Hiroshi Kishikawa

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

Background:u2002 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.

Gastric cancer associated with Dieulafoy's lesion: case report

Dieulafoy’s lesion, also known as a caliber-persistent artery of the stomach, is an uncommon cause of GI bleeding; it accounts for only 2% of episodes of acute and chronic bleeding.1,2 This mucosal lesion, usually occurring along the lesser curvature of the proximal stomach, is small and shallow but can be associated with a massive, life-threatening hemorrhage. Dieulafoy’s lesion may be difficult to diagnose, especially when bleeding is absent. Although initial descriptions were based on surgically resected specimens, endoscopy is a sensitive and accurate means of diagnosis. Dieulafoy’s lesion is now almost always treated endoscopically, with hemostasis achieved in most patients.3,4 A patient is described with gastric cancer who presented with massive upper GI hemorrhage from a Dieulafoy’s lesion in the stomach; hemostasis was established endoscopically. To the investigators’ knowledge, there is only one other report of gastric cancer associated with a histopathologically proven Dieulafoy’s lesion.5 Whenever the slightest suspicion of malignancy is present in cases with atypical endoscopic findings for Dieulafoy’s lesion, follow-up endoscopy with biopsies should be performed for accurate diagnosis.

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.

Fundic gland polyps accurately predict a low risk of future gastric carcinogenesis

OBJECTIVESnFew reports have analyzed the clinical importance of sporadic fundic gland polyps (FGPs). The aim of this study was to investigate the relationship between sporadic FGPs and condition of the gastric mucosa stratified by serum pepsinogen levels and Helicobacter pylori antibody level.nnnMETHODSnThree hundred and seventy-five subjects undergoing gastrointestinal endoscopy were enrolled. Subjects on proton pump inhibitors were excluded. Pathologically proven FGPs, and other endoscopic findings (reflux esophagitis, gastric and duodenal ulcer) were examined and serum pepsinogen levels, H. pylori antibody concentration and gastric juice pH were measured simultaneously. Subjects with normal serum pepsinogen and negative H. pylori antibodies were defined as having low risk stomachs, suggesting low risk of gastric carcinogenesis.nnnRESULTSnOf the 375 subjects, 44 showed FGPs. The prevalence of low risk stomach in subjects with and without FGPs was 98% and 48%, respectively. Multivariable logistic regression analysis indicated three variables as independent factors positively associated with low risk stomachs: FGPs (odds ratio [OR] 38.6), reflux esophagitis (OR 4.8), and age<60 years (OR 1.89). Gastric juice pH, which is associated with mucosal atrophy grade and low pH indicates less mucosal atrophy, was significantly lower in subjects with (1.64 ± 0.64) than without FGPs in low risk (1.94 ± 1.12) and high risk stomachs (3.99 ± 2.31).nnnCONCLUSIONSnSporadic FGPs tend to be related to the least atrophic mucosa among non-gastric atrophy subjects without H. pylori infection, and can be used as predictors of a low risk of gastric carcinogenesis.

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.

Chronic ischemic proctitis: case report and review

The rectum is spared in most patients with spontaneous ischemic colitis because of its abundant collateral blood supply, and thus ischemic proctitis is a rare clinical entity. In most reported cases, it has been of acute onset after aortoiliac surgery, radiotherapy, or other vascular intervention. This report describes the endoscopic diagnosis and the treatment of recurrent rectal hemorrhage in apatient withspontaneous chronic ischemic proctitis. Chronic ischemic proctitis should be included in the differential diagnosis of lower-GI bleeding, especially for elderly, bed-ridden patients with atherosclerotic disease.

