Changes in Helicobacter pylori Immunoglobulin G Levels and Gastric Mucosal Atrophy after Successful Eradication of Helicobacter pylori

BACKGROUND/AIMS: Limited information is available about the relationship between Helicobacter pylori (H. pylori) immunoglobulin (Ig) G and serum pepsinogen (pepsinogen [PG], a marker of gastric mucosal atrophy) concentrations after H. pylori eradication. MATERIALS AND METHODS: Eligible patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer from August 2007 to March 2013 in a tertiary-referral center, and whose serum H. pylori IgG and PG concentrations were measured at the time of performing ESD and one year post-ESD, were selected. Successful H. pylori eradication was achieved after ESD in all the patients. According to the decrease in serum H. pylori IgG concentration after bacterial eradication, the patients were categorized as group 1 (IgG concentration decreased by <50%), and group 2 (IgG concentration decreased by ≥50%). RESULTS: Of the 106 patients, 25 (23.6%) were classified into group 1 and 81 (76.4%) into group 2. One year after H. pylori eradication, the serum PG II concentration was significantly decreased in group 2 (12.46±8.18 vs. 8.28±6.11, P=0.024). Although the serum PG I/II ratio of group 2 was higher than that of group 1 (8.32±4.52 ng/mL vs. 6.39±4.04 ng/mL), the difference was not significant (P=0.058). One year after successful eradication, elevated serum PG I/II ratio was observed in 21 patients (84%) in group 1 and in 77 patients (95.1%) in group 2 (P=0.087). The mean serum PG I/II ratio was also elevated in both groups. Serum PG II concentration was significantly decreased in group 2. CONCLUSIONS: A notable decrease in the concentration of H. pylori IgG antibody after bacterial eradication might reflect gastric mucosal atrophy. However, our study showed no statistically significant difference.

Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection

Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer.

Helicobacter pylori Stool Antigen Levels and Serological Biomarkers of Gastric Inflammation are Associated with Cardio-Metabolic Risk Factors in Type 2 Diabetic Patients

BACKGROUND: Helicobacter pylori infection and subsequent gastric inflammation have been proposed as risk factors for the development of insulin resistance and cardiovascular disease. In this study we assessed the possible association of H. pylori bacterial load, and serum biomarker of gastric inflammation with cardiometabolic risk factors in diabetic patients. METHODS: In this cross-sectional study, 84 H. pylori-infected type 2 diabetic patients were assessed for anthropometrics, biochemical and clinical measurements. Pearson correlation test, linear, and logarithmic regression curve estimation models were used to assess the association of H. pylori stool antigen (HpSAg) levels, and pepsinogen I (PGI) to pepsinogen II (PGII) ratio with fasting serum glucose, insulin, serum lipid and lipoprotein parameters, malondialdehyde, high-sensitive C-reactive protein (hs-CRP), systolic and diastolic blood pressure, body weight, waist circumference and lipid accumulation product (LAP) index. RESULTS: The mean age of participants was 54+/-10 years, and 44% were men. Mean HpSAg levels and PGI/PGII ratio were 0.24+/-0.23 microg/mL and 9.9+/-9.0, respectively. Higher HpSAg as well as lower PGI/PGII was correlated with higher anthropometric measures and LAP. A significant negative correlation between PGI/PGII ratio and blood pressure (r=-0.21 and r=-0.22, systolic and diastolic, respectively, P<0.05), serum insulin (r=-0.17, P=0.05), and hs-CRP (r=-0.17, P=0.05) was observed. A significant linear association between PGI/PGII ratio with serum triglycerides (beta=-0.24, P<0.05), serum high density lipoprotein cholesterol (HDL-C; beta=0.43, P<0.01), and triglycerides/HDL-C ratio (beta=-0.28, P<0.05) were observed. CONCLUSION: Higher H. pylori bacterial load and lower PGI/PGII ratio was associated with higher levels of cardiometabolic risk factors in H. pylori infected type 2 diabetic patients.

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

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 (1x10(9) 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.

