Akiko Shiotani

Recurrent Peptic Ulcers in Patients Following Successful Helicobacter pylori Eradication: A Multicenter Study of 4940 Patients

Objective.u2002 Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection.

Histologic and serum risk markers for noncardia early gastric cancer.

Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori‐positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI] 1.6–7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3–52.6) (p < 0.001)). The best cut‐off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 >60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow‐up is warranted for patients with IM found at the greater curvature of the corpus.

Helicobacter pylori infection is associated with reduced circulating ghrelin levels independent of body mass index.

Background.u2002 Ghrelin stimulates growth hormone and has orexigenic and adipogenic effects. Plasma ghrelin levels are reduced in obesity and possibly in Helicobacter pylori infection.

Pathogenesis and therapy of gastric and duodenal ulcer disease

Despite the decreasing frequency of Helicobacter pylori-induced peptic ulcers, peptic ulcer disease remains a major clinical problem partly because nonsteroidal anti-inflammatory drug ulcers have increased in frequency. The reduction in nonsteroidal anti-inflammatory drug ulcers by use of selective cyclooxygenase-2 inhibitors will not eliminate the problem because of increased use of aspirin for cardiovascular prophylaxis. This article reviews current concepts of peptic ulcer pathogenesis and therapy according to ulcer etiology; discusses potential interactions between etiologies; and considers the therapy for H pylori infection including the effects of antimicrobial resistance, and the role of bismuth quadruple therapy or furazolidone salvage therapy.

Sex differences in irritable bowel syndrome in Japanese university students

BackgroundEpidemiological studies of irritable bowel syndrome (IBS) among young adults are few, especially in Asian countries. Our aim was to examine the prevalence of IBS, whether there was a sex difference, and whether allergic diseases were important risk factors for IBS in young adults.MethodsNewly enrolled university students completed health survey questionnaires regarding general health. Those with gastrointestinal symptoms completed the Gastrointestinal Symptom Rating Scale (GSRS) and an additional questionnaire covering the presence of allergic manifestations. IBS was diagnosed based on the Rome II criteria.ResultsIBS was diagnosed in 268 of 2495 students [10.7%; constipation-predominant type (IBS-C), 128; diarrhea-predominant type (IBS-D), 117; unclassified, 23]. IBS-C was associated with female sex (odds ratio, 6.4; 95% confidence interval, 4.1–9.7; P < 0.001), whereas there was no sex difference in IBS-D. The proportions of subjects with food sensitivity were significantly different among the three groups (4.0%, subjects without IBS; 8.6%, IBS-C group; and 15.4%, IBS-D group) (P < 0.001). The median GSRS scores for pain (1.67 vs 1, P = 0.001), indigestion (1.75 vs 1.5, P < 0.001), and constipation (2.0 vs 1.33, P < 0.001) were higher, and the median diarrhea score was lower (1.33 vs 1.67) (P < 0.001), in women than in men. The median score for diarrhea (2.33 vs 1.67, P = 0.001) was significantly higher in subjects with food sensitivity than in those without.ConclusionsThere was a strong relationship between IBS-C and female sex, and food sensitivity seemed to be an exacerbating factor for IBS-D.

Effects of electroacupuncture on gastric myoelectrical activity in healthy humans

Abstractu2002 The acupuncture point of the wrists (PC6) and the lower legs (ST36) are common points for the treatment of gastric symptoms. However, it remains unclear whether these two acupoints have different effects on gastric myoelectrical activity. We compared the effect of electroacupuncture (EAP) between PC6 and ST36 on gastric myoelectrical activity using surface electrogastrography (EGG). EAP (1u2003Hz, for 30u2003min) was applied at either ST36, or PC6, or both acupoints in eight healthy volunteers. EAP at both PC6 and ST36 did not change the percentage of normal slow waves and tachygastria. While EAP at either PC6 or ST36 did not change period dominant frequency (PDF), EAP at both PC6 and ST36 significantly decreased PDF to 78.1u2003±u20038.4% of baselines. EAP at PC6 reduced period dominant power (PDP) to 47.2u2003±u20035.3% of baselines, while EAP at ST36 increased PDP to 153.6u2003±u200328.3% of baselines. EAP at shoulders (sham acupuncture) did not affect the gastric myoelectrical activity. EAP at either PC6 or ST36 shows an opposite effect on PDP, whereas EAP at both PC6 and ST36 has a synergistic effect on PDF. Understanding site‐specific effects of acupuncture may contribute to the selection of appropriate acupoints for treating functional GI disorders.

Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions.

