Gastrointestinal endoscopic practice during COVID-19 pandemic: a multi-institutional survey.

Introduction. An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities.Methods. The 11-item survey questionnaire was sent to representative respondent of Department of Gastroenterology, Osaka City University Hospital, and its 19 related facilities.Results. A total of 18 facilities submitted valid responses and a total of 373 health care professionals (HCPs) participated. All facilities (18/18: 100%) were screening patients at risk for SARS-CoV-2 infection before endoscopy. During the pandemic, we found that the total volume of endoscopic procedures decreased by 44%. Eleven facilities (11/18: 61%) followed recommendations of the Japan Gastroenterological Endoscopy Society (JGES); consequently, about 35%-50% of esophagogastroduodenoscopy and colonoscopy were canceled. Mask (surgical mask or N95 mask), face shield/goggle, gloves (one or two sets), and gown (with long or short sleeves) were being used by endoscopists, nurses, endoscopy technicians, and endoscope cleaning staff in all the facilities (18/18: 100%). SARS-CoV-2 infection risk assessment of HCPs was conducted daily in all the facilities (18/18: 100%), resulting in no subsequent SARS-CoV-2 infection in HCPs.Conclusion. COVID-19 has had a dramatic impact on the gastrointestinal endoscopic practice. The recommendations of the JGES were appropriate as preventive measures for the SARSCoV-2 infection in the endoscopy unit and its staff.

The prevalence of adverse events associated with double-balloon enteroscopy from a single-centre dataset in Japan.

BACKGROUND: There are few comprehensive reports detailing the prevalence of major adverse events associated with a double-balloon enteroscopy procedure. METHODS: We retrospectively investigated the prevalence of major adverse events in 538 patients (262 males and 276 females; median age, 65 years; age range, 12-95 years) who underwent double-balloon enteroscopy at our Institution between April 2008 and October 2011. RESULTS: Of the 17 adverse events recorded (3.2%), acute pancreatitis (n=5; 0.9%) occurred during both diagnostic (n=3) and therapeutic (n=2) anterograde double-balloon enteroscopy, and all of them were treated conservatively. For these cases, the average duration of the examination was 135 min, which was longer than for the other patients (97 min) (P=0.046). Intestinal bleeding (1.3%) was observed in 6 cases after endoscopic polypectomy and in 1 case following a biopsy procedure during a diagnostic double-balloon enteroscopy. The prevalence rates of intestinal perforation and other complications were 0.2% and 0.7%, respectively. CONCLUSIONS: The rate of adverse events associated with double-balloon enteroscopy was high compared to that associated with conventional upper/lower gastrointestinal endoscopy (0.042%/0.078%). The occurrence of acute pancreatitis may be significantly dependent on the duration of double-balloon enteroscopy examination.

Usefulness of non-magnifying narrow-band imaging in screening of early esophageal squamous cell carcinoma: a prospective comparative study using propensity score matching.

OBJECTIVES: The usefulness of non-magnifying endoscopy with narrow-band imaging (NBI; NM-NBI) in the screening of early esophageal squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN) remains unclear. Here, we aimed to compare NM-NBI and chromoendoscopy with iodine staining (CE-Iodine) in terms of the diagnostic performance, and to evaluate the usefulness of NM-NBI in detecting early esophageal SCC. METHODS: We prospectively enrolled 202 consecutive patients (male/female=180/22; median age, 67 years) with high-risk factors for esophageal SCC. All patients received endoscopic examination with NM-NBI and CE-Iodine to screen for early esophageal SCC or HGIN. We conducted the examinations sequentially, and calculated the accuracy, sensitivity, and specificity through a per-lesion-based analysis. A propensity score matching analysis was performed to reduce the effects of selection bias, and we compared the respective outcomes according to NM-NBI and CE-Iodine after matching. RESULTS: The accuracy, sensitivity, and specificity of NM-NBI were 77.0, 88.3, and 75.2%, respectively, and those for unstained areas by CE-Iodine were 68.0, 94.2, and 64.0, respectively. The accuracy and specificity of NM-NBI were superior to those of CE-Iodine (P=0.03 and P=0.01, respectively). However, the sensitivity did not significantly differ between NM-NBI and CE-Iodine (P=0.67). The accuracy and specificity of NM-NBI before matching were superior to those of CE-Iodine after matching (P=0.04 and P=0.03). CONCLUSIONS: NM-NBI was useful and reliable for the diagnosis of esophageal SCC and can be a promising screening strategy for early esophageal SCC.

Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users.

OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of >20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users.

Endoscopic radial incision and cutting method for refractory esophageal stricture after endoscopic submucosal dissection of superficial esophageal carcinoma.

A 59-year-old woman and a 69-year-old man had esophageal strictures that were refractory to over 10 therapeutic attempts with endoscopic balloon dilation (EBD) after endoscopic submucosal dissections (ESD) for superficial esophageal carcinoma (SEC). The strictured lesions in both patients improved remarkably with a new endoscopic modality (endoscopic radial incision and cutting [ERIC]), which was carried out one to three times, and stricture recurrence was not noted throughout the follow-up period. ERIC is a safe and efficient method for treating refractory strictures after EBD caused by ESD for SEC.

Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage.

BACKGROUND: Few studies have assessed the risk factors associated with nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal damage. AIMS: To evaluate the risk factors for NSAID-induced enteropathy in patients with rheumatoid arthritis. METHODS: A cross-sectional study using capsule endoscopy was conducted. A total of 113 patients who took NSAIDs for over 3 months underwent capsule endoscopies. Endoscopic findings were scored as (0) normal, (1) red spots, (2) 1-4 erosions, (3) >4 erosions, or (4) large erosions/ulcers. Initial scores were grouped into 3 categories: No damage (0-1), mild damage (2), and severe damage (3-4), and the potential risk factors for damage development were assessed. RESULTS: Five patients were excluded because of incomplete visualization of the entire small intestine. Fifty-two (47.2%) and 27 (25%) patients had no damage and mild damage, respectively, while the remaining 30 patients (27.8%) had severe damage and significantly decreased hemoglobin levels. In a multivariate logistic regression analysis, ages of 65 years or more (odds ratio [OR], 4.16; 95% confidence interval [CI], 1.51-11.47), proton pump inhibitor usage (OR, 5.22; 95% CI, 1.36-20.11), and histamine H2 receptor antagonist usage (OR, 3.95; 95% CI, 1.28-12.25) were independent risk factors for severe damage. CONCLUSIONS: Elderly patients and acid suppressant users are more likely to develop severe NSAID-induced enteropathy.

The usefulness of double-balloon enteroscopy in gastrointestinal stromal tumors of the small bowel with obscure gastrointestinal bleeding.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are the most frequently occurring mesenchymal tumors of the GI tract. Double-balloon enteroscopy (DBE) and capsule endoscopy (CE) promise the detection and accurate diagnosis of small bowel diseases in patients with obscure GI bleeding (OGIB). The aim of the present study was to analyze the clinical characteristics of small bowel GISTs and the usefulness of DBE, CE and computed tomography (CT). METHODS: Among 705 cases with OGIB examined between December 2003 and January 2011, 12 (1.7%) cases of small bowel GIST were identified. We analyzed endoscopic appearance, tumor-size and location, detection rate by DBE, CE and CT and clinical course in each of these cases. RESULTS: Of the 12 patients with GIST, eight were men. The mean patient age was 53.6 years. The presenting symptoms in most patients included tarry stools and/or anemia. Six patients required blood transfusions. The detection rates of DBE, CE and CT were 92%, 60% and 67%, respectively. All cases, except for one incomplete study, were identified using DBE; however, one case was not diagnosed as a tumor because of the presence of extramural growth. A pathological diagnosis of GIST was obtained using biopsies during DBE in three (45%) of seven cases. Lower detection rates were found in cases with intramural and extramural growth, larger tumors (≥35 mm) detected by CE and intraluminal growth and smaller tumors (<35 mm) detected by CT. CONCLUSION: DBE or a combination of CE and CT are thus considered to be useful for detecting small bowel GISTs.

High prevalence of gastroesophageal reflux symptoms in patients with non-alcoholic fatty liver disease associated with serum levels of triglyceride and cholesterol but not simple visceral obesity.

