Role of interleukin polymorphisms in gastric cancer: “Pros and cons”

Helicobacter pylori (H. pylori ) infection is the leading cause of gastric cancer worldwide. Infection with this bacterium causes a chronic active immune response that persists for the life of the host. The combination of bacterial factors, environmental insults, and the host immune response drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward GC. Among the host factors, IL-1 gene cluster polymorphisms (IL-1B encoding IL-1β and IL-1RN encoding IL-1ra, its naturally occurring receptor antagonist) play a decisive role in modulating the risk of developing hypochlorhydria, gastric atrophy and GC in the presence of H. pylori infection. In particular, one single nucleotide polymorphism in the IL-1B promoter (IL-1B-511C T), and the short allele of a 86-bp variable number of tandem repeats polymorphism in the IL-1RN second intron (IL-1RN*2) are associated with an increased risk for GC. However this hypothesis is still to be fully confirmed. This review focuses on the divergent results obtained by several epidemiological and functional in vitro and in vivo studies and show that IL-1 genotyping has still no role in the clinical management of patients with H. pylori infection.

How evidence-based are current guidelines for managing patients with peptic ulcer bleeding?

Current guidelines for managing ulcer bleeding state that patients with major stigmata should be managed by dual endoscopic therapy(injection with epinephrine plus a thermal or mechanical modality) followed by a high dose intravenous infusion of proton pump inhibitors(PPIs).This paper aims to review and critically evaluate evidence supporting the purported superiority of a continuous infusion over less intensive regimens of PPIs administration and the need for adding a second hemostatic endoscopic procedure to epinephrine injection.Systematic searches of PubMed,EMBASE and the Cochrane library were performed.There is strong evidence for an incremental benefit of PPIs over H2receptor antagonists or placebo for the outcome of patients with peptic ulcer bleeding following endoscopic hemostasis.However,the benefit of PPIs is unrelated to either the dosage(intensive vs standard regimen) or the route of administration(intravenous vs oral).There is significant heterogeneity among the 15 studies that compared epinephrine with epinephrine plus a second modality,which might preclude the validity of reported summary estimates.Studies without second look endoscopy plus re-treatment of re-bleeding lesions showed a signif icant benef it of adding a second endoscopic modality for hemostasis,while studies with second-look and re-treatment showed equal efficacy between endoscopic mono and dual therapy.Inconclusive experimental evidence supports the current recommendation of the use of dual endoscopic hemostatic means and infusion of high-dose PPIs as standard therapy for patients with bleeding peptic ulcers.Presently,the combination of epinephrine monotherapy with standard doses of PPIs constitutes an appropriate treatment for the majority of patients.