Community-Based Pilot Study of a Screening Program for Gastric Cancer in a Chinese Population.

A majority of gastric cancer cases in China are diagnosed at advanced stages, chiefly due to lack of an established routine nationwide screening program. This study evaluated the effectiveness of a novel screening program for gastric cancer. Seven geographic communities were randomly selected, and residents ages 40-69 years were screened. Serologic tests of Helicobacter pylori antibodies and pepsinogens, and positive family history of gastric cancer in first-degree relatives (FDR), were used to differentiate individuals for further gastroscopic examination and gastric mucosal biopsies. Among 7,773 individuals who underwent examination of serum markers, gastric cancer was detected in 14 (1.8%; 10 men). The rate in terms of gastric cancer cases per 100 gastroendoscopies was 1.6% (14/872), which was greater than 0.87% previously reported. Eleven of 14 patients with gastric cancer (78.6%) were FDRs of patients with gastric cancer. Two-thirds of the subjects with cardia gastric cancer were FDRs of individuals with gastric cancer rather than cardia gastric cancer. Comparative analysis indicated that the gastric cancer subjects were significantly more likely to be FDRs of patients with gastric cancer, in contrast to those without gastric cancer. All the individuals with gastric cancer were aged ≥50 years. After conducting a reverse analysis, we propose a novel screening program for gastric cancer. In conclusions, the populations most vulnerable to gastric cancer are those with positive family history of gastric cancer in FDRs, male gender, and aged 50 years or older. This screening program using fewer serum markers combined individual risk factors, mainly FDRs, is novel for identification of high-risk individuals for further gastroscopy in detecting early gastric cancer.

The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

BACKGROUND: Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. AIM: To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. MATERIALS AND METHODS: Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. RESULTS: The internalization level in the eradication success group was 5.40±5.78 × 10-3  cfu/cell, and the median was 6.194 × 10-3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10-3  cfu/cell, and the median was 10.28 × 10-3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). CONCLUSIONS: The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure.

Profiling of downregulated blood-circulating miR-150-5p as a novel tumor marker for cholangiocarcinoma.

Altered microRNA (miRNA) expression plays a role in cholangiocarcinoma (CCA) development; thus, detection of blood-circulating miRNAs could be useful as CCA markers. This study profiled serum miRNA levels in patients with primary sclerosing cholangitis (PSC) and CCA and then assessed the role of miR-150-5p in CCA progression in vitro. Three samples were randomly selected from each of 50 sera of healthy controls, 30 PSC sera, and 28 CCA sera with matched bile samples for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT-PCR, and miR-150-5p was selected for further in vitro and ex vivo studies. The miRNA microarray identified three dysregulated miRNAs in both CCA and PSC samples, while miR-150-5p level was consistently lower in CCA sera, bile, and tissues than in normal control and PSC sera (P < 0.05). Furthermore, levels of miR-150-5p were associated with serum carbohydrate antigen 19-9 (CA19-9) levels and CCA pathological grade. Bioinformatic Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that miR-150-5p could regulate hand-full gene pathways, including cancer pathway (P < 0.01). However, overexpression of miR-150-5p inhibited proliferation, migration, and invasion capability of CCA cells (P < 0.05). Luciferase reporter assay showed that miR-150-5p bound to an oncogene Ets including gene-1 (ELK1), and Western blot data confirmed that miR-150-5p suppressed ELK1 expression in CCA cell lines. These results suggest that reduced miR-150-5p expression could contribute to CCA development and progression due to uncontrolled ELK1 expression. Thus, further study could evaluate miR-150-5p as a novel target and predictor for CCA prevention and treatment.

Rescue Therapy with a Proton Pump Inhibitor Plus Amoxicillin and Rifabutin for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

Background. To conduct a systematic review and meta-analysis of clinical trials for eradication of Helicobacter pylori (H. pylori) that included a treatment arm with a proton pump inhibitor, rifabutin, and amoxicillin. Materials and Methods. We selected clinical trials that examined the efficacy of H. pylori eradication therapies and included a study arm using the test regimen from major medical literature databases and abstracts from major gastroenterology meetings. We also did subgroup and sensitivity analyses. Results. Twenty-one studies were included in systematic review. The total eradication rates of the test regimen were 70.4% by intent-to-treat (ITT) and 72.0% by per-protocol (PP) analyses. The pooled odds ratio (OR) was 0.55 using fixed effects model (P = 0.283) for the test regimen versus other triple regimens. The total eradication rates were 68.4% for the test regimen and 81.9% in the control group by ITT, while the OR was 1.08 using random effects model (P = 0.019). The pooled eradication rate was 66.4% for the test regimen and 67.4% for the control group by ITT. The total adverse effects incidence were 25.1% for the test regimen. Conclusions. The test regimen for H. pylori rescue therapy may be not superior to control regimens in efficacy.

Meta-analysis: is combination of tetracycline and amoxicillin suitable for Helicobacter pylori infection?

