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Gastric cancer patients with para-aortic lymph node metastases may achieve long-term survival with radical gastrectomy and para-aortic lymph nodal dissection (PAND) following neoadjuvant therapy. We introduced the Cattell-Braasch maneuver to facilitate safe and complete PAND for advanced gastric cancer with extensive lymph node metastases.Between January 2014 and March 2020, 7 patients with highly advanced gastric cancer received preoperative chemotherapy followed by radical gastrectomy and PAND using the Cattell-Braasch maneuver. This maneuver consists of mobilization of the right hemi-colon and the total small intestine.Five patients received preoperative chemotherapy for para-aortic lymph node metastases and 2 for bulky lymph node metastases around the supra-pancreatic area. All patients received S-1 + cisplatin therapy, and one was additionally treated with paclitaxel chemotherapy followed by nivolumab. After chemotherapy, 2 patients with para-aortic lymph node metastases achieved down-staging on imaging tests. Total gastrectomy with PAND by the Cattell-Braasch maneuver was performed on all patients and was accompanied by splenectomy (n = 5) and distal pancreatectomy (n = 1). Pathological assessments revealed that 3 patients had para-aortic lymph node metastases, and the median number of retrieved para-aortic lymph nodes was 16. Three patients without para-aortic lymph node metastasis survived for more than 5 years without recurrence.The Cattell-Braasch maneuver provides a good surgical field and is useful for complete PAND for gastric cancer.

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulant (DOAC) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1010 patients prescribed DOACs from a single-center at the Teikyo University Hospital between April 2011 and June 2018. This study was an exploratory analysis and investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding, and major cardiovascular and cerebrovascular events. Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2272 patient-years. The rate of bleeding was 4.7%/year, gastrointestinal bleeding was 2.8%/year, and major cardiovascular and cerebrovascular events were 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for gastrointestinal bleeding (hazard ratio, 2.046 [95%CI, 1.188-3.526]; P = .010). Nonsteroidal anti-inflammatory drugs were the only significant risk for gastrointestinal bleeding. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or nonsteroidal anti-inflammatory drugs.

Purpose: Heart-type fatty acid binding protein (H-FABP) is primary transporter of free fatty acid and plays an important role in myocardial metabolism, which is characterized by high specificity and rapid appearance under ischemic condition. The objective of this study was to clarify the usefulness of imaging study of targeting H-FABP appearance using radio-labeled antibody, and correlation with myocardial fatty acid metabolism and perfusion in acute reperfusion ischemia. Method: Wistar rats were allotted to sham-operated control group (sham; n=4), ischemia non-reperfused group (IG; n=5), and ischemia-reperfusion group (RG; n=5). Ligation of left coronary artery (LCA) was performed for IG and RG. 20 min of ischemia was followed by 60min of reperfusion for RG. (125)I labeled anti H-FABP antibody (anti H-FABP), BMIPP and (99m)Tc-sestamibi (MIBI) was injected intravenously. Multi-tracer digital autoradiogram was performed using µ-imager(®). The ratio of radioactivity in LCA related (culprit) area to the inferior (remote) area (target uptake ratio=TUR) was generated. Results: In sham group, no visually detectable accumulation was observed for the anti H-FABP image, and TUR(MIBI) and TUR(BMIPP) were equivalent to 1. In IG, TUR(MIBI) and TUR(BMIPP) were remarkably low (0.12±0.01, 0.24±0.07). In RG, TUR(MIBI) was significantly lower (0.20±0.03, p

Factors associated with serious colonic diverticular bleeding (CDB) are unclear, although the incidence of CDB has increased. We carried out this study to clarify factors associated with serious CDB and rebleeding. Subjects included 329 consecutive patients hospitalized for confirmed or suspected CDB between 2004 and 2021. Patients were surveyed regarding backgrounds, treatment, and clinical course. Of 152 with confirmed CDB, 112 showed bleeding from the right colon, and 40 did from the left colon. Patients received red blood cell transfusions in 157 (47.7%), interventional radiology in 13 (4.0%), and surgery in 6 (1.8%) cases. Early rebleeding within one month occurred in 75 (22.8%) patients, and late rebleeding within one year occurred in 62 (18.8%). Factors associated with red blood cell transfusion included confirmed CDB, anticoagulants, and high shock index. The only factor related to interventional radiology or surgery was confirmed CDB, which was also associated with early rebleeding. Late rebleeding was associated with hypertension, chronic kidney disease and past CDB. Right CDB showed higher rates of transfusion and invasive treatment than left CDB. Confirmed CDB had high frequencies of transfusion, invasive treatment, and early rebleeding. Right CDB seemed to be a risk for serious disease. Factors related to late rebleeding were different from those related to early rebleeding of CDB.

