Serum PGI Research Articles

Reference Ranges and Comparison of Pepsinogen by Chemiluminescence Immunoassay and Enzyme-Linked Immunosorbent Assay in Chinese Population.

Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed. 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov-Smirnov test was used to assess the distribution of variables. The Kruskal-Wallis H or Mann-Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods. On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00-110.64 ng/mL, 2.50-19.13 ng/mL, and 3.87-13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93-205.06 ng/mL, 1.65-17.96 ng/mL, and 7.50-33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them. This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.

Risk Assessment of Gastric Cancer and Precancerous Condition Using Serum Pepsinogen and H. Pylori Antibody Test

Objectives: We aimed to determine serum PGs (serum pepsinogens) and H. Pylori IgG in atrophic gastritis and gastric cancer patients and evaluate the gastric cancer risk.Method: We enrolled 40 gastric cancer patients, 40 chronic atrophic gastritis patients and 40 healthy control subjects. Serum PGI, PGII, and H. pylori IgG levels were measured by ELISA. The PGI to PGII ratio was calculated.Results: The mean age of the subjects was 60±10.9 years, We found that 52.6% (n=60) were male. H. Pylori IgG was positive in 67 subjects. The serum PGI and PGR levels were significantly decreased in gastric cancer and atrophic gastritis groups compared to the healthy control. According to classification ABC (D), group D had higher proportion of atrophic gastritis cases, group C had higher proportion of gastric cancer cases than others. Additionally, we evaluated all subjects by giving one point to each of the age ≤40, positive family history of gastric cancer, positive previous gastric disease history, PGI ≤75.07 ng/ml, PGR ≤6.25, or two point to each of PGI ≤35.25 ng/ml, and PGR ≤5.27, with score ranging between 0-7. As score increased, the risk of atrophic gastritis or gastric cancer increased.Conclusion: A combination of methods involving PGs and other risk factors may predict the probability of gastric cancer and could identify individuals who may need upper endoscopy.

Diagnostic Value of Serum Pepsinogen Ⅰ/Pepsinogen Ⅱ Combined with Tumor Markers for Helicobacter pylori-Positive Early-Stage Gastric Cancer

To investigate the diagnostic value of serum pepsinogen (PG) Ⅰ/PGⅡ combined with tumor markers for Helicobacter pylori ( Hp)-positive early-stage gastric cancer. A retrospective study was conducted with the clinical data of 109 patients with gastric cancer (the gastric cancer group), 115 patients with chronic atrophic gastritis (the benign group), 112 cases of low-grade intraepithelial neoplasia (the low grade group), 109 cases of high-grade intraepithelial neoplasia (the high grade group), and 104 healthy subjects who underwent the relevant screening tests as part of their general physical examination (the healthy group). All the subjects were admitted to or received care at our hospital between May 2018 and April 2021. The levels of serum PGⅠ, PGⅡ, carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724), and Hp infection status were examined. The findings for these indicators were compared among the groups, and the differences in serum indicators in Hp-positive and Hp-negative patients were compared. The diagnostic value of serum PGⅠ/PGⅡ combined with tumor markers for Hp-positive early-stage gastric cancer was assessed with receiver operating characteristic (ROC) curve. The serum levels of PGⅠ and PGⅠ/PGⅡ decreased in successive order in the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group ( P<0.05). The serum levels of PGⅡ, CEA, CA199, and CA724 in the gastric cancer group, the high grade group, and the low grade group were all higher than those in the healthy group and the benign group ( P<0.05). The Hp-positive rates of the gastric cancer group, the high grade group, the low grade group and the benign group were higher than that of the healthy group ( P<0.01). The levels of serum PGⅠ, PGⅡ, CEA, CA199, and CA724 of the Hp-positive subjects of the healthy group, the benign group, the low grade group, the high grade group, and the gastric cancer group were higher than those of the Hp-negative subjects ( P<0.05), while their PGⅠ/PGⅡ levels were always lower than those of the Hp-negative persons ( P<0.05). The specificity and area under the curve ( AUC) of serum PGⅠ/PGⅡ, CEA, CA199, and CA724 in the combined diagnosis of Hp-positive early-stage gastric cancer were higher than those of each indicator used alone in diagnosis ( P<0.05). In the gastric cancer group, the proportion of patients with PGⅠ/PGⅡ>2.32 was lower in the Hp-positive patients than that in the Hp-negative patients ( P<0.05), while the proportions of patients with CEA>66.99 ng/mL, CA199>110.35 U/mL, and CA724>44.20 U/mL were higher in the Hp-positive patients than those in the Hp-negative patients ( P<0.05). Testing PGⅠ/PGⅡ in combination with CEA, CA199, and CA724 results in better diagnostic value for Hp-positive early-stage gastric cancer.

