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Prediction of gastric cancer development by serum pepsinogen test and Helicobacter pylori seropositivity in Eastern Asians: a systematic review and meta-analysis.

Terasawa T, Nishida H, Kato K, Miyashiro I, Yoshikawa T, Takaku R, Hamashima C - PLoS ONE (2014)

Bottom Line: The study validity was generally limited.Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests.Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.

View Article: PubMed Central - PubMed

Affiliation: Section of General Internal Medicine, Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, United States of America.

ABSTRACT

Background: To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H. Pylori antibodies, and a risk-prediction model based on these two tests. To investigate whether these tests accurately predict gastric cancer development, we conducted a systematic review and meta-analysis.

Methods: PubMed and other electronic databases were searched for cohort studies published in English or Japanese from January 1985 through December 2013. Six reviewers identified eligible studies, and at least two investigators extracted data on population and study-design characteristics, quality items, and outcomes of interest. Meta-analyses were performed on non-overlapping studies.

Results: Nine prospective cohorts from Eastern Asia reported in 12 publications, including 33,741 asymptomatic middle-aged participants of gastric cancer screening, were eligible. For discriminating between asymptomatic adults at high and low risk of gastric cancer, the pepsinogen test (summary hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.7-4.7; I2 = 0%) and H. pylori antibodies (summary HR, 3.2; 95% CI, 2.0-5.2; I2 = 0%) were statistically significant predictors as standalone tests. Although the risk-prediction model was in general moderately accurate in separating asymptomatic adults into four risk groups (summary c-statistic, 0.71; 95% CI: 0.68-0.73; I2 = 7%), calibration seemed to be poor. The study validity was generally limited.

Conclusions: The serum pepsinogen test, H. pylori antibodies, and the four-risk-group model for predicting gastric cancer development seem to have the potential to stratify middle-aged presumptively healthy adults. Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests. Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.

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Related in: MedlinePlus

Meta-analysis of hazard ratio for four-risk-group prediction model to predict gastric cancer development.The red and blue diamonds depict a summary hazard ratio with extending 95% confidence interval (CI) or 95% credible interval (CrI), estimated from direct meta-analysis or multivariate meta-analysis, respectively. Each square and horizontal line indicates the hazard ratio and corresponding 95% CI, respectively, for each study. NE = not estimable.
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pone-0109783-g002: Meta-analysis of hazard ratio for four-risk-group prediction model to predict gastric cancer development.The red and blue diamonds depict a summary hazard ratio with extending 95% confidence interval (CI) or 95% credible interval (CrI), estimated from direct meta-analysis or multivariate meta-analysis, respectively. Each square and horizontal line indicates the hazard ratio and corresponding 95% CI, respectively, for each study. NE = not estimable.

Mentions: Four studies (a total of 16,943 subjects) that reported HRs [27], [35], [37], [39] were included in the meta-analysis of predictive ability. For predicting gastric cancer development, the 95% CrI of the summary HRs for 5 out of 6 possible contrasts did not include 1, suggesting that in the pairwise contrasts, other than the comparison between Group C and Group D, there was more than 95% probability that one of the two comparators had a higher risk of gastric cancer than the other (Figure 2). Specifically, multivariate meta-analyses suggested that Group A had a lower risk than Group B and Group C, and that compared with Group C and Group D, Group B had a lower risk. There was no significant difference in the risk of gastric cancer between Group C and Group D (summary HR, 1.49; 95% CrI: 0.84–2.65). The ranking analysis showed that Groups A and B, respectively, had the lowest and second-lowest risk of gastric cancer development (posterior cumulative probability to rank the lowest and the second-lowest risk groups was both >99%), whereas Groups C and D could be the highest or second-highest risk groups (92% and 8%, respectively, for being ranked as the second-highest group, and 8% and 92%, respectively, for the highest risk group) (Figure 3). In sensitivity analyses using alternative models, and subgroup analyses of only studies that adopted the recommended cutoff values for the pepsinogen test, the summary HR estimates as well as the results of the ranking analysis were similar to those of the main analysis (Figure S4).


