Serum Pepsinogen Levels Research Articles

Clinical Value of Pepsinogen in the Screening, Prevention, and Diagnosis of Gastric Cancer

To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003). The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.

Diagnostic Value of Serum Pepsinogen Levels for Screening Gastric Cancer and Atrophic Gastritis in Asymptomatic Individuals: A Cross-Sectional Study

BackgroundPepsinogens (PGs) can be used for gastric cancer (GC) screening, but the cutoff levels vary among studies, and PG levels are influenced by numerous factors. The aim of this article is to examine the diagnostic value of PG levels and Helicobacter pylori (Hp) status for GC and atrophic gastritis screening in asymptomatic individuals undergoing health checkup in China.Patients and MethodsThis was a multicenter cross-sectional study of subjects who underwent health checkup from 10/2016 to 10/2018 at nine International Healthcare Centers in China. All participants underwent gastroscopy and pathological examination, serum PG, 13C-urea breath test, and/or Hp serological current infection marker rapid test, all on the same day. PG-related parameters were analyzed in different Hp subgroups and regions.ResultsThe patients were grouped as non-atrophic (NAG, n = 1,590), mild to moderate atrophic (MAG, n = 273), severe atrophic (SAG, n = 49), and GC (n = 10). The serum PG levels in these groups decreased with increasing pathological severity. In the same pathological groups, PGI and PGII levels were higher in the Hp-positive subgroup, while PGR (PGI/PGII ratio) was lower (P < 0.05). The best cutoff values for atrophy diagnosis were PGI ≤73.1 ng/ml and PGR ≤9.8, for severe atrophy were PGI ≤63.9 ng/ml and PGR ≤9.09, and for GC was PGR ≤4.7 (all P < 0.05 and area under the curve >0.7). The cutoff points varied with Hp status and China regions.ConclusionSerum PG levels might be used for the screening of gastric atrophic gastritis lesions. The results suggest that different cutoff values should possibly be used in different Hp status groups and geographical regions, but it will have to be validated in future studies. Future studies should also examine the value of PG levels for GC detection.

Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer

Background:Variations in mtDNA-CN of PBLs, as a potential biomarker for GC screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with sPG I/II ratio, as an established indicator of gastric atrophy. Methods:The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. Results:The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. Conclusion:The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Scoring model for discriminating gastric cancer risk in patients with negative serum pepsinogen and anti‐Helicobacter pylori antibody results

The ABC test measures serum pepsinogen and anti-Helicobacter pylori IgG antibody levels to predict precancerous conditions in the stomach and gastric cancer. However, a limitation of this test is that the gastric cancer risk is not negligible in patients with a negative result. Based on their ABC results, 1157 patients were classified into Groups A (n=392), B (n=479), C (n=247), and D (n=39). In Group A, 24.2% of patients had atrophic gastritis and/or intestinal metaplasia and had thus been incorrectly assigned to Group A. Patients in Group A were then assigned to derivation (n=236) and validation (n=156) cohorts by 3:2 random sampling. Logistic regression analyses were performed to identify the factors discriminating between a correct (true) and incorrect (false) Group A classification. A 4-point discriminative model was constructed based on a high-negative H. pylori IgG antibody titer and the patient's age (50-64 and ≥65years). The areas under the receiver operating characteristic curve for the derivation and validation cohorts were 0.868 and 0.894, respectively. In the validation cohort, the addition of a discriminative model score ≥2 to the ABC method showed a similar accuracy for predicting gastric cancer risk compared with the ABC method alone (93.8% vs. 92.4%). The 4-point discriminative model may help identify patients with a normal serological test who are nonetheless at risk of developing gastric cancer.

Serum pepsinogen II levels are doubled with Helicobacter pylori infection in an asymptomatic population of 40,383 Chinese subjects.