Establishment of Reference Values for Pepsinogens in Healthy Subjects of the Gansu Province: a Cross-Sectional Study.

At present, the pepsinogen reference values applicable to subjects from Gansu province have not been established. Therefore, the current study aimed to establish reference values for PGI, PGII, and the PGI/ PGII ratio in Gansu Province, Northwest China. The present study was a cross-sectional study. Following screening in the physical examination center of Gansu Provincial Hospital, 2,130 healthy subjects were enrolled (age range 18 - 88 years; BMI range 15.35 - 38.89 kg/m2) from March 2018 to December 2020. Serum PGI and PG II concentration levels were detected by chemiluminescence. The reference values were defined according to age and gender by non-parametric 95th percentile intervals. The increase in age caused a gradual increase in the levels of PG I and PG II, while PG I/PG II ratio gradually decreased. The PG I, PG II and PG I/PG II ratio in males were significantly higher than those in females. The reference values for PG I, PG II and PG I/PG II ratio in males: < 40 years old were 22.79 - 119.79 ng/mL, 3.02 - 21.57 ng/mL, and 2.99 - 10.25, respectively; ≥ 40 years old were 17.58 - 125.12 ng/mL, 3.70 - 25.84 ng/mL, and 1.52 - 10.53, respectively. The reference values for PG I, PG II, and PG I/PG II ratio in females: < 40 years old were 22.57 - 103.90 ng/mL, 3.17 - 20.73 ng/mL, and 2.28 - 10.46, respectively; ≥ 40 years old were 14.24 - 117.81 ng/mL, 3.36 - 29.57 ng/mL, and 1.26 - 9.85, respectively. The present study determined the missing reference values of serum PGs for healthy subjects of different gender and ages in Gansu Province.

Human gastric cancer risk screening: From rat pepsinogen studies to the ABC method.

We examined the development of gastric cancer risk screening, from rat pepsinogen studies in an experimental rat gastric carcinogenesis model induced with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and human pepsinogen studies in the 1970s and 1980s to the recent “ABC method” for human gastric cancer risk screening. First, decreased expression or absence of a major pepsinogen isozyme, PG1, was observed in the rat gastric mucosa from the early stages of gastric carcinogenesis to adenocarcinomas following treatment with MNNG. In the 1980s, decreases in PGI in the human gastric mucosa and serum were identified as markers of atrophic gastritis. In the 1990s, other researchers revealed that chronic infection with Helicobacter pylori (Hp) causes atrophic gastritis and later gastric cancer. In the 2000s, a gastric cancer risk screening method combining assays to detect serum anti-Hp IgG antibody and serum PGI and PGII levels, the “ABC method”, was established. Eradication of Hp and endoscopic follow-up examination after the ABC method are recommended to prevent gastric cancer.

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.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer.

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

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.

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.

