Serum Pepsinogen Research Articles

Fundic gland polyps accurately predict a low risk of future gastric carcinogenesis

Few reports have analyzed the clinical importance of sporadic fundic gland polyps (FGPs). The aim of this study was to investigate the relationship between sporadic FGPs and condition of the gastric mucosa stratified by serum pepsinogen levels and Helicobacter pylori antibody level. Three hundred and seventy-five subjects undergoing gastrointestinal endoscopy were enrolled. Subjects on proton pump inhibitors were excluded. Pathologically proven FGPs, and other endoscopic findings (reflux esophagitis, gastric and duodenal ulcer) were examined and serum pepsinogen levels, H. pylori antibody concentration and gastric juice pH were measured simultaneously. Subjects with normal serum pepsinogen and negative H. pylori antibodies were defined as having "low risk" stomachs, suggesting low risk of gastric carcinogenesis. Of the 375 subjects, 44 showed FGPs. The prevalence of "low risk" stomach in subjects with and without FGPs was 98% and 48%, respectively. Multivariable logistic regression analysis indicated three variables as independent factors positively associated with "low risk" stomachs: FGPs (odds ratio [OR] 38.6), reflux esophagitis (OR 4.8), and age<60 years (OR 1.89). Gastric juice pH, which is associated with mucosal atrophy grade and low pH indicates less mucosal atrophy, was significantly lower in subjects with (1.64 ± 0.64) than without FGPs in "low risk" (1.94 ± 1.12) and "high risk" stomachs (3.99 ± 2.31). Sporadic FGPs tend to be related to the least atrophic mucosa among non-gastric atrophy subjects without H. pylori infection, and can be used as predictors of a low risk of gastric carcinogenesis.

Complementary and alternative medicinal effects of broccoli sprouts powder on Helicobacter pylori eradication rate in type 2 diabetic patients: A randomized clinical trial

The effectiveness of high-sulforaphane broccoli sprouts powder, as both complementary and alternative treatment, was compared to the standard triple therapy on Helicobacter pylori eradication in type 2 diabetic patients. Eighty-six type 2 diabetic patients with positive H. pylori stool antigen test (HpSAg) were randomized to receive one of the three following regimens: (STT) standard triple therapy, (BSP) 6g/d broccoli sprouts powder for 28days, and combination of these as STT+BSP. H. pylori eradication rates were assessed both by HpSAg and the urea breath test (UBT). Fasting serum glucose, insulin, insulin resistance, pepsinogen (PG) I and II levels and PGI/II ratio were also assessed. The H. pylori eradication rates, as assessed by UBT and HpSAg, were 85.3% and 89.3% in STT, 36.0% and 56.0% in BSP, and 83.3% and 91.7% in STT+BSP groups, respectively. There were no significant differences in serum pepsinogen I, pepsinogen II and PGI/PGII ratio and glucose homeostasis parameters between the three groups. BSP regimen despite a considerable effect on H. pylori eradication could not compete with the standard triple therapy.

Performance profile of a FDG-PET cancer screening program for detecting gastric cancer: results from a nationwide Japanese survey

It has been reported that gastric cancer is the sixth most common cancer found during the (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening program, which is defined as cancer screening of asymptomatic subjects using FDG-PET(/CT) (in combination with other screening tests or not). The aim of this study was to analyze the detection rate and the effectiveness of the FDG-PET cancer screening program at detecting gastric cancer between 2006 and 2009 in Japan. A total of 153,775 asymptomatic subjects (92,255 men, 61,520 women) between 30 and 80 years old underwent the FDG-PET cancer screening program. Of these, we analyzed 790 cases with findings of possible gastric cancer in any screening test. The number of cases who were verified to have gastric cancer was 124. Among these, only 47 cases were detected by FDG-PET, which resulted in a relative sensitivity of 37.9% and a positive predictive value of 33.6%. The relative sensitivity of FDG-PET was much lower than those of gastric endoscopy and the serum pepsinogen test. The FDG-PET screening program in Japan detected some cases of early-stage gastric cancer, but this was not achieved using FDG-PET alone but in combination with gastric endoscopy. Gastric endoscopy should be included in FDG-PET cancer screening programs to screen for gastric cancer.

