BACKGROUND/AIMS: The association between Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin therapy as a risk factor for peptic ulcer bleeding (PUB) remains unclear. This study investigated the risk of PUB associated with H. pylori infection and NSAID or low-dose aspirin therapy in patients with PUD. MATERIALS AND METHODS: This case-control study investigated 340 patients with PUB between 2012 and 2016. The control group comprised age and sex-matched patients with endoscopically documented non-bleeding ulcers. Using logistic regression analysis, the adjusted odds ratio (AOR) was calculated for the risk of PUB. RESULTS: Of the patients investigated, 57.9% in the study group and 51.8% in the control group were diagnosed with H. pylori infection (P=0.106). Logistic regression analysis showed synergistic interaction between H. pylori infection and low-dose aspirin therapy. Multivariate analysis showed that low-dose aspirin (AOR 3.92, P < 0.001), NSAIDs (AOR 2.98, P=0.001), warfarin (AOR 14.57, P=0.011), gastric ulcer (compared with duodenal ulcer) (AOR 1.65, P=0.01), and smoking (AOR 1.97, P=0.004) increased the risk of PUB compared with the risk of PUD. CONCLUSIONS: Both NSAIDs and aspirin are independent risk factors for bleeding in patients with PUD. Additionally, low-dose aspirin therapy concomitant with H. pylori infection produced a synergistic effect. Therefore, H. pylori eradication may be crucial in aspirin users. Moreover, a proton pump inhibitor should be prescribed in patients with a history of bleeding ulcers who need long-term NSAID treatment.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Case-Control Studies ; Helicobacter pylori ; Helicobacter ; Hemorrhage ; Humans ; Logistic Models ; Multivariate Analysis ; Odds Ratio ; Peptic Ulcer ; Proton Pumps ; Risk Factors ; Smoke ; Smoking ; Stomach Ulcer ; Ulcer ; Warfarin

The eradication of Helicobacter pylori and the widespread use of effective antisecretory therapies, including proton pump inhibitors, have improved the management of peptic ulcer disease. However, in some patients, peptic ulcer disease is refractory to 8 to 12 weeks of standard antisecretory drug treatment. For refractory peptic ulcer disease, further evaluation of the risk factors and causes of refractory peptic ulcer disease, including patient risk factors and noncompliance (smoking, nonsteroidal anti-inflammatory drug use, and noncompliance with medical treatment), persistent H. pylori infection, and non-H. pylori-related factors (giant ulcer, gastrinoma, infections other than H. pylori, and malignancy), is essential. The treatment should focus on the cause of the refractory peptic ulcer disease, avoiding smoking and nonsteroidal anti-inflammatory drug, the treatment of persistent H. pylori, use of high-dose proton pump inhibitors, or surgical excision of gastrinomas. Surgery should be considered in patients who are at high risk for complications and recurrent peptic ulcer disease despite medical treatment. In this review, I describe the diagnosis and treatment of refractory peptic ulcer disease.
Anti-Inflammatory Agents, Non-Steroidal ; Diagnosis ; Gastrinoma ; Helicobacter pylori ; Humans ; Peptic Ulcer ; Proton Pump Inhibitors ; Risk Factors ; Smoke ; Smoking ; Ulcer

Nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA) are the main causes of peptic ulcer (PU), and cause major complication such as bleeding and perforation. The interaction of Helicobacter pylori infection with NSAIDs or LDA is complex and remains unclear. However, H. pylori infection may play additive, synergistic, or antagonistic roles in the development of drug-induced PU. H. pylori infection and NSAID use are independent risk factors for the development of PU, which is thought to be a synergistic effect. Eradication of H. pylori significantly reduces the incidence of PU in NSAID-naïve patients. However, the effect of secondary prevention is controversial, especially in chronic NSAID users. The use of a gastroprotective agent such as a proton pump inhibitor (PPI) is mandatory to prevent the recurrence of PU in patients with a previous history, especially in chronic NSAID users. H. pylori infection may also increase the risk of LDA-associated complicated and uncomplicated PU, including the risk of upper gastrointestinal bleeding. In patients taking LDA, H. pylori eradication alone may prevent the recurrence of PU bleeding. However, PPI maintenance is necessary with concomitant use of an NSAID, steroid, anticoagulant, or other antiplatelet agents.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Helicobacter pylori* ; Helicobacter* ; Hemorrhage ; Humans ; Incidence ; Peptic Ulcer* ; Platelet Aggregation Inhibitors ; Proton Pumps ; Recurrence ; Risk Factors ; Secondary Prevention