血清PGI、PGII、PGR、G-17水平与Hp-IgG联合检测对胃癌早期诊断的临床价值分析

Objective To investigate the clinical value of combined detection of serum pepsinogen (PG)Ⅰ, PGⅡ, PGⅠ/PGⅡ (PGR), gastrin-17 (G-17) and IgG anti-Helicobacter Pylori (IgG anti-Hp) in the diagnosis of early gastric cancer. Methods One hundred and twenty patients with gastric cancer (early gastric cancer group), 60 patients with atrophic gastritis (atrophic gastritis group) and 120 healthy volunteers (control group) who were examined or treated in our hospital from January 2018 to June 2019 were selected as the subjects. The levels of serum PGⅠ, PGⅡ, PGR, G-17 and IgG anti-Hp were compared among the three groups. The indicators and combined diagnostic value were analyzed by receiver operating characteristic (ROC) curve. Results The levels of PGⅠ in early gastric cancer group, atrophic gastritis group and control group were (59.85±8.59)ng/ml, (72.19±9.89)ng/ml, (96.83±8.66)ng/ml, with statistically significant difference (F=530.504, P<0.001). The levels of PGⅡ in the three groups were (23.19±2.45)ng/ml, (20.60±4.19)ng/ml, (16.52±3.34)ng/ml, with statistically significant difference (F=130.085, P<0.001). The levels of PGR in three groups were 2.78±0.69, 4.33±0.95, 6.21±1.46, with statistically significant difference (F=288.801, P<0.001). The levels of G-17 in the three groups were (77.04±10.09)ng/ml, (64.69±7.22)ng/ml, (55.91±8.32)ng/ml, with statistically significant difference (F=170.770, P<0.001). The levels of IgG anti-Hp in the three groups were (70.23±8.11)IU, (58.30±9.37)IU, (33.00±5.24)IU, with statistically significant difference (F=778.431, P<0.001). The levels of serum PGⅠand PGR in early gastric cancer group and atrophic gastritis group were significantly lower than those in control group (all P<0.05). The levels of serum PGⅠand PGR in early gastric cancer group were significantly lower than those in atrophic gastritis group (both P<0.05). While serum PGⅡ, G-17 and IgG anti-Hp in early gastric cancer group and atrophic gastritis group were significantly higher than those in control group (all P<0.05). The levels of PGⅡ, G-17 and IgG anti-Hp in gastric cancer group were significantly higher than those in atrophic gastritis group (all P<0.05). According to the ROC curve, the critical value of serum PGⅠ diagnosis was 73.11 ng/ml, the sensitivity was 63.33%, the specificity was 83.33%, and the area under the curve (AUC) was 0.801. The critical value of serum PGⅡ diagnosis was 19.55 ng/ml, the sensitivity was 75.83%, the specificity was 72.22%, and the AUC was 0.760. The critical value of serum PGR diagnosis was 4.60, the sensitivity was 82.50%, the specificity was 77.22%, and the AUC was 0.816. The critical value of serum G-17 diagnosis was 64.33 ng/ml, the sensitivity was 64.17%, the specificity was 65.56%, and the AUC was 0.631. The critical value of IgG anti-Hp diagnosis was 53.80 IU, the sensitivity was 59.17%, the specificity was 75.00%, and the AUC was 0.708. At the critical tangent point, the sensitivity, specificity and AUC of PG I + IgG anti-Hp were 69.17%, 76.67% and 0.754 respectively; the sensitivity, specificity and AUC of PGR + IgG anti-Hp were 88.33%, 74.44% and 0.798 respectively; the sensitivity, specificity and AUC of G-17 + IgG anti-Hp were 71.67%, 65.56% and 0.718 respectively. The sensitivity of joint detection of the five indexes was 92.50%, the specificity was 72.22%, and the AUC was 0.869. The sensitivity of joint detection was significantly higher than that of individual detection (all P<0.05), and the AUC of joint detection was significantly higher than that of individual indexes (Z=1.848, P=0.032; Z=3.145, P=0.001; Z=1.688, P=0.046; Z=7.726, P<0.001; Z=4.931, P<0.001; Z=3.188, P=0.001; Z=1.783, P=0.037; Z=4.534, P<0.001). Conclusion The combined detection of serum PGⅠ, PGⅡ, PGR, G-17 and IgG anti-Hp can improve the sensitivity of gastric cancer diagnosis and it is of great significance and value for early diagnosis of gastric cancer. Key words: Stomach neoplasms; Pepsinogens; Helicobacter Pylori; Gastrin-17

Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats

To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.

