Pepsinogen Research Articles

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Helicobacter pylori infection and serum pepsinogen concentrations in an elderly population representative of Costa Rica

INTRODUCTION: Costa Rica has among the highest mortality rates from gastric cancer in the world, largely due to late detection. It is therefore important that economically and logistically sustainable screening is implemented in order to detect risk of developing cancer. We have previously shown that low pepsinogen (PG) values and infection with Helicobacter pylori-CagA+ are associated with risk of gastric atrophy and cancer in Costa Rican populations. OBJECTIVES: To determine how markers for gastric cancer risk are distributed in an elderly population representative of Costa Rica in order to design a screening strategy. METHODS: The population studied consists of 2,652 participants in a nationally representative survey of ageing. Information concerning epidemiologic, demographic, nutritional and life style factors is available. Serum PG concentrations as well as H. pylori and CagA status were determined by serology. Possible associations were determined by regression analyses. RESULTS: Antibodies to H. pylori were present in 72% of the population and of those, 58% were CagA positive. Infection with H. pylori was associated with higher PGI concentrations (p=0.000) and infection with H. pylori-CagA+ with lower PGI concentrations (p=0.025). Both showed association with lower PGI/PGII (p=0.006 and p=0.000). Higher age was associated with lower prevalence of H. pylori infection (OR=0.98; p=0.000) and CagA+ (OR=0.98; p=0.000) but not with PG values. Regions with high risk of gastric cancer showed lower PGI (p=0.004) and PGI/PGII values (p=0.021) as well as higher prevalence of H. pylori infection (OR=1.39; p=0.013) but not CagA+. Using cut-off values of PGI&lt;100 µg/L and PGI/PGII&lt;2.0, 2.5 and 3.0, 7-15% of the population would be considered at risk. CONCLUSIONS: H. pylori alone is not a useful marker for risk of gastric cancer. Screening using serum pepsinogen concentrations and infection with H. pylori-CagA+ is feasible in the general elderly population of Costa Rica but appropriate cut-off values have to be determined based on more clinical data and follow up capacity.

Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.

Background and aim:Chronic Atrophic Gastritis (CAG) is a precancerous condition for gastric cancer (GC) as single risk factor, being a consequence of a previous Helicobacter pylori (Hp) infection or based on autoimmune mechanisms. Achlorhydria plays an important role towards the formation of a class I carcinogen, acetaldehyde, after food intake. L-cysteine has been claimed to be able to bind in a covalent way acetaldehyde when administered at meals.Methods:In this study we enrolled two CAG groups of patients, one treated whit 300 mg/daily of L-cysteine for one year, the other one untreated. We assessed gastric function lasting the one-year follow-up by using noninvasive surrogates, i.e. Pepsinogen I (PGI) and gastrin 17 (G17).Results:In the group of 77 CAG on therapy we found a statistically significant increase in PGI values and a decrease in G17 levels, in comparison with unchanged values in control group.Conclusions:L-cysteine seems able to provide a recovery in gastric function when administered in CAG patients and could be proposed as a possible therapy in such patients. (www.actabiomedica.it)

A non-invasive combined strategy to improve the appropriateness of upper gastrointestinal endoscopy.

Background and aim:Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative.Materials and methods:At our Endoscopy Unit of Alto Vicentino Hospital, ULSS 7 Pedemontana, a tertiary center in northeastern Italy, from 2013 to 2015, a senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori.Results:A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases. Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer.Conclusions:This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy. (www.actabiomedica)

Serum gastrin-17 concentration for prediction of upper gastrointestinal tract bleeding risk among peptic ulcer patients.