Age-Dependent Association among Helicobacter pylori Infection, Serum Pepsinogen Levels and Immune Response of Children to Live Oral Cholera Vaccine CVD 103-HgR

BackgroundThrough its effects on gastric secretion, we hypothesized that Helicobacter pylori infection may influence oral immunization. Accordingly, we examined the association between H. pylori infection, serum pepsinogen (PG) (measures for H. pylori gastritis) and vibriocidal antibody (a correlate of protection) seroconversion following oral immunization with CVD 103-HgR live cholera vaccine among children of different ages.MethodsSera from 422 Chilean children who were vaccinated with a single dose of CVD 103-HgR were tested by ELISA for serum IgG antibodies to H. pylori, PG I and PG II levels and antibodies to Shigella flexneri 2a lipopolysaccharide and hepatitis A virus (as markers of low socioeconomic status and exposure to enteric pathogens).ResultsThe likelihood of vibriocidal antibody seroconversion following vaccination with CVD 103-HgR was significantly decreased in H. pylori-seropositive children age 6 months to 4 years with PG II>8 µg/L (adjusted OR 0.14 (95% CI 0.03–0.61; P = 0.009), and also in H. pylori seropositives with lower PG II level (adjusted OR 0.34, 95% CI 0.14–0.83; P = 0.017), compared to H. pylori-seronegatives. H. pylori-seropositive children aged 5–9 years with serum PG I>30 µg/L (indicating more severe gastritis) had higher odds of vibriocidal seroconversion than those with lower PG I levels (adjusted OR 4.41, 95%CI 1.26–15.38; P = 0.02). There was no significant association between exposures to S. flexneri 2a or hepatitis A virus and vibriocidal seroconversion.ConclusionsAs H. pylori gastritis progresses with increasing pediatric age in developing country venues, changes in gastric secretion ensue that we believe explain the observed differences in age-related immune responses to immunization with live oral cholera vaccine. The effect of H. pylori and changes of gastric acid secretion on the immunogenicity of various oral vaccines should be studied in different developing, transitional and industrialized country settings.

Low pepsinogen I level predicts multiple gastric epithelial neoplasias for endoscopic resection.

Background/AimsSynchronous/metachronous gastric epithelial neoplasias (GENs) in the remaining lesion can develop at sites other than the site of endoscopic resection. In the present study, we aimed to investigate the predictive value of serum pepsinogen for detecting multiple GENs in patients who underwent endoscopic resection.MethodsIn total, 228 patients with GEN who underwent endoscopic resection and blood collection for pepsinogen I and II determination were evaluated retrospectively.ResultsThe mean period of endoscopic follow-up was 748.8±34.7 days. Synchronous GENs developed in 46 of 228 (20.1%) and metachronous GENs in 27 of 228 (10.6%) patients during the follow-up period. Multiple GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001). Synchronous GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001).ConclusionsLow pepsinogen I levels predict multiple GENs after endoscopic resection, especially synchronous GENs. Cautious endoscopic examination prior to endoscopic resection to detect multiple GENs should be performed for these patients.

The value of serum pepsinogen levels for the diagnosis of gastric diseases in Chinese Han people in midsouth China

