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Archives of Medical Research Feb 2023Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development.
METHODS
A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio.
RESULTS
A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, β-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk.
CONCLUSION
The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
Topics: Humans; Stomach Neoplasms; Pepsinogen A; Biomarkers; Pepsinogen C; Immunoglobulin G; Ferritins; Iron; Transferrins; Helicobacter Infections
PubMed: 36759293
DOI: 10.1016/j.arcmed.2022.12.012 -
Clinical and Translational... Feb 2023Some gastric cancer prediction models have been published. Still, the value of these models for application in real-world practice remains unclear. We aim to summarize...
INTRODUCTION
Some gastric cancer prediction models have been published. Still, the value of these models for application in real-world practice remains unclear. We aim to summarize and appraise modeling studies for gastric cancer risk prediction and identify potential barriers to real-world use.
METHODS
This systematic review included studies that developed or validated gastric cancer prediction models in the general population.
RESULTS
A total of 4,223 studies were screened. We included 18 development studies for diagnostic models, 10 for prognostic models, and 1 external validation study. Diagnostic models commonly included biomarkers, such as Helicobacter pylori infection indicator, pepsinogen, hormone, and microRNA. Age, sex, smoking, body mass index, and family history of gastric cancer were frequently used in prognostic models. Most of the models were not validated. Only 25% of models evaluated the calibration. All studies had a high risk of bias, but over half had acceptable applicability. Besides, most studies failed to clearly report the application scenarios of prediction models.
DISCUSSION
Most gastric cancer prediction models showed common shortcomings in methods, validation, and reports. Model developers should further minimize the risk of bias, improve models' applicability, and report targeting application scenarios to promote real-world use.
Topics: Humans; Stomach Neoplasms; Helicobacter Infections; Early Detection of Cancer; Helicobacter pylori; Prognosis
PubMed: 36413795
DOI: 10.14309/ctg.0000000000000546 -
Frontiers in Oncology 2022Serum pepsinogens are serological biomarkers of gastric atrophy, and the latter is a risk factor for esophageal squamous cell carcinoma (ESCC). However, the association...
BACKGROUND
Serum pepsinogens are serological biomarkers of gastric atrophy, and the latter is a risk factor for esophageal squamous cell carcinoma (ESCC). However, the association of serum pepsinogens with ESCC risk remains unclear. This systematic review and meta-analysis aimed to assess the relationship between serum pepsinogen I (PGI) and pepsinogen I: pepsinogen II ratio (PGR) and ESCC risk.
METHODS
PubMed, Embase, and Web of Science were searched for articles on the effect of serum PGI and PGR on ESCC risk, published up to the end of February 2022. Meta-analysis with a random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Five case-control studies and three prospective studies were included. In comparison with the high categories, the low categories of serum PGI (OR: 1.92, 95% CI: 1.45-2.56) and PGR (OR: 1.70, 95% CI: 1.01-2.85) were associated with an increased risk of ESCC, although a substantial heterogeneity was observed in serum PGR ( = 60.2%, = 0.028) rather than in serum PGI ( = 46.4%, = 0.070). In stratified analysis by study quality, the significant risk effect on ESCC was remained for PGI (OR: 2.05, 95% CI: 1.48-2.84) and PGR (OR: 2.07, 95% CI: 1.17-3.75) when only the studies with high quality were pooled.
CONCLUSIONS
Based on the available studies, although limited in number, this systematic review along with meta-analysis suggests that low serum PGI and low PGR may be related to an increased risk of ESCC. This present study provides evidence for using serum pepsinogen biomarkers in predicting ESCC. More delicate well-designed cohort studies with high study quality are needed, and dose-response analysis should be performed.
PubMed: 35847871
DOI: 10.3389/fonc.2022.928672 -
Advances in Therapy Feb 2021Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these... (Review)
Review
INTRODUCTION
Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations.
METHODS
We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes.
RESULTS
We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively.
CONCLUSION
Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.