AIM: To access the efficacy of combination with amoxicillin and tetracycline for eradication of Helicobacter pylori (H. pylori), thus providing clinical practice guidelines. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature databases and abstract books of major European, American, and Asian gastroenterological meetings were searched. All clinical trials that examined the efficacy of H. pylori eradication therapies and included both tetracycline and amoxicillin in one study arm were selected for this systematic review and meta-analysis. Statistical analysis was performed with Comprehensive Meta-Analysis Software (Version 2). Subgroup, meta-regression, and sensitivity analyses were also carried out. RESULTS: Thirty-three studies met the inclusion criteria. The pooled odds ratio (OR) was 0.90 (95%CI: 0.42-1.78) for quadruple therapy with amoxicillin and tetracycline vs other quadruple regimens, and total eradication rates were 78.1% by intention-to-treat (ITT) and 84.5% by per-protocol (PP) analyses in the experimental groups. The pooled eradication rates of 14-d quadruple regimens with a combination of amoxicillin and tetracycline were 82.3% by ITT and 89.0% by PP, and those of 10-d regimens were 84.6% by ITT and 93.7% by PP. The OR by ITT were 1.21 (95%CI: 0.64-2.28) for triple regimens with amoxicillin and tetracycline vs other regimens and 1.81 (95%CI: 1.37-2.41) for sequential treatment with amoxicillin and tetracycline vs other regimens, respectively. CONCLUSION: The effectiveness of regimens employing amoxicillin and tetracycline for H. pylori eradication may be not inferior to other regimens, but further study should be necessary.

Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A meta-analysis.

The aim of the present study was to determine whether probiotics could help to improve the eradication rates and reduce the side effects associated with anti-Helicobacter pylori treatment, and to investigate the optimal time and duration of probiotic administration during the treatment, thus providing clinical practice guidelines for eradication success worldwide. By searching Pubmed, Embase, the Cochrane Central Register of Controlled Trials and the Science Citation Index, all the randomized controlled trials (RCTs) comparing probiotics as adjuvant agents of anti-H. pylori standard triple-therapy regimens with placebo or no treatment were selected. Statistical analysis was performed with the Comprehensive Meta Analysis Software. Subgroup, meta-regression and sensitivity analyses were also carried out. Twenty-one RCTs involving a total of 3,814 participants met the inclusion criteria. The pooled eradication rates of the probiotic group were 80.3% (1,709/2,128) by intention-to-treat (ITT) and 83.8% (1,709/2,039) by pro-protocol analyses; the pooled relative risk (RR) by ITT for probiotic supplementation versus treatment without probiotics was 1.12 [95% confidence interval (CI), 1.06-1.19]. A reduced risk of overall H. pylori therapy-related adverse effects was also found with probiotic supplementation (RR, 0.60; 95% CI, 0.40-0.91). The subgroup analyses showed that probiotic supplementation prior and subsequent to the treatment regimen both improved eradication rates for H. pylori infection. Furthermore, probiotic treatment lasting >2 weeks and including Lactobacillus or multiple probiotic strains significantly enhanced the efficacy. In conclusion, supplementation with probiotics for H. pylori eradication may be effective in increasing eradication rates and decreasing therapy-related side effects. Probiotic administration prior or subsequent to therapy and for a duration of >2 weeks may increase the eradication efficacy.

Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of hybrid therapy compared to other pre-existing therapies and to new therapies. METHODS: Through a search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Conference Proceedings Citation Index, two independent reviewers systemically identified randomized, controlled trials that compared hybrid therapy to other pre-existing and new therapies. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). RESULTS: We identified 6 studies, 5 of which compared hybrid therapy and sequential therapy, and 3 of which compared hybrid therapy and concomitant therapy. Pooled estimates of the 5 randomized controlled trials (RCTs) revealed no significant differences between hybrid therapy and sequential therapy and no evidence of heterogeneity (I(2)  = 0%; p = .803), the pooled RRs were 1.02 (95% CI: 0.93-1.12) (intention-to-treat (ITT)), and 1.03 (95% CI: 0.94-1.13) (per protocol (PP)). Pooled estimates of the 3 RCTs showed no significant differences between hybrid therapy and concomitant therapy with no evidence of heterogeneity (I(2)  = 0%; p = .967), the pooled RRs were 0.99 (95% CI: 0.89-1.10) (ITT) and 0.99 (95% CI: 0.89-1.10) (PP). No significant differences in adverse events were noted among hybrid therapy, sequential therapy, and concomitant therapy ((RR: 1.13; 95% CI: 0.87-1.48; I(2)  = 13.2%; p = .327), (RR: 0.89; 95% CI: 0.73-1.08; I(2)  = 0%; p = .978) (ITT), respectively). After consideration of all treatment arms, the ITT eradication rates with hybrid therapy, concomitant therapy, and sequential therapy were 88.6, 86.3, and 84.7%, respectively. And the PP eradication rates were 92.1, 92.5, and 87.5%. No significant differences were observed between the groups in terms of compliance. CONCLUSIONS: All three of these therapies yielded good eradication rates. Hybrid therapy could be an alternative to sequential therapy and concomitant therapy, but additional RCTs are needed to confirm this finding.

Standard triple therapy for Helicobacter pylori infection in China: a meta-analysis.

AIM: To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China. METHODS: Literature searches were conducted in the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database, and the Chinese Biomedical Database. A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0. There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale. The Mantel-Haenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and a cumulative meta-analysis were also performed with CMA 2.0. Publication bias was evaluated using Egger's test, Begg's test or a funnel plot. RESULTS: A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824-0.904], but was not superior to quadruple therapy (RR = 1.073; 95%CI: 0.849-1.357) or other triple therapies (RR = 1.01; 95%CI: 0.936-1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95%CI: 0.99-1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting 14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy (RR = 1.222; 95%CI: 1.021-1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy (RR = 0.790; 95%CI: 0.718-0.868; RR = 0.917; 95%CI: 0.839-1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95%CI: 0.825-1.072; RR = 1.081; 95%CI: 0.848-1.378, respectively). Standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95%CI: 1.066-1.544). CONCLUSION: The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed.