Special Issue "Advances in the Detection and Screening of Gastric Cancer"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 24253

Special Issue Editor

Institute of Clinical and Preventive Medicine, Faculty of Medicine, University of Latvia, Riga, Latvia
Interests: cancer prevention and early detection; gastric cancer; precancerous lesions; H. pylori; microbiota; new technologies; volatile marker testing; breath analysis

Special Issue Information

Dear Colleagues,

The absolute number of new gastric cancer cases is expected to grow to 1.77 million in 2040 despite the decreasing overall incidence, therefore demonstrating the importance of this healthcare problem. The burden of the disease could be decreased either by spotting cancer at an early, ideally precancerous stage or by timely eradication of H. pylori infection, the major cause of gastric cancer. Screening for cancer via endoscopy or photophluoroscopy is included in nationwide programs in Japan and Korea, and a number of other countries are in the process of implementing preventive programs. This Special Issue is planned to summarize recent developments in the field.

Furthermore, non-invasive testing for gastric cancer or precancerous lesions has been at the focus of researchers for decades. In addition to traditional biomarkers, such as pepsinogens and gastrin-17, as well as markers for autoimmunity, the role of potential new approaches, including volatile organic compounds in breath, has shown promise. We intend to also address these issues in this issue by presenting the status of the ongoing studies.

Finally, large data and artificial intelligence are expected to change the mentality in medicine, including also in gastric-cancer-related aspects. We intend to identify the areas where data collaborations could facilitate efforts aimed at gastric cancer mortality reduction.

Therefore, with the current issue, we aim to present the current status in various aspects of gastric cancer screening and prevention and provide an update on screening programs, summary of the currently ongoing major studies globally, as well as give an opportunity to present original research results from groups active in the field.

Prof. Dr. Mārcis Leja
Guest Editor

Manuscript Submission Information

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Keywords

  • Gastric cancer
  • Precancerous lesions
  • Autoimmune gastritis
  • Screening
  • Early detection
  • Helicobacter pylori
  • Biomarkers
  • Pepsinogens
  • ABC method
  • Volatile markers
  • Microbiome
  • Large data
  • Artificial intelligence

Published Papers (20 papers)