Objective Direct oral anticoagulants are frequently used to prevent systemic embolism associated with atrial fibrillation. Gastrointestinal bleeding is a common adverse event of this pharmacotherapy, especially in the lower gastrointestinal tract. However, the prevalence of mucosal injury of the colon in patients taking direct oral anticoagulants has remained unknown. Materials and methods This was a retrospective study using endoscopic records of the colon from patients taking oral anticoagulants. Records from colonoscopies for 120 patients with non-valvular atrial fibrillation who had been prescribed direct oral anticoagulants between April 2011 and June 2017 were reviewed to determine the prevalence of mucosal injury and other findings, compared with those of 140 patients on warfarin. Results The prevalence of mucosal injury was 1.6% in patients taking direct oral anticoagulants and 1.4% in those taking warfarin, lower than other findings such as diverticula, hemorrhoids, and polyps. Bleeding was more frequent with direct oral anticoagulants (18 patients; 15%) than with warfarin (9 patients; 6.4%). Colonic diverticulum was the most common cause of bleeding in patients on direct oral anticoagulants. The prevalence of mucosal injury and causes of bleeding did not differ among direct oral anticoagulants. Conclusion Colonic mucosal injury was infrequent in patients on direct oral anticoagulants. Bleeding was more frequent with direct oral anticoagulants than with warfarin. Colonic diverticulum and vascular ectasia were common causes of bleeding in patients on direct oral anticoagulants. Little difference in cause of bleeding was evident among oral anticoagulants.

Descending necrotizing mediastinitis is a life-threatening disease that extends into the pretracheal, perivascular, retrovisceral, and/or prevertebral spaces, generally sparing the esophagus. We report a case of deep neck abscess complicated by phlegmonous esophagitis and mediastinitis. The patient was successfully treated with antibiotics and surgery, combining transcervical and bilateral thoracoscopic transthoracic mediastinal drainage. However, a pseudo-lumen with a large amount of pus remained in the esophagus. The septum between the true and the pseudo-lumen was cut endoscopically, after which the patient recovered well without any complications.

We have a unique history of using radioactive iodine (RAI) therapy and surgical treatment for thyroid cancer in Japan. Less than total thyroidectomy without RAI therapy was the most common management of papillary thyroid carcinoma (PTC) in the past. Limited availability of dedicated facilities for the RAI administration due to the strict regulations and insufficient coverage of the expenses were the major reasons that impacted on the management decisions. Following the publication of the Japanese clinical practice guidelines for thyroid tumors in 2010, the risk-adapted approach has become a standard where the high-risk and selected intermediate-risk PTC patients undergo total thyroidectomy followed by RAI therapy and thyrotropin suppression therapy. We are on the shoulders of pioneers who made every effort to bring the interventions closer to an ideal environment for patients. Armed with the revised clinical practice guidelines 2018 and devised inpatient/outpatient RAI therapy, Japanese physicians are ready to proceed to more rational management that would improve patients' outcomes. Directions for the future include further advancement of relevant clinical research to fill the gaps between current evidence and recommendations in the guidelines, and obtaining approval for high-dose RAI therapy on an outpatient basis to improve its effectiveness in both adjuvant and treatment settings.

Objective Liver injury is a notable complication of coronavirus disease 2019 (COVID-19). This study aimed to clarify the clinical features and liver injury in Japanese patients with COVID-19. Methods We conducted a multicenter retrospective cohort study. All consecutive patients with COVID-19 who visited or were admitted to our hospital before May 12, 2020, were enrolled. Their demographics, symptoms, laboratory findings, comorbidities, concomitant drugs, treatment, and clinical course were reviewed. We defined liver injury as alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) levels over the upper limit of normal. Results Twenty-two patients with COVID-19 (median age, 47 years old; men/women, 13/9) were enrolled. Two patients had underlying liver diseases, and two were diagnosed as having COVID-19 without any symptoms. Elevated ALT and GGT levels were found in 12 and 12 patients, respectively, and liver injury was observed in 15 patients (68.2%). Compared with the patients without liver injury, those with liver injury had a significantly higher fever during the clinical course (median, 37.5°C vs. 38.8°C, p=0.006). A significant correlation was found between the highest serum liver values and the highest body temperature in each patient. Among the 22 patients, 4 required artificial respiratory support, and 2 died thereafter. Liver injury was not associated with the severity or mortality of COVID-19. Conclusion Elevated levels of liver enzymes in the Japanese patients with COVID-19 were associated with the highest body temperature during the clinical course but not with the severity or mortality of COVID-19.

