Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - a Japanese retrospective cohort study
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BACKGROUND AND AIM: Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. METHODS: Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. RESULTS: Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. CONCLUSIONS: Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
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Endoscopic removal of a denture with clasps impacted in the ileocecum.

We report a case of endoscopic removal of a denture with clasps impacted in the ileocecum. The patient was a 63-year-old man hospitalized at another center with aspiration pneumonia. He had a history of cerebral bleeding, inflicted permanent damage with left hemiplegia, and dysphagia. Abdominal radiography for localization of a catheter in the femoral vein revealed a denture in the right lower quadrant of the abdomen. He was subclinical and could not recall when he might have swallowed the denture. The patient was brought by ambulance to our institution. Computed tomography showed a foreign body with the density of metal in the ileocecum without any severe complications such as obstruction or perforation. Following intestinal lavage from a nasogastric tube, we performed colonoscopy and successfully retrieved the denture. The patient showed no complications associated with endoscopic therapy and returned to the previous hospital 3 days after endoscopic removal of the denture.

[Selective serotonin reuptake inhibitor and gastrointestinal hemorrhage].

Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressants characterized by less-frequent adverse effects compared with classical anti-depressive agents. On the other hand, SSRI can cause hemorrhagic events more due to impaired platelet aggregation induced by a depletion of serotonin in the peripheral platelet. Epidemiological studies have indicated that patients taking SSRI are predisposed to gastrointestinal hemorrhage, especially in case that nonsteroidal anti-inflammatory drugs are prescribed concomitantly. Here we describe a risk of the gastrointestinal hemorrhage in patients taking SSRI.

Right recumbent position on gastric emptying of water evidenced by (13)C breath testing.

AIM: To compare the impact of the right recumbent position with the sitting position on gastric emptying of water. METHODS: In eight healthy male volunteers, the 13C acetate breath test was performed twice to assess gastric emptying of 100 mL tap water. Subjects were seated in one test and lying on their right side in the other. In both positions, pulmonary (13)CO(2) exhalation curves were obtained by plotting breath data against time. Percent gastric retention curves were created by analyzing data using the Wagner-Nelson protocol. RESULTS: No significant posture effect was found in pulmonary (13)CO(2) output curves (P = 0.2150), whereas a significant effect was seen in gastric retention curves (P = 0.0315). The percent retention values at 10 min and 15 min were significantly smaller when subjects were in the right recumbent position compared with the seated position (P < 0.05). Our results verified the accelerating effect of the right recumbent position on gastric emptying of non-nutritive solutions. Concerning clinical implications, this study suggests that placing patients with acute pain on their right side after oral administration of analgesic drugs in solution is justified as an effective practice for rapid pain relief. For patients with gastrointestinal reflux symptoms, sleeping in the right recumbent position may reduce nocturnal symptoms, as delayed gastric emptying can cause reflux symptoms. CONCLUSION: Gastric emptying of water occurs more quickly when a subject lies on the right side compared with sitting.

Severe erosive esophagitis developing after gastric ulcer formation.

A 90-year-old woman visited to our institute due to postprandial obstructive sensation of the esophagus. She had suffered from ischemic heart disease and diabetes mellitus, and taken low-dose aspirin for prophylaxis. She also had a history of a large ulcer located on the upper gastric body at 81 years-old. Esophago-gastric junction was normal excepting mild hiatal hernia at that time. The esophagogastroduodenoscopy showed a lump of food at the lower esophagus with severe stricture and mucosal injury. Rabeprazole 20 mg per day was given, and both the inflammatory change and the symptoms improved after the prescription. A probable reason of the development is impaired gastroesophageal motility and acid regurgitation induced by gastric deformity caused after ulcer formation.

Metronidazole-induced neurotoxicity developed in liver cirrhosis.

A 68 year-old-male with hepatitis C-positive liver cirrhosis was admitted because of liver abscess. After metronidazole was initiated against the infection, mental disturbance appeared. Hepatic encephalopathy was suspected at first, however, the brain MRI showed hyperintense lesion of the bilateral basal dendric nuclei which indicated metronidazole-associated encephalopathy. The symptoms became well after cessation of the drug. Metronidazole is a widely used medicine against various infections. Recent case reports describe that this medicine can induce reversible encephalopathy. However, there have been few reports regarding metronidazole-induced encephalopathy occurred in patients with cirrhosis. Here we report on a case of hepatic cirrhosis and abscess in which reversible metronidazole-induced encephalopathy developed.

Gastric emptying in patients with autoimmune pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) and its extrapancreatic lesions seem to be clinical manifestations of organs involved in IgG4-related systemic disease. To clarify whether the stomach is a target organ, gastric function was evaluated in patients with AIP. METHODS: In 6 patients with AIP, gastric emptying was assessed by Carbon 13 (¹³C) acetate breath test before and after steroid therapy. Based on 4-hour breath samples, the half ¹³CO2 excretion time (T(1/2)) and the time of maximal excretion (T(max)) were calculated as gastric emptying parameters. Data of 20 healthy volunteers were used as controls. The number of IgG4-positive plasma cells in gastrofiberscopic biopsy specimens was counted before and after steroid therapy. RESULTS: Both T(1/2) and T(max) in patients with AIP decreased significantly after steroid therapy (T(1/2): 1.89 ± 0.21 hours vs 1.69 ± 0.15 hours, P = 0.046; and T(max): 1.1 ± 0.2 hours vs 0.96 ± 0.2 hours, P = 0.027), and became similar to those of the controls (T(1/2): 1.69 ± 0.32 hours and T(max): 0.98 ± 0.2 hour). The number of IgG4-positive plasma cells infiltrating the gastric mucosa decreased after steroid therapy. CONCLUSIONS: Gastric emptying was impaired in patients with AIP and improved to the reference range after steroid therapy. The stomach may be a target organ of IgG4-related systemic disease.