BACKGROUND/AIMS: Peptic ulcer disease (PUD) is a common condition, but is difficult to detect in asymptomatic individuals. We aimed to investigate the prevalence of symptomatic and asymptomatic PUD during screening endoscopy and to identify risk factors for the presence of symptoms in patients with PUD. METHODS: We investigated subjects who underwent a health inspection, including endoscopy of the upper gastrointestinal (GI) tract and a serum anti-Helicobacter pylori IgG assay, and who completed a self-report questionnaire about their symptoms. RESULTS: Of the 12,852 subjects included in the study, 124 (1.0%) had symptomatic PUD and 309 (2.4%) had asymptomatic PUD. Old age, current smoking, and H. pylori infection were independent risk factors for symptomatic and asymptomatic PUD. Use of non-steroidal anti-inflammatory drugs (NSAIDs) was an independent risk factor only for symptomatic PUD (p=0.040). Compared to subjects with asymptomatic PUD, subjects with symptomatic PUD were more likely to have active-stage ulcers (p=0.002) and to drink more heavily (p=0.005). CONCLUSIONS: Use of NSAIDs is a risk factor for symptomatic PUD, but not for asymptomatic PUD. Excessive alcohol consumption and active-stage ulcers in patients with PUD are related to the presence of gastroduodenal symptoms.
Alcohol Drinking ; Anti-Inflammatory Agents, Non-Steroidal ; Endoscopy ; Helicobacter pylori ; Humans ; Immunoglobulin G ; Mass Screening ; Peptic Ulcer* ; Prevalence ; Risk Factors* ; Smoke ; Smoking ; Ulcer

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to be associated with serious upper gastrointestinal complications, such as peptic ulcer, bleeding, perforation, and obstruction. Recently, attention has been mainly focused on the small bowel injuries caused by NSAIDs, and new endoscopic techniques such as capsule endoscopy and double balloon endoscopy can help in detecting such injuries. This article reviewed the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of small bowel injuries caused by NSAIDs. Small bowel injures by NSAIDs might occur with a similar frequency and extent as those observed in the upper gastrointestinal tract. The pathogenesis of NSAID-induced enteropathy is complex and not clearly understood. The various lesions observed in the small bowel, including petechiae, reddened folds, loss of villi, erosions, and ulcers can be detected by capsule endoscopy. A drug that could prevent or treat NSAID-induced enteropathy has not yet been developed. Therefore, further investigations should be performed to elucidate the pathogenesis of such enteropathy and develop suitable preventive and treatment strategies.
Anti-Inflammatory Agents, Non-Steroidal ; Capsule Endoscopy ; Diagnosis ; Endoscopy ; Epidemiology ; Hemorrhage ; Peptic Ulcer ; Purpura ; Ulcer ; Upper Gastrointestinal Tract

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.
Aged ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Cardiovascular Diseases ; Cyclooxygenase 2 ; Duodenum ; Helicobacter pylori ; Hemorrhage ; Humans ; Incidence ; Inflammation ; Korea ; Lower Gastrointestinal Tract ; Mucous Membrane ; Peptic Ulcer* ; Prevalence ; Proton Pump Inhibitors ; Stomach ; Stroke ; Ulcer

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Blood Platelets ; Fasting ; Gastrins ; Helicobacter pylori ; Humans ; Peptic Ulcer* ; Plasma ; Prostaglandin-Endoperoxide Synthases ; Proton Pump Inhibitors ; Serologic Tests ; Smoke ; Smoking ; Ulcer ; Zollinger-Ellison Syndrome

BACKGROUND/AIMS: The optimal management of bleeding peptic ulcer with adherent clot remains controversial. The purpose of this study was to compare clinical outcome between endoscopic therapy and medical therapy. We also evaluated the risk factors of rebleeding in Forrest type IIB peptic ulcer. METHODS: Upper gastrointestinal (UGI) bleeding registry data from 8 hospitals in Korea between February 2011 and December 2013 were reviewed and categorized according to the Forrest classification. Patients with acute UGI bleeding from peptic ulcer with adherent clots were enrolled. RESULTS: Among a total of 1,101 patients diagnosed with peptic ulcer bleeding, 126 bleedings (11.4%) were classified as Forrest type IIB. Of the 126 patients with adherent clots, 84 (66.7%) received endoscopic therapy and 42 (33.3%) were managed with medical therapy alone. The baseline characteristics of patients in two groups were similar except for higher Glasgow Blatchford Score and pre-endoscopic Rockall score in medical therapy group. Bleeding related mortality (1.2% vs. 10%; p=0.018) and all cause mortality (3.7% vs. 20.0%; p=0.005) were significantly lower in the endoscopic therapy group. However, there was no difference between endoscopic therapy and medical therapy regarding rebleeding (7.1% vs. 9.5%; p=0.641). In multivariate analysis, independent risk factors of rebleeding were previous medication with aspirin and/or NSAID (OR, 13.1; p=0.025). CONCLUSIONS: In patients with Forrest type IIB peptic ulcer bleeding, endoscopic therapy was associated with a significant reduction in bleeding related mortality and all cause mortality compared with medical therapy alone. Important risk factor of rebleeding was use of aspirin and/or NSAID.
Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Aspirin/therapeutic use ; Cohort Studies ; Female ; *Hemostasis, Endoscopic ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Peptic Ulcer/complications/diagnosis ; Peptic Ulcer Hemorrhage/etiology/*therapy ; Prospective Studies ; Proton Pump Inhibitors/therapeutic use ; Recurrence ; Risk Factors ; Treatment Outcome