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Article
Minimally Invasive and Fast Diagnosis of Gastric Cancer Based on Maspin Levels in Different Biological Samples
Diagnostics 2023, 13(11), 1857; https://doi.org/10.3390/diagnostics13111857 - 26 May 2023
Viewed by 210
Abstract
(1) Background: Human SERPINB5, commonly known as maspin, has diverse functions as a tumor suppressor. Maspin has a novel role in cell cycle control, and common variants were discovered to be associated with gastric cancer (GC). Maspin was proven to also affect the [...] Read more.
(1) Background: Human SERPINB5, commonly known as maspin, has diverse functions as a tumor suppressor. Maspin has a novel role in cell cycle control, and common variants were discovered to be associated with gastric cancer (GC). Maspin was proven to also affect the EMT and angiogenesis of gastric cancer cells via the ITGB1/FAK pathway. Information about the maspin concentrations correlated with different pathological features of the patients may facilitate the fast diagnosis and personalized treatment of patients. The novelty of this study is given by the correlations established for the maspin levels in different biological features and clinicopathological features. These correlations can be extremely useful for surgeons and oncologists. (2) Patients and methods: Patients with clinical and pathological features, given the small number of samples available for this study, were selected from the database of the project GRAPHSENSGASTROINTES, and used in accordance with the Ethics Committee approval nr. 32,647/2018 awarded by the County Emergency Hospital from Targu-Mures. Stochastic microsensors were used as new screening tools for the determination of the concentration of maspin in four types of samples: tumoral tissues, blood, saliva and urine. (3) Results: The results obtained using the stochastic sensors were correlated with those tabulated in the clinical and pathological database. A series of assumptions regarding the values and practice important features for surgeons and pathologists were made. (4) Conclusions: This study provided a few assumptions regarding the correlations between the values of maspin levels in the analyzed samples and the clinical and pathological features. These results may be useful as preoperative investigations in order to help surgeons localize, approximate and choose the best treatment. These correlations may facilitate minim invasive and fast diagnosis of gastric cancer based on reliable detection of maspin concentration in biological samples (tumoral tissues, blood, saliva and urine). Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Breath Volatile Organic Compounds in Surveillance of Gastric Cancer Patients following Radical Surgical Management
Diagnostics 2023, 13(10), 1670; https://doi.org/10.3390/diagnostics13101670 - 09 May 2023
Viewed by 545
Abstract
As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, [...] Read more.
As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, we aimed to prove the yield of the markers in surveillance, i.e., following curative surgical management. Patients were sampled in regular intervals before and within 3 years following curative surgery for GC; gas chromatography-mass spectrometry (GC-MS) and nanosensor technologies were used for the VOC assessment. GC-MS measurements revealed a single VOC (14b-Pregnane) that significantly decreased at 12 months, and three VOCs (Isochiapin B, Dotriacontane, Threitol, 2-O-octyl-) that decreased at 18 months following surgery. The nanomaterial-based sensors S9 and S14 revealed changes in the breath VOC content 9 months after surgery. Our study results confirm the cancer origin of the particular VOCs, as well as suggest the value of breath VOC testing for cancer patient surveillance, either during the treatment phase or thereafter, for potential relapse. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study
Diagnostics 2023, 13(9), 1599; https://doi.org/10.3390/diagnostics13091599 - 30 Apr 2023
Viewed by 464
Abstract
Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning [...] Read more.
Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31–0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
The Association of Circulating L-Carnitine, γ-Butyrobetaine and Trimethylamine N-Oxide Levels with Gastric Cancer
Diagnostics 2023, 13(7), 1341; https://doi.org/10.3390/diagnostics13071341 - 04 Apr 2023
Viewed by 614
Abstract
Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, γ-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. There is evidence suggesting that higher levels of TMAO and its precursors in blood [...] Read more.
Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, γ-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. There is evidence suggesting that higher levels of TMAO and its precursors in blood can be indicative of either a higher risk of malignancy or indeed its presence; however, GC has not been studied in this regard until now. Our study included 83 controls without high-risk stomach lesions and 105 GC cases. Blood serum L-carnitine, GBB and TMAO levels were measured by ultra-high-performance liquid chromatography–mass spectrometry (UPLC/MS/MS). Although there were no significant differences between female control and GC groups, we found a significant difference in circulating levels of metabolites between the male control group and the male GC group, with median levels of L-carnitine reaching 30.22 (25.78–37.57) nmol/mL vs. 37.38 (32.73–42.61) nmol/mL (p < 0.001), GBB–0.79 (0.73–0.97) nmol/mL vs. 0.97 (0.78–1.16) nmol/mL (p < 0.05) and TMAO–2.49 (2.00–2.97) nmol/mL vs. 3.12 (2.08–5.83) nmol/mL (p < 0.05). Thus, our study demonstrated the association between higher blood levels of L-carnitine, GBB, TMAO and GC in males, but not in females. Furthermore, correlations of any two investigated metabolites were stronger in the GC groups of both genders in comparison to the control groups. Our findings reveal the potential role of L-carnitine, GBB and TMAO in GC and suggest metabolic differences between genders. In addition, the logistic regression analysis revealed that the only significant factor in terms of predicting whether the patient belonged to the control or to the GC group was the blood level of L-carnitine in males only. Hence, carnitine might be important as a biomarker or a risk factor for GC, especially in males. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Performing the ABC Method Twice for Gastric Cancer Risk Stratification: A Retrospective Study Based on Data from a Large-Scale Screening Facility