Analysis of serum gastric function and Helicobacter pylori infection in patients with gastric hyperplastic polyps and gastric fundic gland polyps

Objective To analyze the serum gastric function and Helicobacter pylori (HP) infection in patients with gastric hyperplastic polyps and gastric fundic gland polyps. Methods From December 2017 to December 2018, 135 patients with gastric polyps and pathologically confirmed gastric hyperplastic polyps and gastric fundic gland polyps were enrolled in the hospital of Xuzhou Medical University.Among them, 68 patients with hyperplastic polyps, 67 cases of the gastric fundic gland polyps.Serum Hp antibodies (UreA, UreB, VacA, CagA antibodies) were qualitatively detected by immunoblotting.Eighty patients with chronic superficial gastritis were selected as the control group.Three groups of serum pepsinogen-I (PG-I), pepsinogen-Ⅱ (PG-Ⅱ), gastrin were detected by enzyme-linked immunosorbent assay (ELISA). Gastrin-17(G-17) and calculate PGⅠ and PGⅡ ratio(PGR). Results The levels of serum PGⅡ (13.13(8.15, 20.30) μg /L) and G17 (8.44(3.72, 27.17) pmol/L) in the gastric hyperplastic polyp group were higher than those in the control group (9.16(5.56, 15.14) μg/L and 1.83(0.87, 5.95) pmol/L) (P<0.05), and the PGR level was lower than the control group (P<0.05); serum PGI (120.12(86.72, 174.70) μg/L), PGII (11.92(7.27, 22.26) μg/L), G17 (5.68(1.79, 14.65) pmol/L) in the gastric fundic gland polyp group was higher than the control group ((101.32(79.17, 131.33) μg /L, 9.16(5.56, 15.14) μg /L, 1.83(0.87, 5.95) pmol/L)(P均<0.05)) (P<0.05); serum G17 (8.44(3.72, 27.17) pmol/L) level in gastric hyperplastic polyp group was higher than gastric fundus polyp group (5.68(1.79, 14.65) pmol/L) (P<0.05); Hp infection rate in gastric hyperplastic polyp group61.76%(42/68)was higher than that in the gastric fundic gland polyp group40.30%(27/67) (P<0.05), and type I Hp was the main one (P<0.05). The serum PGⅡ and G17 levels in the gastric hyperplastic polyp group were higher than those of Hp negative (all P<0.05). There were no significant differences in serum PGI, PGⅡ, G17, and PGR levels between the HP-positive and negative-positive patients in the gastric fundus polyp group.The serum PGI and PGR levels in the hypertrophic polyp group were higher than those in the HPⅡ type (all P<0.05). There was no significant difference in the levels of serum PGⅠ, PGⅡ, G17, and PGR between the gastric fundic gland polyps group and the type Ⅱ. Conclusion Serum PG and G17 levels in patients with gastric hypertrophic polyps and gastric fundic gland polyps are higher than those in patients with chronic superficial gastritis.Patients with gastric hyperplastic polyps have higher HP infection rate and abnormal gastric function than gastric fundic gland polyps. Key words: Gastric hyperplastic polyp; Gastric fundus polyp; Helicobacter pylori; pepsinogen; Gastrin

Clinical study on Anzhong-Fuyuan decoction combined with western routine therapy for helicobacter pylori positive chronic atrophic gastritis

