Low Pepsinogen Research Articles

Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis

OBJECTIVES: Food-cobalamin malabsorption is common in patients with low cobalamin levels. However, characterization of affected subjects has been limited. The aim of this study was to analyze demographic and gastric data in a large study population. METHODS: Data were collected prospectively in 202 subjects (43 volunteers and 159 patients) who underwent the egg yolk-cobalamin absorption test (EYCAT). H. pylori status was determined in 167 of the subjects, serum gastrin and antiparietal cell antibody in 158 and pepsinogen (PG) I and PG II levels in 133. RESULTS: Latin American and black patients had lower EYCAT results than did white or Asian-American ones ( p = 0.0001) and had severe food-cobalamin malabsorption (EYCAT < 1%) more often ( p = 0.0001). Age correlated inversely with EYCAT results ( p = 0.02). H. pylori infection was associated with food-cobalamin malabsorption ( p = 0.0001), especially with severe malabsorption where 29/37 subjects (78.4%) were infected. Malabsorption was also associated with higher gastrin levels ( p = 0.0001) and lower PG I levels ( p = 0.01) and PG I:PG II ratios ( p = 0.0001). Multivariate analysis showed that ethnic origin, gastrin levels, H. pylori infection and, to a lesser extent, age were independently associated with the EYCAT results. CONCLUSIONS: Latin American and black patients have food-cobalamin malabsorption more often than do white and Asian-American patients. This association is independent of the malabsorption’s association with H. pylori infection, markers of gastritis, such as gastrin, and older age. The patterns of gastric tests suggest that malabsorption may be due to diverse mechanisms, not just atrophic gastritis. The possible role of H. pylori infection in many cases of severe food-cobalamin malabsorption also suggests avenues of treatment and prevention.

Expression and prognostic significance of pepsinogen C in gastric carcinoma.

In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P < .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P < .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P < .001), and in 71 patients with resectable carcinomas (P < .005). Multivariate analysis according to Cox's model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P < .05, for both). The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.

Atrophic gastritis and Helicobacter pylori infection in outpatients referred for gastroscopy

BACKGROUNDAtrophic gastritis has been shown to be one of the long term sequelae ofHelicobacter pylori infection.AIMSTo determine the prevalence of atrophic gastritis in outpatients, to study the accuracy of serological...

Helicobacter pylori infection: relationship between seroprevalence and dietary preference in a rural area.

In order to evaluate the relationship between Helicobacter pylori (H. pylori) infection and dietary preference, a cross-sectional study was performed among 626 residents in a rural area of Japan. Seropositive rates were 88.7% in males and 71.4% in females, and these increased with age for both sexes [male P < 0.05 and female P < 0.01]. The relationship between H. pylori-seropositivities and salted-food intake, after adjustment for age, demonstrated a significant result in the "almost every day" group in males with an odds ratio (OR) of 8.39 and with 95% confidence intervals (CI) of 1.02-69.30. As regards an association between seropositivities of H. pylori and levels of serum pepsinogens for the screening of chronic atrophic gastritis (low pepsinogen values used were a pepsinogen I level below 70 ng/ml and a pepsinogen I/pepsinogen II ratio below 3.0), the ORs of H. pylori-seropositivities for low pepsinogen cases were 6.32 [95% CI: 1.42-28.03] in males and 12.72 [95% CI: 4.57-35.46] in females. With regard to the relationship between low pepsinogen cases and light-colored vegetables intake, a significant low OR for the low pepsinogen cases was obtained in the "almost every meal" group in females after adjustment for age and seropositivities of H. pylori with an OR of 0.37 and with 95% CI of 0.15-0.92.