BackgroundSerum pepsinogen (PG) levels are valuable in the diagnosis of gastric diseases. However, PG levels are affected by many factors such as the area and race. This study aimed to investigate serum PG levels in patients with different gastric diseases who were Chinese Han people in Hunan Province, midsouth China.MethodsA total of 248 gastric disease patients and 34 healthy controls were enrolled. The patients included those with non-atrophic and chronic atrophic gastritis, gastric and duodenal ulcer, early and advanced gastric cancer. Serum PG I and II levels were detected by Biohit ELISA kit (Finland), and PG I/II ratio was calculated. Differences in patients with gastric disease and healthy controls were analyzed using paired t-test.ResultsCompared with controls, patients with early and advanced gastric cancer had a significantly lower PG I level and PG I/II ratio (p <0.005). In contrast, patients with gastric and duodenal ulcer had a significantly higher PG I level (p <0.005). Compared with atrophic gastritis patients, patients with early and advanced carcinoma of the stomach had a significantly lower PG I/II ratio (p < 0.001). Combination of the cut-off levels of PG I (70 μg/L) and PG I/II ratio (6) provided 62.1% sensitivity of and 94.2% specificity for the diagnosis of gastric cancer.ConclusionsDecreased PG I level and PG I/II ratio are risk factors for gastric cancer. Combined use of serum PG I level and PG I/II ratio may help the early diagnosis of gastric cancer.

Cutoff Serum Pepsinogen Values for Predicting Gastric Acid Secretion Status

Measurement of the gastric acid secretion is useful for estimating the risk for various diseases in the upper gastro-intestinal tract; however, the procedure causes significant distress to the subjects. Pepsinogens I and II are secreted from the gastric fundic glands, and thus, the serum pepsinogen levels reflect the gastric functional statuses. The aim of this study is to establish appropriate serum pepsinogen cutoff points for predicting the gastric acid secretion status. In a total of 627 Japanese subjects, gastric acid secretion was measured with an endoscopic gastrin test, and the serum pepsinogen values and serum Helicobacter (H.) pylori-IgG antibody were also measured. After checking the correlation between gastric acid secretion and serum pepsinogen, the receiver operating characteristics analyses were employed for determining the most suitable cutoff points of serum pepsinogen for the gastric acid secretion status (i.e., hypochlorhydria, profound hypochlorhydria, and hyperchlorhydria). The pepsinogen I/II ratio and pepsinogen I showed the best correlation with gastric acid secretion in H. pylori-positive and H. pylori-negative subjects, respectively. The serum pepsinogen I/II ratio (or pepsinogen I in cases of H. pylori-negative subjects) was useful to determine the gastric acid secretion status with acceptable to outstanding diagnostic accuracy (the range of the area under the curve: 0.79-0.93). The diagnostic accuracy was further improved after stratifying the subjects by H. pylori-infection status. Estimating gastric acid secretion levels by simple measurement of serum pepsinogens will have significant clinical implications in estimating the risks for various diseases of the upper gastrointestinal tract.

False Sero-Negative Results for Helicobacter Pylori Infection Indicate Increased Risk of Severe Atrophic Gastritis in Japanese Patients

Background/objective: H. pylori infection is commonly diagnosed using an anti-H. pylori IgG antibody test. However, a proportion of results are falsely sero-negative. We investigated characteristics of patients falsely seronegative for H. pylori in relation to gastric atrophy. Methods: H. pylori infection (Hp+ or Hp-) was determined based on culture test, rapid urease test (RUT), and polymerase chain reaction (PCR) test in 280 outpatients. Anti-H. pylori antibody titers ≥ 10 U/ml were diagnosed as sero-positive for H. pylori (IgG+), while those <10 U/ml were sero-negative (IgG-). Serum pepsinogen (PG) I/PG II ratios were calculated as a serological marker of gastric atrophy. Endoscopic gastric mucosal atrophy was also assessed according to the Kimura-Takemoto classification system. Results: The mean PG I/PG II ratio in each group was as follows: Hp-/IgG- (4.99 ± 1.04, n=10), Hp+/IgG+ (2.59 ± 1.51, n=240), Hp-/IgG+ (5.65 ± 2.72, n=4) and Hp+/IgG- (3.02 ± 2.61, n=26). The mean serum PG I/PG II ratio in the Hp+/IgG- group was lower than those of Hp-/IgG- and Hp-/IgG+ groups (P=0.028 and 0.072). Incidence of severe gastric mucosal atrophy in the Hp+/IgG- group was highest of the four groups. Conclusions: Individuals falsely sero-negative for H. pylori infection is at increased risk of severe atrophic gastritis, which is well known as precancerous lesion.

Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans.