BACKGROUNDSerum gastrin-17 (G-17), pepsinogen I (PGI), and pepsinogen II (PGII) concentrations regulate gastric acid secretion, and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestinal bleeding. These associations suggest that serum G-17, PGI, and (or) PGII may predict gastrointestinal bleeding risk among peptic ulcer patients. AIMTo evaluate the efficacies of serum G-17, PGI, PGII, and PGI/PGII ratio (PGR) for predicting upper gastrointestinal bleeding among peptic ulcer patients.METHODSA total of 199 patients diagnosed with peptic ulcer confirmed by gastroscopy and positivity for Helicobacter pylori by the 14C-urea breath test were recruited, including 107 patients with simple peptic ulcer and 92 cases complicated by upper gastrointestinal bleeding. Serum PGI, PGII, G-17, and PGR were measured by immune methods and compared between bleeding and non-bleeding groups by univariate analysis. The specificity and sensitivity of PGs and G-17 for evaluating upper gastrointestinal bleeding risk were then assessed by constructing receiver operating characteristic (ROC) curves.RESULTSSerum G-17 was significantly higher among peptic ulcer patients with upper gastrointestinal bleeding compared to simple peptic ulcer patients (25.34 ± 14.29 vs 8.84 ± 8.03 pmol/L, t = 9.822, P < 0.01), whereas serum PGI, PGII, and PGR did not differ significantly between bleeding and non-bleeding groups (all P > 0.05). The risk of bleeding was significantly higher among peptic ulcer patients with elevated serum G-17 (> 15 pmol/L) compared to patients with normal or low serum G-17 (73.2% vs 27.4%, χ2 = 40.72, P < 0.01). The area under the ROC curve for serum G-17 was 0.866 ± 0.024, and a cut-off of 9.86 pmol/L yielded 90.2% sensitivity and 68.2% specificity for distinguishing peptic ulcer with and without upper gastrointestinal bleeding.CONCLUSIONSerum G-17 is significantly upregulated in peptic ulcer patients and higher levels are predictive of upper gastrointestinal bleeding. Conversely, serum PGI, PGII, and PGR have no predictive value. Further prospective studies are warranted to examine if high G-17 can be used to assess risk of bleeding prior to onset.

Preliminary Study on Reference Interval of Serum Pepsinogen in Healthy Subjects.

ObjectiveThis study determined the reference interval of pepsinogen (PG) of healthy people in the local region to provide a basis for early screening of gastric cancer.MethodsAmong the healthy people who underwent a physical examination in our hospital from January 2020 to December 2020, 2568 subjects were selected based on the relevant screening criteria. Their serum PG I and II levels and PG I:PG II ratio were determined by chemiluminescent microparticle immunoassay (CIMA), and the results were statistically analyzed. Finally, according to document CLSI-C28-A3, the PG reference interval of the local region was determined.ResultsThe PG I and II levels of the males in all age groups were higher than those of the females in the corresponding age groups, and the differences were statistically significant (P < 0.05). However, the differences in the PG I:PG II ratio between the genders in the different age groups were not statistically significant (P > 0.05). The PG I and II levels increased with age in both men and women, while the PG I:PG II ratio was not correlated with age in either gender.ConclusionThe PG reference interval of the local region was initially determined as providing a reliable reference basis for clinical treatment.

Association of serum pepsinogen with degree of gastric mucosal atrophy in an asymptomatic population.

BACKGROUNDAtrophic gastritis is a precancerous lesion of the stomach. It has been reported that pepsinogen (PG) can reflect the morphology and function of the gastric mucosa, and it is therefore used as a marker for the early diagnosis of atrophic gastritis.AIMTo evaluate the diagnostic value of serum PG for degree of gastric mucosal atrophy in asymptomatic Chinese upon physical examination.METHODSMedical data were collected from subjects who underwent transnasal gastroscopy between October 2016 and October 2018. For each study subject, serum PG levels and presence of Helicobacter pylori (H. pylori) infection were investigated. Pathology was evaluated using the Operative Link for Gastritis Assessment (OLGA) classification and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems. All statistical analyses were carried out using SPSS statistical software.RESULTSA total of 2256 subjects were enrolled and 1922 cases were finally included in the study. Based on the OLGA grading system, the levels of PGI were slightly decreased, while those of PGII were slightly increased. The PGI/PGII ratio (PGR) was reduced with increasing atrophy. The association between PG and OLGA grading was higher compared with that between PG and the OLGIM grading system. Compared with the OLGA-0 group, a statistically significant difference was observed in the mean age of OLGA-I, III, and IV groups (P < 0.05). In the H. pylori-positive subjects, the PGR levels were notably lower in the OLGA-I, II, and III groups compared with the OLGA-0 group (P < 0.05). H. pylori-positive subjects exhibited significantly higher PGI and PGII serum levels and a significantly lower PGR compared with H. pylori-negative patients in different OLGA groups (P < 0.05). CONCLUSIONSerum PG levels may represent a non-invasive screening marker for gastric mucosal atrophy in asymptomatic subjects.