Evaluation of Blood Tests to Predict Normal Gastric Mucosa

Background: To determine the accuracy of blood tests in predicting normal gastric mucosa confirmed by histological examination of gastric biopsy specimens. Methods: In total, 207 consecutive patients referred for upper endoscopy were included. Two biopsy specimens each from the antrum and corpus were assessed histologically for the presence of Helicobacter pylori, gastritis, and atrophy. Serum samples were studied for H. pylori antibodies by enzyme immunoassay (Pyloriset EIA-G and EIA-A) and by a rapid latex agglutination test (Pyloriset Dry); pepsinogen I was measured by an immunoenzymometric assay (Gastroset PGI), gastrin by radioimmunoassay, and parietal cell antibodies by indirect immunofluorescence. Results: In 101 (49%) of 207 patients, the gastric mucosa on histologic examination was normal. In the 63 patients aged 45 years or less, H. pylori IgG serology was negative in all 47 patients with normal gastric mucosa and none had low serum pepsinogen I levels. Among 144 patients over age 45 years, 72 had negative H. pylori IgG serology. Combining the serum pepsinogen I assay with the results of H. pylori IgG serology, 12 patients with normal serology but low serum pepsinogen I were found. Thus, 60 patients, 52 of whom showed normal gastric histology, had normal IgG serology and serum pepsinogen I. In the remaining eight patients with normal blood tests, the histologic changes were very mild. Conclusions: Although negative H. pylori IgG serology alone in younger patients, and in combination with normal serum pepsinogen I levels in older patients, reliably predicted the presence of normal gastric mucosa, gastroscopy is still recommended for patients over 45 years.

Implications of Serum Pepsinogen I in Early Endoscopic Diagnosis of Gastric Cancer and Dysplasia

The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

ペプシノゲンの基礎と臨床

As the lecture of Predisent of the 50th Spring Meeting of the Japanese Electrophoresis Society, covered the own group's research field during the past about 20 years periods. Basic aspect and clinical significance of pepsinogens were reviewed. Contents of the lecture were the cellular localization of pepsinogen granules in the one cell, the activation mechanism of it, the entire human pepsinogen A and C genes, and the nucleotide sequence of all the exon and the 5'-and 3'-flanking regions. Topics of isozymes of human pepsinogen A (I), the schema of pepsinogen-producing mechanisms from mRNA, and electrophoretic pattern of pepsinogen A (I) from human gastric mucosa using agargel, were included. On the other hand, as for the clinical significance of pepsinogens, the first case report of pepsinogen producing gastric carcinoma with high pepsinogen II levels in both serum and ascites, and pepsinogen I and II immunohistochemical staining in gastric carcinoma tissues using the monoclonal antibodies, were presented. Finally, the clinical application of the serum pepsinogen levels in the research of Helicobacter pylori infection, gastric cancer development in the course of carcinogenesis from atrophic gastritis to gastric cancer in the population level, gastric cancer screening using serum pepsinogen test kits, which were commercially available now in Japan, and the significance of low serum pepsinogen levels to detect stomach cancer associated with extentive chronic gastritis, which was a precancerous condition of gastric cancer, were discussed.

Gastric cancer, cytotoxin-associated gene A–positive Helicobacter pylori, and serum pepsinogens: An international study

Background & Aims: CagA-positive Helicobacter pylori infection has been more closely associated with gastric disease than CagA-negative infection. This study evaluated whether geographic variation in the prevalence of CagA could explain variation in gastric cancer rates. Methods: The Eurogast study was conducted in 17 centers in 13 countries. Gastric cancer rates were calculated for each center, and serum samples from approximately 2850 subjects were assayed for immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C. Results: The proportion of CagA-positive H. pylori infections varied across the centers, but this variation did not explain any more of the variation in gastric cancer rates than H. pylori alone. Subjects with CagA-positive infection had, however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio than subjects with CagA-negative infection; this pattern was observed consistently across the study centers. Conclusions: Variation in the seroprevalence of CagA did not explain geographic variation in gastric cancer rates any better than H. pylori alone. However, the consistent variation in pepsinogen levels with CagA status across the study centers supports the importance of the role of CagA in the development of gastric disease. GASTROENTEROLOGY 1999;116:269-276

Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects.