Evaluation of the Performance of Lumipulse G1200 for Tumor Marker Assays

BACKGROUND: Tumor markers are used for diagnosing cancers and monitoring responses to cancer therapy. In this study, we evaluated the performance of Lumipulse G1200 (Fujirebio, Japan), a fully automated serum analyzer, for immunoassays of tumor markers. METHODS: We determined the precision and linearity of assays performed using Lumipulse G1200 and the correlation between the results of this and other analyzers used for tumor markers according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). We used 9 tumor markers, namely, carcinoembryonic antigen, alpha-fetoprotein, cancer antigen 125, cancer antigen 15-3 (CA 15-3), cancer antigen 19-9, prostate specific antigen, protein induced by vitamin K absence or antagonist-II, and pepsinogens I and II. Further, we validated reference intervals using 20 serum samples of healthy individuals. RESULTS: Lumipulse G1200 yielded acceptable precision with total CV0.975 for all markers, except pepsinogen I (0.9569). The reference intervals provided by the manufacturer met the criteria mentioned in the CLSI guideline. CONCLUSIONS: Assays using Lumipulse G1200 had high precision, clinically acceptable linearity, and good correlation with the established assays. This indicates that Lumipulse G1200 can be potentially used in routine laboratories.

Evaluation of the Performance of Lumipulse G1200 for Tumor Marker Assays

BACKGROUND: Tumor markers are used for diagnosing cancers and monitoring responses to cancer therapy. In this study, we evaluated the performance of Lumipulse G1200 (Fujirebio, Japan), a fully automated serum analyzer, for immunoassays of tumor markers. METHODS: We determined the precision and linearity of assays performed using Lumipulse G1200 and the correlation between the results of this and other analyzers used for tumor markers according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). We used 9 tumor markers, namely, carcinoembryonic antigen, alpha-fetoprotein, cancer antigen 125, cancer antigen 15-3 (CA 15-3), cancer antigen 19-9, prostate specific antigen, protein induced by vitamin K absence or antagonist-II, and pepsinogens I and II. Further, we validated reference intervals using 20 serum samples of healthy individuals. RESULTS: Lumipulse G1200 yielded acceptable precision with total CV0.975 for all markers, except pepsinogen I (0.9569). The reference intervals provided by the manufacturer met the criteria mentioned in the CLSI guideline. CONCLUSIONS: Assays using Lumipulse G1200 had high precision, clinically acceptable linearity, and good correlation with the established assays. This indicates that Lumipulse G1200 can be potentially used in routine laboratories.

Low Levels of Pepsinogen I and Pepsinogen I/II Ratio are Valuable Serologic Markers for Predicting Extensive Gastric Corpus Atrophy in Patients Undergoing Endoscopic Mucosectomy

BACKGROUND/AIMS: The levels of pepsinogen (PG) I and the PGI/II ratio are useful serologic markers for chronic atrophic gastritis. This study evaluated the performance and clinical implications of these markers in patients undergoing endoscopic mucosectomy. METHODS: We enrolled 142 consecutive patients with early gastric tumors and Helicobacter pylori infection who were eligible for mucosectomy. Chronic gastritis and atrophy were assessed using four defined biopsy procedures. Serum PGs were measured by an enzyme immunoassay. Optimal diagnostic cut-offs and performance were determined using receiver operating characteristic curves. RESULTS: The PGI level and the PGI/II ratio decreased with corpus-dominant gastritis and as atrophy advanced toward the corpus greater curvature (GC). For the presence of corpus GC atrophy, the areas under the PGI and PGI/II-ratio curves were 0.82 and 0.77, respectively. The optimal cut-off levels were 59.3microg/L for PGI (sensitivity, 83.3%; specificity, 78.4%) and 3.6microg/L for PGI/II ratio (sensitivity, 70.0%; specificity, 78.4%). Using these serologic cut-off levels, we found that the frequency of corpus tumor location differed significantly (32.9% vs 11.1% for PGI or =59.3microg/L, respectively; and 31.1% vs 14.8% for PGI/II ratio or =3.5, respectively; p<0.05). CONCLUSIONS: A low PGI level and PGI/II ratio are valuable serologic markers for predicting corpus GC atrophy, and have clinical implications with respect to the corpus location of tumors in mucosectomy patients.