Objective To evaluate the efficacy of Anzhong-Fuyuan decoction combined with western routine therapy in the treatment of helicobacter pylori(H.pylori)-positive chronic atrophic gastritis (CAG). Methods A total of 110 H.pylori positive CAG patients who met the inclusion criteria were divided into two groups according to random number table method, 55 in each group. The control group was treated with quadruple therapy. On the basis of the control group, the study group was treated with Anzhong-Fuyuan decoction. Both groups were treated continuously for 40 days. The serum level of pepsinogen I (Pepsinogen Ⅰ, PG Ⅰ), pepsinogen Ⅱ (PG Ⅱ), gastrin (GAS), endothelin (ET), CRP, IL-6 and TNF-α were detected by ELISA. The eradication rate of H.pylori was measured by 14C urea breath test, and the clinical efficacy was evaluated. Results The total effective rate was 92.7% (51/55) in the study group and 78.2% (43/55) in the control group. There were significant differences between the two groups (χ2=4.681, P=0.031). The eradication rate of H.pylori was 89.1% (49/55) in the study group and 76.4% (42/55) in the control group. There was significant difference between the two groups (χ2=3.911, P=0.048). After treatment, the level of serum PGⅠ(84.87 ± 13.95 g/L vs. 78.05 ± 12.69 g/L, t=3.434) and PGⅠ/PGⅡ (6.71 ± 1.26 vs. 5.86 ± 1.13, t=2.861) in the study group was significantly higher than those in the control group (P<0.05), and PGⅡ (12.64 ± 1.94 g/L vs. 13.31 ± 2.10 g/L, t=3.725) was significantly lower than those in the control group (P<0.01). The serum level of gastrin (10.76 ± 3.06 mmol/L vs. 8.11 ± 2.84 mmol/L, t=4.707) was higher than that of control group (P<0.01), endothelin (56.64 ± 4.42 ng/L vs. 60.42 ± 5.13 ng/L, t=4.140) was significantly lower than that of control group (P<0.01). After treatment, the level of CRP, IL-6 and TNF-α in the study group was significantly lower than those in the control group (t=11.100, 9.571 and 8.687, respectively, all Ps< 0.001). Conclusions The Anzhong-Fuyuan decoction combined with routine therapy can significantly enhance the gastric mucosal secretion ability of H.pylori positive CAG patients, increase the ratio of PGⅠ/PGⅡ, promote the repair and regeneration of gastric mucosa, reduce the level of inflammatory cytokines. Key words: Helicobacter pylori; Gastritis, atrophic; Anzhong-Fuyuan decoction; Quadruple therapy; Clinical application

Clinical significance of serum markers reflecting gastric function and H. pylori infection in colorectal cancer.

Purpose: The study was conducted to investigate the relationship of serum pepsinogens PGI, PGII, gastrin-17, and Hp-IgG with colorectal cancer (CRC), aiming to explore the clinical significance of serum markers reflecting gastric function and H. pylori infection in CRC.Methods: A total of 569 CRC cases and 569 age and sex-matched controls were enrolled in this study between June 2012 and April 2016 from The First Hospital of China Medical University. The serum markers reflecting gastric function and H. pylori infection were detected using ELISA, including PGI, PGII, PGI/II ratio, G-17 and Hp-IgG. Information of clinicopathological parameters and tumor biomarkers was collected from the medical records of inpatients, including CEA, CA199, CA125, CA153 and AFP.Results: Serum PGII, G-17 levels and Hp-IgG were increased in CRC, while PGI and PGI/II ratio appeared no significant difference between CRC and controls. In subgroup analysis, PGII was more significant in males (P=0.014). Hp-IgG was demonstrated higher in age<60y (P=0.001). With respect to the association with serum tumor biomarkers, G-17 level was associated with the rise of CA125 (P=0.005, OR (95%CI): 4.89 (1.90-12.57)), Hp-IgG increasing was associated with the rise of CA125 (P=0.024, OR (95%CI): 4.10 (1.54-10.93)).Conclusions: Serum PGII, G-17 and Hp-IgG were associated with CRC risk. The serum levels of G-17 and Hp-IgG were associated with the rise of CA125 in patients with CRC

Prevalence and determinants of serological evidence of atrophic gastritis among Arab and Jewish residents of Jerusalem: a cross-sectional study

ObjectiveUnderstanding the correlates of premalignant gastric lesions is essential for gastric cancer prevention. We examined the prevalence and correlates of serological evidence of atrophic gastritis, a premalignant gastric condition, using...

