Evidence of Epstein-Barr Virus Infection Association With Gastric Cancer and Gastroduodenal Diseases

Background: Epstein-Barr virus (EBV) is detected in epithelial tumors, such as nasopharyngeal carcinoma and gastric cancer (GC). EBV-associated gastric cancer is a distinct molecular subtype of gastrointestinal carcinomas as defined by Cancer Genome Atlas. This gamma-Herpes virus is present in approximately 10% of gastric carcinomas.Methods: The present study aimed to investigate the presence of EBV genome in gastric cancer and other gastroduodenal diseases either alone or together with Helicobacter pylori (HP). We examined 237 samples from Iranian patients diagnosed with GC and gastroduodenal disease for EBV infection by quantitative Real-Time PCR.Results: Of the 237 samples tested, EBV DNA was detected in 37 samples (15.6%), in 13 of the 81 GC cases (16%), and 24 of the 156 non-cancerous samples (15.4%). All samples containing EBV were gastric cancer of the intestinal type. Of 37 EBV-positive samples, 20 (54.1%) were over 55 years old and 20 (54.1%) were male. The EBV-EBER (EBV-encoded small RNA) DNA copy number in the gastric cancer group (mean = 2.14×10-1 copies/cell) was higher than that in the gastroduodenal disease group (mean = 1.39×10-2 copies/cell), and this difference was statistically significant (P> 0.001). Moreover, the concurrent infections with EBV and HP were detected in 17 out of 35 EBER-positive samples (48.6%), 6 (17/1%) cases were in the gastric cancer group and 11 (31/4%) cases were in the gastroduodenal disease group.Conclusions: In the present study, a high incidence (16%) of EBVaGC was observed in Babol city, Northern Iran. Also, the higher number of copies of EBV EBER DNA in the GC group than in the non-cancer group confirmed the possible role of EBV in inducing cancer. EBVaGC is not endemic in any region and varies in different nations. Therefore, further studies are needed to determine the role of this virus in the development of GC and other gastroduodenal diseases.

Helicobacter pylori type 4 secretion systems as gastroduodenal disease markers

Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1–14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1–27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.

Prevalence of Helicobacter pylori cagA and vacA Genes and Their Correlation with Gastrointestinal Diseases

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium, producing gastric ulcer, mild to severe gastritis, gastric carcinoma and lymphoma to the gastric mucosa-associated lymphoid tissue through many virulence influences. Among the virulence factors identified; vacuolating cytotoxin A (vacA) and cytotoxin-associated gene A (cagA) play an important role. Objective: In this study, we try to discover the relation between vacA variant and cagA genes with the clinical illness occurring in H. pylori patients Methodology: One hundred and forty patients were included in our study. Dual biopsy samples were taken from the stomach; one was examined by the urease test, and the other one was stored at −80°C for DNA extraction followed by PCR. The existence of H. pylori in the tissue was recognized by the existence of glmM gene and its detection by PCR. All the positive samples were additionally tested by PCR for the occurrence of cagA and vacA variant genes. Results: Our study demonstrated that cagA and vacA genes were found among 50% and 57% respectively of H. pylori patients complaining from gastrointestinal illnesses and that vacA s1/s2 was the main genotype found in H. pylori persons with gastroduodenal disease. Significant relation between vacA s1 gene and cagA gene was found. Conclusion: vacA s1 genotype has a vital role in upper gastrointestinal illnesses progress.

Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland

The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(−)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder.

Crohn's Disease of the Esophagus, Duodenum, and Stomach

Upper gastrointestinal Crohn's is an under-reported, under-recognized phenotype of Crohn's disease. Routine screening in the pediatric population has shown a higher prevalence compared with adults; however, most adult patients remain asymptomatic with respect to upper gastrointestinal Crohn's disease. For the patients who are symptomatic, medical treatment is the first line of management, except for cases of obstruction, perforation, or bleeding. Though most patients respond to medical therapy, mainly steroids, with the addition of immunomodulators and more recently biologics agents, surgical intervention is usually required only for obstructing gastroduodenal disease secondary to strictures. Strictureplasty and bypass are safe operations with comparable morbidity, although bypass has higher rates of dumping syndrome and marginal ulceration in the long term. Rare cases of gastroduodenal fistulous disease from active distal disease may involve the stomach or duodenum, and esophageal Crohn's disease can fistulize to surrounding structures in the mediastinum which may require the highly morbid esophagectomy.

Gastroduodenal Surgery: A Persistent and Continuing Challenge

The number of patients being treated surgically for gastroduodenal disease has decreased over the past five decades as a result of focus on medical treatment. However, perforated and bleeding peptic ulcer disease (PUD) continues to represent a significant percentage of patients who require emergency surgery. The aim of this study was to characterize these critically ill surgical patients treated for gastroduodenal disease in our hospital. A retrospective, single-center, consecutive cohort study of all patients identified from the hospital National Surgical Quality Improvement Program database who were admitted to our institution requiring emergent surgical intervention over the past two years was conducted. Of 423 patients, 33 (7.8%) had operative procedures for complications of PUD, of which 19 patients (57.6%) had perforation; nine patients (27.3%) had hemorrhage; one patient (3.0%) had both perforation and hemorrhage; two patients (6.1%) had distal gastrectomies for ulcers refractory to medical management alone, and two patients (6.1%) had gastrectomies for malignant gastric neoplasms. There is a significant population of patients who present with life-threatening complications of PUD, despite the decline in PUD worldwide. These patients are critically ill and require careful and diligent management for good outcomes.