The Relationship of Gastrin, Pepsinogen, and Helicobacter pylori in Erosive Reflux Esophagitis / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is known as a major cause of atrophic gastritis and is associated with serum gastrin, pepsinogen, and gastric acid secretion. There is still a controversial association between gastroesophageal reflux disease and H. pylori infection. This study was designed to investigate the relationship among serum gastrin, pepsinogen, and H. pylori infection in the erosive reflux esophagitis (ERD) patients. METHODS: Patients who were diagnosed as ERD by one gastroenterologist at the Kangnam St. Marys hospital were prospectively enrolled. The persons without ERD in the control group were matched for age and sex. We examined the gastrin, pepsinogen I (PG I), PG II, PG I/II ratio, and H. pylori infection. RESULTS: Forty five patients were enrolled in ERD group and 66 persons in control group. The H. pylori infection rate in ERD group was lower than that in the control group (11.1% vs. 43.9%, p<0.001). PG I/II ratio in ERD group was higher than that in the control group (7.0+/-3.1 vs. 5.3+/-2.6, p=0.003). The PG II (p=0.016) and gastrin (p=0.029) in ERD group were lower than those in the control group. BMI in ERD group was higher than that in the control group (24.5 vs. 23.1 kg/m(2), p=0.013). CONCLUSIONS: The H. pylori infection rate in ERD group was lower and PG I/II ratio was higher than that in the control group. Reflux esophagitis is thought to be reversely associated with the atrophy of gastric mucosa.

Prognostic value of serum pepsinogen isoenzymes in H. pylor eradication and other treatment modalities on the course of congestive gastropathy

Portal hypertensive gastropathy [PRG] is a common finding in patients with liver cirrhosis. Reduced gastric mucosal defense caused by H pylon may account for the pathogenesis of GI lesions in liver cirrhosis. Pepsinogens are secreted by chief cells in the fundus and body, The ratio of pepsinogen isozymes I and II in serum has good correlation with presence of metaplastic atrophic gastritis Most of the studies showed no relationship between H. pylon infection and congestive gastropathy in Fiver cirrhosis. The aim of this work is to estimate the prognostic value of serum levels of pepsinogen isoenzymes I and II and their ratio in addition to investigate the role and the eradication of H. pylon in the treatment of portal hypertensive gastropathy in comparison with other suggested treatments such as Daflon, sucralfait, propranolol and verapamil. Our intimate aim is to find .a simple treatment; if possible, for such common gastro-intestinal disease. This study included 64 cirrhotic patients divided into three groups: Group I: included 21 patients with congestive gastropathy and H. pylon infection and were treated with eradication therapy for H. pylon. Group 11: included 20 patients without H. pylon infection and without history of injection sclerotherapy are treated with sucralfait and Daflon. Group III: 23 patients without H. pylon infection and with history of injection sclerotherapy are treated with propranolol and verapamil. Upper endoscopy and gastric biopsies for histopathology and H. pylon staining before and after treatment were done in all patients in addition to pepsinogen isoenzymes I and II, serology and other routine tests. The three types of therapy showed significant clinical improvement in these patients. Most of these patients are suffering from dyspeptic symptoms in the form of epigastric discomfort and pain after meals, flatulence and distension. This was more marked in patients with H pylon infection. Serum Pepsinogen I levels and PG I/lI ratio were significantly less in group I with H pylon infection than groups II and III [P<0.001]. There is substantial improvement after treatment in all patients that was most marked in patients of group I after eradication of H pylon. Serum Pepsinogen I levels and PG I/Il ratio in group I showed significant increase after eradication of H pylon [P<0.001]. PHG was improved significantly in all groups. Also, there were no differences in the response of PHG in the three groups. Comparison of the response of oesophageal varices to therapy between the three groups found that oesophageal varices improved significantly in group I in comparison to group II. It is concluded from this study that H pylon may aggravate this disease process as estimated by reduction of pepsinogen I level and PG I/lI ratio, and its eradication may be beneficial in patients with liver cirrhosis and portal hypertension, as estimated by normalization of pepsinogen level. Also, other treatment modalities were effective in decreasing the severity of this disease, which means that this disease process may be aggravated by other factors than H pylon

