Difference between the Upper and the Lower Gastrointestinal Bleeding in Patients Taking Nonvitamin K Oral Anticoagulants.

Nonvitamin K oral anticoagulants (NOACs) sometimes cause hemorrhage, and the gastrointestinal tract is a common site of involvement. However, clinical characteristics of gastrointestinal bleeding (GIB) during NOAC therapy have not been fully elucidated. We studied 658 patients who were prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and November 2015. Medical charts were reviewed to examine whether clinically relevant bleeding (Bleeding Academic Research Consortium criteria type 2 or greater) developed. The incidence of GIB was 2.0%/year, and one-third was from the upper GI. Among all hemorrhagic events, GIB was the most common cause. The extent of bleeding from the GI tract, particularly the upper GI tract, was more serious than bleeding from the other site. Multiple regression analysis showed that both past digestive ulcer and absence of concomitant proton pump inhibitors were significantly associated with the incidence of upper GIB, while concomitant nonsteroidal anti-inflammatory drugs, dual antiplatelets, and past GIB were significant factors regarding lower GIB. GIB was common and serious in patients taking NOACs. Upper GIB tended to become more serious than lower GIB. Proton pump inhibitors seem to be key drugs for preventing upper GIB during NOAC therapy.

Preoperative biliary drainage using a fully covered self-expandable metallic stent for pancreatic head cancer: A prospective feasibility study.

Background/Aims: The role of endoscopic preoperative biliary drainage (PBD) for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. This study was performed to evaluate the feasibility and safety of PBD using a fully covered self-expandable metallic stent (FCSEMS). Patients and Methods: This multicenter prospective study involved 26 patients treated for pancreatic head cancer with distal bile duct obstruction from April 2011 to March 2013. An FCSEMS was endoscopically placed in 24 patients. Among these, 7 patients were diagnosed with unresectable cancer, and 17 underwent surgery at a median of 18 days after FCSEMS placement. The main outcome measure was preoperative and postoperative adverse events. Results: Two adverse events (cholecystitis and insufficient resolution of jaundice) occurred between FCSEMS placement and surgery (12%). Postoperative adverse events occurred in eight patients (47%). The cumulative incidence of stent-related adverse events 4 and 8 weeks after FCSEMS placement among the 24 patients who underwent this procedure were 19%. Conclusions: PBD using an FCSEMS is feasible in patients with resectable pancreatic head cancer. Placement of an FCSEMS can be an alternative PBD technique when surgery without delay is impossible. A larger randomized controlled trial is warranted.

Extensive gastric mucosal atrophy is a possible predictor of clinical effectiveness of acotiamide in patients with functional dyspepsia
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BACKGROUND: Acotiamide is known as an effective agent for functional dyspepsia. However, clinical factors related to its effectiveness have not been fully elucidated, so it is difficult to predict the drug's effectiveness prior to its administration in patients. AIMS: The present retrospective study was conducted to examine the relationship between clinical factors and the effectiveness of acotiamide for functional dyspepsia. MATERIALS AND METHODS: The study subjects were 149 patients with functional dyspepsia who were prescribed acotiamide. Based on medical records and clinical factors, including endoscopic findings, the effectiveness of acotiamide was investigated. RESULTS: Significant clinical factors associated with acotiamide's effectiveness were identified. These included postprandial syndrome, concomitant mental disorder, and extensive gastric mucosal atrophy. On multiple regression analysis, extensive gastric mucosal atrophy showed the strongest relationship with the clinical effectiveness of acotiamide; the other significant factor was concomitant mental disorder. CONCLUSION: Although the pathophysiology of the relationship between mucosal atrophy and acotiamide remains uncertain, a decrease in hormonal secretion, such as that of ghrelin, may be a possible mechanism.
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Impact of lubiprostone on gastric-emptying profile and the possible effect of concomitant domperidone in healthy adults
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BACKGROUND: Lubiprostone is effective for patients with chronic constipation. This agent sometimes causes upper gastrointestinal symptoms, such as nausea, which is one of the chief reasons for discontinuation. However, the etiology of and strategy against bothersome gastrointestinal symptoms of lubiprostone remain unclear. AIMS: The goal of this study was to investigate the influence of lubiprostone on the gastric-emptying profile of healthy adults. The effect of domperidone on gastric emptying and gastrointestinal symptoms after lubiprostone administration were also assessed. MATERIALS AND METHODS: 80 healthy male participants underwent 13C acetate breath testing to evaluate gastric emptying. The test meal comprised 200 kcal of a standard liquid nutrient. Each participant underwent 3 random breath tests with: 1) no premedication; 2) 24 µg of lubiprostone 30 minutes prior to the study; and 3) 24 µg of lubiprostone plus 10 mg of domperidone 30 minutes prior to the study. Gastrointestinal symptoms (heartburn, regurgitation, epigastric pain, fullness, distress feeling) during testing were evaluated using a 7-point scoring system. RESULTS: Gastric emptying was significantly delayed by the administration of lubiprostone. Among all 8 subjects, 4 reported heartburn after taking lubiprostone, whereas this symptom was not found when subjects received concomitant domperidone. However, gastric emptying showed little change between lubiprostone alone and lubiprostone plus domperidone. CONCLUSION: Lubiprostone delayed gastric emptying of liquid in healthy adults, which could be associated with the gastrointestinal symptoms caused by the agent. Domperidone seemed effective against such gastrointestinal symptoms after administration of lubiprostone. This effect seemed unrelated to gastric motility.
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Possible Effect of Concomitant Prokinetics and Herbal Medicines against Nausea in Patients Taking Lubiprostone.