Diagnostics 2023, 13(7), 1284; https://doi.org/10.3390/diagnostics13071284 - 28 Mar 2023
Viewed by 617
Abstract
The ABC method is a classification method used for stratifying the risk of gastric cancer. However, whether the ABC method should be performed only once or multiple times throughout an individual’s lifetime remains unclear. Therefore, this study aimed to analyze whether performing ABC [...] Read more.
The ABC method is a classification method used for stratifying the risk of gastric cancer. However, whether the ABC method should be performed only once or multiple times throughout an individual’s lifetime remains unclear. Therefore, this study aimed to analyze whether performing ABC screening twice in a lifetime is useful. We retrospectively analyzed the data of individuals who participated in health checkups in 2010 and 2015. We collected data on patient characteristics, pepsinogen levels, anti-Helicobacter pylori antibody titers, and the presence of gastric cancer. Overall, 7129 participants without a history of H. pylori eradication were included in this study. The participants’ average age in 2010 was 48.4 ± 8.3 years, and 58.1% were male. In addition, 11 and 20 cases of new H. pylori infection (0.15%) and spontaneous eradication (0.28%), respectively, were recorded. No significant difference was found in the incidence of gastric cancer between participants who underwent the ABC method once and those who underwent it twice (Group A: 0.16% vs. 0.16%; Group B: 0.47% vs. 0.39%; and Group C + D: 1.97% vs. 1.82%). Therefore, performing the ABC method twice, 5 years apart, does not significantly improve gastric cancer risk stratification. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Identification of Key Volatile Organic Compounds Released by Gastric Tissues as Potential Non-Invasive Biomarkers for Gastric Cancer
Diagnostics 2023, 13(3), 335; https://doi.org/10.3390/diagnostics13030335 - 17 Jan 2023
Cited by 1 | Viewed by 915
Abstract
Background: Volatilomics is a powerful tool capable of providing novel biomarkers for medical diagnosis and therapy monitoring. The objective of this study is to identify potential volatile biomarkers of gastric cancer. Methods: The volatilomic signatures of gastric tissues obtained from two distinct populations [...] Read more.
Background: Volatilomics is a powerful tool capable of providing novel biomarkers for medical diagnosis and therapy monitoring. The objective of this study is to identify potential volatile biomarkers of gastric cancer. Methods: The volatilomic signatures of gastric tissues obtained from two distinct populations were investigated using gas chromatography with mass spectrometric detection. Results: Amongst the volatiles emitted, nineteen showed differences in their headspace concentrations above the normal and cancer tissues in at least one population of patients. Headspace levels of seven compounds (hexanal, nonanal, cyclohexanone, 2-nonanone, pyrrole, pyridine, and phenol) were significantly higher above the cancer tissue, whereas eleven volatiles (ethyl acetate, acetoin, 2,3-butanedione, 3-methyl-1-butanol, 2-pentanone, γ-butyrolactone, DL-limonene, benzaldehyde, 2-methyl-1-propanol, benzonitrile, and 3-methyl-butanal) were higher above the non-cancerous tissue. One compound, isoprene, exhibited contradictory alterations in both cohorts. Five compounds, pyridine, ethyl acetate, acetoin, 2,3-butanedione, and 3-methyl-1-butanol, showed consistent cancer-related changes in both populations. Conclusions: Pyridine is found to be the most promising biomarker candidate for detecting gastric cancer. The difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes, or pathways. The results of this study confirm that the chemical fingerprint formed by volatiles in gastric tissue is altered by gastric cancer. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Establishment and Systematic Evaluation of Gastric Cancer Classification Model Based on Pyroptosis
Diagnostics 2022, 12(11), 2858; https://doi.org/10.3390/diagnostics12112858 - 18 Nov 2022
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Abstract
Background: Gastric cancer (GC) is considered the fifth most prevalent type of cancer and the third leading cause of cancer deaths worldwide. This in-depth investigation was performed to generate fresh concepts for the clinical classification, diagnosis, and prognostic evaluation of GC. Methods: The [...] Read more.
Background: Gastric cancer (GC) is considered the fifth most prevalent type of cancer and the third leading cause of cancer deaths worldwide. This in-depth investigation was performed to generate fresh concepts for the clinical classification, diagnosis, and prognostic evaluation of GC. Methods: The data were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Unsupervised cluster analysis was used to divide up the GC patients using pyroptosis-related differentially expressed genes (DEGs), which were discovered to be significantly linked with GC prognosis. The therapeutic importance of pyroptosis in GC patients was discovered using PCA analysis of genes associated with pyroptosis. The models were then carefully scrutinized. Results: Three hub genes, ELANE, IL6, and TIRAP, exhibit significant predictive importance among the 15 pyroptosis-related genes. Unsupervised clustering analysis revealed that the DEGs were enriched in the pathway of cytokine–cytokine receptor interactions, and Clusters 1 and 2 had statistically distinct prognoses. PCA analysis revealed significant differences in the area under the curve, immunological checkpoints, immunogenic cell death, and prognostic value between the high- and low-risk groups. Conclusions: These two GC classification models, based on pyroptosis, have significant clinical value for patients with GC. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