Helicobacter pylori-eliminating effects of FEMY-R7, composed of fucoidan and evening primrose extract, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1×109 CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with 10 or 100 mg/kg FEMY-R7 for 2 weeks. In Campylobcter-like organism-detection test, FEMY-R7 markedly reduced the urease-positive reactivity. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with a capsule containing 150 mg FEMY-R7 for 8 weeks. FEMY-R7 significantly decreased both the Delta over baseline-value in urea breath test and the serum pepsinogens I and II levels. The results indicate that FEMY-R7 not only eliminates H. pylori from gastric mucosa of animals and humans, but also improves gastric function.

Analysis on variation of serum pepsinogen in our gastric cancer screening test

Analysis on variation of serum pepsinogen in our gastric cancer screening test

Meta-analysis on validity of serum pepsinogen measurement for mass screening of gastric carcinoma in the high-risk population

Meta-analysis on validity of serum pepsinogen measurement for mass screening of gastric carcinoma in the high-risk population

Clinical significance of serum pepsinogens in screening of gastric cancer and gastric ulcer

Clinical significance of serum pepsinogens in screening of gastric cancer and gastric ulcer

Comparison of a barium X-ray examination and a combination test using a urine anti-Helicobacter pylori IgG antibody and serum pepsinogen levels

Comparison of a barium X-ray examination and a combination test using a urine anti-<I>Helicobacter pylori</I> IgG antibody and serum pepsinogen levels

Serum Helicobacter pylori CagA antibody titer as a useful marker for advanced inflammation in the stomach in Japan

Subjects infected with Helicobacter pylori containing cagA do not always induce serum CagA antibody. Our previous meta-analysis showed that serum CagA seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum CagA-positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti-CagA antibody titer and the levels of pepsinogen (PG), and histological score. Eighty-eight H. pylori-positive Japanese patients with gastritis were included. Serum CagA antibody titer, PG I, and PG II were evaluated by ELISA. Histological scores were evaluated according to Update Sydney System. CagA expression was examined by immunoblot. Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA antibody titer was significantly correlated with PG I and PG II levels (P = 0.003 and 0.004, respectively). Serum CagA antibody titer was also significantly correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand, bacterial density was not related with CagA antibody titer. CagA expression level of the strains was irrespective of the status of PG and serum CagA antibody. Subjects with higher serum CagA antibody titer can be considered as high-risk population for the development of gastric cancer from the point of strong gastric inflammatory response even in Japan. Host recognition rather than bacterial colonization might be associated with the difference of serum CagA antibody titer.

Abstract C13: Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening

Abstract Objective: This study evaluated the role of multiple serological tests (including serum pepsinogen I (PGI), PGII, PGI/II ratio, anti-H. pylori IgG antibody, and gastrin-17 tests) individually and in combination in gastric cancer (GC) screening. Design: Data were from the Zhuanghe Gastric Cancer Study, a 15-year, population-based endoscopic, gastric diseases screening program in northern China. From 1997 to 2011, esophagogastroduodenoscopies with gastric mucosal biopsies were conducted on 10,693 participants. All serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. Logistic regression was used to calculate odds ratios (OR) with 95 percent confidence intervals (95% CI) and produce receiver operator characteristic (ROC) curves with corresponding c statistics. In addition, results were replicated in an independent hospital-based population. Results: PGI/II ratio monotonically decreased as gastric mucosa progresses from normal mucosa to precancerous conditions, and to GC, and a low PGI/II ratio (≥ 6.6) was associated with an increased risk of prevalent GC (OR = 2.34, 95% CI: 1.62, 3.39). PGI/II ratio individually or in combination with PGI, PGII, anti-H. pylori IgG antibody and gastrin-17 provided the same c statistic of 0.62 for screening for GC. PGI, PGII, anti-H. pylori IgG antibody or gastrin-17 tests individually provided c statistics less than or equal to 0.55. For identifying abnormal gastric conditions including GC, the five serological tests in combination provided adequate discriminatory performance (c = 0.77), and yielded a sensitivity of 84.0% and specificity of 50.0%. The results from the independent hospital-based population were similar. Conclusion: Our results suggest that serum PGI, PGII, PGI/II ratio, anti-H. pylori IgG and gastrin-17 tests can be used as prescreening tests for patients at high risk for GC. Citation Format: Huakang Tu, Liping Sun, Yuehua Gong, Qian Xu, Qi Long, Roberd Bostick, Yuan Yuan. Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C13.