Functionally graded (FG) rods with three layers in the radial direction were fabricated by a spark plasma extrusion (SPE) process. The FG rods consisted of a pure Ti compact in the center, a 15TiB/Ti composite layer in the middle, and a 25TiC/Ti composite layer on the outside. Extrusion was carried out at a temperature of 1000 °C, at a pressure of 50 MPa with extrusion ratios (cross-sectional area before extrusion/cross-sectional area after extrusion) of 2.3 (from di = 15 mm to do = 10 mm) and 3.5 (from di = 15 mm to do = 8 mm). An FG rod with a length of over 40 mm and a high relative density could be obtained by the SPE process. The cross-sectional area ratio of the pure Ti layer after extrusion significantly decreased compared to the 15TiB/Ti and 25TiC/Ti composite layers due to the higher ductility of the pure Ti. On the contrary, the cross-sectional area ratio of the 25TiC/Ti composite layer increased after the extrusion, because the 25TiC/Ti composite layer had quite low ductility. Due to the sufficient material flow during the extrusion, the TiC particles in the 25TiC/Ti composite layer of the FG rod were uniformly distributed along the extrusion direction. Furthermore, during the SPE process, the TiB clusters in the TiB/Ti composite layer were transformed into TiB whiskers, and the TiB whiskers were mainly oriented parallel to the extrusion direction. The tensile strength of the TiB/Ti composite layer fabricated by the SPE process improved due to the transformation of the TiB whiskers and their orientation along the extrusion direction.

Background Parathyroid carcinoma as a cause of primary hyperparathyroidism in children is extremely rare. We report a case of parathyroid carcinoma which occurred in a 13-year-old girl who survived for more than 45 years after the first operation. Case presentation A woman was admitted to our hospital for the treatment of recurrent parathyroid carcinoma in the neck. She had been diagnosed with primary hyperparathyroidism from a fibula fracture and underwent parathyroidectomy at 13 years old. She had no family history of multiple endocrine neoplasia or jaw tumor syndrome. Genetic testing was not performed, and the histopathological diagnosis of the tumor had been parathyroid adenoma at the time. At 22 years old, she showed hypercalcemia after a femur fracture. Pulmonary metastases of parathyroid carcinoma in the bilateral lungs were found and surgically removed. Regarding the clinical course, her diagnosis was corrected from parathyroid adenoma to parathyroid carcinoma. At 33 years old, re-resection of the lung metastases was performed. For 10 years, her serum calcium level stayed within the normal range. However, her serum calcium level and intact parathyroid hormone eventually began to increase. Two masses suspected of being parathyroid carcinoma recurrence were found in the neck when she was 57 years old. En bloc resection was performed. Pathologically, the tumors were diagnosed as parathyroid adenoma. The serum calcium level and intact parathyroid hormone did not decrease after the operation. A 99mTc-methoxy-isobutyl-isonitrile- and 18F-fluorodeoxyglucose-negative, 11C-methionine-positive tumor was detected at the right side of the trachea in the neck. The tumor was removed, along with the thyroid, muscle, and trachea that were involved. The pathological diagnosis was parathyroid carcinoma recurrence. The serum calcium level and intact parathyroid hormone decreased temporarily but had increased again 8 months later. Methionine-positive tumors were found at the right side of the trachea and suspected of being a recurrence. Denosumab reduced her serum calcium level, and radiation successfully suppressed the growth of the recurrent tumors. Conclusion We have reported a rare case of parathyroid carcinoma in a child who has survived for over 40 years. Positron emission tomography of 11C-methionine was useful for detecting local recurrence. This patient’s long-term survival has been attributed to multimodality treatment including repeated surgery, medication, and radiation.

Background Bochdalek hernia in an adult is very rare and often needs an immediate surgical repair for the herniation. Although its etiology and surgical techniques have frequently been reported, perioperative complications, especially cardiopulmonary problems, remain unknown. We reported two adults with Bochdalek hernia and reviewed the published literatures with a focus on these issues. Case presentation We experienced two adult cases of Bochdalek hernia with gastrointestinal strangulation. One case had massive herniation of the stomach, colon, spleen, and pancreas in the left chest, causing repeated vomiting. The other had a right-side hernia with strangulation of the colon. We successfully performed emergency repairs of these diaphragmatic hernias without any postoperative complications. Conclusions Our literature review revealed that life-threatening cardiopulmonary complications, such as empyema or cardiac arrest caused by the tamponade effect of the herniated viscera, sometimes occurred in patients with Bochdalek hernia. These complications were found in Bochdalek hernia with gastrointestinal strangulation.