Serum Assay Findings after Successful Helicobacter pylori Eradication

Serum pepsinogen (PG), anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG), and gastrin-17 (G-17) are plasma biomarkers for gastritis. H. pylori serology titers and PG levels increase during active H. pylori infection; moreover, elevated PG II levels indicate a high risk for diffuse-type gastric cancer in East Asian populations. Serum PG I/II ratios and PG I levels decrease with the progression of gastric corpus atrophy; thus, a combination of serum PG I levels ≤70 ng/mL and a PG I/II ratio ≤3 (serologic atrophy) indicates a high risk of intestinal-type gastric cancer. Serum G-17 is often not used as an indicator in H. pylori-seroprevalent populations because it is usually elevated in subjects with H. pylori infections. When H. pylori is eradicated, most patients show a rapid decrease in serum PG II levels and anti-H. pylori IgG titers within a few months. Seroreversion is required for several months to years after regression of H. pylori. Moreover, seroreversion may not always be achieved in all eradicated cases. The serum PG I/II ratio starts to increase after eradication; therefore, serologic atrophy improves accordingly, unless severe atrophy is present. Thus, some eradicated patients may show normal serum assay findings but have a higher risk for developing gastric cancer than H. pylori-naive subjects. Furthermore, serum PG levels decrease after gastrectomy and increase with the intake of certain drugs (e.g., aspirin or acid suppressants) or in renal failure patients. Due to such wide variations, serum assays are inadequate for the confirmation of H. pylori eradication. It is useful when interpreted with gastroscopy and other H. pylori test findings.

Clinical Value of Combined Detection of Serum sTim-3 and Pepsinogen for Gastric Cancer Diagnosis.

PurposeThe present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis.Patients and MethodsThe double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed.ResultsSerum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL).ConclusionsTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.

Value of GastroPanel in the diagnosis of atrophic gastritis.

Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as precursor of the intestinal type of gastric cancer, is of growing interest. The combination of pepsinogen (PG), gastrin-17 (G17) and anti-Helicobacter pylori (H. pylori) antibody serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test remains uncertain. The aim of our study was to assess the diagnostic performance of the serum panel test (GastroPanel) for the diagnosis of atrophic gastritis. From dyspeptic patients, endoscopic biopsy samples (two from the gastric corpus and two from the antrum) and blood samples were collected. The determination of sPGI, sPGII, sG17 and IgG antibodies to H. pylori (H.p IgG) was performed using an enzyme-linked immunosorbent assay (GastroPanel; Biohit Oyj). Histopathology results were compared with GastroPanel values. Sixty patients were included: 35 (58.3%) females and 25 (41.66%) males; mean age 67.63±9.36 years; 45% H. pylori-positive. A total of 65% of patients had atrophic gastritis. There were no significant differences between the levels of biomarkers and localization of atrophy. The ratio PG1/PG2 was lower in patients with multifocal atrophy; the difference being close to the threshold of statistical significance. In cases of intestinal metaplasia the values of G17, PG1, PG2, H.p IgG were not statistically altered compared to those without intestinal metaplasia; only the ratio PG1/PG2 was lower in intestinal metaplasia; the difference being almost of statistical significance. Our results revealed that, GastroPanel values did not differ depending on the severity of the atrophy. Biomarkers used by GastroPanel do not have enough accuracy for use in the diagnosis of atrophy in the population studied. A low accuracy only for the ratio PG1/PG2 in patients with multifocal atrophy was found. However, our data revealed a correlation in detecting intestinal metaplasia.