BackgroundGastric cancer is typically an end result of Helicobacter pylori-associated chronic gastritis. The pathogenesis is thought to involve effects on gastric mucosal epithelial cell turnover. In this study, we aimed to compare apoptosis and proliferation in the noncancer-containing mucosa of H. pylori-positive patients with early gastric cancer with these phenomena in H. pylori-positive controls.MethodsTwo specimens each were obtained from the greater and lesser curvatures of the corpus and from the greater curvature of the antrum. The histopathological grading used was the updated Sydney System. Apoptotic epithelial cells were detected using the terminal deoxy nucleotidyl transferase-mediated deoxy-uridine triphosphate (dUTP) biotin nick-end labeling (TUNEL) method. The expression of Ki 67 was evaluated by immunostaining.ResultsForty-five H. pylori-positive patients with endoscopic mucosal resection for early gastric cancer and 52 H. pylori-positive controls were studied. Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (IM; odds ratio [OR], 19.1; 95% confidence interval [CI], 6.9–53.2; P < 0.001). The apoptotic index (AI) in the greater curvature of the corpus and the proliferation index (PI) in each part were significantly higher in cancer patients than in the control group. The median PI in the antrum was significantly higher in the incomplete IM group than that in the complete IM group (17.6 vs 12.6; P = 0.009). The PI and the AI in the greater curvature of the corpus correlated with the activity score, and the PI correlated with the IM score.ConclusionsIn the cancer patients, H. pylori-induced gastritis was associated with increased cell proliferation and apoptosis compared with mucosal findings in the controls. IM seems to be one of the most important factors affecting cell proliferation and may be one of the components of carcinogenesis that results in proliferation-dominant cell kinetics.

Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression

The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia.

Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer

Background :u2002In patients with Helicobacter pylori infection, the concentration of nitrite in gastric juice is elevated. The degree of elevation correlates with that of inflammation and H. pylori density.

Linking Helicobacter pylori and chronic bronchitis: fact or fancy?

nary diseases. Follow-up of patients surgically treated for peptic ulcer showed that they were more likely to die of pulmonary problems and lung cancer than gastric cancer.11 This finding is consistent with the known role of cigarette smoking as an independent variable in ulcerogenesis and in chronic pulmonary diseases. Recently, Caselli and colleagues,12 in Italy, found an 81.6% seroprevalence of H. pylori infection in 60 consecutive patients with chronic bronchitis and a 57.9% seroprevalence in 69 control subjects (P 0.008). After adjustment for age and social status, the odds ratio (OR) for chronic bronchitis in the presence of H. pylori infection was 3.4. A large epidemiological study, involving about 3000 Danish adults, also demonstrated that the seroprevalence of H. pylori infection was associated with chronic bronchitis, in Danish women (OR, 1.6, with a 95% confidence interval of 1.1–2.5).13 As reported in this issue of the Journal of Gastroenterology Roussos et al.,14 in Greece, performed a case-control study in 144 patients with chronic bronchitis and 120 age-, sex-, and social class-matched controls, and they also reported a higher H. pylori seroprevalence among patients with chronic bronchitis compared with controls (83.3% vs 60%; P 0.007). While these three studies12–14 suggest an association between H. pylori infection and chronic bronchitis, the potential pathogenetic mechanisms remain unclear. Patients with chronic bronchitis frequently receive antibiotics, and one might expect that the prevalence of H. pylori would be lower than in a control group. Gastroesophageal reflux disease (GERD) may also be a potential cause of chronic bronchitis. Several studies have suggested that the prevalence of H. pylori infection may be significantly lower in patients with GERD compared with controls, and that the cure of H. pylori infection results in symptomatic GERD in those with corpus gastritis, due to the recovery of acid secretion.15,16 Interestingly, Tibbling et al.17 reported that patients who were operated on with fundoplication and crural Helicobacter pylori colonizes the gastric mucosa and induces a strong inflammatory response, with the release of various bacterial and host-dependent cytotoxic substances.1 H. pylori has been recognized as a causative factor in gastritis and peptic ulcer, and it is also strongly linked to gastric adenocarcinoma and lowgrade B cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT).2–4 Although H. pylori infections have been associated with a wide variety of nongastrointestinal tract conditions, including vascular diseases (coronary heart disease, primary Raynaud phenomenon, and migraine), autoimmune diseases (Sjögren’s syndrome, Schönlein Henoch purpura, and hypothyroidism), skin diseases (rosacea, chronic urticaria, and alopecia areata), and diabetes mellitus, among others,1–4 when looked at overall, the studies are conflicting regarding these associations.5,6 The difficulty with accepting many of the associations relates to the small numbers of patients enrolled and the failure to do analyses that also consider known important confounding variables, such as differences in age and social status. In addition, a biological rationale for the proposed association with H. pylori infection is often lacking. H. pylori infection often triggers a marked local inflammatory response and a chronic systemic immune response. One hypothesis is that the persistent inflammatory response related to H. pylori infection could induce vascular disorders through an immune-mediated release of substances associated with vasospasm or platelet aggregation. Mediators that have been considered to participate in the pathogenesis of extradigestive diseases include interleukin (IL)-1, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, leukotrien (LT) C4, and platelet-activating factor (PAF).2,7–10 There is epidemiologic evidence that duodenal ulcer occurs more commonly in patients with chronic pulmo-