Low Serum Pepsinogen Research Articles

Serum pepsinogen level, atrophic gastritis and the risk of incident pancreatic cancer—A prospective cohort study

Background: Pancreatic cancer is a highly fatal disease without screening tests. Studies have suggested possible etiologic similarities between gastric and pancreatic cancers. Atrophic gastritis, a pre-malignant condition for gastric cancer, is characterized by low serum pepsinogen I (SPGI) level. We hypothesized that low SPGI level may be associated with an increased risk of pancreatic cancer and be a useful biomarker for the disease. Methods: Our analytic cohort included 20,962 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) who had SPGI level measured. Of these, 1663 (7.9%) subjects had low SPGI levels (<25 μg/l) and were invited for gastroscopy which was completed in 1059 (63.7%) participants. Atrophic gastritis was histologically confirmed in 1006 (95.0%) subjects. We used Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Results: During follow-up of up to 16.3 years (mean = 10.8 years; 226,325 person-years), 227 incident pancreatic cancers were diagnosed. The incidence rates were 9.9, 11.3, and 12.7 per 10,000 person-years of follow-up for participants with normal pepsinogen level (≥25 μg/l), low pepsinogen level and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal pepsinogen levels, there was no statistically significant increased risk of pancreatic cancer among subjects with low pepsinogen level (adjusted HR = 1.01; 95% CI: 0.63–1.62) or those with histologically confirmed atrophic gastritis (adjusted HR = 1.13; 95% CI: 0.66–1.95). Conclusions: Atrophic gastritis, serological or histological, is not associated with increased risk of pancreatic cancer. These findings do not provide any evidence for potential usefulness of SPGI for pancreatic cancer screening.

Serum pepsinogens and risk of gastric and oesophageal cancers in the General Population Nutrition Intervention Trial cohort

Objective:Low serum pepsinogen I (PGI) and low pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy. We aimed to prospectively test the association between serum PGI/II ratio...

Serum pepsinogens and risk of esophageal squamous dysplasia

Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC. We measured serum PGI and PGII, using enzyme-linked immunosorbent assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles) or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08-4.18), comparing the lowest versus the highest quartile. The association between the lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03. Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC.

Serum pepsinogens and gastrin-17 and gastric and esophageal cancers: A long-term prospective study

4561 Background: Recent studies have suggested that gastric atrophy, as indicated by low serum pepsinogen I/ pepsinogen II ratio (PGI/II ratio), is associated with increased risks of esophageal squ...

Helicobacter pylori infection in combination with the serum pepsinogen I/II ratio and interleukin-1β-511 polymorphisms are independent risk factors for gastric cancer in Thais

Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1beta-511 polymorphisms are suspected to be risk factors for gastric cancer. A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1beta-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups. The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10-4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4-6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50-0.81; P = 0.014). A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1beta-511 C/C genotype may be independent risk factors for gastric cancer in Thais.

Racial differences in Helicobacter pylori, serum pepsinogen and gastric cancer incidence in an urban Asian population

In Singapore, the highest incidence of gastric cancer occurs in the Chinese (C), with lower rates among Malay (M) and Indian (I) subjects. The purpose of the present paper was to examine whether racial differences in the prevalence of Helicobacter pylori and serum pepsinogen (PG) could account for this difference. A randomized community health survey involving 7000 asymptomatic healthy individuals was conducted. Among the Chinese, Malay and Indian respondents, subjects were matched for age, gender and race and a total of 595 sera were obtained. The H. pylori seropositivity and serum PG levels were determined by ELISA. The dependency of the cumulative gastric incidence rate on H. pylori seroprevalence was evaluated by linear regression. The racial difference in the seroprevalence of H. pylori and low serum PG was determined. The H. pylori seroprevalence was similar between Chinese and Indian subjects, but significantly lower among Malay subjects (C, 46.3%; M, 27.9%; I, 48.1%). The gastric cancer incidence rates correlated with H. pylori seropositivity for the Chinese and Malay subjects, but not for the Indian subjects. The prevalence of low PG was highest in Indian subjects (PG I low: C, 2.1%; M, 5.4%; I, 14.2%; P < 0.0001; PG I:II ratio low: C, 5.3%; M, 5.9%; I, 12.6%; P = 0.012), even when adjusted for gender and the presence of H. pylori. The difference in gastric cancer incidence correlated with H. pylori seroprevalence for Chinese and Malay subjects. The lower incidence of gastric cancer among Indian subjects cannot be explained by differences in H. pylori or serum PG. Other modifying factors such as host and environmental factors may be important.

Normal serum pepsinogen I levels in adults: A population‐based study with special reference to Helicobacter pylori infection and parietal cell antibodies

Objective. Low serum pepsinogen I (PG I) values are common in subjects with advanced corpus atrophy with or without parietal cell antibodies (PCA). Elevated values are usual during Helicobacter pylori infection. Material and methods. PG I levels were determined in two randomly selected cross‐sectional adult population samples using the Gastroset PGI test kits. The sera (408 in 1973 and 504 in 1994), tested earlier for H. pylori infection and now for PCA, represented subjects living in Vammala, Finland. Results. In the PCA‐negative population, the mean (±SD) PG I level was significantly higher in men than in women among both H. pylori‐negative (88.13±34.16 µg/l versus 72.43±29.31 µg/l; p<0.0001) and H. pylori‐positive (110.50±50.59 µg/l, versus 97.74±44.82 µg/l, p<0.0001) subjects; the difference between all H. pylori‐positive and ‐negative subjects was also significant (p<0.001). In the 10‐year age groups, age had no impact on the mean PG I levels in H. pylori‐negative subjects (p = 0.860). In the PCA‐positive population, the 10 H. pylori‐positive subjects had higher mean PG I levels (112.96±53.62 µg/l) than the 13 H. pylori‐negative subjects (32.57±27.59 µg/l; p = 0.002); the latter mean was also significantly lower than that of the PCA‐ and H. pylori‐negative subjects (80.08±32.69 µg/l; p<0.0001). Conclusions. Men had higher normal PG I values than women, but there was no significant variation by age. H. pylori infection was associated with elevated PG I levels and a small decrease with increasing age. Non‐infected PCA‐positive subjects showed the lowest mean PG I level.