Gastric cancer (GC) and adenoma (GA) are reported to be related to atrophic gastritis, in which the serum pepsinogen (PG) I level and the PGI/PGII ratio (I/II ratio) are reduced. To verify that the finding of a low PG level increases the risk for GC and GA, we investigated the correlation between low PG levels and the prevalence of GC and GA in individuals. The 2,039 subjects (734 Japanese men, mean age 68.5 yr, and 1,305 women, mean age 66.7 yr), selected from among 10,996 local residents who underwent health check-ups based on reductions in their serum PG levels, underwent upper gastrointestinal endoscopy. Gastrointestinal endoscopy detected 21 GCs and 15 GAs. The prevalence of GC was higher than that in the residents without low serum PG. The percentage of early stage of GC (90%) was significantly higher than that of GC detected in unscreened residents (56.9%). The prevalence of GC in men was closely and significantly correlated with the I/II ratio (r = 0.935, p = 0.0063), whereas there was less correlation with age (r = 0.842, p = 0.0734). The prevalence of GA was also closely and significantly correlated with the I/II ratio in men (r = 0.881, p = 0.0203), but not with age (r = 0.163, p = 0.7928). In women the prevalence of GC (r = 0.744, p = 0.090) and GA (r = 0.678, p = 0.1392) did not correlate as strongly with the I/II ratio, although the highest prevalence was seen in the group with the lowest I/II ratio. Our study verified that a low I/II ratio signifies a high risk for GC and GA and that measuring serum PG levels can be used as a screening method for GC and GA.

Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects

Objective: Gastric cancer (GC) and adenoma (GA) are reported to be related to atrophic gastritis, in which the serum pepsinogen (PG) I level and the PGI/PGII ratio (I/II ratio) are reduced. To verify that the finding of a low PG level increases the risk for GC and GA, we investigated the correlation between low PG levels and the prevalence of GC and GA in individuals. Methods: The 2,039 subjects (734 Japanese men, mean age 68.5 yr, and 1,305 women, mean age 66.7 yr), selected from among 10,996 local residents who underwent health check-ups based on reductions in their serum PG levels, underwent upper gastrointestinal endoscopy. Results: Gastrointestinal endoscopy detected 21 GCs and 15 GAs. The prevalence of GC was higher than that in the residents without low serum PG. The percentage of early stage of GC (90%) was significantly higher than that of GC detected in unscreened residents (56.9%). The prevalence of GC in men was closely and significantly correlated with the I/II ratio (r = 0.935, p = 0.0063), whereas there was less correlation with age (r = 0.842, p = 0.0734). The prevalence of GA was also closely and significantly correlated with the I/II ratio in men (r = 0.881, p = 0.0203), but not with age (r = 0.163, p = 0.7928). In women the prevalence of GC (r = 0.744, p = 0.090) and GA (r = 0.678, p = 0.1392) did not correlate as strongly with the I/II ratio, although the highest prevalence was seen in the group with the lowest I/II ratio. Conclusion: Our study verified that a low I/II ratio signifies a high risk for GC and GA and that measuring serum PG levels can be used as a screening method for GC and GA.

Low pepsinogen a levels and pepsinogen a: C ratio in a population of children and adults from Soweto, South Africa

Low pepsinogen a levels and pepsinogen a: C ratio in a population of children and adults from Soweto, South Africa

Gastric Cancer and Premalignant Lesions in Atrophic Gastritis: A Controlled Trial on the Effect of Supplementation with Alpha-Tocopherol and Beta-Carotene

Background: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis. Methods: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years. Results: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates. Conclusions: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.

血清ペプシノゲン検査を契機に発見された胃腺腫，十二指腸腺腫，直腸癌合併の1例

血清ペプシノゲン検査を契機に発見された胃腺腫，十二指腸腺腫，直腸癌合併の1例

血清ペプシノゲン低値者の胃癌発生に関する追跡調査

血清ペプシノゲン低値者の胃癌発生に関する追跡調査

Effect of chemoprophylaxis with an ivermectin sustained-release bolus on acquired resistance to gastrointestinal parasites in cattle

The influence of chemoprophylaxis with an ivermectin sustained-release bolus in the first grazing season on the resistance of cattle to gastrointestinal nematodes during the following grazing season was investigated. In...

Enhanced Cellular Proliferation and p53 Accumulation in Gastric Mucosa Chronically Infected With Helicobacter pylori

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.

Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study.

