Abstract
The two major risk factors of Gastric Cancer (GC) are Helicobacter pylori (HP) infection and Atrophic Gastritis (AG) It is currently possible to diagnose HP-infection and AG by using serological testing with a panel of biomarkers (GastroPanel®, Biohit Oyj, Finland): Pepsinogen I (PGI), Pepsinogen II (PGII), Gastrin-17 (G-17) and HP-antibodies. In this review, an introduction is made to the GastroPanel® test as the first non-invasive diagnostic tool for: i) Dyspeptic symptoms, ii) Screening of asymptomatic subjects for the risks of GC, iii) A comprehensive diagnosis of HP-infection. GastroPanel® test is based on stomach physiology both in health and disease. Accordingly, pepsinogen levels and their ratio is decreased in corpus atrophy (AGC), accompanied by elevated G-17b (basal) G-17b level also sensitively responds to gastric acid output, being low with high acid output and high when the stomach is acid-free (due to PPI-treatment or AGC) In Antrum Atrophy (AGA), G-17b is low and, importantly, does not respond to protein stimulation (G-17s), because the G-cells are disappeared. The results of GastroPanel® test are interpreted by a special software (GastroSoft®) identifying 8 diagnostic marker profiles. Of those, four (profiles 1, 2, 3, and 8) represent purely functional disorders (of acid output), while three others specify structural abnormalities (profiles 5, 6, and 7 for AGC, AGA, and AGpan, respectively) the remaining (profile 4) is typical to HPinfection, with three possible outcomes: a) Active HPinfection, b) Successful eradication, and c) Failed eradication. GastroPanel® test has been validated in both clinical and screening settings. The entire published literature was subjected to systematic review and meta-analysis, including 27 eligible studies that comprise almost 9.000 patients. GastroPanel® was shown to perform better in diagnosis of AGC than AGA, with 70.2% vs. 51.6% pooled SE, and 93.9% vs. 84.1% pooled SP, respectively. This first meta-analysis corroborates the recently launched statement of 16 international experts, advocating the use of this non-invasive serological test as the first-line diagnostic tool for dyspeptic symptoms and for screening of the risks of GC among asymptomatic subjects. The two most commonly used HP tests (UBT and SAT) are prone to false-negative results in conditions with decreased bacterial loads in the stomach: 1) Use of PPI medication; 2) Use of antibiotics; 3) Bleeding peptic ulcer; 4) AG; 5) GC; 6) MALT lymphoma, and 7) Partial gastrostomy. False-positive results do occur in cases where urease-producing bacterial species are colonizing an acid-free stomach (AG or PPI users) it is mandatory that these serious limitations in the use of UBT and SAT are properly acknowledged while these two HP tests are being promoted. Given that this bacteria is the single most important risk factor of GC, it is time to move a step forward also in the diagnosis of HP-infections, and start using the test (GastroPanel®) that is: i) Free from the shortcoming of the conventional HP tests, and ii) Provides an added value by detecting also the other key risk factor of GC, i.e., AG with all its potentially serious clinical sequels.
Highlights
Gastric Cancer (GC) continues to be one of the most common cancers and causes of global cancer mortality; nearly one million new cases and 736.000 annual deaths worldwide© Copyright iMedPub | This article is available from: http://biomarkers.imedpub.com/archive.php [1]
For G-17 assessment, there are two options; G-17 basal (G-17b) values and G-17 stimulated (G-17s) values, the latter being important in distinguishing between functional disturbance of the antrum (G-17s normal) and Atrophic gastritis in the antrum (AGA) (G-17s does not increase upon protein stimulation) [31,32]
N=normal; L=low; H=high; *Test pump inhibitor (PPI) medication for two weeks, G17b should normalize; **Stop PPI medication, G-17b should normalize within two weeks; ND, no need for testing;^PGI, Pepsinogen II (PGII) and G-17 can be elevated due to mucosal inflammation; ^^Helicobacter pylori (HP) antibodies can disappear in mucosal atrophy with protracted clinical course; @Pepsinogen I cut-off value 30 μg/l is consonant with moderate/severe Atrophic Gastritis (AG); †HP antibody levels can remain elevated for months after successful eradication of HP
Summary
Gastric Cancer (GC) continues to be one of the most common cancers and causes of global cancer mortality; nearly one million new cases and 736.000 annual deaths worldwide. As the only abnormal marker, HPAb implicates an [16,17,18] [HP-associated superficial gastritis (non-AG)], while associated with abnormalities in the other three markers, elevated HPAb levels confirm the diagnosis of HP-associated AG (AGA or AGC) [37,38] This biomarker is included in GastroPanel® to identify patients who have mucosal atrophy in the gastric corpus (AGC), for which the plasma PGI is a highly specific biomarker [36,38,39,40,41,42]. Both the USS and the GastroSoft® use five diagnostic categories to classify the biopsies and GastroPanel® results, respectively These include: 1) Normal mucosa, 2) Superficial (HP) gastritis, 3) AGA, 4) AGC, and 5) AG in both antrum and corpus (AGpan) [14,69].
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