BACKGROUND/AIMS: Visceral obesity is commonly involved in the pathogenesis of gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, other characteristic factors different from visceral obesity are associated with the pathogenesis of NAFLD. We investigated the prevalence of GERD symptoms in patients with NAFLD and its associated risk factors. METHODS: NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD. RESULTS: GERD symptom score and its prevalence rate were higher in the NAFLD group (7.4 ± 0.7, 37%) than those seen in the control groups (4.5 ± 0.4, 20%), which was independent of sex, age, and body mass index (BMI). GERD symptoms were correlated with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r = 0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms of the NAFLD group were significantly severer in the higher group of T-CHO and TG levels than those in the lower group. Multivariate analysis proved that risk factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31-11.9) and T-CHO (OR 3.39, 95% CI 1.11-10.3). CONCLUSION: The severity and prevalence of GERD symptoms in patients with NAFLD were high, which was associated with serum levels of TG and T-CHO but not BMI.

High mobility group box 1 promotes small intestinal damage induced by nonsteroidal anti-inflammatory drugs through Toll-like receptor 4.

Release of high mobility group box 1 (HMGB1) from damaged cells, which is involved in many types of tissue injuries, activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor 2 (TLR2), TLR4, and receptor for advanced glycation end-products (RAGE). Our objective was to determine the role of HMGB1 in nonsteroidal anti-inflammatory drug (NSAID)-induced damage of the small intestine. Oral indomethacin (10 mg/kg) induced damage to the small intestine and was associated with increases in intestinal HMGB1 expression and serum HMGB1 levels. In wild-type mice, recombinant human HMGB1 aggravated indomethacin-induced small intestinal damage; enhanced the mRNA expression levels of tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1, and KC; activated nuclear factor kappa B; and stimulated phosphorylation of the mitogen-activated protein kinases p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). In contrast, blocking HMGB1 action with neutralizing antibodies prevented damage and inhibited both inflammatory cytokine overexpression and activation of these intracellular signaling pathways. TLR2-knockout (KO) and RAGE-KO mice exhibited high sensitivities to indomethacin-induced damage, similar to wild-type mice, whereas TLR4-KO mice exhibited less severe intestinal damage and lower levels of TNF-α mRNA expression. Exogenous HMGB1 aggravated the damage in TLR2- and RAGE-KO mice but did not affect the damage in TLR4-KO mice. Thus, our results suggest that HMGB1 promotes NSAID-induced small intestinal damage through TLR4-dependent signaling pathways.

Pathogenesis of proton-pump inhibitor-refractory non-erosive reflux disease according to multichannel intraluminal impedance-pH monitoring.

BACKGROUND AND AIM: Proton-pump inhibitor (PPI) therapy is the first-line treatment for gastroesophageal reflux disease; however, there are some reports of PPI failure in cases of non-erosive reflux disease (NERD). Among the pathogenic factors associated with PPI-refractory NERD, reflux other than acid reflux can not be detected by conventional pH monitoring. The purpose of this study was to clarify the usefulness of multichannel intraluminal impedance-pH (MII-pH) monitoring for PPI-refractory NERD patients and examine the pathogenesis. METHODS: We used MII-pH monitoring to examine 29 PPI-refractory NERD patients on PPI treatment. Reflux parameters, symptom index (SI: positive if ≥ 50%), and proximal migration were analyzed. The acidity of the reflux was divided into acid (nadir pH ≤ 4) and non-acid (nadir pH > 4). Subjects were classified into reflux-related disease (abnormal reflux parameters or positive SI) and non-reflux-related disease (normal reflux parameters and negative SI). RESULTS: Of the 29 subjects, 21 were diagnosed with reflux-related disease, including 6 with acid reflux type and 15 with non-acid reflux type, and 8 were diagnosed with non-reflux-related disease. Of the total 1816 liquid reflux episodes, 834 showed proximal migration, which was more common in symptomatic reflux than in asymptomatic reflux. CONCLUSIONS: MII-pH monitoring could distinguish reflux-related disease (especially non-acid type) from PPI-refractory NERD. Proximal migration was associated with symptomatic reflux in PPI-refractory NERD patients.

Internal hypoechoic feature by EUS as a possible predictive marker for the enlargement potential of gastric GI stromal tumors.

