Shogo Kaida

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status.

Background:  The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated.

Helicobacter pylori Antibody Titer and Gastric Cancer Screening

The “ABC method” is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (−) PG (−)], Group B [H. pylori (+) PG (−)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (−) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered.

Lipopolysaccharides stimulate adrenomedullin synthesis in intestinal epithelial cells: release kinetics and secretion polarity

Adrenomedullin (AM), a potent vasodilator peptide initially isolated from a human pheochromocytoma, functions as an antimicrobial peptide in host defense. In this study, we investigated changes in AM levels in intestinal epithelial cells and the mechanism of its secretion and cellular polarity after exposure to lipopolysaccharides (LPS). When a rat small intestinal cell line (IEC-18 cells) was exposed to LPS, enzyme-linked immunosorbent assay revealed a dose-dependent increase in AM together with an increase in AM mRNA expression, as determined by real-time polymerase chain reaction. Up-regulation of AM by LPS was dose-dependently inhibited by LY294002, PD98059, SP600125 and calphostin-C, suggesting the involvement of the phosphatidylinositol 3 kinase, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase and protein kinase C pathways, respectively, in this process. When polarized IEC-18 cells in a Transwell chamber were stimulated with LPS, AM secretion was directed primarily toward the side of LPS administration (either the apical or basolateral side). In situ hybridization revealed that AM mRNA was expressed in epithelial cells and in the connective tissue in the lamina propria of the jejunum after intraperitoneal or oral administration of LPS. Higher levels of AM mRNA expression were observed in rats treated with LPS via the intraperitoneal route, compared with those treated via the oral route. These findings suggest that intestinal AM plays an important role in mucosal defense in the case of intestinal luminal infection, as well as in the modulation of hemodynamics in endotoxemia.

Serum Nitrate/Nitrite Concentration Correlates with Gastric Juice Nitrate/Nitrite: A Possible Marker for Mutagenesis of the Proximal Stomach

Background/Aims: In the normal acid-secreting stomach, luminally generated nitric oxide, which contributes to carcinogenesis in the proximal stomach, is associated with the concentration of nitrate plus nitrite (nitrate/nitrite) in gastric juice. We investigated whether the serum nitrate/nitrite concentration is associated with that of gastric juice and whether it can be used as a serum marker. Methods: Serum and gastric juice nitrate/nitrite concentration, Helicobacter pylori antibody, and gastric pH were measured in 176 patients undergoing upper endoscopy. Results: Multiple regression analysis revealed that serum nitrate/nitrite concentration was the best independent predictor of gastric juice nitrate/nitrite concentration. On single regression analysis, serum and gastric juice nitrate/nitrite concentration were significantly correlated, according to the following equation: gastric juice nitrate/nitrite concentration (µmol/l) = 3.93 – 0.54 × serum nitrate/nitrite concentration (µmol/l; correlation coefficient = 0.429, p < 0.001). In analyses confined to subjects with gastric pH less than 2.0, and in those with serum markers suggesting normal acid secretion (pepsinogen-I >30 ng/ml and negative H. pylori antibody), the serum nitrate/nitrite concentration was an independent predictor of the gastric juice nitrate/nitrite concentration (p < 0.001). Conclusion: Measuring the serum nitrate/nitrite concentration has potential in estimating the gastric juice nitrate/nitrite concentration. The serum nitrate/nitrite concentration could be useful as a marker for mutagenesis in the proximal stomach.

Association between increased gastric juice acidity and sliding hiatal hernia development in humans

Objectives Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia. Methods A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia) who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia. Results Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH <2.1 (OR = 2.60, 95% CI: 1.38–4.90) was independently associated with hiatal hernia. Moreover, previously reported risk factors including male gender (OR = 2.32, 95% CI: 1.23–4.35), body mass index >25 (OR = 3.49, 95% CI: 1.77–6.91) and age >65 years (OR = 1.86, 95% CI: 1.00–3.45), were also significantly associated with hiatal hernia. Conclusions This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces hiatal hernia development.

Cutoff Pepsinogen Level for Predicting Unintendedly Eradicated Cases of Helicobacter pylori Infection in Subjects with Seemingly Normal Pepsinogen Levels

Backgrounds/Aims: In the ABC method, which is a method for risk stratification of gastric cancer using serum anti-Helicobacter pylori antibody and pepsinogen (PG) test, subjects with normal PG and seronegative for H. pylori are named as “Group A” and are regarded as having a low risk of gastric cancer. These “Group A” subjects include unintentionally eradicated cases at relatively high risk, and this study aimed to identify these subjects. Methods: Of the 109 subjects, 76 were classified as uninfected Group A subjects with negative histologic H. pylori infection and no histologic and endoscopic atrophy, and 33 subjects were classified serologically as Group A after successful eradication, which are serologically equal to the unintendedly eradicated cases in Group A. The usefulness of measuring PG levels to detect post-eradication cases was validated by using a receiver operating characteristic (ROC) curve analysis. Results: The area under the ROC curve for PGI level was 0.736 ± 0.06 (p < 0.01; cutoff value, 37.0 ng/mL; sensitivity, 77.6%; specificity, 72.7%), and that for the PGI/II ratio was 0.660 ± 0.06 (p < 0.01; cutoff value, 5.1; sensitivity, 84.2%; specificity, 43.4%). Conclusion: PGI levels of ≤37 ng/mL and PGI/II ratios of ≤5.1 effectively identified unintendedly eradicated cases in Group A.

Two cases of cystic artery pseudoaneurysm rupture due to acute cholecystitis with gallstone impaction in the neck

A cystic artery aneurysm is a rare cause of hemobilia. Herein, we report two cases of acute cholecystitis with a ruptured cystic artery pseudoaneurysm. Two patients (a 69-year-old man and an 83-year-old man) were admitted to our hospital because of acute cholecystitis with gallstone impaction in the neck. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed for both patients. After a few days of PTGBD, gallbladder hemorrhage was observed. Abdominal angiography showed cystic artery aneurysm. A transcatheter arterial embolization was therefore performed, followed by an open cholecystectomy.