Absence of Plasma Gastric Biomarker Elevations with Chronic Dosing of Avatrombopag, a Novel Oral Thrombopoietin Receptor Agonist, in Patients with Chronic Immune Thrombocytopenia in Phase 3 Trials

Background: Avatrombopag (AVA) is an oral, thrombopoietin receptor agonist approved by FDA for the treatment of thrombocytopenia in patients with chronic liver disease scheduled to undergo a procedure. AVA is also being developed for other indications including chronic immune thrombocytopenia (cITP) (Bussel et al, Blood, 2014; Wojciech et al, Br J Haematol, in press 2018). In repeated-dose studies in mice, rats and cynomolgus monkeys, there were AVA dose, concentration, and duration-dependent histologic changes in gastric fundic glands that reversed by 4 weeks after dosing was stopped. This was associated with decreased gastric acid production, hypergastrinemia, and increased intragastric pH in all species. The NOAEL in 2-year toxicology studies was defined at exposures 4 to 21-fold the recommended human AVA dose.Hypergastrinemia and parietal cell hyperplasia have also been reported with proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RA). These findings may be secondary to suppression of gastric acid production, and, in rodents, may lead to gastric carcinoids. Findings of hypergastrinemia-related gastric hyperplasia in rodents have a low risk/relevance to humans.To further evaluate the preclinical findings and screen for atrophic gastritis, gastric biomarkers (gastrin, gastrin-17, and pepsinogen I/II [PG-I/PG-II]) were measured in 2 Phase 3 trials with chronic AVA dosing. These multicenter, randomized, controlled Phase 3 trials were conducted in patients with cITP, and assessed clinical safety and efficacy of AVA versus placebo (PBO) (Study 1- NCT01438840) or eltrombopag (ELT) (Study 2- NCT01433978); Study 2 was terminated early due to enrollment challenges.Methods: Both Phase 3 trials enrolled adults (≥18 years) with chronic ITP (Baseline platelet count (PC) <30x109/L), who were randomized 2:1 to receive either 20 mg/day AVA or PBO (Study 1) or 1:1 to 20 mg/day AVA or ELT (50 mg/day) (Study 2) orally with food for 26 weeks. Individual patient AVA (5-40 mg/day) or ELT (25-75 mg/day) dose titration was permitted.Patients with Baseline fasting gastrin-17 levels greater than upper limit of normal (ULN) were excluded from the study, as were patients taking PPIs or H2RAs if not on a stable dose or if gastrin-17 levels were >1.5 times the ULN.Safety analyses included adverse event (AE) monitoring and laboratory testing, including fasting gastric biomarkers. Patients who developed 2 consecutive fasting gastrin-17 levels >2.5 times the ULN or low serum PG-I levels or low PG-I/PG-II ratio (with low fasting gastrin-17 levels) were to be discontinued from the trials. Patients with elevations >5 times the ULN were to undergo endoscopy to assess the gastric mucosa.Results: A total of 64 patients were treated with AVA across the two trials (Study 1 n=47; Study 2 n=17); the majority were white (92.2%) and female (64.1%), with a mean age of 46.6 years. The median duration of exposure to AVA was 35.1 weeks, with a mean daily dose of 24.6 mg; 75% of subjects received AVA doses between 5 and 40 mg for ≥20 weeks. AVA was shown to be superior to PBO in the median cumulative number of weeks of platelet response (PC ≥50×109/L in the absence of rescue therapy) in Study 1 (12.4 vs. 0.0 weeks, respectively; p <0.0001). Mean Baseline PCs in Study 1 were similar in AVA- and PBO-treated subjects (14.1 and 12.7x109/L, respectively), and peaked at 205.4 and 11.6x109/L on Week 2; mean Baseline PCs were lower in Study 2 in AVA- compared to ELT-treated subjects (13.0 and 18.2x109/L, respectively), and increased to 184.8 and 91.6x109/L at Week 2.Of the AVA-treated patients, no significant changes in the mean fasting gastrin, gastrin-17, PG-I, PG-II, or the PG-I/PG-II ratio were observed from Baseline over the course of the trial (Figure 1). In addition, no patients met the gastric biomarker change criteria for discontinuation or to undergo endoscopy. Common AEs in Study 1 included headache, contusion and upper respiratory tract infections, with 4 cases of thromboembolic events.Conclusions: In Phase 3 trials, AVA was shown to be effective and well tolerated in the treatment of thrombocytopenia in patients with cITP, with most patients demonstrating substantial platelet increases. In particular, treatment of cITP with AVA was not associated with an increase in gastric biomarkers including gastrin, gastrin-17 or pepsinogen and, therefore, no signal of gastric toxicity was identified with chronic AVA dosing of up to 26 weeks. [Display omitted] DisclosuresBussel:Prophylix: Consultancy, Research Funding; Protalex: Consultancy; Amgen Inc.: Consultancy, Research Funding; Uptodate: Honoraria; Rigel: Consultancy, Research Funding; Momenta: Consultancy; Novartis: Consultancy, Research Funding. Allen:Dova Pharmaceuticals: Employment, Equity Ownership. Tian:Dova Pharmaceuticals: Employment, Equity Ownership. Kuter:Pfizer: Consultancy; ONO: Consultancy; Amgen Inc.: Consultancy; Novartis: Consultancy; Syntimmune: Consultancy; Protalex: Research Funding; Rigel: Consultancy, Research Funding; Argenx: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Consultancy, Research Funding; BMS: Research Funding; Principia: Research Funding.