BACKGROUND: There is no clinical predictor for the enlargement potential of gastric GI stromal tumors (GISTs) during the follow-up observation period. OBJECTIVE: The aim of our study was to identify predictive markers for the enlargement potential of gastric GISTs on the basis of various endosonographic features determined at the initial examination. DESIGN: Single-center retrospective analysis. SETTING: Academic university hospital in Japan. PATIENTS: All patients (n = 74) with histologically diagnosed GISTs in the stomach underwent EUS. INTERVENTION: EUS. MAIN OUTCOME MEASUREMENTS: We analyzed the following endoscopic and EUS features: mucosal ulceration, irregular shape, irregular border, heterogeneity, internal hyperechoic spot, hypoechoic area, and anechoic area of gastric GISTs in 3 groups according to tumor size. Furthermore, we compared the characteristics between increased growth and unchanged growth of GISTs, that were defined on the basis of the novel tumor growth index: changes in tumor volume/follow-up interval (days between initial EUS and second EUS) (mm(3)/day). RESULTS: The presence of heterogeneity (P = .016) and anechoic area (P = .003) was significantly highest in the group with the largest tumor size. The increased growth group had a higher presence of hypoechoic area than did the unchanged growth group (84.2% vs 51.9%, P = .023). Multivariate analysis showed that the presence of a hypoechoic area was an enlargement-associated factor (odds ratio 5.38; 95% confidence interval 1.19-24.39; P = .029). LIMITATIONS: Retrospective design of the study. CONCLUSIONS: The internal hypoechoic area determined by EUS may be a predictor for the enlargement potential of gastric GISTs.

Cigarette smoking and its association with overlapping gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome.

BACKGROUND: Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common gastrointestinal diseases. Several studies have shown a significant occurrence of overlap among these 3 diseases. The purpose of this study was to examine the factors associated with such disease overlap in Japanese adults. METHODS: We performed a cross-sectional study on Japanese workers who visited a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. GERD was defined as episodes of heartburn and/or acid regurgitation at least once a week, and the diagnosis of FD and IBS was based on Rome III criteria. A logistic regression model was used to identify risk factors, and odds ratio (OR) was calculated with 95% confidence intervals (CIs). RESULTS: Disease overlaps were found in 160 (6.0%) of the 2680 eligible subjects. Female gender was associated with GERD + IBS (OR=1.99; 95% CI, 1.06-3.75), and FD + IBS (OR=1.72; 95% CI, 1.03-2.85), and lower body mass index was negatively associated with FD + IBS (OR=0.54; 96% CI, 0.34-0.87). Cigarette smoking was a common factor associated with the overlaps: GERD + FD (OR=2.14; 95% CI, 1.22-3.76), GERD + IBS (OR=3.16; 95% CI, 1.75-3.71), FD + IBS (OR=2.26; 95% CI, 1.40-3.66), and GERD + FD + IBS (OR=4.08; 95% CI, 1.66-10.07). The associations between smoking habits and overlaps were stronger in smokers who smoked ≥1 pack per day as compared to those who smoked <1 pack per day. CONCLUSION: Cigarette smoking was significantly associated with overlaps among GERD, FD, and IBS in Japanese adults.

Role of Th-2 cytokines in the development of Barrett's esophagus in rats.

BACKGROUND: Barrett's esophagus is characterized by a distinct Th-2-predominant cytokine profile, unlike the pro-inflammatory nature of reflux esophagitis. The aim of this study was to examine the role of Th-2 cytokines during the development of Barrett's esophagus, using a rat model. METHODS: Barrett's esophagus was induced by Levrat's esophagojejunostomy technique in Brown-Norway (BN) rats. Rats were killed at 8, 15, 30, and 50 weeks after the operation. We studied the incidences of esophagitis and Barrett's esophagus, and the mRNA expression of cytokines and CDX2 by real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining. Finally, we compared the incidence of Barrett's esophagus in BN rats with that in Sprague-Dawley (SD) rats. RESULTS: Esophagitis was found in all rats. Barrett's esophagus appeared 8 weeks after the operation, and its incidence and length increased over time. Levels of Th-2 cytokines such as interleukin (IL)-4, IL-10, and IL-13 were significantly increased in Barrett's esophagus as compared to those in non-Barrett's esophagus, while there were no differences in the levels of pro-inflammatory cytokines. The peak of elevated IL-4 mRNA was observed before that of CDX2 mRNA. IL-4 was co-localized in CD4-positive cells and CDX2-positive goblet cells. The incidence of Barrett's esophagus was more common in BN rats (8/10, 80%) than in SD rats (2/7, 28%) at 30 weeks. CONCLUSION: Th-2 cytokines, especially IL-4, may play a crucial role in the development of Barrett's esophagus in an early phase. These results provide understanding of the pathogenesis of Barrett's esophagus from the aspect of the Th-2 immune response.

