Yoshiyuki Yamanaka

Upper gastrointestinal ulcer in Japanese patients taking low-dose aspirin

BackgroundThere are few studies on the association of the risks of upper gastrointestinal (GI) ulcer induced by aspirin combined with other medicines. We investigated the association between peptic ulcer and clinical parameters, including Helicobacter pylori infection and combinations of medicines.MethodsPatients taking 100 mg aspirin for cardiovascular diseases who were planning to undergo endoscopy were enrolled. Serum H. pylori IgG antibody was measured.ResultsA total of 305 patients were enrolled, and 38 patients (12.4%) had ulcer lesions. Sex, smoking, drinking, body mass index, endoscopic findings for gastric atrophy (open type), or presence of H. pylori were not significantly associated with ulcer lesions. Cotreatment with anticoagulants [ticlopidine, 34.2% vs. 21.3%; adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 1.4–7.1; ticlopidine plus warfarin, 13.2% vs. 3.7%; adjusted OR, 4.4; 95% CI, 1.3–15], proton pump inhibitor (PPI 5.3% vs. 34.8%; adjusted OR, 0.10; 95% CI, 0.02–0.43), and antihypertensive medicine were significantly associated with peptic ulcer. Among antihypertensive medicines, AT1 receptor blocker and angiotensin-converting enzyme (ACE) inhibitor tended to be associated with upper GI ulcer.ConclusionsPPI was superior to H2-receptor antagonist for prevention of peptic ulcer, and cotreatment with AT1 receptor blocker or ACE inhibitor seemed to reduce peptic ulcer among patients taking low-dose aspirin.

Aspirin-induced peptic ulcer and genetic polymorphisms.

There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)‐induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase‐1 (COX‐1), A‐842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX‐1‐1676T alleles was a significant risk factor for peptic ulcer in users of non‐steroidal anti‐inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non‐aspirin NSAID‐related GI bleeding. The polymorphisms of interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL‐1β‐511 T allele was significantly associated with peptic ulcer among low‐dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro‐inflammatory cytokines seems to reduce NSAIDs or aspirin‐related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large‐scale clinical studies are required.

Sonic hedgehog and CDX2 expression in the stomach.

Sonic hedgehog (Shh) is an essential regulator of patterning processes throughout development, and CDX proteins act as the master regulators for intestinal development and differentiation. Shh and CDX2 seem to be interdependently linked with cellular differentiation through different signal cascades. We have recently shown that the loss of Shh and aberrant expression of CDX2 in Helicobacter pylori (H. pylori)–associated atrophic gastritis can be modified by H. pylori eradication prior to incomplete intestinal metaplasia. On the other hand, abnormal signaling of the hedgehog pathway has been reported in gastric cancer, especially diffuse‐type cancer and advanced gastric cancer, and Shh acts as a proliferation factor in both the normal mucosa and malignant lesions. CDX2 expressed in the early stage of gastric carcinogenesis is associated with the intestinal phenotypic region and thus with a better outcome. However, it remains unclear how Shh and CDX2 are involved with intestinal transformation and further carcinogenesis.

Safety of gastrointestinal endoscopic biopsy in patients taking antithrombotics

Current Japanese gastrointestinal (GI) endoscopic guidelines permit endoscopic biopsy without cessation of antiplatelet agents and warfarin in patients with a therapeutic range of prothrombin time–international normalized ratio (PT‐INR) levels, although the evidence levels are low. We evaluated the safety of endoscopic biopsy in patients currently taking antithrombotics.

NODULAR GASTRITIS WITH HELICOBACTER PYLORI INFECTION IS STRONGLY ASSOCIATED WITH DIFFUSE‐TYPE GASTRIC CANCER IN YOUNG PATIENTS

Background:  Nodular gastritis (NG), a particular type of gastritis, is now defined as antral nodularity. Recent studies have shown that NG is strongly associated with Helicobacter pylori infection, and we recently showed that it may be associated with diffuse‐type gastric cancer of the corpus. We retrospectively investigated the relation between NG and gastric cancer in patients aged 29 years or less.

Relationship between Gastroesophageal Junction Adenocarcinoma and Helicobacter pylori Infection in Japan

Background/Aims: The relationship between gastroesophageal junction adenocarcinoma (GEJA) and Helicobacter pylori infection is not well defined; thus, we retrospectively investigated this relationship. Methods: We examined 852 cases (646 men) of gastric cancer. GEJA was defined as type II according to the classification system of Siewert and Stein. We compared the prevalence of H. pylori infection and corporal gastritis in GEJA patients with distal gastric cancer. Results: GEJA was observed in 80 (including 6 cases of Barrett’s esophageal cancer) of the 852 cases of gastric cancer examined (9.4%). The rate of H. pylori infection was significantly lower in patients with GEJA than in patients with distal gastric cancer (73.8 vs. 94.1%, p < 0.05). The prevalence of corporal gastritis was also significantly lower in patients with GEJA than in patients with distal gastric cancer (80.7 vs. 94.6%, p < 0.05). Concurrent H. pylori infection and corporal gastritis were not observed in patients with Barrett’s esophageal cancer. Conclusion: Our study demonstrated that GEJA has 2 etiologic types; one of these types is associated with H. pylori infection and resembles distal gastric cancer, and the other one is not associated with H. pylori infection or Barrett’s esophageal cancer.

Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus

BACKGROUND Decreases in Sonic hedgehog (SHH) and CDX2 expression are associated with atrophy and intestinal metaplasia in the gastric mucosa. The pathogenesis of development of Barretts oesophagus is still unclear. OBJECTIVE To examine the gene expression of CDX2 and SHH and their signalling pathways in the columnar epithelium and the association with endoscopic appearance, gastric pH or bile acids. SUBJECTS/METHODS Sixty-three patients with metaplastic columnar epithelium of the lower oesophagus were studied. Whole biopsy specimens and microdissected tissues were examined for messenger RNA. RESULTS BMP4 expression was significantly higher in patients with tubular mucosal patterns of columnar epithelium visualised by Narrow Band Imaging with magnification. The expression of SHH was significantly lower and that of CDX2 was higher in the goblet columnar epithelium than in non-goblet columnar epithelium. CDX2 expression was significantly higher in the patients with hypoacidity than in the others. BMP4 and PTCH1 expression was significantly higher in the group with higher concentrations of deoxycholic acid than in the group with lower concentrations. CONCLUSIONS SHH might be the initial factor inducing columnar metaplasia, and subsequent or simultaneous BMP4 stimuli might induce the CDX2 expression that causes goblet-cell metaplasia.

Analysis of small-bowel capsule endoscopy reading by using Quickview mode: training assistants for reading may produce a high diagnostic yield and save time for physicians.

Goal: The aim was to investigate the clinical utility of RAPID Access 6.5 Quickview software and to evaluate whether preview of the capsule endoscopy video by a trained nurse could detect significant lesions accurately compared with endoscopists. Background: As reading capsule endoscopy is time consuming, one possible cost-effective strategy could be the use of trained nonphysicians or newly available software to preread and identify potentially important capsule images. Study: The 100 capsule images of a variety of significant lesions from 87 patients were investigated. The minimum percentages for settings of sensitivity that could pick up the selected images and the detection rate for significant lesions by a well-trained nurse, two endoscopists with limited experience in reading, and one well-trained physician were examined. Results: The frequency of the selected lesions picked up by Quickview mode using percentages for sensitivity settings of 5%, 15%, 25%, and 35% were 61%, 74%, 93%, and 98%, respectively. The percentages for sensitivity significantly correlated (r=0.78, P<0.001) with the reading time. The detection rate by the nurse or the well-trained physician was significantly higher than that by the physician with limited capsule experience (87% and 84.1% vs. 62.7%; P<0.01). The clinical use of Quickview at 25% did not significantly improve the detection rate. Conclusions: Quickview mode can reduce reading time but has an unacceptably miss rate for potentially important lesions. Use of a trained nonphysician assistant can reduce physician’s time and improve diagnostic yield.

Overexpression of CD55 from Barrett's esophagus is associated with esophageal adenocarcinoma risk.

Although several molecular biomarkers for esophageal adenocarcinoma (EAC) have been shown to be useful disease indicators, none has been established as a reliable indicator for risk of EAC or have progressed to routine use. The aim was to identify biomarkers of high risk for EAC in patients with Barretts esophagus (BE).

Evaluation of Duodenal Hypersensitivity to Acid Using Transnasal Endoscopy

According to the Rome ІІІ classification, functional gastroduodenal disorders (FGIDs) in adults are subdivided into six domains. Functional dyspepsia (FD) is a subcategory of the FGIDs. It is characterized by the presence of symptoms that are believed to be associated with gastroduodenal lesions, particularly epigastric pain or burning, postprandial fullness, or early satiation, without the evidence of organic disease to explain the onset of these symptoms at least 6 months before diagnosis (Tach J et al., 2006). Furthermore, FD is divided into 2 subtypes postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The diagnostic criteria for PDS include the presence of 1 or both of the following symptoms several times in a week: bothersome postprandial fullness occurring after ordinary-sized meals, and early satiation that prevents finishing a regular meal. The diagnostic criteria for EPS include the presence of all of the following symptoms: moderately severe pain or burning localized to the epigastrium at least once per week, and intermittent pain, not generalized or localized to other abdominal or chest regions, not relieved by defecation or passage of flatus, and not fulfilling the criteria for gallbladder and sphincter of Oddi disorders. FD is a functional disorder that affects 10-30% of the population worldwide. The results of an Itarian population-based study, indicated that the prevalence rates of FD were 11%. Of these, PDS, EPS, and PDS accompanied with EPS were 67.5%, 48.2%, and 15.8% respectively (Zagari RM et al.,2010).The results of a Swedish population-based study, indicated that the prevalence rates of FD, PDS, EPS, and PDS accompanied with EPS were 15.7%, 12.2%, 5.5%, and 1.7%, respectively (Aro P et al., 2009). The results of a Norwegian population-based study, showed that the lifetime prevalence rate of FD was 23% in men and 18% in women (Johnsen et al., 1988), and that in the United States, was 29% (Shaib Y et al., 2004).