Significance of serum pepsinogens in atrophic gastritis

Chronic atrophic gastritis is a precancerous lesion. A commonly used test for the diagnosis of chronic atrophic gastritis, gastric endoscopy with biopsy collection, and a good serological test would be best include low levels of pepsinogen I [PGI] or a low PGI/PGII ratio. To confirm the use of serum pepsinogens as a screening marker in atrophic gastritis. A study was conducted in the period between December 2005 and March 2006 on 25 patients with artophic gastritis attending Gastroenterology and Hepatology Teaching Hospital in Baghdad, and 25 healyh control subjects. Sera were tested for PGI and PGII by ELISA test the serum PGI were decreased significantly with artophic gastritis and the PGI/PGII ratio were decreased in [78%] of patient group and not affected in healthy people

No association of an SDHC gene polymorphism with gastric cancer.

It is widely reported that reactive oxygen species (ROS) cause apotosis and carcinogenesis. Marked infiltration of activated leukocyte and enhanced production of ROS appear to occur in the gastric mucosa infected with Helicobacter pylori (H. pylori). The previous studies reported that the mutation of the succinate dehydrogenase subunit C (SDHC) gene caused the increase in superoxide anion (O(2)(-)) and oxidative stress. To extend these findings, we epidemiologically investigated the association of a SDHC polymorphism at 3'-untranslated region of exon 6 (JST173800) with H. pylori infection, gastric atrophy and gastric cancer risk in Japan. The subjects consisted of 454 health checkup examinees without a history of cancer and 202 gastric cancer patients. The SDHC polymorphism was not associated with H. pylori infection seropositivity, gastric atrophy, and cancer risk in this study. Although the polymorphism at the 3'-untranslated region could be hypothesized to be functional, this study did not demonstrate any significant association of the SDHC gene polymorphism with gastric atrophy and cancer.

The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis.

Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided evidence that the D/D genotype is associated with gastric tumor progression and numbers of lymph node metastases, but not with the overall risk of gastric cancer. The highest levels of circulating and tissue ACE activity were found in carriers of the D/D genotype. Here, we further investigated the association using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The ACE polymorphism was not found to be linked with H. pylori seropositivity or gastric atrophy. However, among H. pylori seropositive subjects with atrophy, those with the I/D genotype had an increased risk of gastric cancer (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not lower the age at diagnosis of gastric cancer. Confirmation of the association between ACE polymorphisms and development of gastric cancer requires much larger studies, and the biological role also needs to be fully elucidated.

The significance of pepsinogen with its subgroup and CA72-4 associate detect applied to early diagnostic and prognosis judgment on gastric cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To find out the connection of serum pepsinogen and it's subgroups (PGI, PGII) with CA72-4 to early diagnosis and postoperative recurrence on gastric cancer.</p><p><b>METHODS</b>RIA was applied to detect the results of serum PGI, PGII and CA72-4 on gastric cancer and other stomach diseases, then the clinic value of associating detection on gastric cancer diagnosis and prognosis judgment were assessed.</p><p><b>RESULTS</b>The serum PG levels of GC patients were significantly lower comparing to those of healthy controls (P < 0.01), apparent changes had taken place on earlier period GC (P < 0.05), and aggressive GC were even lower (P < 0.01). On the earlier period of GC diagnosis, CA72-4 levels were not apparently different to healthy controls (P > 0.05), and aggressive GC were significantly higher (P < 0.01). Compared preoperative with postoperative, the serum PGI and PGII and CA72-4 levels were significantly different (P < 0.01). In the patients underwent total gastrectomy, both of pepsinogen levels were lower than those of subtotal or large partial gastrectomy (P < 0.05). The serum PGI, PGII and CA72-4 levels of patients with recurrence of GC after total gastrectomy were significantly higher than those without. Compared before recurrence patients with after ones, the serum PGI and PGII levels of partial gastrectomy were no apparent difference (P > 0.05), however apparent changes had taken place on CA72-4 levels. The associate detection had even higher specificity (P < 0.01).</p><p><b>CONCLUSIONS</b>Apply to detect the serum PG levels on crowds, especially pGI, PGI/II levels decrease, which may be expected to become the index to earlier period GC screening. The associating detection to PG and CA72-4 levels may significantly improve sensitivity and specificity, which have chances to be applied to monitoring to postoperative gastrectomy.</p>

