Statistical Methods in Medical Research.

Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection with H. pylori is the strongest known risk factor for gastric cancer, which is the second leading cause of cancer-related deaths worldwide. Once H. pylori colonizes the gastric environment, it persists for the lifetime of the host, suggesting that the host immune response is ineffective in clearing this bacterium. In this review, we discuss the host immune response and examine other host factors that increase the pathogenic potential of this bacterium, including host polymorphisms, alterations to the apical-junctional complex, and the effects of environmental factors. In addition to host effects and responses, H. pylori strains are genetically diverse. We discuss the main virulence determinants in H. pylori strains and the correlation between these and the diverse clinical outcomes following H. pylori infection. Since H. pylori inhibits the gastric epithelium of half of the world, it is crucial that we continue to gain understanding of host and microbial factors that increase the risk of developing more severe clinical outcomes.

Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk

Helicobacter pyloricauses gastric adenocarcinoma in a minority of infected individuals. What have we learned about bacterial and host-specific factors that lead to malignancy, and what canH. pyloritell us about inflammatory carcinomas that develop beyond the gastric niche? Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host–microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.

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Helicobacter pylori: gastric cancer and beyond

With few exceptions, the most commonly recommended triple Helicobacter pylori regimen (proton pump inhibitor (PPI), amoxicillin and clarithromycin) now provides unacceptably low treatment success. A review of worldwide results suggests that successful eradication using a triple regimen is not consistently observed in any population. Clinicians should use ‘only use what works locally’ and ignore consensus statements and society guidelines if they are not consistent with local results. Clinical trials should be result based, with the goal of identifying regimens with >90–95% success. New treatments should be only be compared with the currently locally effective treatment (>90%) or a historical untreated control (which has been shown to reliably yield 0% eradication); trials using placebos or treatments known to be inferior are with rare exceptions unethical. If a highly effective regimen is not available locally, we recommend trying a 14 day concomitant quadruple treatment regimen containing a PPI, amoxicillin, clarithromycin and a nitroimidazole; 10 day sequential treatment (PPI plus amoxicillin for 5 days followed by a PPI, clarithromycin and a nitroimidazole for 5 days); or 14 day bismuth-containing quadruple treatments. Treatments needing further evaluation include those containing furazolidone or nitazoxanide, hybrids of sequential–concomitant therapies and amoxicillin–PPI dual therapy with PPI doses such that they maintain intragastric pH >6.

https://gut.bmj.com/content/gutjnl/59/8/1143.full.pdf

Helicobacter pylori treatment in the era of increasing antibiotic resistance

Host-Bacterial Interactions in Helicobacter pylori Infection

Intracellular, Intercellular, and Stromal Invasion of Gastric Mucosa, Preneoplastic Lesions, and Cancer by Helicobacter pylori

Type or extension of intestinal metaplasia and immature/atypical “indefinite-for-dysplasia” lesions as predictors of gastric neoplasia

Department of Pathology, University of Pavia and IRCCS Policlinico San Matteo, 27100 Pavia, Italy Gastrointestinal Endoscopy Service, IRCCS Policlinico San Matteo, 27100 Pavia, Italy Biometry and Clinical Epidemiology, IRCCS Policlinico San Matteo, 27100 Pavia, Italy Planning, Managing and Control Department, ASL Pavia, 27100 Pavia, Italy Department of Pathology, University of Genoa, 16100 Genoa, Italy

Type or extension of intestinal metaplasia and immature/atypical bindefinite-for-dysplasiaQ lesions as predictors of gastric neoplasia B

The limited prognostic value of currently used histologic classifications of gastric cancer and their failure to account for the complexity of the disease as revealed by more recent investigations prompted a combined reinvestigation of histologic, molecular, and clinicopathologic patterns in 294 extensively sampled, invasive gastric cancers representing all main histotypes and stages of the disease and followed for a median of 150 months. Among histologic parameters tested, only cellular atypia, angio-lympho- or neuroinvasion, Ki67 proliferation index, expansile/infiltrative type growth, and T8 cell-rich high lymphoid intra-/peritumor response (HLR) proved to be stage-independent predictors of patient survival. Among molecular tests, p53 gene exon 7 (loop 3) and 8 (loop-sheet-helix motif and S-10 band), but not p53 protein overexpression, TP53 LOH or 18qLOH, were found to worsen prognosis. Microsatellite DNA instability was a favorable prognostic factor when coupled with HLR. Patient survival analysis of the main histotypes and their subtypes confirmed the favorable prognosis of HLR, well-differentiated tubular, muconodular, and low grade diffuse desmoplastic cancers, and highlighted the worse prognosis of anaplastic and infiltrative-lymphoinvasive mucinous cancers compared to ordinary cohesive and diffuse cancers. Distinct roles of individual morphologic and molecular factors in tumor progression of the different histotypes have been recognized. The combination of survival-predictive histotypes and individual histologic or molecular parameters allowed us to develop a classification of all gastric cancers into three grades of increasing malignancy which proved to be of high prognostic value.

Francesca Tava

Papers

Intracellular, Intercellular, and Stromal Invasion of Gastric Mucosa, Preneoplastic Lesions, and Cancer by Helicobacter pylori

Type or extension of intestinal metaplasia and immature/atypical “indefinite-for-dysplasia” lesions as predictors of gastric neoplasia

Type or extension of intestinal metaplasia and immature/atypical bindefinite-for-dysplasiaQ lesions as predictors of gastric neoplasia B

A combined histologic and molecular approach identifies three groups of gastric cancer with different prognosis.

Lower- and higher-grade subtypes of diffuse gastric cancer