Background & Aims Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H ...pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. Methods We searched PubMed, Cochrane Library, and ClinicalTrials.gov , reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up. Results After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44−0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication ( P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer ( P = .018, in comparison with the linear model). The benefit also modestly increased with age ( P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49−0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35−0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. Conclusions In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.
Background and Aim
The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal.
Methods
Mass eradication of H. pylori began in 2004 in a ...high‐risk population. After eradication, a screening program involving first‐stage serological tests (pepsinogen‐I, pepsinogen‐II, H. pylori immunoglobin G, and gastrin‐17) and second‐stage endoscopic examination was launched in 2015–2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to “rule in” and “rule out” the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA‐124a‐3 in the stomach were measured to indicate genetic damage.
Results
Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin‐17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin‐17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non‐atrophic‐appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 95% confidence interval: 2.92–5.77; negative likelihood ratio: 0.14 0.10–0.19). Gastrin‐17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 1.21–3.42 and 0.57 0.34–0.95). DNA methylation levels in the post‐eradication mucosa were more discriminative for predicting index lesions (3.89 2.32–6.54 and 0.25 0.15–0.42).
Conclusions
After eradication, pepsinogen false‐negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Bismuth oxychloride produced by interaction of bismuth compounds with gastric acid is believed to damage Helicobacter pylori. The effect of bismuth salts on H. pylori in the presence of ...strong acid suppression is unknown. This randomized trial aimed to determine effects of bismuth subcitrate on H. pylori with and without acid suppression.
Methods
H. pylori ‐positive participants were allocated (1:1:1) to receive (a) no treatment (control), (b) colloidal bismuth subcitrate (CBS, 125 mg/tab), or (c) CBS plus high‐dose proton‐pump inhibitor (PPI), esomeprazole 40 mg q.i.d. for 3 days. In the treatment groups, CBS was given: 1 dose, 1 hour before endoscopy, 1 dose, 4 hours before endoscopy, or q.i.d. 24 hours before endoscopy. The study end‐points were evaluated using transmission electron microscopy to observe the morphological changes of H. pylori in antral and corpus biopsies.
Results
Twenty‐seven H. pylori carriers were enrolled in this trial with qualitative end‐points. In the no treatment group, active budding and replication of H. pylori were observed. In the CBS group, cellular swelling, vacuolization, structural degradation, and cell wall eruption of H. pylori were observed, with no apparent association with when the CBS was given. Among those receiving high‐dose PPI‐plus CBS or CBS only, there were no differences in number of H. pylori present or severity of bacterial damage whether CBS was given 1, 4, or 24 hours before endoscopy.
Conclusions
Based on direct morphological evaluation, the toxic effect of CBS treatment on H. pylori was demonstrated independent of acid suppression with PPI.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background and Aim
The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in ...Indigenous communities.
Methods
First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006–2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy.
Results
Gastric cancer incidence (24.4 vs 12.3 per 100 000 person‐years) and mortality rates (15.8 vs 6.8 per 100 000 person‐years) were higher in Indigenous than in non‐Indigenous, with 2.19‐fold (95% confidence interval CI: 2.06–2.33) and 2.47‐fold (2.28–2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non‐Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89‐fold (95% CI: 1.34–2.66) and 1.73‐fold (95% CI: 1.24–2.41) increased risk for H. pylori infection, respectively, as compared with non‐Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle‐aged, and older adults. Program eradication rates using clarithromycin‐based triple therapy were suboptimal (73.7%, 95% CI: 70.0–77.4%); the habits of smoking (1.70‐fold, 95% CI: 1.01–2.39) and betel nut chewing (1.54‐fold, 95% CI: 0.93–2.16) were associated with the higher risk of treatment failure.
Conclusion
Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non‐Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be ...prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
An idiopathic peptic ulcer is defined as an ulcer with unknown cause or an ulcer that appears to arise spontaneously. The first step in treatment is to exclude common possible causes, including ...Helicobacter pylori infection, infection with other pathogens, ulcerogenic drugs, and uncommon diseases with upper gastrointestinal manifestations. When all known causes are excluded, a diagnosis of idiopathic peptic ulcer can be made. A patient whose peptic ulcer is idiopathic may have a higher risk for complicated ulcer disease, a poorer response to gastric acid suppressants, and a higher recurrence rate after treatment. Risk factors associated with this disease may include genetic predisposition, older age, chronic mesenteric ischemia, smoking, concomitant diseases, a higher American Society of Anesthesiologists score, and higher stress. Therefore, the diagnosis and management of emerging disease should systematically explore all known causes and treat underlying disease, while including regular endoscopic surveillance to confirm ulcer healing and the use of proton-pump inhibitors on a case-by-case basis.
Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear.
A retrospective cohort study in a single ...referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates.
A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (<24 h after onset or continued bleeding, n = 64), 24–72 h (n = 28), 3–7 days (n = 41), and >7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P < 0.0001). Diagnostic yield rates were different between emergency and 24–72 h groups (P < 0.0001), and between 3 and 7 days and >7 days groups (P < 0.05), but not between 24 and 72 h and 3–7 days groups (P = 0.97). In multivariate regression analysis, emergency, ≤ 3 days, and ≤7 days SBEs had greater yield rates than SBEs at later timings.
The likelihood of diagnostic yield was highest when SBE was performed during continued bleeding or within 24 h of onset, and gradually declined as waiting time increased. We therefore recommend that SBE should be performed as soon as possible, preferably no later than seven days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa's gastric cancer model.
First, we estimated the state-to-state transition ...rates following Correa's five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores.
The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%.
We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa's cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Serum pepsinogen (PG) is recommended as a screening test for premalignant gastric lesions. However, real-world evidence demonstrating its applicability and equivalence between different test brands ...is limited.
Mass screening began in 2018 in a high-risk Taiwanese population after eradication of Helicobacter pylori, with the first stage of two PG tests (GastroPanel
, Helsinki, Finland and LZ-Test
, Tokyo, Japan) and the second stage of endoscopy. A positive test was defined as PG-I < 30 ng/mL or PG-I/II ratio < 3 for GastroPanel
and PG-I ≤ 70 ng/mL and PG-I/II ratio ≤ 3 for LZ-Test
. Index lesions included atrophic gastritis and intestinal metaplasia. Test performance was evaluated based on the participation rate, positivity rate, referral rate, positive predictive value (PPV), and the detection rate.
Among 7616 eligible participants, 5117 (67.2%) received PG tests and 284 (5.6%) tested positive. Of those who tested positive, 105 (37.0%) underwent endoscopy. Overall PPVs for atrophic gastritis and intestinal metaplasia were 12.4% and 18.9%, respectively, with detection rates of 2.5 and 3.9 per 1000, respectively. Correlations of numerical measures between tests were high and the agreements of test results were substantial. The PPVs (16.3% vs. 16.3% and 23.8% vs. 21.3%, P = 1.00 and 0.71, respectively), detection rates (2.5 vs. 2.5 and 3.7 vs. 3.3 per 1000, P = 1.00 and 0.27, respectively), and the stage distributions of gastritis were all comparable, which were confirmed by multiple regression analyses.
PG testing is effective for mass screening after eradication of H. pylori. Tests from different manufacturers, even using different analytical methods and cutoff criteria, can perform equivalently.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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