To assess the risk of gastric carcinoma in patients with histologically verified dysplasia and atrophic gastritis of the stomach. One hundred and one patients with mild (n = 84), moderate (n = 14), or severe (n = 3) dysplasia among 359 elderly men who smoked underwent gastroscopy because of low serum pepsinogen. Patients with dysplasia were prospectively followed up for an average of four years with repeated gastroscopies and multiple biopsies. Four of the 84 (4.8%) cases of mild dysplasia had progressed to moderate dysplasia during the follow up. Most of the cases of mild dysplasia had resolved spontaneously. No surgical intervention was required. Three of the 14 (21%) cases of moderate dysplasia had progressed to severe dysplasia, but no carcinomas were observed during follow up. Five moderately dysplastic lesions were removed surgically or endoscopically. In two of these five cases, moderate or severe dysplasia recurred. Two of the three severe dysplasias progressed to carcinoma. In atrophic gastritis progression of mild and moderate dysplastic lesions seems to be a slow process and is rare in mild dysplasia. However, severe dysplasia is highly predictive of subsequent cancer. It is suggested that a five year follow up interval is sufficient in cases with mild dysplasia and two years in those with moderate dysplasia. Local removal of moderate dysplasia is indicated but does not guarantee that the lesion will not progress. Severe dysplasia requires immediate surgical intervention.

Circulating anti-Helicobacter pylori immunoglobulin A antibodies and low serum pepsinogen I level are associated with increased risk of gastric cancer.

Helicobacter pylori infection has been suggested to be associated with an increased risk of gastric cancer, and low levels of serum pepsinogen I (PG I) have been linked to atrophic gastritis, which is a risk factor for gastric cancer. In Finland, 39,268 persons from 25 cohorts participated during 1968-1972 in a health examination survey and were followed for up to 13 years. A nested case-control study was performed on 84 stomach cancer patients identified from the Finnish Cancer Registry and 146 controls matched for age, sex, and municipality. Serum samples drawn at the baseline study were analyzed. An elevated level of serum anti-H. pylori immunoglobulin A (IgA) antibodies (a titer > or = 70) and a low serum PG I level ( < 49 micrograms/liter) were associated with an increased risk of gastric cancer. The odds ratios were 2.52 (95% confidence interval (CI) 1.14-5.57) for high IgA and 2.68 (95% CI 1.35-5.30) for low PG I. For high immunoglobulin G (IgG) ( > or = 700), the odds ratio was only 1.50 (95% CI 0.70-3.22). When both high IgA and low PG I were present, the odds ratio was 5.96 (95% CI 2.02-17.57). The association of H. pylori infection with cancer became stronger with longer follow-up times, whereas that of low PG I was strongest at shorter follow-up times. Our findings support the hypothesis that H. pylori infection is a prevalent and potentially preventable cause of gastric cancer. They stress the value of IgA antibody determinations and provide new evidence for a pathogenesis leading from prolonged infection through atrophic gastritis to gastric cancer.

Tissue and serum pepsinogen I and II in gastric cancer identified using immunohistochemistry and rapid ELISA.

To investigate the immunohistochemical expression and the serum concentrations of pepsinogen I and II in different histological types of gastric cancer as compared with other gastric disorders. Formalin fixed, paraffin wax embedded tissue specimens of 38 gastric cancers obtained from surgical cases were used for the immunohistochemical studies performed with the avidin-biotin complex method using monoclonal antibodies against purified pepsinogen I and II. Pepsinogen concentrations from serum obtained from the above patients, from patients with various other gastric disorders, and from normal controls were measured with a rapid non-radioactive one step enzyme linked immunosorbent assay (ELISA). Eight of 38 (21%) and seven of 38 (18%) gastric carcinomas showed immunoreactivity to pepsinogen I and pepsinogen II, respectively, without any correlation to histological classification or differentiation. Decreased pepsinogen I concentrations and low pepsinogen I:II ratios were found specifically in cases of gastric carcinoma and polyp, in good accordance with the immunohistochemical results. Low serum pepsinogen I concentrations and a low pepsinogen I:II ratio are predictive of gastric neoplasia, correlating with low tissue immunoreactivity to monoclonal antibodies raised against pepsinogen I and II. For mass screening of gastric disease including carcinoma, ELISA using a one step immunoassay performed in the present study is a rapid and reliable non-radioactive method of detecting serum pepsinogen. In addition, immunohistochemical studies showed that pepsinogen production may be increased or diminished as a result of tumour histogenesis, depending on the area of origin and the processes of cell transformation and dedifferentiation.