The Association Between Serum Pepsinogen and Cardiovascular Disease

Background: Serum pepsinogen (PG), as a valuable biomarker for gastric mucosal injury, has been proposed as a risk factor for development of metabolism diseases. The research is to systematically evaluate the features of PG in cardiovascular disease (CVD) in Northwest China. Methods: 14,886 patients were enrolled in this cross-sectional study. The bias and the differences in the baseline characteristics were matched by propensity- score matching. Multivariate logistic regression was applied to evaluate the association of PG levels with CVD risk and to further assess the effects of a series of risk factors on the PG levels in CVD. Results: Serum PGⅠ, PGⅡlevels and PGR were significantly different in CVD patients compared with the non-CVD patients (p 200 ng/ml (OR=1.678, 95% CI= 1.23-2.29, p=0.001), (OR=2.525, 95% CI=1.274-5.004, p=0.008), respectively), PG Ⅱ>6.5 ng/ml (OR=1.709, 95% CI =1.389-2.102, p˂0.001), PGR≤3 (OR=2.434, 95% CI=1.886-3.142, p˂0.001). And, the analysis further showed that age, body mass index, monocyte number, diuretic use, homocysteine level, cardiomyopathy and coronary heart disease were contributed to the abnormal levels of serum PG. Conclusions: The abnormal levels of serum PG were significantly associated with CVD risk. The role of serum PG played in vascular homeostasis need to be investigated in the future for exploring the pathogenesis of CVD and balancing the potential causal effects from one disease to the other disease. Funding Statement: This work was supported by the Talent Innovation and Entrepreneurship Project of Lanzhou (No. 2017-RC-43); Gansu Youth Science and Technology Fund Project (No.18JR3RA057). Declaration of Interests: The authors state none to disclosures. Ethics Approval Statement: The study was approved by the Ethics Committee of Gansu Provincial Hospital. The authors followed the hospital’s privacy guidelines to keep all patients’ electronic data confidential.

Clinical significance of Serum Pepsinogen I/II and gastrin-17 determination in gastric cancer diagnosis and prognosis