The Diagnostic Value of Anti-Parietal Cell and Intrinsic Factor Antibodies, Pepsinogens, and Gastrin-17 in Corpus-Restricted Atrophic Gastritis
Diagnostics 2022, 12(11), 2784; https://doi.org/10.3390/diagnostics12112784 - 14 Nov 2022
Viewed by 1048
Abstract
We aimed to determine the diagnostic value of anti-parietal cell antibodies (anti-PCA), anti-intrinsic factor antibodies (anti-IFA), pepsinogen ratio (PGI/II), and gastrin-17 (G-17) in corpus-restricted atrophic gastritis (CRAG) detected by ELISA (Inova, Biohit). Our study compared 29 CRAG cases against 58 age- and sex-matched [...] Read more.
We aimed to determine the diagnostic value of anti-parietal cell antibodies (anti-PCA), anti-intrinsic factor antibodies (anti-IFA), pepsinogen ratio (PGI/II), and gastrin-17 (G-17) in corpus-restricted atrophic gastritis (CRAG) detected by ELISA (Inova, Biohit). Our study compared 29 CRAG cases against 58 age- and sex-matched controls with mild or no atrophy. Anti-PCA and anti-IFA positive cutoff values were ≥25 units for both. PGI/II value <3 was considered characteristic for atrophy; positive cutoff values for G-17 and anti-H. pylori IgG were >5 pg/L and >30 EIU. Anti-PCA was positive in 65.5% For CRAG cases and 13.8% of the controls (p < 0.0001), anti-IFA was positive in 13.8% and 0% (p = 0.01), respectively. Decreased pepsinogen levels were present in 79.3% of CRAG cases and 10.3% of the controls (p < 0.0001). PGI/II ratio was the best single biomarker, with sensitivity = 79%, specificity = 90%, and AUC 0.90. The combined use of PGI/II and anti-PCA resulted in AUC 0.93 for detecting CRAG. Our study suggests that the best combination of non-invasive biomarkers for detecting CRAG is PGI/II with anti-PCA. The addition of G-17 and anti-IFA is of little utility in clinical application. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment—Results from the GISTAR Pilot Study
Diagnostics 2022, 12(7), 1746; https://doi.org/10.3390/diagnostics12071746 - 19 Jul 2022
Cited by 2 | Viewed by 1251
Abstract
Introduction––Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods––Within the [...] Read more.
Introduction––Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods––Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results––Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4–31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33–45% while specificity decreased (range: 61.1–62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions––Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer
Diagnostics 2022, 12(6), 1502; https://doi.org/10.3390/diagnostics12061502 - 20 Jun 2022
Viewed by 1053
Abstract
Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as [...] Read more.
Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial–mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Dynamics of Oxidative Stress in Helicobacter pylori-Positive Patients with Atrophic Body Gastritis and Various Stages of Gastric Cancer
Diagnostics 2022, 12(5), 1203; https://doi.org/10.3390/diagnostics12051203 - 11 May 2022
Cited by 1 | Viewed by 1094
Abstract
Gastric cancer is a global health problem. The pathogenesis of this disease remains unclear. This study included 198 H. pylori (+) men aged 45 to 60 years old. Group A included 63 practically healthy men, group B included 45 men with severe atrophic [...] Read more.
Gastric cancer is a global health problem. The pathogenesis of this disease remains unclear. This study included 198 H. pylori (+) men aged 45 to 60 years old. Group A included 63 practically healthy men, group B included 45 men with severe atrophic body gastritis, group C included 37 men with epithelial gastric cancer stages I–II according to TNM, and group D included 54 men with epithelial gastric cancer stages III–IV according to the TNM scale. The content of malondialdehyde (MDA), diene conjugates (DCs), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPO) was detected using an enzyme immunoassay (ELISA) or spectrophotometric methods in the blood plasma. The concentrations of MDA and DC were increased in the patients of group B compared with group A, and in patients of groups C and D compared with groups A and B. The ratio of MDA/SOD and MDA/CAT was decreased in the patients in group D compared with the patients in group C, and was significantly higher compared with group A. The ratios of MDA/GPO and MDA/GST increased linearly and were at a maximum in groups C and D. Our work determined that indicators of oxidative stress may be the biochemical substrate, which brings together the various stages of the Correa cascade, and may explain disease progression. The dynamics of changes in the content of SOD and CAT in the plasma in patients with gastric cancer may be a target of future investigations. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Factors Associated with False Negative Results in Serum Pepsinogen Testing for Precancerous Gastric Lesions in a European Population in the GISTAR Study
Diagnostics 2022, 12(5), 1166; https://doi.org/10.3390/diagnostics12051166 - 07 May 2022
Viewed by 792
Abstract
The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to [...] Read more.
