The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial

Objective Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. Design We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naive to treatment were randomised (1: 1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative C-13-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. dResults The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. Conclusions S10 was not superior to T14 in areas with low clarithromycin resistance

Levofloxacin-Based and Clarithromycin-Based Triple Therapies as First-Line and Second-Line Treatments for Helicobacter Pylori Infection: A Randomised Comparative Trial with Crossover Design

Background The efficacy of a levofloxacin-based regimen as the first-line treatment and a clarithromycin-based regimen as the second-line treatment for Helicobacter pylori infection remains unknown. The aim of this study was to assess the eradication rates of these two regimens using different administration sequences. Methods Eligible patients were randomised to receive LAL: levofloxacin (750 mg once a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days, or CAL: clarithromycin (500 mg twice a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days . Patients with positive [C- 13] urea breath test after treatment were retreated with the rescue regimen in a crossover manner for 10 days. Result When used as first-line treatment (n = 432), the eradication rates of LAL (n 217) and CAL (n 215) were 74.2 and 83.7% (p = 0.015) in the intent-to-treat (ITT) analysis, and 80.1 and 87.4% (p = 0. 046) in the per-protocol (PP) analysis, respectively. When used as second-line treatment, the eradication rates of LAL (n = 26) and CAL (n = 40) were 76.9 and 60% (p = 0.154) in the ITT analysis, and 80 and 61.5% (p = 0.120) in the PP analysis, respectively. The overall eradication rates of CAL followed by LAL were better than the reverse sequence in both the ITT analysis (93% vs 85.3%, p = 0.01) and the PP analysis (97.6% vs 92.5%, p = 0.019). The eradication rate was significantly lower in the presence of levofloxacin resistance in the LAL group (50% vs 84.4%, p = 0.018) and clarithromycin resistance in the CAL group (44.4% vs 90.7%, p = 0.002). Conclusion CAL achieved a higher eradication rate than LAL as the first-line treatment, but not as the second-line treatment. The strategy of using CAL as the initial treatment and LAL as the rescue regimen achieved higher eradication rates than the reverse sequence

Asia-Pacific Consensus Guidelines on Gastric Cancer Prevention

Background and Aim: Gastric cancer is a major health burden in the Asia- Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. Methods: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence , strength of recommendation, and level of consensus were graded. Results: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor . Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high- risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. Conclusion: A strategy of H . pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus

Gastrointestinal: Burkitt's Lymphoma

Lymphomas are solid malignancies of lymphoid tissue that can be categorized as either Hodgkin's disease or non-Hodgkin's lymphoma. It is rare for Hodgkin's disease to involve the gastrointestinal tract. Although the majority of non-Hodgkin 's lymphomas are thought to arise from lymph nodes, at least 30% arise in other organs and are called extranodal or primary lymphomas. Of these extranodal lymphomas, up to 40% are located in the gastrointestinal tract, particularly in the stomach and small bowel. Most of these lymphomas are of B-cell lineage. The most common are the diffuse large cell lymphoma and the marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma). Other B-cell lymphomas include Burkitt's lymphoma, mantle cell lymphoma and follicular lymphoma. The images shown below were from a 76- year-old man who was admitted to hospital with malaise, weight loss and pain in the left flank. He subsequently had two significant episodes of hematemesis and melena. Upper gastrointestinal endoscopy revealed bleeding from multiple doughnut-like tumors in the body and antrum of the stomach ( Fig. 1). He also had giant gastric folds. A computed tomography scan of the abdomen showed thickening of the wall of the jejunum and tumor infiltration of the left renal pelvis and parts of the right kidney. Histopathological examination of gastric biopsy specimens showed sheets of intermediate-sized lymphoid cells crowding between glands with an interspersed starry-sky pattern (Fig . 2;HE: ×200). Immunohistochemical stains were positive for CD20 ( indicating B-cell lineage) and almost all cells were positive for Ki-67 ( indicating an extremely high proliferation rate). The diagnosis was that of Burkitt's lymphoma. Apart from Burkitt's lymphoma, multiple gastric polypoid lesions with central ulceration can be seen in Kaposi's sarcoma, stromal cell tumors, metastatic gastric tumors and other lymphomas. Although only 1–2% of adult non -Hodgkin's lymphoma are of the Burkitt's variety, substantially higher percentages have been described in the pediatric setting and in patients with HIV

Age and Distal Colonic Findings Determine the Yield of Advanced Proximal Neoplasia in Chinese Patients with Rectal Bleeding

Background and Aims: Few data were available on the optimal diagnostic strategy for Chinese patients with hematochezia. We aimed to evaluate the impact of age and distal colonic findings on the yield of diagnostic strategies in young Chinese patients with hematochezia. Methods: Consecutive outpatients aged less than 50 years were analyzed using a hypothesized mixed diagnostic strategy to determine the optimal cut-off age for the use of sigmoidoscopy and colonoscopy. The efficacy and cost of the diagnostic strategy and the number of colonoscopies needed to detect one advanced proximal neoplasm (APN) using different cut-off ages were assessed. Results: In the hypothesized mixed diagnostic strategy for young patients, the sensitivities for the detection of APN were 100%, 92% and 75% if the cut- off ages were 30, 35 and 40 years, respectively. The cost needed to detect one APN would be $US 3155,$US 3179 and $US 3497 if the cut-off ages were 30, 35 and 40 years, respectively. Colonoscopy would be performed in 84%, 69% and 51% of patients if the cut-off ages were 30, 35 and 40 years, respectively. Conclusion: Colonoscopy should be considered for Chinese patients with rectal bleeding who are aged >= 35 years or those aged < 35 years who have adenoma in the distal colon

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial

Background Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. Methods For this multicentre, open-label, randomised trial, we recruited patients (&gt;= 20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. Findings Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients:300 to each group. The eradication rate was 90.7% (95% CI 87.4-94.0; 272 of 300 patients) in the S-14 group, 87.0% (83.2-90.8; 261 of 300 patients) in the S-10 group, and 82.3% (78.0-86.6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12.0 [95% CI 7.2-34.5]; p=0.003) and PP analyses (13.7 [8.3-40], p=0.003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. Interpretation Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection

Rantes-403 Polymorphism Is Associated with Reduced Risk of Gastric Cancer in Women

Background. Men are more susceptible to gastric cancer (GC) than women. However, the genetic factors associated with the sex difference are not well understood. Chemokines have been shown to modulate tumor behavior, and the sex-specific effect of the chemokine polymorphisms on the host susceptibility to several diseases has been reported. We aimed to determine the role of chemokine polymorphisms on host susceptibility to GC , with special interest on their sex-specific effect. Methods. A hospital- based case-control study, including 177 patients with GC and 217 age- matched unaffected healthy controls, was performed in three major tertiary care hospitals. Genotyping for regulated upon activation, normal T-cell expressed and secreted (RANTES) - 403 A/G and -28 C/G, CC chemokine receptor 5 (CCR5) deletion , and CCR2-V64I was performed using peripheral blood DNA. Results. The RANTES -403 GA and AA genotypes were independently associated with a 2.3-fold reduced risk of developing GC (OR = 0.44,95% CI 0.22- 0.90, P = 0.025) compared with GG genotype in women, but not in men. The RANTES -28C/G and CCR2-V64I polymorphisms were not associated with different risk of developing GC. The tumor stage, histological features, and survival rate were not different when stratified by RANTES - 403 and -28 and CCR2V64 I genotypes. Conclusions. Our data indicate that women who inherit A allele at RANTES -403 may be at reduced risk of GC