Topics: Biomarkers; Early Detection of Cancer; Gastrointestinal Neoplasms; Humans; Pancreatic Neoplasms; Prevalence
PubMed: 33306189
DOI: 10.1007/s12325-020-01571-z -
Endoscopy International Open Sep 2020Gastric neoplasms are one of the leading types of cancer in the world and early detection is essential to improve prognosis. Endoscopy is the gold-standard diagnostic... (Review)
Review
Gastric neoplasms are one of the leading types of cancer in the world and early detection is essential to improve prognosis. Endoscopy is the gold-standard diagnostic procedure and allows adequate treatment in selected cases. Endoscopic submucosal dissection (ESD) has been reported to safely address most early gastric cancers (EGCs), with high curability rates. However, data on prognostic factors related to ESDs of EGCs are conflicting. Therefore, we aimed to systematically review the available literature and to perform a meta-analysis to identify the relevant prognostic factors in this context. We performed this study according to PRISMA guidelines. Comparative studies assessing the relationship between curative resection or long-term curability rates and relevant prognostic factors were selected. Prognostic factors were demographic data, lesion features (location, morphology of the lesion, size, and depth of invasion), histological findings, (HP) infection, presence of gastric a atrophy and body mass index (BMI). Finally, we also evaluated risk factors related to metachronous gastric neoplasm. The initial search retrieved 2829 records among which 46 studies were included for systematic review and meta-analysis. The total sample comprised 28366 patients and 29282 lesions. Regarding curative resection, pooled data showed no significant influence of sex [odds ratio (OR): 1.15 (0,97, 1.36) = 0.10 I = 47 %] , age [OR: 1.00 (0.61, 1.64) = 1.00 I = 58 %], posterior vs non-posterior location [OR: 1.35 (0.81, 2.27) = 0.25 I = 84 %], depressed vs von-depressed macroscopic type[OR: 1.21 (0.99, 1.49) = 0.07 I = 0 %], non-upper vs upper location [OR: 1.41 (0.93, 2.14) = 0.10 I = 77 %] and BMI [OR: 0.84 (0.57; 1.26) = 0.41 I = 0 %]. Differentiated neoplasms presented greater chance of cure compare to undifferentiated [OR: 0.10 (0.07, 0.15) < 0.00001 I = 0 %]. Ulcerated lesions had lower curative rates compared to non-ulcerated [OR: 3.92 (2.81, 5.47) < 0.00001 I = 44 %]. Lesions smaller than 20 mm had greater chance of curative resection [OR: 3.94 (3.25, 4.78) < 0.00001 I = 38 %]. Bleeding during procedure had lower curative rates compared to non-bleeding [OR: 2.13 (1.56, 2.93) < 0.0001 I = 0 %]. Concerning long-term cure, female gender [OR 1.62 (1.33, 1.97) < 0.00001 I = 0 %] and the mucosal over SM1 cancers were protective factors [OR: 0.08 (0.02, 0.39) = 0.002 I = 86 %]. Gastric atrophy [OR: 0.60 (0.45, 0.81) = 0.0006 I = 42 %] and the pepsinogen I/pepsinogen II ratio [OR 2.29 (1.47, 3.57) = 0.0002 I = 0 %] were risk factors to metachronous gastric neoplasm. Ulcerated lesions, histology, bleeding and size > 20 mm are prognostic factors concerning curative resection. Regarding long-term cure, female gender and mucosal over SM1 cancer are predictive factors. Gastric atrophy and the pepsinogen ratio are risk factors for metachronous gastric neoplasm.
PubMed: 32904802
DOI: 10.1055/a-1201-3089 -
Translational Cancer Research Mar 2020The risk for gastric cancer among patients with gastric atrophy is unclear. We investigated the association between the risk for gastric cancer and gastric atrophy.
BACKGROUND
The risk for gastric cancer among patients with gastric atrophy is unclear. We investigated the association between the risk for gastric cancer and gastric atrophy.
METHODS
We performed a comprehensive literature search in the PubMed and Embase databases and extracted relevant data from eligible studies. A fixed- or random-effects model was applied to pool study-specific risk according to heterogeneity across studies.
RESULTS
Thirteen cohort or nested case-control studies with 655,937 participants and 2,794 patients with gastric cancer were analyzed. The pooled results suggested that gastric atrophy was associated with an elevated risk for gastric cancer [pooled risk ratio (RR) =2.91, 95% confidence interval (CI): 2.58-3.27]. The pooled RR (3.10, 95% CI: 2.58-3.73) of studies that used serum levels of pepsinogen for diagnosis of gastric atrophy was similar to that of those that used (pooled RR =2.79, 95% CI: 2.37-3.27) (for endoscopy). Gastric atrophy was positively associated with the risk for gastric cancer in both prospective and retrospective studies. Moreover, the pooled RRs did not significantly vary by country of origin (Asia and Europe) or gastric cancer subtype (cardia and non-cardia).
CONCLUSIONS
Gastric atrophy is associated with an elevated risk for gastric cancer, and endoscopy and serum levels of pepsinogens can be used to predict the risk.
PubMed: 35117509
DOI: 10.21037/tcr.2020.01.54 -
Cancer Management and Research 2019Serum pepsinogen I (PGI) concentration and PGI/PGII ratio (PGR) are often used as serological markers for gastric fundus atrophy (AGA) and gastric carcinoma. However,...
Serum pepsinogen I (PGI) concentration and PGI/PGII ratio (PGR) are often used as serological markers for gastric fundus atrophy (AGA) and gastric carcinoma. However, their diagnostic value in esophageal carcinoma (EC) is inaccurate. This study evaluated the diagnostic value of PGI and PGR in EC by searching the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases for literature on the diagnosis of EC with PGI and PGR from January 1, 2000 to October 2, 2018. The included literature were systematically evaluated using QUSDAS-2 software. Meta-analysis was conducted using STATA 15.0 software. The summary receiver operating characteristic curve (SROC) accuracy was plotted, the area under the curve was calculated. A total of 84 papers were selected, and after screening, nine papers on esophageal squamous cell carcinoma (ESCC) were finally included. Results showed low an ESCC-specific diagnostic sensitivity (0.27), high specificity (0.85), and 0.63 AUC of SROC when PGI≤70 ng/mL. When PGR≤3, the ESCC-specific diagnostic sensitivity was low (0.29), the specificity was high (0.83), and the AUC of SROC was 0.63. According to the current research results, PGI≤70 ng/mL or PGR≤3 diagnostic ESCC sensitivity is low, and specificity is high. These findings indicate that neither PGI≤70 ng/mL nor PGR≤3 can be used as an ESCC-screening index.