Currently, the diagnosis of atrophic gastritis and gastric cancer are mainly made by endoscopy and histopathology. Our study aimed to explore the practical value of Serum Pepsinogen I/II and gastrin-17 in gastric cancer diagnosis and prognosis. We collected 60 cases of gastric ulcer from February 2015 to November 2016 as gastric ulcer group, and 40 cases of gastric cancer treated in the same period as gastric cancer group. In 3 years after gastric cancer, 20 patients were served as postoperative gastric cancer group, and 70 healthy subjects as control group. The results showed that serum Pepsinogen I/II, gastrin-17, and other serum gastric function indexes were tested by enzyme-linked immunosorbent assay (ELISA). The serum PGI level of gastric ulcer group was higher than control group ( P &lt; 0.05). The serum G-17 concentrations in gastric ulcer group, gastric cancer group, and postoperative gastric cancer group were all higher than control group ( P &lt; 0.05). The area under receiver operating characteristic (ROC) curve of PGI screening was 0.905 and the best cutoff point was PGI &lt; 75 µg/L. Their sensitivity and specificity were 87.2% and 75.1%; the area under ROC curve of PGI/PGII rate screening was 0.761 and the best cutoff point was PGI/PGII &lt; 4. Their sensitivity and specificity were 88.9% and 62.3%. Multi logistical regression showed that the level of serum PGI, PGI, and G-17 and the odds ratio (OR) level of gastric cancer risk were 2.093, 2.653, and 0.494 ( P &lt; 0.05). The examination of Serum Pepsinogen I/II, gastrin-17, and other serum gastric function indexes can be used in the diagnosis and prognosis of gastric cancer and has a rather high practical value in monitoring recurrence in postoperative gastric cancer patients.

The diagnosis value of serum PGI, PGII and IgG anti-Hp in patients with gastric cancer

Objective To explore the relationship between the serum PGⅠ, PGⅡ, PGⅠ/PGⅡ ratio(PGR), IgG anti-HP and gastric cancer and the diagnostic value. Methods The levels of serum PGⅠ, PGⅡ, PGⅠ/PGⅡ ratio(PGR) and IgG anti-HP were detected by emulsio immunoturbidimetry and ELISA in 30 patients with gastric cancer and 30 healthy subjects as controls. Then, the best cut-off value was established to screen gastric cancer. Results The levels of serum PGⅠ, PGⅡ, PGR and IgG anti-HP in the gastric cancer group were (33.72±6.49)ng/L, (8.36±1.26)ng/L, (3.67±0.72), (69.74±15.86)IU, respectively, which in the control group were (111.36±15.86)ng/L, (10.57±1.71)ng/L, (10.53±1.34), (34.62±8.94)IU, respectively. The levels of serum PGⅠ, PGⅡ and PGR in the gastric cancer group were significantly lower than those in the control group(t=25.58, 5.60, 24.67, all P<0.01), while the level of serum IgG anti-HP was significantly higher than that in the control group(t=10.55, P<0.01). Compare the serum PGⅠ, PGR between IgG anti-HP positive group and IgG anti-HP negative group, there was statistically significant differences(t=5.77, 4.02, 3.76, all P<0.01). According to the ROC curves, the best cut-off points of PGⅠ, PGⅡ, PGR, IgG anti-HP were 32.54 ng/L[sensitivity 80.7%, specificity 75.0%, area under curve (0.775±0.075)], 7.73 ng/L[sensitivity 75.4%, specificity 70.5%, area under curve (0.742±0.071)], 3.48[sensitivity 86.4%, specificity 72.5%, area under curve (0.859±0.067)] and 69.11 IU[sensitivity 59.1%, specificity 75.0%, area under curve (0.667±0.089)]. Conclusion Detection of serum PGⅠ, PGR, and IgG anti-HP levels can be useful as a way to screen gastric cancer, the PGR may the best single measure to diagnosis of gastric cancer. Key words: Stomach neoplasms; Pepsinogen A; Pepsinogen C; Helicobacter pylori

The correlation between histological gastritis staging- ‘OLGA/OLGIM’ and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China

Background: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years.Goals: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM.Methods: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson’s χ2 test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test.Results: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7 ± 10.8 years. Patients among OLGA/OLGIM Stage III–IV were presented with a lower level of serum PGI and PGI/PGII (p < .05), especially for Stage IV (p = .01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p = .022; p = .028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p = .036; p = .013). In addition, the percentage of G-17 <1 pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p = .029). The proportion of G-17 > 15 pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p = .023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p < .001, p < .001).Conclusions: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.