Effect of Helicobacter pylori eradication therapy on clinical and laboratory biomarkers associated with gastric damage in healthy school-aged children: A randomized non-blinded trial.

Helicobacter pylori (H.pylori) is the primary cause of gastric cancer and eradication in healthy adults has proven effective in decreasing cancer incidence. H.pylori is acquired largely in early childhood, however, the benefits of eradication in children are controversial. We aimed to determine the effect of H.pylori eradication on clinical and laboratory markers associated with gastric damage in apparently healthy school-aged children. This was a pilot non-blinded trial including 61 children persistently infected with H.pylori who were randomized to eradication/no treatment and followed for at least 12months, evaluating clinical and blood markers (Pepsinogen I (PGI) and II (PGII) determined by ELISA) associated with gastric damage. The treatment consisted of a sequential scheme including 7days of omeprazole+amoxicillin followed by 7days of omeprazole+clarithromycin+metronidazole; adherence and tolerance were surveyed. Eradication rates were assessed by stool antigen detection or urea breath test 1month following treatment every 4months thereafter to detect reinfection. Eradication occurred in 30/31 treated children (median age: 8.8, range: 7.9-10.8) and in 0/30 non-treated controls (median age: 8.6, range: 7.9-11) (p<.001). Treatment was associated with mild transient symptoms (altered taste, nocturnal upper abdominal pain, nausea, and diarrhea). Baseline frequency of symptoms was low and eradication did not change symptoms compared to controls. PGI, PGII, and anti-H.pylori seropositivity were similar in both groups at baseline and significantly decreased only in eradicated patients; PGI (92.5 vs. 74.4, p<.001), PGII (15.2 vs. 8.9, p<.001) levels, and frequency of anti-H.pylori seropositivity (100 vs. 68%, p<.001) respectively. Four eradicated children (13%) were reinfected during follow-up. H.pylori eradication therapy in apparently asymptomatic school-aged children was well tolerated and associated with decreased serum PGI and PGII levels. Future studies should expand on the middle-long-term effect of early H.pylori eradication, especially on preventing gastric cancer.

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.

Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG.

ObjectiveThe aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients.MethodsmiR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed.ResultsIn the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others.ConclusionThese results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.

Five Autoimmune Gastritis Patients with Positive Findings of Serum Anti-parietal Cell Antibodies

Autoimmune gastritis is a corpus-dominant type of gastritis with positive serum anti-parietal cell antibodies (APCA) and/or anti-intrinsic factor antibodies. Serum APCA and pepsinogen (PG) assays were performed in subjects with corpus-dominant gastritis detected by endoscopy. Serum APCA was positive in five patients. All these patients were postmenopausal women (four Koreans and one Caucasian from the Russian Federation) with a mean age of 59.0±3.2 years. They displayed low PG I levels ranging from 8.1 to 18.8 ng/mL (mean, 11.4±4.8 ng/mL) and low PG I/II ratios ranging from 0.7 to 2.4 (mean, 1.2±0.7). Three of the patients were being treated for autoimmune thyroiditis. Multiple gastric neuroendocrine tumors were observed in two Helicobacter pylori (H. pylori)-naive patients with high serum gastrin levels exceeding 700 pg/mL and serum chromogranin A levels exceeding 1,000 ng/mL. In the remaining three patients, intestinal metaplasia was observed in the biopsied specimens from the antrum, suggesting a history of H. pylori infection. Our findings indicate the value of positive serum APCA findings, low serum PG I levels, and low serum PG I/II ratios in confirming autoimmune gastritis in patients showing corpus-dominant atrophy, regardless of their H. pylori infection status.

Pepsinogen and Serum IgG Detection Is a Valuable Diagnostic Method for Helicobacter pylori Infection in a Low-Prevalence Country: A Report from Sri Lanka.

