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: 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

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

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

Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. There are, however, distinct differences in incidence rates in different geographic regions. While the incidence rate of gastric cancer has been falling, that of gastric cardia cancers is reportedly on the rise in some regions. Helicobacter pylori (H. pylori) infection is a major risk factor of non-cardia gastric cancer, and data has emerged concerning the role of H. pylori eradication for primary prevention of gastric cancer. Dietary, lifestyle and metabolic factors have also been implicated. Although addressing these other factors may contribute to health, the actual impact in terms of cancer prevention is unclear. Once irreversible histological changes have occurred, endoscopic surveillance would be necessary. A molecular classification system offers hope for molecularly tailored, personalised therapies for gastric cancer, which may improve the prognosis for patients.
Female ; Global Health ; Helicobacter Infections ; complications ; prevention & control ; Helicobacter pylori ; Humans ; Incidence ; Male ; Obesity ; complications ; Risk Factors ; Stomach Neoplasms ; epidemiology ; genetics ; microbiology ; prevention & control

Gastric cancer is the second most common cause of cancer death worldwide and is usually detected at a late stage, except in Korea and Japan where early screening is in effect. Results from animal and epidemiological studies suggest that Helicobacter pylori infection, and subsequent gastritis, promote development of gastric cancer in the infected mucosa. Relatively effective treatment regimens are available to treat H. pylori infection, and in general, mass eradication of the organism is not currently recommended as a gastric cancer prevention strategy. However, regional guidelines vary regarding the indications and recommendations for H. pylori treatment for gastric cancer prevention. In this review, we discuss the results from intervention studies, provide insight regarding current guideline recommendations, and discuss future study directions.
Anti-Bacterial Agents/*therapeutic use ; Drug Therapy, Combination ; Early Detection of Cancer ; Evidence-Based Medicine ; Gastrectomy ; Gastritis/diagnosis/*drug therapy/microbiology ; Helicobacter Infections/complications/diagnosis/*drug therapy/microbiology ; Humans ; Neoplasm Recurrence, Local ; Practice Guidelines as Topic ; Proton Pump Inhibitors/*therapeutic use ; Risk Factors ; Stomach Neoplasms/diagnosis/microbiology/*prevention & control/surgery ; Treatment Outcome

BACKGROUND/AIMS: This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates and the eradication rate of H. pylori could be different between cancer and non-cancer patients. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens obtained from 269 Koreans, who did not have any eradication therapy history and were diagnosed as one of the following diseases; chronic gastritis, benign gastric ulcer, duodenal ulcer or gastric cancer. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin were examined with the agar dilution method. In addition, eradication rate of H. pylori was evaluated. RESULTS: There was no significant difference in the primary antibiotic resistance to above eight antibiotics among chronic gastritis, peptic ulcer disease and gastric cancer. Furthermore there was no difference of antibiotic resistance between cancer and non-cancer patients, and there was no difference of eradication rate of H. pylori according to disease. CONCLUSIONS: Primary antibiotic resistance and H. pylori eradication rate were not different between cancer and non-cancer patients.
2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use ; Adult ; Aged ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Chronic Disease ; Clarithromycin/therapeutic use ; *Drug Resistance, Bacterial ; Drug Therapy, Combination ; Duodenal Ulcer/complications/microbiology ; Female ; Gastritis/complications/microbiology ; Helicobacter Infections/drug therapy/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Omeprazole/therapeutic use ; Peptic Ulcer/complications/microbiology ; Proton Pump Inhibitors/therapeutic use ; Republic of Korea ; Stomach Neoplasms/complications/microbiology

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
Aged ; Female ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Intestinal Diseases/*genetics/microbiology/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions/metabolism/pathology ; Stomach Neoplasms/etiology/*genetics/microbiology

Intrahepatic abscess is an unusual complication of peptic ulcer disease. We present a case of gastric cancer in which the ulcer penetrated into the left lobe of liver with subsequent abscess and fistula formation. Esophagogastroduodenoscopy confirmed ulcers and a fistula opening in the antrum. Abdominal computed tomogram showed a subcapsular liver abscess adjacent to the gastric antrum. Subtotal gastrectomy with curettage of the fistulous tract was performed. The final diagnosis was the signet ring cell gastric carcinoma complicating subcapsular liver abscess. To our knowledge, this is the first reported case in Korea.
Endoscopy, Gastrointestinal ; Female ; Humans ; Klebsiella pneumoniae/isolation & purification ; Liver Abscess/diagnosis/*etiology/microbiology ; Middle Aged ; Peptic Ulcer Perforation/*complications/diagnosis ; Stomach Neoplasms/complications/*diagnosis/surgery ; Tomography, X-Ray Computed

OBJECTIVETo investigate the main risk factors associated with intra-abdominal infection(IAI) following gastrectomy in gastric cancer patients.

METHODSCase-control study was used to investigate the clinical data of 1728 gastric carcinoma cases retrospectively by Logistic regressive analysis.

RESULTSUnivariate Logistic regressive analysis showed 16 factors, including age, malnutrition, chronic obstructive pulmonary disease(COPD), diabetes mellitus(DM), heart diseases, prothrombin time, lymphocyte count, tumor size, ascites, invasion to the adjacent organ, neoplasm TNM staging (UICC, 1997), methods of gastrectomy, blood loss, operative time, blood transfusion and extent of lymph nodal dissection,were associated with postoperative intra-abdominal infection. Binary Logistic regression analysis found that extent of lymph nodal dissection(N(2)(+) approximately N(3) and N(2)), invasion to the adjacent organ, DM, operative time, age and lymphocyte count were the independent risk factors associated with mortality.

CONCLUSIONNecessary interventions should be carried out to prevent IAI referring to above risk factors.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Gastrectomy ; adverse effects ; Humans ; Logistic Models ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Postoperative Complications ; etiology ; Risk Factors ; Stomach Neoplasms ; microbiology ; pathology ; surgery ; Surgical Wound Infection ; etiology ; Young Adult