Pepsinogen (PG) I and II are crucial in the gastric digestive processes. This study is to examine the relationship of serum PGI, PGII, and PGI/PGII ratio with Helicobacter pylori (Hp) infection, age, sex, and body mass index (BMI) in subjects in Beijing, China.A total of 40,383 asymptomatic subjects, who underwent medical examination in Beijing Rehabilitation Hospital, were included in this study. Serum PG levels were measured using chemoluminescence techniques. The age, sex, and BMI data were collected, and Hp infection was identified with 13C-urea breath test. Statistical analysis was conducted with Python, Pandas and Seaborn software.Asymptomatic subjects with Hp infection (Hp+) had a significantly higher level of PGI in the serum (111 ng/mL [median]) than those without Hp infection (Hp−) (94 ng/mL, P < .001). The asymptomatic Hp+ subjects had 2-fold higher PGII levels (7.2 ng/mL) than Hp− subjects (3.2 ng/mL, P < .001). These changes produced significantly lower PGI/II ratio in Hp+ patients than in Hp− subjects (16:30, P < .001). The serum PGI and PGII levels were higher in males than in females (PGI: 104 ng/mL vs 95 ng/mL, PGII: 4.3 ng/mL vs 3.7 ng/mL, both P < .001), PGI/II ratio of males is at 95% of that in females (P < .001). PGI and PGII levels gradually increased in older people (P < .001), whereas the PGI/II ratio decreased significantly with age (P < .001). The levels of the two serum PGs were decreased and the ratio increased when BMI were higher than 28 kg/cm2 (P < .05).The levels of serum PGI, especial PGII, were increased by Hp infection, and also influenced by age, sex, and BMI. Therefore, these influencing factors should be considered during clinical practice.

Serum pepsinogen levels in different regions of China and its influencing factors: a multicenter cross-sectional study

BackgroundThe aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors.MethodsFrom October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis.Results1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors.ConclusionInfluenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.

The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio <3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P < 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P < 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.

Serum pepsinogen as a biomarker for gastric cancer: A nested case-control study using the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial data.

188 Background: Gastric cancer (GC) lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, which is an intermittent phase in the development of GC. A serum based biomarker that indicates increased risk of GC would be useful for targeted prevention strategies. Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large randomized trial conducted over 10 centers in the US between 1993 and 2001. Serum samples were collected at baseline and participants were followed for development of incident GC. ELISA-based pepsinogen tests were conducted on pre-diagnostic serum samples of patients who developed GC and age, sex, and race-matched controls. Pepsinogen negative (PG-) and positive (PG+) status was determined using pepsinogen I (PGI) and pepsinogen I to II ratio (PGR). Those with PGR ≥ 3 and PGI &gt; 70µg/L were considered PG- while those with lower levels on either or both were considered PG+. Cox proportional hazard models were used to determine the hazard ratio (HR) and 95% confidence intervals (95%CI) of PG+ for GC. To examine the association of PG with non-cardia and cardia GC separately, propensity matching was used to create control subsets matched on age, sex, and race. Results: Pepsinogen test results were available on 105 GC cases (70 non-cardia and 35 cardia) and 220 matched controls. Median and range of time from pepsinogen measurement to incident GC diagnosis was 78.6 and 3.0-152.2 months, respectively. GC patients were more likely to be PG+ (31.4% vs 5.5%, p &lt; 0.001) and current smokers (20.0% vs 7.7%, p = 0.004) at baseline than controls. Compared to PG-, PG+ were at an increased risk of any GC (HR = 3.77; 95%CI = 2.50-5.71). After adjusting for family history of GC, smoking, and BMI, PG+ were still at a significantly increased risk of GC compared to PG- (adjusted HR = 4.42; 95%CI = 3.14-6.21). For 138 controls matched to 70 non-cardia cancers, PG+ were at an increased risk of non-cardia GC compared to PG- (HR = 5.65, 95%CI = 3.67-8.70; adjusted HR = 7.26, 95%CI = 4.84-10.90). For 70 controls matched to 35 cardia cancers, PG+ were not at greater risk of cardia GC compared to PG- (HR = 1.79, 95%CI = 0.72-4.44; adjusted HR = 1.95, 95%CI = 0.81-5.37). Conclusions: Pre-diagnostic serum pepsinogen levels from a large prospective cohort study predicted development of non-cardia GC but not cardia GC. PG could be considered as a potential risk biomarker to identify individuals at higher risk of non-cardia GC for targeted screening or interventions.

