Helicobacter pylori (H. pylori) is the causative agent of chronic gastritis and peptic ulcer diseases and is an important risk factor for the development functional dyspepsia, peptic ulceration, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. H. pylori has very high rates of infection in human populations, and it is estimated that over 50% of the world population is infected. Recently, certain extra-gastric manifestations, linked to H. pylori infection, have been widely investigated. Noteworthy, a growing body of evidences supports an association between H. pylori infection with lung cancer. The present review intend to highlight not only the most recent evidences supporting this association, but also some missed points, which must be considered to validate this emerging association.
Helicobacter Infections ; complications ; Helicobacter pylori ; physiology ; Humans ; Lung Neoplasms ; complications ; microbiology

BACKGROUND/AIMS: Controversy exists regarding the characteristics of Helicobacter pylori infection-negative gastric cancer (HPIN-GC). The aim of this study was to evaluate clinicopathologic features of HPIN-GC compared to H. pylori infection-positive gastric cancer (HPIP-GC) using a comprehensive analysis that included genetic and environmental factors. METHODS: H. pylori infection status of 705 resectable gastric cancer patients was determined by the rapid urease test, testing for anti-H. pylori antibodies, histologic analysis and culture of gastric cancer tissue samples, and history of H. pylori eradication. HPIN-GC was defined as gastric cancer that was negative for H. pylori infection based on all five methods and that had no evidence of atrophy in histology or serology. RESULTS: The prevalence of HPIN-GC was 4% (28/705). No significant differences with respect to age, sex, smoking, drinking, family history of gastric cancer or obesity were observed between the two groups. HPIN-GC tumors were marginally more likely to involve the cardia (14.3% for HPIN-GC vs 5.3% for HPIP-GC, p=0.068). The Lauren classification, histology, and TNM stage did not differ according to H. pylori infection status. Microsatellite instability was not different between the two groups, but p53 overexpression in HPIN-GC was marginally higher than in HPIP-GC (56.0% for HPIN-GC vs 37.0% for HPIP-GC, p=0.055). CONCLUSIONS: The prevalence of HPIN-GC was extremely low, and its clinicopathologic characteristics were similar to HPIP-GC.
Antibodies, Bacterial/analysis ; Female ; Helicobacter Infections/*complications/epidemiology/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Republic of Korea/epidemiology ; Stomach Neoplasms/epidemiology/*microbiology/*pathology/surgery ; Urease/analysis

It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy.
Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Biopsy ; Female ; Follow-Up Studies ; Gastric Mucosa/*pathology ; Gastritis/diagnosis/etiology/microbiology ; Gastroscopy ; Helicobacter Infections/complications/*diagnosis/drug therapy ; Humans ; Lymphoma, B-Cell, Marginal Zone/complications/*diagnosis/pathology ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies

Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.
Health Priorities ; Helicobacter Infections/complications/diagnosis/microbiology/*therapy ; Helicobacter pylori ; Humans ; Mass Screening ; Stomach Neoplasms/microbiology/*prevention & control

BACKGROUND/AIMS: The interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori remains controversial. We retrospectively investigated whether H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users. METHODS: From January 2010 to December 2013, a total of 245 long-term NSAID (including low-dose aspirin) users who had undergone an esophagogastroduodenoscopy and had been evaluated for H. pylori infection were enrolled at Okayama University Hospital and Tsuyama Chuo Hospital. The degree of gastric mucosal injury was assessed according to the modified Lanza score (MLS). Severe gastric mucosal injury was defined as an MLS > or =4. Univariate and multivariate logistic regression analyses were performed. RESULTS: In the univariate analysis, age > or =75 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.2), H. pylori-positivity (OR, 2.0; 95% CI, 1.2 to 3.5), and the concomitant use of proton pump inhibitors (PPIs) (OR, 0.48; 95% CI, 0.26 to 0.86) were significantly associated with severe gastric mucosal injury. The multivariate analysis was adjusted by age and sex and demonstrated that H. pylori-positivity (OR, 1.8; 95% CI, 1.0 to 3.3) and the concomitant use of PPIs (OR, 0.53; 95% CI, 0.28 to 0.99) significantly contributed to severe gastric mucosal injury. CONCLUSIONS: H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Case-Control Studies ; *Disease Progression ; Endoscopy, Digestive System ; Female ; Gastric Mucosa/*drug effects/*microbiology ; Helicobacter Infections/*complications/microbiology/pathology ; *Helicobacter pylori/drug effects ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Proton Pump Inhibitors/adverse effects ; Retrospective Studies

BACKGROUND/AIMS: Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma. METHODS: RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated. RESULTS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant. CONCLUSIONS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma.
Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*metabolism ; Bacterial Proteins/*metabolism ; Cell Line, Tumor ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Methylation ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; Retrospective Studies ; Stomach Neoplasms/complications/microbiology/*pathology

BACKGROUNDHelicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.

METHODSPatients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.

RESULTSThere were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).