The accuracy of plasma pepsinogen (Pg) as a marker for precancerous gastric lesions (PGL) has shown variable results. We aimed to identify factors associated with false negative (FN) cases in Pg testing and to adjust cut-off values for these factors in order to improve Pg yield. Plasma Pg was measured and upper endoscopy with biopsy was performed within the “Multicentric randomized study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study”. A multivariable logistic model was built for FN and multiple factors. Values of Pg were compared and sensitivity and specificity were calculated using pre-existing Pg cut-offs for factors showing strong associations with FN. New cut-offs were calculated for factors that showed substantially lower sensitivity. Of 1210 participants, 364 (30.1%) had histologically confirmed PGL, of which 160 (44.0%) were FN. Current smokers, men, and H. pylori positives were more likely FN. Smoking in H. pylori negatives was associated with a higher Pg I/II ratio and substantially lower sensitivity of Pg testing than in other groups. Adjusting Pg cut-offs for current smokers by H. pylori presence improved sensitivity for detecting PGL in this group. Our study suggests that adjusting Pg cut-offs for current smokers by H. pylori status could improve Pg test performance. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Impact of Selected Serum Factors on Metastatic Potential of Gastric Cancer Cells
Diagnostics 2022, 12(3), 700; https://doi.org/10.3390/diagnostics12030700 - 12 Mar 2022
Cited by 3 | Viewed by 1525
Abstract
(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. [...] Read more.
(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. (2) Methods: 21 gastric cancer patients and 19 healthy controls were included in the study. SDF-1, HGF and VEGF levels were evaluated in sera by ELISA. Patients and control sera were used to stimulate CRL-1739 GC cell line, and chemotaxis, adhesion and proliferation potential were assessed. (3) Results: Concentrations of SDF-1, HGF and VEGF were significantly higher in patients than in controls. Chemotaxis and adhesion assays revealed a significant response of GC cells to patients’ serum. Furthermore, significant relationships were seen between chemotactic/adhesion response and tumor stage. Serum from intestinal early GC patients produced significantly stronger chemotactic response when compared to patients with metastatic spread. In turn, serum from patients with distal metastases significantly increased the adhesion of GC cells when compared to sera from the patients with no distal metastases. We also observed that HGF strongly stimulated the proliferation of CRL-1739 cells. (4) Conclusions: We observed that the sera from GC patients, but also SDF-1, HGF and VEGF used alone, have a strong pro-metastatic effect on CRL-1739 cells. We also demonstrated that the concentration of these cytokines is specifically elevated in the sera of patients in an early stage of malignancy. Our results indicate that SDF-1, HGF and VEGF are very important molecules involved in gastric cancer progression. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Serum Pepsinogens Combined with New Biomarkers Testing Using Chemiluminescent Enzyme Immunoassay for Non-Invasive Diagnosis of Atrophic Gastritis: A Prospective, Multicenter Study
Diagnostics 2022, 12(3), 695; https://doi.org/10.3390/diagnostics12030695 - 12 Mar 2022
Cited by 4 | Viewed by 1782
Abstract
Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using [...] Read more.
Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. Material and Methods: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. Results: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8–87.9) and 92.6% (88.2–95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5–90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9–93.4) for the detection of moderate to severe AG at any location. Conclusion: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. Mini-abstract: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Modular Point-of-Care Breath Analyzer and Shape Taxonomy-Based Machine Learning for Gastric Cancer Detection
Diagnostics 2022, 12(2), 491; https://doi.org/10.3390/diagnostics12020491 - 14 Feb 2022
Cited by 8 | Viewed by 1807
Abstract
Background: Gastric cancer is one of the deadliest malignant diseases, and the non-invasive screening and diagnostics options for it are limited. In this article, we present a multi-modular device for breath analysis coupled with a machine learning approach for the detection of cancer-specific [...] Read more.
Background: Gastric cancer is one of the deadliest malignant diseases, and the non-invasive screening and diagnostics options for it are limited. In this article, we present a multi-modular device for breath analysis coupled with a machine learning approach for the detection of cancer-specific breath from the shapes of sensor response curves (taxonomies of clusters). Methods: We analyzed the breaths of 54 gastric cancer patients and 85 control group participants. The analysis was carried out using a breath analyzer with gold nanoparticle and metal oxide sensors. The response of the sensors was analyzed on the basis of the curve shapes and other features commonly used for comparison. These features were then used to train machine learning models using Naïve Bayes classifiers, Support Vector Machines and Random Forests. Results: The accuracy of the trained models reached 77.8% (sensitivity: up to 66.54%; specificity: up to 92.39%). The use of the proposed shape-based features improved the accuracy in most cases, especially the overall accuracy and sensitivity. Conclusions: The results show that this point-of-care breath analyzer and data analysis approach constitute a promising combination for the detection of gastric cancer-specific breath. The cluster taxonomy-based sensor reaction curve representation improved the results, and could be used in other similar applications. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Article
Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?
Diagnostics 2022, 12(1), 133; https://doi.org/10.3390/diagnostics12010133 - 06 Jan 2022
Cited by 6 | Viewed by 1800
Abstract
Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case [...] Read more.
Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. Aims. To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. Methods. Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. Results. In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serology-negative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. Conclusions. Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Review