Dysregulated upregulation of T-cell immunoglobulin and mucin domain-3 on mucosal T helper 1 cells in patients with Crohn's disease.

OBJECTIVE: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a unique cell surface molecule expressed on T helper 1 (Th1) cells. Engagement of TIM-3 by ligand galectin-9 leads to dampened Th1 immunity. We investigated TIM-3 and galectin-9 expression in inflammatory bowel disease (IBD) patients and in healthy controls, and evaluated the immune role of the TIM-3 pathway in Crohn's disease (CD) pathogenesis. MATERIAL AND METHODS: We used flow cytometry to investigate TIM-3 expression on mononuclear cells isolated from the intestinal mucosa and peripheral blood cells of patients with IBD and healthy controls. We also evaluated galectin-9 mRNA expression on endoscopically obtained intestinal mucosal cells. RESULTS: TIM-3 was constitutively expressed on Th cells isolated from the intestinal mucosa of IBD patients and healthy controls. While we observed low TIM-3 expression on Th cells isolated from peripheral blood mononuclear cells (PBMCs), high TIM-3 expression was induced by Th1 stimulation. The level of TIM-3 expression on Th cells isolated from intestinal mucosa and stimulated PBMCs was significantly lower in CD patients than in healthy controls. CONCLUSIONS: Our data show that TIM-3 upregulation on Th1 cells is dysregulated in patients with CD. Low TIM-3 expression on Th1 cells may provide a clue toward resolution of the inflammation associated with chronic inflammatory disease. These findings should contribute to develop understanding of CD pathogenesis.

Mitochondrial disorders in NSAIDs-induced small bowel injury.

Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury.

Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase.

Prostaglandin E(2) plays an important role in the maintenance of gastric mucosal integrity. The level of biologically active prostaglandin E(2) in the tissue is regulated by the balanced expression of its synthetic enzymes, such as cyclooxygenase, and its catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase. We examined the effect of rebamipide, a mucoprotective drug, on prostaglandin E(2) production and metabolism in the gastric tissue and its effect on indomethacin-induced gastric mucosal injury in mice. Rebamipide suppressed indomethacin-induced gastric mucosal injury. Suppressive effect of rebamipide on indomethacin-induced gastric mucosal injury was also observed in cyclooxygenase-2-knockout mice. The mice that were treated with rebamipide showed a 2-fold increase in cyclooxygenase-2 mRNA expression in the gastric tissue, whereas 15-hydroxyprostaglandin dehydrogenase mRNA expression markedly decreased as compared to vehicle-treated control mice. Rebamipide did not affect the expression of cyclooxygenase-1 in the gastric tissue. Rebamipide did not increase prostaglandin E(2) production in the gastric tissue; however, it induced a 1.4-fold increase in the concentration of prostaglandin E(2) in the gastric tissue as compared to vehicle-treated control mice. These results suggest that the suppressive effect of rebamipide on non-steroidal anti-inflammatory drugs-induced gastric mucosal injury can be attributed to reduced 15-hydroxyprostaglandin dehydrogenase expression, which increases the prostaglandin E(2) concentration in the gastric tissue.

Gastrointestinal bleeding after percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H2 receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.

[Gastric ulcer in the elderly: general concept and clinical features].

The total number of elderly persons with gastric ulcers in Japan is increasing with an improvement in the average life expectancy. So far, gastric ulcer in elderly persons is considered proximal gastric ulcer due to corpus-predominant atrophic gastritis. However, the clinical features of the disease will change with a decrease in the number of persons with Helicobacter pylori infection. On the other hand, the numbers of persons with gastric ulcers associated with aging-related diseases and those with gastric ulcers induced by drugs such as nonsteroidal anti-inflammatory drugs and aspirin are increasing. Even recently, there have been no changes in the mortality of patients with severe gastric ulcers. Management based on pathological conditions of gastric ulcers in the elderly persons is required.