as second-line therapy. Eradication was tested 4-8 weeks after Pylera® using a C13-urea breath test. Treatment-related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases.Of 103 subjects fulfilling the selection criteria, 101 were included in the intention-to-treat (ITT) analysis and 97 in the per-protocol (PP) analysis. In an area of high antibiotic resistance to H. pylori, 10-day Pylera® plus double-dose PPI emerged as an alternative as third-line therapy, although not achieving optimal eradication rates

Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists

Reactivation of latent Mycobacterium tuberculosis (Mtb) infection is a major complication of anti-tumour necrosis factor (TNF)-α treatment, but its mechanism is not fully understood. We evaluated the effect of the TNF antagonists infliximab (Ifx), adalimumab (Ada) and etanercept (Eta) on anti-mycobacterial immune responses in two conditions: with ex vivo studies from patients treated with TNF antagonists and with the in vitro addition of TNF antagonists to cells stimulated with mycobacterial antigens. In both cases, we analysed the response of CD4(+ )T lymphocytes to purified protein derivative (PPD) and to culture filtrate protein (CFP)-10, an antigen restricted to Mtb. The tests performed were lymphoproliferation and immediate production of interferon (IFN)-γ. In the 68 patients with inflammatory diseases (rheumatoid arthritis, spondylarthropathy or Crohn's disease), including 31 patients with a previous or latent tuberculosis (TB), 14 weeks of anti-TNF-α treatment had no effect on the proliferation of CD4(+ )T lymphocytes. In contrast, the number of IFN-γ-releasing CD4(+ )T lymphocytes decreased for PPD (p < 0.005) and CFP-10 (p < 0.01) in patients with previous TB and for PPD (p < 0.05) in other patients (all vaccinated with Bacille Calmette-Guérin). Treatments with Ifx and with Eta affected IFN-γ release to a similar extent. In vitro addition of TNF antagonists to CD4(+ )T lymphocytes stimulated with mycobacterial antigens inhibited their proliferation and their expression of membrane-bound TNF (mTNF). These effects occurred late in cultures, suggesting a direct effect of TNF antagonists on activated mTNF(+ )CD4(+ )T lymphocytes, and Ifx and Ada were more efficient than Eta. Therefore, TNF antagonists have a dual action on anti-mycobacterial CD4(+ )T lymphocytes. Administered in vivo, they decrease the frequency of the subpopulation of memory CD4(+ )T lymphocytes rapidly releasing IFN-γ upon challenge with mycobacterial antigens. Added in vitro, they inhibit the activation of CD4(+ )T lymphocytes by mycobacterial antigens. Such a dual effect may explain the increased incidence of TB in patients treated with TNF antagonists as well as possible differences between TNF antagonists for the incidence and the clinical presentation of TB reactivation

From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

<p>Abstract</p> <p>Background</p> <p><it>elicobacter pylori </it>infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach.</p> <p>Results</p> <p>A set of 254 <it>H. pylori </it>genes was used to perform array-based comparative genomic hybridization among 120 French <it>H. pylori </it>strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with <it>cag</it>PAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released <it>H. pylori </it>genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest <it>H. pylori </it>genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the <it>vacA</it>s2m2 allele and lacks the genes encoding the major virulence factors (absence of <it>cag</it>PAI, <it>bab</it>B, <it>bab</it>C, <it>sab</it>B, and <it>hom</it>B). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 <it>H. pylori </it>sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38.</p> <p>Conclusion</p> <p>These isolates are deprived of the main <it>H. pylori </it>virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.</p