Serum pepsinogen levels and OLGA/OLGIM staging in the assessment of atrophic gastritis types

BackgroundWe assessed the validity of using serum pepsinogen tests (sPGTs) to differentiate autoimmune atrophic gastritis (AAG) from environmental atrophic gastritis (EAG). We also investigated the correlation and prognostic value between...

Changes of serum pepsinogen level and ABC classification after bariatric surgery

Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict gastric cancer risk after bariatric surgery. We enrolled 94 obese subjects that received bariatric surgery, including 41 sleeve gastrectomy (SG) and 53 Roux-en-Y gastric bypass (RYGB). The serum pepsinogen I (PGI), pepsinogen II (PGII), PGI/II ratio and seropositivity of Helicobacter pylori ( H. pylori ) were measured before and one year after surgery. Patients were classified according to ABC classification and post-operative change was evaluated. Preoperatively, four (4.2%) patients were classified into high risk group (classification C and D) for gastric cancer. Significant reduction of PGI, PGII and decrease of PGI/II ratio were noted after bariatric surgery. H. pylori seropositive patients had a greater postoperative change of PGI (-38.6μg/L vs -22.1μg/L, p=0.003) and PGII (-8.0μg/L vs -2.5μg/L, p <0.001) but a less postoperative change of PGI/II ratio (-0.6 vs -2.1, p =0.04) than H. pylori seronegative patients. One year after surgery, the portion of high risk group of ABC classification for gastric cancer increased markedly from 4.2% to 23.7%. Both of SG and RYGB resulted in significant reduction of serum PGI and PGII after bariatric surgery, and significantly influenced the ABC classification. The application of ABC classification for gastric cancer screening was limited after bariatric surgery.

Helicobacter pylori Infection and Serum Pepsinogen Level With the Risk of Gastric Precancerous Conditions: A Cross-sectional Study of High-risk Gastric Cancer Population in China.

Gastric precancerous conditions are generally considered to play an essential role in the gastric carcinogenesis cascade. This study identified risk factors of gastric precancerous conditions in a nationwide multicenter cross-sectional study. Individuals who made their visit to 115 hospitals in China for gastric cancer screening were recruited. Lifestyle habits and personal information were collected through a series of questionnaires. Serum biomarker test (pepsinogen I, pepsinogen II, gastrin-17, and anti-Helicobacter pylori immunoglobulin G antibody) and endoscopy were then performed. Risk factors for gastric precancerous conditions were identified by univariate and multivariate analyses. Of 14,929 subjects eligible for analysis, 4477 (30.0%) developed gastric precancerous conditions and 405 (2.71%) developed gastric cancer. In multiple logistic regression, precancerous conditions were associated with advanced age [odds ratio (OR)=1.027; 95% confidence interval (Cl), 1.023-1.032; P<0.001], male gender (OR=1.303; 95% Cl, 1.188-1.429; P<0.001), H. pylori infection (OR=1.377; 95% Cl, 1.272-1.490, P<0.001), and smoking (OR=1.142; 95% Cl, 1.005-1.298, P=0.004), whereas they were inversely correlated with white meat intake (OR=0.731; 95% Cl, 0.673-0.794; P<0.001) and pepsinogen I level (30 to 70 subgroup OR=1.536; 95% Cl, 1.163-2.028; P=0.002; <30 subgroup OR=1.354; 95% Cl, 1.206-1.520; P<0.001). Also, the authors observed a statistically lower prevalence of reflux esophagitis (2.8% vs. 4.7%) and of gastric polyps (11.0% vs. 13.7%) in H. pylori-infected population. Patients with H. pylori have a 1.4-fold higher risk of having gastric precancerous conditions. Besides, precancerous conditions were associated with advanced age, male gender, H. pylori infection, and smoking in a large population. However, regular white meat intake and higher pepsinogen I level were associated with reduced risk of having precancerous lesions.

Establish a Scoring Model for High-Risk Population of Gastric Cancer and Study on the Pattern of Opportunistic Screening.