Evaluacion de la concentracion serica de pepsinogeno como metodo de tamizaje para gastritis atrofica y cancer gastrico / Evaluation of serum concentration of pepsinogen as screening for athropic gastritis and gastric cancer

El cáncer gástrico en Colombia es un problema de salud pública por su alta incidencia y su diagnóstico tardío, con un porcentaje de cáncer temprano menor de 5 por ciento. Por estas razones, es imprescindible constituir un programa de tamizaje para cáncer gástrico que sea sensible, costo-efectivo y tolerable por los pacientes. El pepsinógeno I y el II han ido sustituyendo en el Japón al método de tamizaje con fluoroscopia ya que, como ha sido demostrado por varios autores, tiene una tasa de detección de cáncer gástrico de 0,168 por ciento comparado con el 0,066 por ciento de la fluoroscopia. Con esto en mente, decidimos evaluar el uso del pepsinógeno I para detectar gastritis crónica atrofia y cáncer gástrico. Para esto se tomaron dos poblaciones: 66 pacientes con cáncer gástrico y 110 tomados de la población general; a todos se les tomó muestra para pepsinógeno I y anticuerpos para Helicobacter pylori (IgG e IgA), con endoscopio y biopsia posterior. Se construyó una curva ROC para definir el mejor punto de corte para el pepsinógeno I, encontrándose que el mejor punto era un valor < 150 ng/ml con una sensibilidad de 84,3 por ciento y una especificidad de 71,3 por ciento. Podemos entonces concluir que el uso de pepsinógeno I es un buen método para detectar gastritis crónica atrófica y cáncer gástrico, y que se debería asociar la determinación del pepsinógeno II en nuestra población por la alta prevalencia de infección por H. pylori que en nuestro estudio fue de 97 por ciento

Serum gastrin and pepsinogen I, II concentrations in children with Helicobacter pylori infection: the role of CagA and VacA

Serum gastrin and pepsinogen concentrations were measured in 51 children infected with Helicobacter pylori, to investigate the clinical significance and influence of CagA and VacA on serum concentrations of these peptides. CagA+ was 44/51 (86%) and VacA+ was 42/51 (82%). Type I (CagA+/VacA+) included 39/51 (76%), type II (CagA-/VacA-) was 4/51 (8%), and intermediate (CagA-/VacA+, CagA+/VacA-) was 8/51 (16%). There was no significant correlation between endoscopic diagnosis and the state of CagA/VacA. Serum gastrin concentrations were not significantly correlated with the state of CagA/VacA. Serum pepsinogen I and II concentrations were significantly higher in CagA+ than in CagA-, but there was no significant difference between VacA+ and VacA-, Serum pepsinogen I/II ratio was not significantly correlated with the state of CagA/VacA. There was no significant difference between serum concentrations of gastrin, pepsinogen I and H. pylori phenotypes. However, pepsinogen II concentration was significantly higher in type I than type II. Pepsinogen I/II ratio was significantly lower in type I and intermediate than in type II. These findings suggest that CagA positively and phenotype of H. pylori could play a role in the development of upper gastrointestinal diseases in children.

Serum pepsinogen levels in patients with gastro-duodenal lesions.

Serum pepsinogen (SP) levels were studied in 100 patients with gastroduodenal lesions, and 100 healthy volunteers. SP levels were significantly elevated in patients with duodenal ulcer (DU) and duodenitis compared to the controls. SP values above 150 ug Tyr/ml/24 hr were highly suggestive of duodenal ulcer disease. Age and sex of patients and controls did not influence SP levels. The mean values of SP in North India were found to be lower in both normal and DU subjects compared to the west.