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Review
Diagnostic Principles for Chronic Gastritis Associated with Duodenogastric Reflux
Diagnostics 2023, 13(2), 186; https://doi.org/10.3390/diagnostics13020186 - 04 Jan 2023
Cited by 1 | Viewed by 1641
Abstract
This article systematizes available data from the literature on biliary gastritis (BG) in order to increase the awareness of specialists about the latest possibilities for diagnosing the disease. BG occurs as a result of pathological duodenogastric reflux. In patients with a preserved duodenogastric [...] Read more.
This article systematizes available data from the literature on biliary gastritis (BG) in order to increase the awareness of specialists about the latest possibilities for diagnosing the disease. BG occurs as a result of pathological duodenogastric reflux. In patients with a preserved duodenogastric junction, the dominant factor is represented by motor disorders of the upper digestive tract (primary biliary gastritis), while in patients recovering from surgical interventions it is represented by structural changes (secondary biliary gastritis). Progressive BG can lead to atrophy of the gastric mucosa, intestinal metaplasia, epithelial dysplasia, and eventually to gastric cancer. Diagnostic methods for BG are carried out to identify risk factors, exclude alarm symptoms and identify persistent motor disorders and pathological reflux (24 h pH-impedancemetry, hepatobiliary scintigraphy, 24 h monitoring of bilirubin content in the reflux using a Bilitec 2000 photometer), as well as to diagnose gastritis itself (esophagogastroduodenoscopy, morphological gastrobiopsy examination). The diagnosis of BG should be based on a multidisciplinary approach that combines a thorough analysis of a patient’s complaints, an anamnesis of the disease, and the results of endoscopic and histological research methods. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Review
Artificial Intelligence for Upper Gastrointestinal Endoscopy: A Roadmap from Technology Development to Clinical Practice
Diagnostics 2022, 12(5), 1278; https://doi.org/10.3390/diagnostics12051278 - 21 May 2022
Cited by 4 | Viewed by 2860
Abstract
Stomach cancer is the third deadliest type of cancer in the world (0.86 million deaths in 2017). In 2035, a 20% increase will be observed both in incidence and mortality due to demographic effects if no interventions are foreseen. Upper GI endoscopy (UGIE) [...] Read more.
Stomach cancer is the third deadliest type of cancer in the world (0.86 million deaths in 2017). In 2035, a 20% increase will be observed both in incidence and mortality due to demographic effects if no interventions are foreseen. Upper GI endoscopy (UGIE) plays a paramount role in early diagnosis and, therefore, improved survival rates. On the other hand, human and technical factors can contribute to misdiagnosis while performing UGIE. In this scenario, artificial intelligence (AI) has recently shown its potential in compensating for the pitfalls of UGIE, by leveraging deep learning architectures able to efficiently recognize endoscopic patterns from UGIE video data. This work presents a review of the current state-of-the-art algorithms in the application of AI to gastroscopy. It focuses specifically on the threefold tasks of assuring exam completeness (i.e., detecting the presence of blind spots) and assisting in the detection and characterization of clinical findings, both gastric precancerous conditions and neoplastic lesion changes. Early and promising results have already been obtained using well-known deep learning architectures for computer vision, but many algorithmic challenges remain in achieving the vision of AI-assisted UGIE. Future challenges in the roadmap for the effective integration of AI tools within the UGIE clinical practice are discussed, namely the adoption of more robust deep learning architectures and methods able to embed domain knowledge into image/video classifiers as well as the availability of large, annotated datasets. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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Other