Prediction of gastric cancer development by serum pepsinogen test and Helicobacter pylori seropositivity in Eastern Asians: a systematic review and meta-analysis.

Terasawa T, Nishida H, Kato K, Miyashiro I, Yoshikawa T, Takaku R, Hamashima C - PLoS ONE (2014)

Meta-analysis of hazard ratio for four-risk-group prediction model to predict gastric cancer development.The red and blue diamonds depict a summary hazard ratio with extending 95% confidence interval (CI) or 95% credible interval (CrI), estimated from direct meta-analysis or multivariate meta-analysis, respectively. Each square and horizontal line indicates the hazard ratio and corresponding 95% CI, respectively, for each study. NE = not estimable.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196955&req=5

pone-0109783-g002: Meta-analysis of hazard ratio for four-risk-group prediction model to predict gastric cancer development.The red and blue diamonds depict a summary hazard ratio with extending 95% confidence interval (CI) or 95% credible interval (CrI), estimated from direct meta-analysis or multivariate meta-analysis, respectively. Each square and horizontal line indicates the hazard ratio and corresponding 95% CI, respectively, for each study. NE = not estimable.
Mentions: Four studies (a total of 16,943 subjects) that reported HRs [27], [35], [37], [39] were included in the meta-analysis of predictive ability. For predicting gastric cancer development, the 95% CrI of the summary HRs for 5 out of 6 possible contrasts did not include 1, suggesting that in the pairwise contrasts, other than the comparison between Group C and Group D, there was more than 95% probability that one of the two comparators had a higher risk of gastric cancer than the other (Figure 2). Specifically, multivariate meta-analyses suggested that Group A had a lower risk than Group B and Group C, and that compared with Group C and Group D, Group B had a lower risk. There was no significant difference in the risk of gastric cancer between Group C and Group D (summary HR, 1.49; 95% CrI: 0.84–2.65). The ranking analysis showed that Groups A and B, respectively, had the lowest and second-lowest risk of gastric cancer development (posterior cumulative probability to rank the lowest and the second-lowest risk groups was both >99%), whereas Groups C and D could be the highest or second-highest risk groups (92% and 8%, respectively, for being ranked as the second-highest group, and 8% and 92%, respectively, for the highest risk group) (Figure 3). In sensitivity analyses using alternative models, and subgroup analyses of only studies that adopted the recommended cutoff values for the pepsinogen test, the summary HR estimates as well as the results of the ranking analysis were similar to those of the main analysis (Figure S4).

Bottom Line: The study validity was generally limited.Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests.Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.

View Article: PubMed Central - PubMed

Affiliation: Section of General Internal Medicine, Department of Emergency and General Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, United States of America.

ABSTRACT

Background: To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H. Pylori antibodies, and a risk-prediction model based on these two tests. To investigate whether these tests accurately predict gastric cancer development, we conducted a systematic review and meta-analysis.

Methods: PubMed and other electronic databases were searched for cohort studies published in English or Japanese from January 1985 through December 2013. Six reviewers identified eligible studies, and at least two investigators extracted data on population and study-design characteristics, quality items, and outcomes of interest. Meta-analyses were performed on non-overlapping studies.

Results: Nine prospective cohorts from Eastern Asia reported in 12 publications, including 33,741 asymptomatic middle-aged participants of gastric cancer screening, were eligible. For discriminating between asymptomatic adults at high and low risk of gastric cancer, the pepsinogen test (summary hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.7-4.7; I2 = 0%) and H. pylori antibodies (summary HR, 3.2; 95% CI, 2.0-5.2; I2 = 0%) were statistically significant predictors as standalone tests. Although the risk-prediction model was in general moderately accurate in separating asymptomatic adults into four risk groups (summary c-statistic, 0.71; 95% CI: 0.68-0.73; I2 = 7%), calibration seemed to be poor. The study validity was generally limited.

Conclusions: The serum pepsinogen test, H. pylori antibodies, and the four-risk-group model for predicting gastric cancer development seem to have the potential to stratify middle-aged presumptively healthy adults. Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests. Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.

Show MeSH
Related in: MedlinePlus