Objective To investigate and study the related risk factors of gastric cancer (GC) patients, to establish a high-risk scoring model of GC by multiple logistic regression analysis, and to explore the establishment of a GC screening mode with clinical opportunistic screening as the main method, and by using the pattern of opportunistic screening to establish the screening of high-risk GC patients and the choice of screening methods in the clinical outpatient work. Methods Collected the epidemiological questionnaire of 99 GC cases and 284 non-GC patients (other chronic gastric diseases and normal) diagnosed by the General Hospital of Ningxia Medical University from October 2017 to March 2019. Serum pepsinogen (PG) levels were measured by enzyme-linked immunosorbent assay (ELISA) and confirmed Helicobacter pylori (Hp) infection in gastric mucosa tissues by Giemsa staining. Determined the high-risk factors and established a scoring model through unconditional logistic regression model analysis, and the ROC curve determined the cut-off value. Then, we followed up 26 patients of nongastric cancer patients constituted a validation group, which validated the model. Results The high-risk factors of GC included age ≥ 55, male, drinking cellar or well water, family history of GC, Hp infection, PGI ≤ 43.6 μg/L, and PGI/PGII ≤ 2.1. Established the high-risk model: Y = A × age + 30 × gender + 30 × drinking water + 30 × Hp infection + 50 × family history of GC + B × PG level. The ROC curve determined that the cut-off value for high-risk GC population was ≥155, and the area under the curve (AUC) was 0.875, the sensitivity and specificity were 87.9% and 71.5%. Conclusions According to the risk factors of GC, using statistical methods can establish a high-risk scoring model of GC, and the score ≥ 155 is divided into the screening cut-off value for high-risk GC population. Using this model for clinical outpatient GC screening is cost-effective and has high sensitivity and specificity.

Associations of Helicobacter pylori seropositivity and gastric inflammation with pediatric asthma.

Controversy exists regarding an association between Helicobacter pylori infection and asthma in children. We examined the hypotheses of inverse associations of H. pylori seroprevalence and pepsinogen (PG) levels, as markers of gastric inflammation, with asthma in children. A hospital-based case-control study was conducted among children aged 4.8 to 17.3 years in Israel. Confirmed asthma cases (n = 75) were recruited through a pulmonary clinic, and controls (n = 160) without asthma were enrolled. Using enzyme-linked immunosorbent assays we measured the presence of H. pylori immunoglobulin G (IgG) antibodies, IgG antibodies to cytotoxin-associated gene A antigen (CagA) (virulent factor), serum PG levels and exposure to other enteric pathogens (Shigella flexneri). Multivariable logistic regression models were applied. H. pylori IgG seropositivity was 25% and 40% among cases and controls, respectively (P = .03). H. pylori CagA IgG seropositivity was associated with reduced risk of asthma (adjusted odds ratio [OR], 0.33 [95% CI, 0.11-0.95] but not for the CagA negative serology (adjusted OR, 0.70 [95% CI, 0.32-1.54]). Children who were H. pylori seropositive with a PGI:PGII of ≤6.78 (severe gastric inflammation) had a lower likelihood of asthma (adjusted OR, 0.31 [95% CI, 0.10-0.89]) than did seronegative children. Exposure to Shigella flexneri did not differ between cases and controls, nor according to H. pylori seropositivity. Among the asthmatic children, pulmonary function did not differ according to H. pylori seropositivity. H. pylori infection and its related gastric inflammation may have a protective role in the risk of pediatric asthma and further research into a potential causal pathway is required.

The Role of Helicobacter pylori and Serum Pepsinogen Levels in Metachronous Gastric Cancer After Endoscopic Gastrectomy.

The current study aimed to explore the role of Helicobacter pylori (Hp) infection and serum pepsinogen (PG) levels in the occurrence of metachronous gastric cancer after endoscopic gastrectomy. Totally, 50 patients with metachronous gastric cancer, 50 patients with chronic atrophic gastritis and 50 healthy subjects were collected from October 2015 to October 2018. Patients in the gastric cancer group underwent endoscopic gastrectomy. Serum samples were collected for detection and correlation analysis of serum PG I, PG II, and Hp. In addition, the contents of serum PG and gastrin and postoperative adverse events were statistically analyzed. There was a statistically significant difference in serum PG I levels, positive Hp infection rate, the number of mast cells, plasma motilin levels and postoperative adverse events among the 3 groups (P<0.01). There was also a significant difference in PG II levels among the groups (P<0.05). On the basis of the results, the amount of inflammatory cells in the gastric cancer group was significantly higher than that in the gastritis group, and there was a remarkable difference in gastric cancer patients before and after operation. Through data analysis, it was found that the levels of PG I and II were the highest in the healthy control group and the lowest in the gastric cancer group, the number of mast cells was the largest in the gastric cancer group, and the level of motilin was the highest in the healthy control group. Hp infection and serum PG levels are associated with metachronous gastric cancer.