BACKGROUND AND AIM: Lubiprostone is a novel laxative that sometimes causes nausea, but preventive strategies remain unconfirmed. METHODS: We retrospectively chose 126 patients prescribed lubiprostone from 2013 to 2016. Medical records were reviewed to clarify whether nausea developed after administration of the drug. Background characteristics, including concomitant medicines, were also reviewed. RESULTS: The most common adverse symptom was diarrhea (23.8%). Nausea occurred in 16 patients (12.7%). Patients taking either prokinetics or herbal medicines or both were unlikely to develop nausea (p = 0.007). CONCLUSIONS: Concomitant prokinetics and/or herbal medicines may help alleviate lubiprostone-induced nausea.

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.

Status of the gastric mucosa with endoscopically diagnosed gastrointestinal stromal tumor.

Background. Since gastrointestinal stromal tumor (GIST) is a mesenchymal submucosal tumor, the endosonographic, CT, and MRI features of gastric GISTs have been widely investigated. However, the GIST-bearing gastric mucosa status has not been reported. Objective. To characterize the GIST-bearing gastric mucosa status in terms of the degree of inflammation and atrophy, assessed endoscopically. Subjects and Methods. The subjects were 46 patients with submucosal tumors (histologically proven gastric GISTs) who had undergone upper gastrointestinal endoscopy in our hospital between April 2007 and September 2012. They were retrospectively evaluated regarding clinicopathological features, the endoscopically determined status of the entire gastric mucosa (presence or absence and degree of atrophy), presence or absence and severity of endoscopic gastritis/atrophy (A-B classification) at the GIST site, and presence or absence of H. pylori infection. Results. Twenty-three patients had no mucosal atrophy, but 17 and 6 had closed- and open-type atrophy, respectively. Twenty-six, 5, 12, 1, 1, and 1 patients had grades B0, B1, B2, B3, A0, and A1 gastritis/atrophy at the lesion site, respectively, with no grade A2 gastritis/atrophy. Conclusion. The results suggest that gastric GISTs tend to arise in the stomach wall with H. pylori-negative, nonatrophic mucosa or H. pylori-positive, mildly atrophic mucosa.

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

BACKGROUND AND AIM: Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma. METHODS: We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days. RESULTS: TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002). CONCLUSION: These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach.

Electrocautery therapy combined with oral steroid administration for refractory corrosive esophageal stenosis prevents restenosis.

A 61-year-old female with refractory corrosive esophageal stenosis repeatedly underwent endoscopic balloon dilation at another hospital; however, no improvements were observed in the esophageal stenosis. Consequently, she had been on a liquid diet for the previous three years. She was admitted to our department for further treatment. A radial incision was made, by use of the SB knife Jr, for a pinhole-like stenosis in a short segment 39 cm from the incisor, and dilation was safely performed by use of a CRE balloon dilator. Subsequently, prednisolone was orally administered to prevent re-stenosis. This was followed by a favorable clinical course.

Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model.

BACKGROUND: Stricture formation is one of the major complications after endoscopic removal of large superficial squamous cell neoplasms of the esophagus, and local steroid injections have been adopted to prevent it. However, fundamental pathological alterations related to them have not been well analyzed so far. The aim of this study was to analyze the time course of the healing process of esophageal large mucosal defects resulting in stricture formation and its modification by local steroid injection, using an animal model. METHODS: Esophageal circumferential mucosal defects were created by endoscopic mucosal dissection (ESD) for four pigs. One pig was sacrificed five minutes after the ESD, and other two pigs were followed-up on endoscopy and sacrificed at the time of one week and three weeks after the ESD, respectively. The remaining one pig was followed-up on endoscopy with five times of local steroid injection and sacrificed at the time of eight weeks after the ESD. The esophageal tissues of all pigs were subjected to pathological analyses. RESULTS: For the pigs without steroid injection, the esophageal stricture was completed around three weeks after the ESD on both endoscopy and esophagography. Histopathological examination of the esophageal tissues revealed that spindle-shaped α-smooth muscle actin (SMA)-positive myofibroblasts arranged in a parallel fashion and extending horizontally were identified at the ulcer bed one week after the ESD, and increased contributing to formation of the stenotic luminal ridge covered with the regenerated epithelium three weeks after the ESD. The proper muscle layer of the stricture site was thinned with some myocytes which seemingly showed transition to the myofibroblast layer. By contrast, for the pig with steroid injection, esophageal stricture formation was not evident with limited appearance of the spindle-shaped myofibroblasts, instead, appearance of stellate or polygocal SMA-positive stromal cells arranged haphazardly in the persistent granulation tissue of the ulcer site. CONCLUSIONS: Proliferation of spindle-shaped myofibroblasts arranged in a parallel fashion is likely to play an important role in stricture formation after circumferential mucosal defects by esophageal ESD, which may be related to the thinning of the proper muscle layer in the healing course of the defects. Local steroid injection seems to be effective to prevent the stricture through the modification of this process.

Role of narrow band imaging in endoscopic submucosal dissection.

Narrow band imaging (NBI) is a new image enhancement system employing optic digital methods to enhance images of blood vessels on mucosal surfaces, allowing improved visualization of mucosal surface structures. Studies have progressed over the last several years, and the clinical usefulness has been demonstrated. NBI has become frequently applied for preoperative diagnosis before endoscopic submucosal dissection (ESD) of digestive tract cancers, as well as for assessment of the range of ESD for en-bloc resection of large lesions. Consensus has been reached with regard to the usefulness of NBI for detecting micro-lesions of esophageal squamous cell carcinoma indicated for ESD, for the diagnosis of the range and depth. NBI has also been attracting attention for diagnosing gastric cancer based on the observation of micro blood vessels on the mucosal surface and mucosal surface microstructures. The usefulness of NBI has been reported in relation to various aspects of colon cancer, including diagnoses of the presence, quality, range, and depth of lesions. However, as NBI has not surpassed diagnostic methods based on magnifying observation combined with the established and widely employed dye method, its role in ESD is limited at present. Although NBI is very useful for the diagnosis of digestive tract cancers, comprehensive endoscopic diagnosis employing the combination of conventional endoscopy including dye spraying, EUS, and NBI may be important and essential for ESD.

Usefulness of the DL in ME with NBI for determining the expanded area of early-stage differentiated gastric carcinoma.

AIM: To investigate whether magnifying endoscopy with narrow band imaging (ME-NBI) is useful for evaluating the area of superficial, depressed- or flat-type differentiated adenocarcinoma of the stomach. METHODS: This procedure was performed in Saitama Medical University International Medical Center, Japanese Red Cross Kumamoto Hospital and Kitakyushu Municipal Medical Center. The subjects were 31 patients in whom biopsy findings, from superficial, depressed- or flat-type gastric lesion, suggested differentiated adenocarcinoma in the above 3 hospitals between January and December 2009. Biopsy was performed on the lesion and non-lesion sides of a boundary (imaginary boundary) visualized on ME-NBI. The results were pathologically investigated. We evaluated the accuracy of estimating a demarcation line (DL) on ME-NBI in comparison with biopsy findings as a gold standard. RESULTS: The DL that could be recognized at 2 points on the orifice and anal sides of each lesion during ME-NBI was consistent with the pathological findings in 22 patients with 0-IIc lesions, 7 with 0-IIb lesions, and 2 with 0-IIb + IIc lesions, showing an accuracy of 100%. CONCLUSION: The results suggest the usefulness of ME-NBI for evaluating the area of superficial, depressed- and flat-type differentiated adenocarcinoma of the stomach.