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Comment
Comment on Skrebinska et al. Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection? Diagnostics 2022, 12, 133
Diagnostics 2022, 12(6), 1424; https://doi.org/10.3390/diagnostics12061424 - 09 Jun 2022
Viewed by 754
Abstract
In their article, Skebrinska and colleagues analysed the potential pitfalls of detecting Helicobacter pylori (H. pylori) by serology, histological (Giemsa) and immunohistochemical (IHC) staining. However, in the Introduction, the authors state: “…IHC is recommended only in individuals with active gastritis without [...] Read more.
In their article, Skebrinska and colleagues analysed the potential pitfalls of detecting Helicobacter pylori (H. pylori) by serology, histological (Giemsa) and immunohistochemical (IHC) staining. However, in the Introduction, the authors state: “…IHC is recommended only in individuals with active gastritis without H. pylori identification by histochemistry”. Although this is a widely-held view, it does not seem to hold up in view of the results of the study by Kocsmár et al., which showed that the diagnostic sensitivity of Giemsa in the absence of activity is only 33.6%, but it is 92.6% in the presence of active gastritis, which is close to the 99.4% sensitivity of IHC. Considering that chronic active gastritis with the features of H. pylori gastritis is also common in other entities, if active inflammation is present in the sample, there is a very small chance that a Giemsa-negative case will be confirmed as H. pylori-positive by IHC. Based on this, the use of IHC is more reasonable in Giemsa-negative cases with no activity in which the etiological role of H. pylori is suggested by clinical, anamnestic or other data. However, it may also be reasonable to routinely use IHC as the primary staining method instead of Giemsa. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
Protocol
Introducing the Sanguis-Filum for Detection of Gastric Mucosal Lesions Prior to Endoscopy: A Study Protocol
Diagnostics 2022, 12(5), 1160; https://doi.org/10.3390/diagnostics12051160 - 07 May 2022
Viewed by 827
Abstract
Early diagnosis of gastric cancer (GC) is compromised by a lack of specific signs to enable identification of affected individuals. We designed the Sanguis-filum (S-filum) as a simple bedside tool that could be used to detect the presence of gastric mucosal lesions prior [...] Read more.
Early diagnosis of gastric cancer (GC) is compromised by a lack of specific signs to enable identification of affected individuals. We designed the Sanguis-filum (S-filum) as a simple bedside tool that could be used to detect the presence of gastric mucosal lesions prior to endoscopy. We previously published evidence that at a sensitivity of 91%, the presence of free blood in the stomach was associated with mucosal lesions. The S-filum is made of an inert but absorbent string coiled up in a gelatin capsule (Capsuline, FL, USA), which can be swallowed and the string retrieved to test for free blood. Preliminary testing of the S-filum was successfully conducted on healthy volunteers. We now intend to test it on actual patients, comparing the results to oesophagogastroduodenoscopy (OGD) findings. This will enable us to determine the diagnostic accuracy of the S-filum at detecting GC and other mucosal lesions. The S-filum as a bedside tool has the potential to assist healthcare providers to identify individuals likely to have early gastric mucosal lesions and requiring OGD examination. The S-filum could, in the long run, facilitate population-wide screening for early GC prior to endoscopy. Full article
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)
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