The use of serum anti-Helicobacter pylori IgG and pepsinogen (PG) detection as a diagnostic method was evaluated in Sri Lanka. Gastric biopsies were performed (353 patients), and the prevalence of H. pylori infection was 1.7% (culture) and 2.0% (histology). IgG serology testing showed an area under the curve (AUC) of 0.922 (cut-off, 2.95 U/mL; specificity, 91.56%; sensitivity, 88.89%). Histological evaluation showed mild atrophy (34.3%), moderate atrophy (1.7%), metaplasia (1.7%), chronic gastritis (6.2%), and normal tissue (56%). The PGI/PGII ratio was significantly higher in H. pylori-negative patients (p < 0.01). PGII and PGI/PGII levels were lower in patients with metaplasia than in those with normal mucosa (p = 0.049 and p < 0.001, respectively). The PGI/PGII ratio best discriminated metaplasia and moderate atrophy (AUC 0.88 and 0.76, respectively). PGI and PGII alone showed poor discriminative ability, especially in mild atrophy (0.55 and 0.53, respectively) and chronic gastritis (0.55 and 0.53, respectively). The best cut-off to discriminate metaplasia was 3.25 U/mL (95.19% specificity, 83.33% sensitivity). Anti-H. pylori IgG and PG assessment (ABC method) was performed (group B, 2.0%; group A, 92.1%). The new cut-off more accurately identified patients with metaplasia requiring follow-up (group B, 5.4%). Assessment of anti-H. pylori IgG and PG is valuable in countries with a low prevalence of H. pylori infection.

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.

LGR5-Expressing Cells in the Healing Process of Post-ESD Ulcers in Gastric Corpus.

LGR5 is a promising stem cell marker in gastric pylorus, but there are few reports on its expression in human gastric corpus. To investigate the involvement of LGR5 expression in gastric corpus ulcer regeneration in humans. LGR5 expression was analyzed in five post-ESD ulcers during the healing process of regenerating epithelial cells of the gastric corpus. LGR5 expression was detected by mRNA in situ hybridization using an RNA scope kit. Immunohistochemistry of MUC6, HIK1083, and pepsinogen 1 (PG1) was performed to identify cell differentiation. We defined MUC6+/HIK1083-/PG1-, MUC6+/HIK1083+/PG1-, MUC6+/HIK1083+/PG1+, MUC6+/HIK1083-/PG1+, and MUC6-/HIK1083-/PG1+cells as pseudopyloric mucosa (PPM) phase 1 (PPM1), PPM phase 2 (PPM2), PPM phase 3 (PPM3), immature chief cells (ICC), and mature chief cells (MCC) in order from the ulcer center, respectively. In the regenerated mucosa around post-ESD ulcers, LGR5 expression was observed throughout the gland in PPM1-PPM3, but it was limited to the bottom of the gland in ICC and MCC. Furthermore, LGR5 expression was not identified in the normal gastric corpus. The H-score of PPM2 was significantly higher than that of PPM3 (P = 0.0313). The H-score of PPM3 was significantly higher than that of ICC (P = 0.0313). The LGR5 H-score was higher at the immature stage, which decreased gradually with progression of the differentiation stage. LGR5 expression appears to contribute to mucosal regeneration in the human gastric corpus. The application of LGR5 expression analysis to mucosal regeneration and fundic gland-type gastric tumors is expected.

Application of serum pepsinogen and carbohydrate antigen 72-4 (CA72-4) combined with gastrin-17 (G-17) detection in the screening, diagnosis, and evaluation of early gastric cancer