[Treatment and prevention of NSAIDs-induced gastrointestinal injury--the role of gastroenterologist].

According to many clinical researches, it is obvious that patients taking NSAIDs including low-dose aspirin have upper GI injury frequently than those without. Recently, the GI event of those medicines becomes more serious clinical problem in Japan in which aging population is getting larger year by year. Evaluation of GI risk and appropriate use of anti -ulcer drugs, especially proton-pump inhibitors, are recommended for the prevention. Additionally, the close communication and cooperation between doctors who prescribe the medicines and gastroenterologists is essential for minimizing such adverse reaction. Here we describe on the role of gastroenterologists on the prevention of GI event caused by NSAIDs and aspirin.

Endoscopic hemostasis techniques for upper gastrointestinal hemorrhage: A review.

Upper gastrointestinal hemorrhage (UGIH) is an urgent disease that is often encountered in daily medical practice. Endoscopic hemostasis is currently indispensable for the treatment of UGIH. Initially, when UGIH is suspected, a cause of UGIH is presumed from the medical interview and physical findings. After ample primary treatment, urgent endoscopy is performed. Many methods of endoscopic hemostasis are in wide use, including hemoclip, injection and thermo-coagulation methods. Although UGIH develops from a wide variety of diseases, such as esophageal varices and gastric and duodenal ulcer, hemostasis is almost always possible. Identification of the causative diseases, primary treatment and characteristic features of endoscopic hemostasis are needed to allow appropriate treatment.

Gastroduodenal mucosal injury in patients taking low-dose aspirin and the role of gastric mucoprotective drugs: possible effect of rebamipide.

The present study was conducted to investigate the prevalence of mucosal injury in patients taking low-dose aspirin in Japan and examine the effect of gastric mucoprotective drugs on aspirin-related gastroduodenal toxicity. We selected 530 patients who had taken low-dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at Teikyo University Hospital, Tokyo, Japan. Endoscopic records were retrospectively reviewed to determine the presence of massive bleeding and mucosal injury (ulcer or erosion). The influence of clinical factors, including co-administration of gastroprotective drugs, was also examined. Hemorrhage was observed in 25 patients (3.7%) and mucosal injury (36.2%) in 192 patients. The presence of Helicobacter pylori antibody was a significant risk factor associated with mucosal injury. Patients taking any gastroprotective drug showed a significantly lower rate of mucosal injury than those not taking these drugs. Patients taking rebamipide concomitantly with proton pump inhibitors or histamine 2 receptor antagonists had mucosal injury less frequently than those taking acid suppressants plus other mucoprotective drugs. In conclusion, these results show the possible gastroprotective effects of rebamipide, suggesting that it may be a good choice in aspirin users with gastroduodenal toxicity that is not suppressed by acid suppressants alone.

Arousals in obstructive sleep apnea patients with laryngopharyngeal and gastroesophageal reflux.

OBJECTIVE: We hypothesized that differences exist in the effect of apnea severity and those of laryngopharyngeal reflex (LPR) versus gastroesophageal reflex (GER) on arousals during sleep in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Japanese patients having witnessed snoring or excessive daytime sleepiness with a frequency scale for symptoms of GER of 10 or more or with visualization of inflammatory changes on pharyngolaryngeal endoscopy underwent polysomnography with pH monitoring using double pH catheter in a sleep laboratory. RESULTS: Most reflux events in patients with severe OSAS with LPR (n=16) and GER (n=21) were accompanied with respiratory arousals. On the other hand, among patients with mild-to-moderate OSAS, 64.0% and 24.8% of reflux events were accompanied with spontaneous arousals in those with LPR (n=12) and GER (n=12), respectively, and 9.4% and 8.3% of reflux events were not accompanied by arousals. There were no significant differences in other sleep parameters between mild-to-moderate OSAS patients with LPR versus GER and between severe OSAS patients with LPR versus GER. CONCLUSIONS: Among patients with reflux, the types of arousal differed significantly between those with mild-to-moderate versus severe OSAS. In patients with mild-to-moderate OSAS, LPR induces more spontaneous arousals than does GER.

Prevalence of erosive esophagitis among Japanese patients taking low-dose aspirin.

BACKGROUND AND AIM: The risk for erosive esophagitis (EE) with low-dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. METHODS: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 +/- 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age- and sex-matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well-experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. RESULTS: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7-3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5-8.8). CONCLUSION: In Japanese patients taking ASA, EE was not as common as peptic ulcers.

Effects of proton pump inhibitors on gastric emptying: a systematic review.

The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.