PubMed: 31303787
DOI: 10.2147/CMAR.S196760 -
Journal of Clinical Medicine May 2019Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic...
Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic gastritis (CAG) and gastric neoplasms. Although various cut-off values have been suggested, PG I ≤70 ng/mL and a PG I/PG II ratio of ≤3 have been proposed. However, previous meta-analyses reported insufficient systematic reviews and only pooled outcomes, which cannot determine the diagnostic validity of sPGA with a cut-off value of PG I ≤70 ng/mL and/or PG I/PG II ratio ≤3. We searched the core databases (MEDLINE, Cochrane Library, and Embase) from their inception to April 2018. Fourteen and 43 studies were identified and analyzed for the diagnostic performance in CAG and gastric neoplasms, respectively. Values for sensitivity, specificity, diagnostic odds ratio, and area under the curve with a cut-off value of PG I ≤70 ng/mL and PG I/PG II ratio ≤3 to diagnose CAG were 0.59, 0.89, 12, and 0.81, respectively and for diagnosis of gastric cancer (GC) these values were 0.59, 0.73, 4, and 0.7, respectively. Methodological quality and ethnicity of enrolled studies were found to be the reason for the heterogeneity in CAG diagnosis. Considering the high specificity, non-invasiveness, and easily interpretable characteristics, sPGA has potential for screening of CAG or GC.
PubMed: 31083485
DOI: 10.3390/jcm8050657 -
Gastroenterology Research and Practice 2019The current gold standard for gastric cancer (GC) screening is pathology or a barium meal followed by X-ray. This is not applicable to a wide range of screening...
BACKGROUND
The current gold standard for gastric cancer (GC) screening is pathology or a barium meal followed by X-ray. This is not applicable to a wide range of screening capabilities due to the lack of operability. This article used a meta-analysis to evaluate the value of pepsinogen (PG) screening for GC.
METHODS
PubMed, EMbase, the Cochrane Library, CNKI, WanFang, VIP, and CBM databases were systematically searched for published studies that used serum PG to diagnose GC. Articles were searched from January 2003 to January 2018. Two reviewers independently screened the literature according to specified inclusion and exclusion criteria. The data were extracted and evaluated, and the quality of the methodologies evaluated using the QUADAS entry. The meta-analysis (MA) was performed using Meta-DiSc 1.4 software. Stata 12.0 software was used to assess publication bias.
RESULTS
A total of 19 studies were finally included from a total of 169,009 cases. The MA showed a combined sensitivity and specificity of 0.56 (95% CI (0.53-0.59), < 0.01) and 0.71 (95% CI (0.70-0.71), < 0.01), respectively. The combined likelihood ratios were +LR = 2.82 (95% CI (2.06-3.86), < 0.01) and -LR = 0.56 (95% CI (0.45-0.68), < 0.01). The combined DOR was 5.41 (95% CI (3.64~ 8.06), < 0.01), and the area under the SROC curve was 0.7468.
CONCLUSIONS
Serum PG provides medium levels of sensitivity and specificity for GC assessment. To be used in a clinical setting, further high-quality research must be performed and verified.
PubMed: 30804996
DOI: 10.1155/2019/7087232 -
Acta Bio-medica : Atenei Parmensis Dec 2018Upper-GI diseases are one of the most relevant issue in primary care. Nowadays they are still responsible for about 100 million ambulatory care visits only in the US....
Upper-GI diseases are one of the most relevant issue in primary care. Nowadays they are still responsible for about 100 million ambulatory care visits only in the US. The diagnosis of almost every upper-GI condition is still deputed to invasive tests such as upper gastrointestinal endoscopy, gastroesophageal manometry or radiography. The possibility of analysing serum markers like Pepsinogens I and II, produced by gastric mucosa, in order to assess the functional characteristics of the upper GI tract has spread itself since the 80's especially in the diagnosis of peptic ulcer. The discovery of Helicobacter pylori by Marshall and Warren in 1983 and the scientific consecration of its role in the pathogenesis of gastric cancer and peptic ulcer (crystallized in Peleo Correa's Cascade, 1992), led to an increase importance of non-invasive tests, raising the attention towards the assessment of both immunoglobulins anti-H.p. and Gastrin hormone produced by antral G cells, as an implementation of the panel of gastric markers. This narrative review aims to analyze the huge landscape of non-invasive tests for diagnosis of GI diseases, studying the literature of the recent years.
Topics: Antibodies, Bacterial; Biomarkers; Diagnostic Techniques, Digestive System; Dyspepsia; Endoscopy, Gastrointestinal; Esophageal Diseases; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Stomach Diseases
PubMed: 30561417
DOI: 10.23750/abm.v89i8-S.7917