Pepsinogen Serology and Gastritis OLGA Staging in Mucosal Atrophy Assessment: A Cross-Sectional Study Involving East China Endoscopy Population.

The histological gastric stage (OLGA) plays an important role in evaluating gastric atrophy, a symptom which suggests a risk of gastric cancer (GC). However, gastroscopy is an invasive examination, which has limited application in populations undergoing physical examination. Serum pepsinogen (PG) and gastin-17 (G-17) levels are noninvasive indexes which are recommended when screening for GC. We aim to explore the correlation between PG/G-17 and OLGA stage, in order to provide reliable indexes for GC screening. The study included 453 asymptomatic individuals from East China undergoing physical examination, who then underwent endoscopy including collection of biopsy samples. Assays for serum PG, G-17, and Helicobacter pylori (Hp) were performed. Atrophy of gastric mucosa was graded according to OLGA for each individual. 453 participants, average age 52.46 ± 10.30 years, 253 male and 200 female, were included. In the asymptomatic physical examination population, serum PGI, PGII, and PGR levels decreased with increasing OLGA scores. PGI and PGR were inversely correlated with increasing OLGA stage in both Hp-positive and Hp-negative groups. The levels of serum PGI, PGII, and G-17 in the Hp-positive group were higher than those in the Hp-negative group; conversely, the PGR levels were lower. Furthermore, OLGA scores increased with age in the Hp-positive group. In conclusion, there is a significant correlation between OLGA stage and serum PG in populations from East China undergoing physical examination. Serum PG and G-17 combined with Hp test plays an important role in evaluating gastric atrophy.

Long‐term follow up of serum pepsinogens in patients with gastric cancer or dysplasia after Helicobacter pylori eradication

Few studies have evaluated the change in serum pepsinogen (sPG) levels after the eradication of Helicobacter pylori. The aim of this study was to evaluate the effect of H.pylori eradication on sPG levels in patients with gastric cancer/dysplasia in comparison to a control group. We prospectively enrolled 368 patients with gastric cancer/dysplasia and 610 control subjects. H.pylori status and sPG levels were measured before and after eradication. The follow-up time points were classified as <12, 12-23, 24-35, and ≥36months. In 179 H.pylori-eradicated patients with gastric cancer/dysplasia and 168 control group subjects, sPG I significantly decreased, and the sPG I/II ratio significantly increased after eradication compared to baseline, and this improvement in sPG values was maintained during all follow-up time points. Significant differences in sPG I and the sPG I/II ratio were observed between the gastric cancer/dysplasia group and the control group <24months after eradication. However, these differences in sPG values disappeared after ≥24months of follow up. Moreover, significant differences in the intestinal metaplasia grade were observed between these two groups before eradication until <24months after eradication. However, these differences in the intestinal metaplasia grade disappeared after ≥24months of follow up in the corpus. The sPG values and intestinal metaplasia grade (corpus) in the gastric cancer/dysplasia group became similar to those in the control group at long-term follow up after H.pylori eradication. It might be related with the reduction of metachronous gastric neoplasm.

Precision Medicine Approaches to Prevent Gastric Cancer.

Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is Helicobacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutting-edge technologies.

Associations Between Gastric Atrophy and Its Interaction With Poor Oral Health and the Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Region of China: A Population-Based Case-Control Study.

Previous findings concerning gastric atrophy as a potential risk factor for esophageal squamous cell carcinoma (ESCC) have been inconsistent. We aimed to test whether gastric atrophy and, further, its interaction with poor oral health elevated the risk of ESCC in a high-risk region of China. Our population-based case-control study in Taixing, China (2010–2014), recruited cases from local hospitals and the local cancer registry. Controls were selected randomly from the local population registry. Ultimately, 1,210 cases and 1,978 controls answered questionnaires and provided blood samples for assay of pepsinogens. Unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. Gastric atrophy (defined as a serum level of pepsinogen I of <55 μg/L) was associated with an increased risk for ESCC (odds ratio = 1.61; 95% confidence interval: 1.33, 1.96), even after full adjustment for potential confounding factors. In addition, suggestion of an additive interaction between gastric atrophy and poor oral health was observed (relative excess risk due to interaction = 1.28, 95% confidence interval: 0.39, 2.18). We conclude that gastric atrophy appears to be a risk factor for ESCC in a high-risk region of China, and there is a suggested additive interaction with poor oral health that increases this risk even further.