“Circular reddish lesions”: a possibly characteristic endoscopic finding in Henoch–Schönlein purpura

endoscopic finding in Henoch–Schönlein purpura Henoch–Schönlein purpura is a systemic vasculitis that presents with palpable purpura, abdominal pain, arthritis, and hematuria [1]. The initial clinical symptom of the characteristic purpura makes diagnosis easy. However, the disease is often under-recognized in the 10%–15% of patients in whom gastrointestinal symptoms precede the cutaneous lesions [2]. We report some possibly characteristic endoscopic findings in two cases of Henoch–Schönlein purpura that would be useful in diagnosing precisely this clinical manifestation of the condition. Our first patient was a man in his forties with Henoch–Schönlein purpura who had been treated with 30mg prednisolone for proteinuria and was admitted with abdominal colic, melena, diarrhea and purpura. A computed tomography (CT) scan showed segmental wall thickening in the small and large intestines (● Fig.1). Colonoscopy showed scattered but distinct circular areas of redness (● Fig.2) throughout the colon. Histological examination of biopsy specimens revealed typical leukocytoplastic vasculitis. Video capsule endoscopy revealed multiple circular areas of redness in the ileum (● Video 1) and patchy erosions throughout the jejunum (● Fig.3). The second patient was also a man in his forties with a past history of Henoch–Schönlein purpura and admitted for abdominal colic, diarrhea, and purpura. An abdominal CT scan showed multiple areas of segmental wall thickening in the jejunum (● Fig.4). Single balloon enteroscopy showed scattered circular hyperemic lesions in the duodenum (● Fig.5). Both patients thus showed the endoscopic finding of “circular reddish lesions” and were diagnosed as having Henoch–Schönlein purpuraassociated enteritis. The lesions resolved after dose escalation (patient 1) or administration of oral prednisolone (patient 2). In some cases of Henoch–Schönlein purpura, laparotomy has been carried out for “acute abdomen”when the patient ideally should have been treated conservatively [3]. Although endoscopy is required to confirm the diagnosis of Henoch–Schönlein purpura with gastrointestinal manifestations, characteristic endoscopic findings of the disease in the small intestine have not yet been elucidated [4]. Our two Fig.1 Computed tomography (CT) scan in a man with known Henoch–Schönlein purpura (patient 1) showing segmental wall thickening in the ascending colon (arrow) and terminal ileum (arrowhead).

Video capsule endoscopy findings in Ehlers-Danlos syndrome with recurrent gastrointestinal bleeding.

A man in his forties with Ehlers–Danlos syndrome (classic type) was admitted to our hospital because of melena and dizziness. His past history included two episodes of gastrointestinal bleeding of unknown origin. Upper and lower gastrointestinal endoscopy revealed a diverticulum of the esophagus and multiple diverticula in the sigmoid colon (● Fig.1) but no evidence of recent bleeding. Colonoscopy also revealed several erosions in the terminal ileum (● Fig.2). We therefore carried out video capsule endoscopy, which revealed multiple diverticula with adjacent erosions in the distal jejunum (● Video1), and numerous erosions in most of the ileum (● Fig.3). On the basis of these findings, the most likely origin of the bleeding was the small intestine. Ehlers–Danlos syndrome is a rare inherited connective tissue disorder with hypermobile joints, hyperextensive skin, and fragile tissues; diverticulum formation in the gastrointestinal tract due to the fragility of the connective tissues has been reported [1,2]. One of the uncommon but potentially fatal complications of Ehlers–Danlos syndrome is gastrointestinal bleeding [3], but the focus of the bleeding has not yet been elucidated. The present case suggests that the small intestine is an important candidate bleeding site in Ehlers–Danlos syndrome. Some patients with Ehlers–Danlos syndrome (vascular type) require close medical follow-up to prevent sudden death by organ rupture at a young age. Thus, we believe that Ehlers–Danlos syndrome should be considered in the differential diagnosis when a clinician encounters the unusual capsule endoscopic finding of multiple diverticula with erosions in the small intestine. The findings in our present patient also suggest that the focus of smallintestinal bleeding in Ehlers–Danlos syndrome is not the diverticula but the multiple erosions in the small intestine.