Satoshi Ishihama

Clinical Application of Serum Pepsinogen I and II Levels for Mass Screening to Detect Gastric Cancer

A considerable number of gastric cancers derive from stomach mucosa where chronic atrophic gastritis is severe and extensive. Based on the fact that the serum pepsinogen levels provide a precise measure of the extent of chronic atrophic gastritis, we have devised a mass screening method involving serum pepsinogen measurement to identify subjects at high risk of gastric cancer. In 1991, we screened 4,647 workers (male: 4,113, female: 534, mean age: 49.0 years) at a Japanese company using this method. Out of 875 subjects (18.8%) with a serum pepsinogen I level of less than 50 μg/liter and a pepsinogen I/II ratio of less than 3.0, 676 subjects (14.5%) were selected for further investigation by endoscopy. This led to the detection of four subjects (0.086%) with gastric cancer (three in an early stage) and four subjects with adenoma. The cancer detection rate of this new screening method was comparable, and in some respects superior, to that of the traditional barium X‐ray screening. Since the incidence of test‐positive subjects was as low as 10% amongst subjects aged less than 40, this screening method appears to be especially useful for screening of younger generations. The new method is less expensive than the traditional barium X‐ray and subjects experience little discomfort. Further, many serum samples can be quickly measured simultaneously. The results of this study have indicated that serum pepsinogen screening provides a valuable method for detecting gastric cancers.

The Clinical Application of the Serum Pepsinogen I And II Levels as a Mass Screening Method for Gastric Cancer

Gastric cancer, despite a recent decline in the incidence, is still a leading cause of death in Japan. For this reason, much effort has been directed to the early detection of the cancer through mass screening programs throughout the country. In most workplaces in Japan, an indirect X-ray examination, using 10 cm square film, is the conventional first screening step, after which those suspected of having some abnormalities in the gastric mucosa are further investigated either with a higher quality X-ray examination or by endoscopy. However, the sensitivity of the conventional X-ray screening step is by no means high. To improve the effectiveness of gastric cancer screening, we have devised a new screening method that utilizes measurement of serum pepsinogen (pepsinogen I and II) levels. This new screening system is based on the facts that a considerable part of gastric cancers develop in gastric mucosa affected by severe and extensive atrophic gastritis (1) and that serum pepsinogen levels serve as a sensitive marker of chronic atrophic gastritis (2). We report the first application of serum pepsinogen measurement for mass screening of gastric cancer at a certain workplace and compare the results with those of the conventional X-ray screening method.

Effects of Omeprazole, a Proton Pump Inhibitor, on Pepsinogen-Producing Cells, with Special Reference to Neonatal Development

Omeprazole, a proton pump inhibitor, exerts its effects by binding covalently to the H+/K+-ATPase that is located in the apical membrane of gastric parietal cells. However, its effects on pepsinogen-producing cells have not been investigated in detail and results of previous relevant studies on pepsinogen secretion are conflicting. Gastric mucosal cells proliferate and differentiate under an acidic environment in the gastric lumen. Thus, it is probable that omeprazole-induced reduced acidity in the gastric lumen has some influences on the proliferation and differentiation of the mucosal cells. As the first step to elucidate the effects of omeprazole on pepsinogen-producing cells, we analyzed the processes from the gene expression to the secretion of pepsinogen in vivo in adult rat glandular stomach. Next, we investigated the effects of omeprazole on the development of rat gastric mucosa biochemically and histologically, with special reference to pepsinogen expression as a marker of terminal differentiation.

Serum Pepsinogen Values as Possible Markers for Evaluating the Possibility of Peptic Ulcer Recurrence under H2-Blocker Half-Dose Maintenance Therapy

The introduction of Hrblockers and proton pump inhibitors has made peptic ulcer a curative disease without surgery. However, prevention of the ulcer recurrence is still a difficult problem. Various maintenance therapies have been set up and tried. But there has been almost no indicator to select a proper therapy for each case. Thus, a marker for predicting ulcer recurrence has been long desired. Serum pepsinogen (PG) values, PG I originating from fundic gland ( I ) and PG II from throughout stomach mucosa and Brunner gland (2), have been reported to reflect morphology and function of the gastroduodenal mucosa (3,4). Some of the previous studies suggested their possible roles as markers for peptic ulcer diseases and recurrence. For the ulcer incidence, a high PG II value and a low PG IIII ratio in gastric ulcer patients and high PG I value in duodenal ulcer patients were reported to be observed against normal control subjects (5). For the ulcer recurrence, high PG I values in recurrent peptic ulcer patients were reported to be observed against no recurrent ones (6). For evaluating the clinical usefulness as a marker of ulcer recurrence,