CONCLUSIONSBased on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Adolescent ; Adult ; Aged ; Amoxicillin ; therapeutic use ; Esomeprazole ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; etiology ; microbiology ; Female ; Gastroesophageal Reflux ; drug therapy ; etiology ; microbiology ; Helicobacter Infections ; complications ; drug therapy ; Helicobacter pylori ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Tinidazole ; therapeutic use ; Young Adult

BACKGROUND/AIMS: The connection between Helicobacter pylori and complicated peptic ulcer disease in peptic ulcer bleeding (PUB) patients taking nonsteroidal anti-inflammatory drugs has not been established. In this study, we sought to determine whether delayed H. pylori eradication therapy in PUB patients increases complicated recurrent peptic ulcers. METHODS: We identified inpatient PUB patients using the Taiwan National Health Insurance Research Database. We categorized patients into early (time lag < or =120 days after peptic ulcer diagnosis) and late H. pylori eradication therapy groups. The Cox proportional hazards model was used. The primary outcome was rehospitalization for patients with complicated recurrent peptic ulcers. RESULTS: Our data indicated that the late H. pylori eradication therapy group had a higher rate of complicated recurrent peptic ulcers (hazard ratio [HR], 1.52; p=0.006), with time lags of more than 120 days. However, our results indicated a similar risk of complicated recurrent peptic ulcers (HR, 1.20; p=0.275) in time lags of more than 1 year and (HR, 1.10; p=0.621) more than 2 years. CONCLUSIONS: H. pylori eradication within 120 days was associated with decreased complicated recurrent peptic ulcers in patients with PUB. We recommend that H. pylori eradication should be conducted within 120 days in patients with PUB.
Adult ; Aged ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Patient Readmission/*statistics & numerical data ; Peptic Ulcer/complications/*epidemiology/microbiology ; Peptic Ulcer Hemorrhage/complications ; Proportional Hazards Models ; Recurrence ; Time-to-Treatment/*statistics & numerical data ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Tumor necrosis factor alpha (TNF-alpha) encoded by TNFA is a key mediator in inflammation, a precursor condition for peptic ulceration. Promoter polymorphisms of TNFA that influence its transcriptional activity and TNF-alpha production are known. TNFA-308G>A (rs1800629) and TNFA-1031T>C (rs1799964), which are responsible for increased TNFA transcription, could influence the risk of peptic ulceration. This study aimed to investigate these polymorphisms and to evaluate their association with peptic ulcer disease and Helicobacter pylori infection in the Polish population. METHODS: Gastric mucosa specimens obtained from 177 Polish peptic ulcer patients were used to conduct rapid urease tests and to assess the investigated polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data were compared with the results obtained from healthy individuals of Polish origin. RESULTS: There were no significant differences in genotype and allele frequency of the investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between the frequencies of particular genotypes and alleles for both single-nucleotide polymorphisms (SNPs) and the presence of H. pylori infection in peptic ulcer patients and in subgroups of men and women with peptic ulcer disease were found. CONCLUSIONS: The investigated SNPs are not risk factors for either peptic ulcer or H. pylori infection development in the Polish population. The results require verification in a larger cohort.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; European Continental Ancestry Group/genetics ; Female ; Gastric Mucosa/*metabolism/microbiology ; Genetic Predisposition to Disease ; Genotype ; Helicobacter Infections/complications/*genetics ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer/complications/*genetics ; Poland ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/*genetics ; Young Adult

OBJECTIVETo establish an animal model of gastric cancer by long-term infection of Helicobacter pylori (H.pylori) and to elucidate the pathogenesis by proteomics analysis.

METHODSFifty male Mongolian gerbils (4-5 week-old and weighted 60-100 g) were infected with H.pylori and the gastric tissues were obtained after the infection at 3, 6, 12 and 24 months. Histological changes were evaluated by H-E staining of the gastric tissue sections. Detection of H.pylori was performed by in-vitro culture of fresh gastric tissue samples, PCR amplification of H.pylori 16s rRNA and localization by silver staining. In addition, proteins extracted from gastric tissue samples were subjected to two-dimensional electrophoresis (2-DE) at various infection time points. Protein spots with increased quantity over the course of H.pylori infection were selected and analyzed by LC-MS/MS. Finally, differentially expressed proteins between human gastric cancer tissue samples and lymph nodes were analyzed by real-time RT-PCR.

RESULTSColonization of H.pylori was observed in gastric tissue of gerbils as early as 3 months after H.pylori infection, and persisted till 24 months. Pathological examination of infected animals showed various histological changes including acute gastritis, atrophic gastritis, intestinal metaplasia and gastric carcinoma. Seventy-eight differentially expressed proteins were identified by proteomics analysis, among which 36 proteins were up-regulated and 42 were down-regulated. Analyzed by LC-MS/MS, ten proteins were identified, including lactate dehydrogenase, ATP synthase, fatty acid-binding protein, COX5B, peroxiredoxin-4, peroxide reductase, transgelin, succinyl-CoA ligase, keratin and protein disulfide-isomerase A2, among which transgelin, ATP synthase and lactate dehydrogenase were highly expressed in human gastric carcinoma and lymph nodes.

CONCLUSIONSH.pylori infection induces the expression of transgelin, ATP synthase and lactate dehydrogenase, implying possible roles in the pathogenesis of gastric diseases including cancer.

Animals ; Disease Models, Animal ; Gastritis ; microbiology ; pathology ; Gerbillinae ; Helicobacter Infections ; complications ; metabolism ; Helicobacter pylori ; genetics ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Male ; Metaplasia ; Microfilament Proteins ; metabolism ; Muscle Proteins ; metabolism ; Proteomics ; Proton-Translocating ATPases ; metabolism ; RNA, Ribosomal, 16S ; analysis ; Stomach Neoplasms ; metabolism ; microbiology ; Tandem Mass Spectrometry