Non-invasive laboratory markers assessing efficacy of Helicobacter pylori eradication therapy

Effective eradication of Helicobacter pylori infection is an important means to reduce the risk of precancerous changes in the gastric mucosa and prevention of gastric cancer. A search for non-invasive diagnostic tools for Helicobacter pylori infection, evaluation of the effectiveness of eradication remains of high importance.The aim of the study was to assess an informative value of detecting pepsinogen I and II as well as serum antibodies to Helicobacter pylori while assessing an efficacy of treated chronic Helicobacter gastritis and identifying preneoplastic changes in the stomach mucosa. There enrolled 113 male patients with chronic gastritis aged 41 to 76, average age- (56.7±0.7) years. Examination of patients was carried out at admission to the clinic, as well as at 2 and 12 months after administering a standard eradication therapy. It was found that Helicobacter pylori infection was detected in 101 (89.4%) patients. Groups of patients with effective eradication therapy were noted. A time-dependent level of antibodies to Helicobacter pylori, as well as measured concentration of pepsinogen I and II after the onset of eradication treatment were determined. Which were analyzed in connection with the results of histology examination of gastric mucosa biopsy specimens and expression of oncoproteins Ki-67, Bcl-2, c-erbB-2, p16 in the gastric mucosa depending on efficacy of eradication therapy. It is shown that effective eradication therapy was characterized by significantly decreased serum level of IgG antibodies to Helicobacter pylori 2 months after the onset of treatment. Moreover, a significantly decreased pepsinogen II and serum IgG antibodies to Helicobacter pylori during eradication therapy were accompanied by a significant decrease in Ki-67 expression in the gastric epithelium. Decreased concentration of pepsinogen II within the first year after Helicobacter pylori eradication therapy was due to a greater decrease in activity of inflammatory changes in the gastric mucosa than to dynamic changes in gastric atrophy and metaplasia. An inverse relation between the serum level of pepsinogen I and atrophy as well as intestinal metaplasia within the gastric mucosa were found.

Analysis of factors associated with recovery of the serum pepsinogen ratio after Helicobacter pylori eradication: a long-term follow-up study in Korea

Objective: Serum levels of pepsinogen (PG) are related to Helicobacter pylori-induced inflammation of the gastric mucosa. This study aimed to examine the influence of H. pylori eradication on serum PG, analyze its associated factors, and evaluate the long-term outcomes.Methods: H. pylori-positive patients who underwent gastroscopy and serum PG measurement were enrolled in a single academic hospital. After H. pylori eradication, the measurement of serum PG level was performed. Recovery of serum PG I/II ratio was defined as a PG I/II ratio after eradication of >3.0 in patients with a PG I/II ratio ≤ 3.0 before eradication. Follow-up involved serum PG measurement and gastroscopy with a rapid urease test annually.Results: In all, 327 patients were eligible for study inclusion. Compared to those before H. pylori eradication, serum PG I (74.9 vs. 44.3 ng/mL, p < .001) and PG II (25.4 vs. 9.1 ng/mL, p < .001) levels significantly decreased after successful eradication. In addition, there was a significant increase in serum PG I/II ratio after eradication (3.07 vs. 4.98, p < .001). In multivariate analyses, the following were independently associated with failed recovery of serum PG I/II ratio despite successful eradication: age ≥ 60 years (odds ratio [OR] = 0.231, 95% confidence interval [CI] = 0.084–0.629, p = .004) and severe gastric atrophy (OR = 0.156, 95% CI = 0.055–0.440, p < .001).Conclusions: Recovery of serum PG I/II ratio after H. pylori eradication may be achieved in H. pylori-infected patients aged <60 years without severe gastric atrophy.