Helicobacter pyloriinfection and low serum pepsinogen I level as risk factors for gastric carcinoma

To study whether examination of CagA antibodies could increase the odds ratio for gastric cancer in a case-control study, and how often other serum markers of gastric cancer risk could be found in Helicobacter pylori -negative patients. H pylori CagA and parietal cell antibodies (PCAs), and serum pepsinogen I (SPGI) levels were compared between patients with gastric cancer and controls who received endoscopic examination due to reasons other than gastrointestinal malignancy. The odds ratio (OR) for gastric cancer was 2.9 (95% CI 1.4-5.8) in H pylori + patients, and 2.4 (95% CI 1.2-4.9) in CagA+ patients. When results of H pylori and CagA antibodies were combined, OR increased to 5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were excluded, the OR increased to 6.8 (95% CI 3.1-14.8). Among patients with a low SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant only in the older age group. The number of patients with low SPGI was significantly higher in H pylori -/CagA+ patients as compared to other cancer patients. Examination of both H pylori and CagA antibodies increases the OR for gastric cancer in our case-control study. CagA antibodies are important in detecting previous H pylori infection in advanced atrophic gastritis or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be helpful in screening elderly gastric cancer patients.

Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori.

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. The effects of Helicobacter pylori infection on plasma ghrelin concentration and gastric ghrelin production still have not been well known. We determined plasma ghrelin concentration in a total of 160 consecutive individuals with normal body mass index including 110 H. pylori-infected and 50 H. pylori-negative subjects. The expression levels of ghrelin mRNA and ghrelin-producing cells in the gastric mucosa were quantified with real-time quantitative RT-PCR and immunohistochemistry, respectively. The severity of gastric atrophy was evaluated by serum pepsinogen concentrations. Plasma ghrelin concentration, gastric ghrelin mRNA, and ghrelin-positive cell numbers in gastric mucosa were significantly lower in H. pylori-infected subjects. The decrease in plasma ghrelin concentration in H. pylori-positive subjects was accompanied by an attenuation of ghrelin mRNA expression and a reduction of ghrelin-positive cell numbers in the gastric mucosa. Moreover, lower serum pepsinogen I concentrations and I/II ratio were significantly associated with lower plasma ghrelin concentrations in H. pylori-positive subjects. These findings suggest that impaired gastric ghrelin production in association with atrophic gastritis induced by H. pylori infection accounts for the decrease in plasma ghrelin concentration.

Development of Barrett's Esophagus after ‘Spontaneous’ Healing of Atrophic Corpus Gastritis

We report here the case of a 58-year-old asymptomatic male smoker who had a gastroscopy performed in 1990 because of a low serum pepsinogen I level (16 microg/l). The patient had severe atrophic corpus gastritis and elevated Helicobacter pylori antibody titers, but no histologic evidence of the bacteria. Additionally, a hiatal hernia without esophagitis was seen. He was followed up endoscopically because of the atypical changes (indefinite for dysplasia) in addition to atrophic gastritis in some of the gastric biopsy samples. During the follow-up period, H. pylori antibody titers declined to normal levels without eradication therapy, and atrophic gastritis healed. The patient developed first erosive esophagitis, and, 5 years later, a 3-cm-long Barrett's esophagus was detected.

The Course of Helicobacter pylori Infection in Kidney Transplantation Patients

Background: Helicobacter pylori has been found to be only a minor risk factor for gastroduodenal complications in kidney transplantation patients. The aim of the study was to follow up the course of H. pylori infection in a group of immunosuppressed kidney transplantation patients. Methods: After a median follow-up of 6.8 years, control serum samples were taken from 93 originally seropositive and 88 originally seronegative kidney transplant recipients. H. pylori antibodies of the IgG and IgA classes and serum pepsinogen I levels were measured from pretransplant and follow-up samples in parallel. In addition, CagA antibodies were measured from the baseline samples of the seropositive patients. Results: 83 of the 93 seropositive patients were also cagA-positive. In addition to the 10 patients who received H. pylori eradication therapy, 27 (29%) of the 92 patients with originally elevated H. pylori IgG antibody titres showed IgG titres at normal level or levels decreased by more than 70% and below 2000 (regarded as seroreverters) after the follow-up. One of the originally seronegative patients seroconverted during the study period. After transplantation, the decrease of serum pepsinogen I values was in accordance with improved kidney function. Patients with lower serum pepsinogen I levels before the transplantation seroreverted more easily. Conclusions: A spontaneous H. pylori seroreversion occurred in 29% of the immunosuppressed kidney transplantation patients. After a successful kidney transplantation, serum pepsinogen I values declined significantly.

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...

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.

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.

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