Effects of Hydrocortisone on the Pepsinogen-Producing Cells in Rat Stomach Mucosa

Pepsinogen is a marker of the terminal differentiation of stomach mucosa. At present, controlling mechanisms of differentiation in stomach mucosa is not fully understood. Previous studies demonstrated that administration of hydrocortisone to developing rats induces a precocious increase in the mucosal pepsinogen level in the stomach (1–3), indicating that glucocorticoids are somehow involved in the differentiation of the stomach mucosa. However, the physiological significance of glucocorticoids in the regulation of pepsinogen gene expression is not well understood. In addition, the effects of glucocorticoids on pepsinogen-producing cells in fully-differentiated stomach mucosa are less clear (4,5). In this study, we examined the effects of hydrocortisone on infant and adult rat stomach mucosa, especially on pepsinogen gene expression and the morphology of pepsinogen-producing cells.

Two Cases of Early Colorectal Cancer Associated with Gastric Adenoma Detected by Serum Pepsinogen Screening Method

It is widely accepted that the serum pepsinogen levels reflect the morphological and functional status of gastric mucosa and the diagnostic value in atrophic gastritis is now established (1). Since a considerable number of gastric cancer develop in gastric mucosa affected by severe and extensive atrophic gastritis, it is considered as a precancerous condition that leads to the development of gastric cancer (2). Indeed, the prevalence rates of atrophic gastritis diagnosed by the serum pepsinogen test show a high correlation with standardized mortality ratios (3) or age-adjusted mortality rates for gastric cancer among prefectures (4). Thus, the serum pepsinogen levels could be an objective marker that selects the high risk population of gastric cancer (5). On the basis of the above mentioned facts, mass screening that utilizes the measurement of the serum pepsinogen levels has been performed in a certain workplace in Tokyo since 1991. Subjects showing low serum pepsinogen levels (pepsinogen I of less than 70 ng/ml and a I/II ratio of 3.0) were considered to have advanced stage of atrophic gastritis and further investigated by endoscopy as the second step of screening. As a result, 13 gastric adenocarcinomas and 7 gastric adenomas were found during the first two years. It is interesting that of 7 patients with gastric adenomas, two colorectal adenocarcinomas were accidentally found. Here we report the two cases of colorectal adenocarcinomas associated with gastric adenoma screened by the serum pepsinogen test.

Cathepsin E is expressed in fetal rat glandular stomach epithelial cells in primary culture in the absence of mesenchymes.

The glandular stomach epithelium consists of surface mucous, mucous neck, parietal, chief and endocrine cells, but it remains to be solved how their differentiation is controlled. The importance of epithelial-mesenchymal interaction in inducing differentiation of glandular stomach epithelial cells has been repeatedly reported using avian embryos [1]. We have also found that the differentiation of glandular stomach epithelial cells is affected by the type of combined mesenchymes in fetal mice in organ culture [2], and that disorganization of stroma alters differentiation of glandular stomach epithelial cells in adult mice in vivo [3], demonstrating that tissue interactions play important roles in regulating the differentiation of glandular stomach epithelial cells in mammals.

A Minute Gastric Cancer Detected by a New Screening Method Using Serum Pepsinogen I and II

A gastric cancer, despite a recent decline in the mortality rate, is still a leading cause of cancer death in Japan, so that considerable effort continues to be focused on the early detection of the cancer through mass screening programs throughout the country. In most workplaces, an indirect barium x-ray examination combined with endoscopic inspection has been the standard screening method used in Japan. However, this method has certain drawbacks in detecting early gastric cancers, for exsample due to the low sensitivity of the barium x-ray procedure, which is the first step of the screening process. Therefore, to improve the effectiveness of gastric cancer screening, we have established a new screening system that uses serum pepsinogen tests instead of the indirect barium x-ray method, since it has been found that the serum tests are better able to detect advanced stages of chronic atrophic gastritis [1] [2], which is thought to be a precancerous condition that lead to the development of gastric cancer. In 1991, the first gastric mass screening using this system was carried out in the workplace and here we report on the first case of minute gastric cancer detected by this new screening method.