Helicobacter pylori can cause variety of upper gastrointestinal disorders such as peptic ulcer, mucosa associated lymphoid tissue (MALT)-lymphoma, and gastric cancer. The prevalence of H. pylori infection has significantly decreased in Korea since 1998 owing to active eradication of H. pylori. Along with its decrease, the prevalence of peptic ulcer has also decreased. However, the mean age of gastric ulcer increased and this is considered to be due to increase in NSAID prescription. Gastric cancer is one of the leading causes of cancer deaths in Korea and Japan, and IARC/WHO has classified H. pylori as class one carcinogen of gastric cancer. Despite the decreasing prevalence of H. pylori infection, the total number of gastric cancer in Korea has continuously increased from 2006 to 2011. Nevertheless, the 5 year survival rate of gastric cancer patients significantly increased from 42.8% in 1993 to 67% in 2010. This increase in survival rate seems to be mainly due to early detection of gastric cancer and endoscopic mucosal dissection treatment. Based on these findings, the prevalence of peptic ulcer is expected to decrease even more with H. pylori eradication therapy and NSAID will become the main cause of peptic ulcer. Although the prevalence of gastric cancer has not changed along with decreased the prevalence of H. pylori, gastric cancer is expected to decrease in the long run with the help of eradication therapy and endoscopic treatment of precancerous lesions.
Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Gastrointestinal Diseases/complications/*epidemiology ; Helicobacter Infections/complications/drug therapy/epidemiology ; Humans ; Lymphoma, B-Cell, Marginal Zone/epidemiology ; Peptic Ulcer/epidemiology/etiology ; Prevalence ; Stomach Neoplasms/etiology/mortality/pathology

BACKGROUND/AIMS: Increased incidence of coronary artery disease has led to the increased use of dual antiplatelet therapy composed of aspirin and clopidogrel. We investigated the incidence of gastrointestinal complications in patients who received single or dual antiplatelet therapy and analyzed their clinical characteristics in order to predict the prognostic factors. METHODS: Between January 2009 and December 2011, we retrospectively reviewed the medical records of patients who underwent coronary angiography at Chung-Ang University Hospital (Seoul, Korea). One hundred and ninety-four patients were classified into two groups: aspirin alone group and dual antiplatelet group. Clinical characteristics, past medical history, and presence of peptic ulcer were analyzed. RESULTS: During the follow-up period, 11 patients had duodenal ulcer; the event rate was 2.02% in the aspirin alone group and 9.47% in the dual antiplatelet group (hazard ratio [HR] 5.24, 95% CI 1.03-26.55, p<0.05). There was no significant difference in the rate of significant upper gastrointestinal bleeding: 0% vs. 4.2% (p=0.78). In patients who received proton pump inhibitor (PPI), 24 patients had gastric ulcer; the event rate was significantly different between the two groups: 4.87% vs. 22.98% (HR 3.40, 95% CI 1.02-11.27, p<0.05). CONCLUSIONS: Dual antiplatelet groups had a higher incidence of duodenal ulcers without significant bleeding compared with the aspirin alone group. In patients who received PPI, the dual antiplatelet therapy group had a higher incidence of gastric ulcers without significant bleeding compared with the aspirin alone group. Therefore, physicians must pay attention to high risk groups who receive dual antiplatelet therapy and aggressive diagnostic endoscopy should also be considered.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use/toxicity ; Aspirin/*therapeutic use/toxicity ; Coronary Angiography ; Coronary Artery Disease/*prevention & control ; Drug Therapy, Combination ; Female ; Gastrointestinal Hemorrhage/chemically induced/prevention & control ; Humans ; Incidence ; Male ; Middle Aged ; Peptic Ulcer/*diagnosis/epidemiology/etiology ; Platelet Aggregation Inhibitors/*therapeutic use/toxicity ; Proportional Hazards Models ; Proton Pump Inhibitors/therapeutic use ; Retrospective Studies ; Risk Factors ; Ticlopidine/*analogs & derivatives/therapeutic use/toxicity