Serum pepsinogen reference intervals in apparently healthy Chinese population with latex enhanced turbidimetric immunoassay

AimSerum pepsinogen (sPG) has been used to help in diagnosing atrophic corpus gastritis and in screening for gastric cancer non-invasively. There are as yet no reports on sPG reference intervals...

A possible association of low pepsinogen I and pepsinogen I/II with low and high body weight in Japanese men

BackgroundIt is unknown whether low serum pepsinogen I and pepsinogen I/II ratio (PGI–PGI/II), a marker for chronic atrophic gastritis, is associated with low or high body weight. MethodsWe investigated the association between low PGI–PGI/II and both ends of the spectrum of body mass index (BMI) in 819 apparently healthy Japanese men aged 20–75years who received a medical check-up in 2008. ResultsIn univariate analysis, serum pepsinogen I, but not pepsinogen II or pepsinogen I/II, was significantly reduced across the increasing BMI categories. Multivariate regression analysis showed that, compared with BMI 21.0–22.9kg/m2, BMI of 20.9kg/m2 and less or 25.0kg/m2 and above was significantly associated with low PGI–PGI/II (pepsinogen I<50ng/ml combined with PG I/II<3.0), even after adjustment for relevant confounders. These associations showed a J-shaped curve against BMI. ConclusionLow PGI–PGI/II may be independently associated with both low body weight and obesity in Japanese men.

Screening of Gastric Cancer: Who, When, and How

Gastric cancer (GC) remains the leading cause of cancer mortality worldwide. Conceivably, early diagnosis may be achievable through screening of the high-risk population. Therefore, it is important to identify individuals harboring premalignant lesions that include atrophic gastritis, intestinal metaplasia, and mucosal dysplasia. The age threshold for GC screening depends on the regional incidence and the individual risk. In high-incidence countries such as Japan and Korea, the age to screen GC may be as early as 40 years. The mass screening by endoscopy in these countries would be able to detect a substantial portion of patients with early GCs as well as precancerous lesions. For the purpose of eliminating GC, however, these screening programs should be conducted in conjunction with Helicobacter pylori eradication. In low-incidence countries, it seems feasible to adopt a stepwise approach to identify high-risk individuals at first. The initial screening should focus on epidemiologic factors, genetic or hereditary risks, and the status of H pylori infection. Measurement of serum pepsinogen I and II and gastrin may detect atrophic gastritis in a noninvasive manner. Patients with these premalignant lesions should then receive endoscopic examination and enter surveillance. To date, there is no cost-effective strategy for an average-risk individual from a population with low incidence of GC, and therefore screening is unwarranted and cannot be recommended for them.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer

Background:Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue and previous reports have suggested the possibility of serum miRNAs as complementary tumour markers. The aim of the study was to investigate serum miRNAs and pepsinogen levels in individuals at high risk for gastric cancer both before and after H. pylori eradication.Methods:Patients with recent history of endoscopic resection for early gastric cancer and the sex- and age-matched controls were enrolled. Serum was collected from subjects before or after eradication and total RNA was extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II levels were measured using enzyme-linked immunosorbent assay kits.Results:Using miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before and after H. pylori eradication and miR-21 after eradication were significantly higher in the high-risk group than in the controls. H. pylori eradication significantly decreased miR-106b levels and increased let-7d only in the control group. After eradication, the combination MiR-106b with miR-21 was superior to serum pepsinogen and the most valuable biomarker for the differentiating high-risk group from controls.Conclusion:Serum miR-106b and miR-21 may provide a novel and stable marker of increased risk for early gastric cancer after H. pylori eradication.