Gastric cancer is a common malignant tumor. The aim of the present study was to analyze the application value of serum pepsinogen (PG), carbohydrate antigen 72-4 (CA72-4), and gastrin-17 (G-17) detection in the screening, diagnosis, and evaluation of early gastric cancer. In total, 122 patients with gastric cancer treated in our hospital from January 2018 to January 2021 were selected as the gastric cancer group and subdivided into the early gastric cancer (group A) and advanced gastric cancer (group B) groups. Sixty-five patients with benign gastric disease treated in the same hospital during the same period were selected as the control group, and 122 healthy people who underwent physical examination during the same period were allocated to the control group. The differences in the levels of G-17, PGI, PGII, PGI/PGII, and CA72-4 were compared; receiver-operating characteristic curves were drawn; and the efficacy of different factors in the diagnosis of early gastric cancer was calculated. G-17, PGI, and PGI/PGII levels in the gastric cancer group were significantly lower than those in the healthy group, and CA72-4 was significantly higher than that in the healthy group (P<0.05), but there was no significant difference in PGII between the 2 groups (P>0.05). G-17, PGI, and PGI/PGII levels in groups A and B were significantly lower than those in the control group. CA72-4 in groups A and B was significantly higher than that of the control group, and was highest in group B (P<0.05). The areas under the curve (AUC) of G-17, PGI, PGI/PGII, and CA72-4 were 0.671, 0.726, 0.769, and 0.602, respectively, and the AUC of combined detection was 0.883, which was significantly higher than that of single detection. Serum PG, CA72-4 combined with G-17 detection has high sensitivity and specificity in the screening and diagnosis of early gastric cancer, and has high clinical application value.

The Diagnostic Value of Serum Gastrin-17 and Pepsinogen for Gastric Cancer Screening in Eastern China.

Objective To evaluate the diagnostic value of gastrin-17 (G-17) and pepsinogen (PG) in gastric cancer (GC) screening in China, especially eastern China, and to determine the best diagnostic combination and threshold (cutoff values) to screen out patients who need gastroscopy. Methods The serum concentrations of G-17 and pepsinogen I and II (PGI and PGII) in 834 patients were analyzed, and the PGI/PGII ratio (PGR) was calculated. According to pathological results, patients can be divided into chronic nonatrophic gastritis (NAG)/chronic atrophic gastritis (CAG)/intraepithelial neoplasia (IN)/GC groups. The differences in G-17, PG, and PGR in each group were analyzed, and their values in GC diagnosis were evaluated separately and in combination. Results There were differences in serum G-17, PGII, and PGR among the four groups (NAG/CAG/IN/GC) (P ≤ 0.001). In total, 54 GC cases were diagnosed, of which 50% were early GC. There was no significant difference in the PGI levels among the four groups (P = 0.377). NAG and CAG composed the chronic gastritis (CG) group. The G-17 and PGII levels in the IN and GC groups were higher than those in the CG group (both P ≤ oth C), while the PGR levels were lower (P ≤ lower). When distinguishing NAG from CAG, the best cutoff value for G-17 was 9.25 pmol/L, PGII was 7.06 μg/L, and PGR was 12.07. When distinguishing CG from IN, the best cutoff value for G-17 was 3.86 pmol/L, PGII was 11.92 μg/L, and PGR was 8.26. When distinguishing CG from GC, the best cutoff value for G-17 was 3.89 pmol/L, PGII was 9.16 μg/L, and PGR was 14.14. The sensitivity, specificity, accuracy, and positive and negative predictive values of G-17/PGII/PGR for GC diagnosis were 83.3%/70.4%/79.6%, 51.8%/56.3%/47.8%, 53.8%/57.2%/49.9%, 10.7%/10.9%/9.6%, and 97.8%/96.5%/97.1%, respectively. The sensitivity, specificity, accuracy, and positive predictive and negative predictive values of PGII/G-17 vs. PGR/G-17 vs. PGR/PGII in the diagnosis of GC were 63.0% vs. 70.4% vs. 64.8%, 70.5% vs. 70.1% vs. 60.4%, 70.0% vs. 70.1% vs. 60.7%, 12.9% vs. 14.0% vs. 10.2%, and 96.5% vs. 97.2% vs. 96.1%, respectively. Conclusion The PGII and G-17 levels in patients with gastric IN and GC were significantly increased, while the serum PGR level was significantly decreased. Serological detection is effective for screening GC. The combination of different markers can improve the diagnostic efficiency. The highest diagnostic accuracy was G-17 combined with PGR, and the best cutoff values were G − 17 > 3.89 pmol/L and PGR < 14.14.