The crucial question is if serologic testing is adequate to screen for the GC itself or if it gives only information about the prevalence and severity of preneoplastic conditions. In a recent study from Japan, different cut-off levels for both pepsinogen I and the pepsinogen I/II ratio have been applied [10]. This resulted in a sensitivity and specificity to detect the occurence of GC of 71.0% and 69.2% for pepsinogen I ≤ 59 ng/mL and the pepsinogen I/II ratio ≤ 3.9. Performance of this test was significantly improved when analysis of H. pylori

antibodies has been included [10]. Similar cut-offs, although higher for the pepsinogen I/II ratio (≤5.0), have been identified by an Iranian group Nutlin-3 for the detection of atrophy [11]. The data also support the role of pepsinogen II being an adequate marker for non-atrophic pangastritis, which is also considered as a risk condition for GC development. However, serum pepsinogen testing serves as high-risk indicator for GC development but not as a screening tool for the cancer itself [12]. A large cohort study in a population from Portugal followed up a total of 13,118 individuals for 5 years [13]. Endoscopy was performed in 274 individuals of the 446 with a positive pepsinogen test in the whole population (3.4%). Six GC have been detected resulting in one learn more per 2200 tests or one case per 74 positive tests. Three GC have been detected in the 96.6% with negative test results

[13]. In contrast, a recent study from Japan evaluated the value of this screening method in

a rural population with a high incidence Loperamide of GC [14]. Concluding from their data, the authors stated that in an aging population with high incidence of GC there is also a high prevalence of gastric mucosal atrophy and H. pylori infection. Therefore, the number of subjects identified for further endoscopic examinations might be too high in such populations [14]. We assessed the influence of specific biologic characteristics of gastric adenocarcinomas on the outcome of tests for serum pepsinogens [15]. The aim was the identification of modifiers that can be used to improve the diagnostic value of this method for GC screening. Neither Laurén type nor tumor localization or tumor stage had an influence on the serum values for pepsinogen I, II, and the pepsinogen I/II ratio. Only the degree of atrophy as well as the positive CagA status were independent factors influencing the outcome. This limitation of the pepsinogen method needs to be considered, but its role as a reliable screening method for preneoplastic conditions of the stomach in other populations is well established [16]. Thus, recent European guidelines and consensus recommend serologic screening for preneoplastic conditions like severe gastric atrophy and IM of the stomach [1, 17]. Although not yet generally accepted, a regular endoscopic follow-up for patients who present with atrophic gastritis is suggested at 3-year intervals [17].