Possibilities of interventional endoscopic ultrasound.

Since endoscopic ultrasound (EUS) was developed in the 1990s, EUS has become widely accepted as an imaging tool. EUS is categorized into radial and linear in design. Radial endoscopes provide cross-sectional imaging of the mediastinum, gastrointestinal tract, liver, spleen, kidney, adrenal gland, and pancreas, which has highly accuracy in the T and N staging of esophageal, lung, gastric, rectal, and pancreatic cancer. Tumor staging is common indication of radial-EUS, and EUS-staging is predictive of surgical resectability. In contrast, linear array endoscope uses a side-viewing probe and has advantages in the ability to perform EUS-guides fine needle aspiration (EUS-FNA), which has been established for cytologic diagnosis. For example, EUS-FNA arrows accurate nodal staging of esophageal cancer before surgery, which provides more accurate assessment of nodes than radial-EUS imaging alone. EUS-FNA has been also commonly used for diagnose of pancreatic diseases because of the highly accuracy than US or computed tomography. EUS and EUS-FNA has been used not only for TNM staging and cytologic diagnosis of pancreatic cancer, but also for evaluation of chronic pancreatitis, pancreatic cystic lesions, and other pancreatic masses. More recently, EUS-FNA has developed into EUS-guided fine needle injection including EUS-guided celiac plexus neurolysis, celiac plexus block, and other "interventional EUS" procedures. In this review, we have summarized the new possibilities offered by "interventional EUS".

Endoscopic submucosal dissection for removal of superficial gastrointestinal neoplasms: A technical review.

Endoscopic submucosal dissection (ESD) is now the most common endoscopic treatment in Japan for intramucosal gastrointestinal neoplasms (non-metastatic). ESD is an invasive endoscopic surgical procedure, requiring extensive knowledge, skill, and specialized equipment. ESD starts with evaluation of the lesion, as accurate assessment of the depth and margin of the lesion is essential. The devices and strategies used in ESD vary, depending on the nature of the lesion. Prior to the procedure, the operator must be knowledgeable about the treatment strategy(ies), the device(s) to use, the electrocautery machine settings, the substances to inject, and other aspects. In addition, the operator must be able to manage complications, should they arise, including immediate recognition of the complication(s) and its treatment. Finally, in case the ESD treatment is not successful, the operator should be prepared to apply alternative treatments. Thus, adequate knowledge and training are essential to successfully perform ESD.

A case of gastric mucosa-associated lymphoid tissue lymphoma in which magnified endoscopy with narrow band imaging was useful in the diagnosis.

Recently, we reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma presenting with unique vascular features. In the report, we defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost. The 67-year-old female was diagnosed with gastric MALT lymphoma. The patient received eradication therapy for H. pylori. Conventional endoscopy revealed multiple ill-delineated brownish depressions in the stomach and cobblestone-like mucosa was observed at the greater curvature to the posterior wall of the upper gastric body 7 mo after successful eradication. Unsuccessful treatment of gastric MALT lymphoma was suspected on conventional endoscopy. Conventional endoscopic observations found focal depressions and cobblestone-like appearance, and these lesions were subsequently observed using magnified endoscopy combined with narrow band imaging to identify abnormal vessels presenting with a TLA within the lesions. Ten biopsies were taken from the area where abnormal vessels were present within these lesions. Ten biopsies were also taken from the lesions without abnormal vessels as a control. A total of 20 biopsy samples were evaluated to determine whether the diagnosis of MALT lymphoma could be obtained histologically from each sample. A positive diagnosis was obtained in 8/10 TLA (+) sites and in 2/10 TLA(-) sites. Target biopsies of the site with abnormal blood vessels can potentially improve diagnostic accuracy of gastric MALT lymphoma.