Patients with adrenal Cushing's syndrome have a poor prognosis due to the autonomous hypersecretion of endogenous cortisol from the adrenal gland. Although several clinical examinations have been developed to manifest the autonomous hypersecretion of endogenous cortisol in this syndrome, it is unknown which parameter of cortisol overproduction is best associated with the adrenal cortisol content and bone and vascular complications of this syndrome. Therefore, the present study was undertaken to evaluate the parameter(s) associated with the adrenal cortisol content in patients with adrenal Cushing's syndrome, as well as to assess the associations between these parameters and the vascular and bone complications of this syndrome. Cardiovascular factors such as blood pressure and pulse rate, glucose metabolism, lipid metabolism, renal function, and indices of arteriosclerosis, except for diastolic blood pressure, failed to show an association with the adrenal cortisol content. Twenty-four-hour urinary free cortisol excretion (ρ = 0.893, P = 0.007) and plasma cortisol levels after the 1-mg (ρ = 0.857, P = 0.014) or 8-mg (ρ = 0.900, P = 0.037) overnight dexamethasone suppression test, but not plasma cortisol levels in the morning or late at night or indices of

We report a case of a 64-year-old man suspected of myocardial infarction two months previously. Coronary angiography revealed total occlusion of the left anterior descending (LAD), and left ventriculography (LVG) showed remarkably reduced cardiac function and anterior dyskinesis. Electrocardiogram-gated thallium-201 Single Photon Emission Tomography (TL-SPECT) and (18)F fluorodeoxyglucose positron emission tomography (FDG) were performed separately, and revealed large anterior myocardial infarction with markedly reduced tracer uptake, suggestive of non-viable myocardium. Percutaneous coronary intervention (PCI) was performed and stent was implanted successfully. Six months after PCI, LVG showed remarkable recovery in global function. Significant wall motion improvement and recovered glucose metabolism were observed in the infarcted myocardium despite having previously been diagnosed as lacking viability.

Although standard treatment for autoimmune hepatitis (AIH) comprises prednisolone (PSL) and azathioprine (AZA), some patients are intolerant to or do not respond to PSL and/or AZA. The clinical practice guidelines of AIH in Europe and North America recommend mycophenolate mofetil (MMF) as second-line treatment in these patients. We administered MMF as second-line therapy to 7 patients with AIH (male/female 1/6, age range 27-79 years) who were intolerant to or failed to respond to standard treatment. At the commencement of MMF, the median ALT value was 84U/L (28-254U/L), and the PSL dose was 15.0mg/day (0-45mg/day). In terms of adverse effects of PSL, diabetes mellitus was observed in 4 patients (insulin injection in 2) and femoral head necrolysis in 2. Adverse effects of AZA were present in 2, and 5 patients were not treated with AZA. At 24 weeks of MMF treatment, the median ALT and daily PSL dose were decreased to 16U/L (6-41U/L) and 7.0mg, respectively. Blood sugar control improved, and insulin injection was discontinued in both the patients. While intractable diarrhea developed in 1 patient with cirrhosis, no adverse effect was observed in other 6 patients. In conclusion, MMF appeared effective and safe in at least non-cirrhotic patients with AIH who were intolerant or failed to respond to standard treatment with PSL and AZA in Japanese clinical practice.

Background Gastrobronchial fistulas are rare, but life-threatening, complications of esophagectomy. They are caused by anastomotic leakage and mainly occur around anastomotic sites. In the present paper, we report a rare case of leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer, which was successfully treated using an intercostal muscle flap and lung resection. Case presentation A 61-year-old male underwent subtotal esophagectomy with regional lymphadenectomy for esophageal cancer. The sutures along the staple line of the gastric tube failed 11 days after surgery, and a pulmonary abscess was also found on imaging. The abscess did not heal after conservative treatment; therefore, right lower lobectomy, gastrobronchial fistula resection, primary closure, and patching of the leaking portion of the gastric tube with an intercostal muscle flap were performed 9 months after the first operation. The patient’s postoperative course was uneventful, and he was discharged on the 354th day. Conclusions We experienced a case involving a gastrobronchial fistula caused by leakage from the staple line of a gastric tube and successfully treated it by performing right lower lobectomy and patching the leak with an intercostal muscle flap.

Context Radioactive 131I (RAI) for the treatment of differentiated thyroid cancer is known to induce bone marrow suppression, which occurs approximately 1 month after treatment. However, it is unknown whether RAI therapy for Graves’ disease causes bone marrow suppression. Objective This study aimed to evaluate the short- and long-term effects of RAI therapy on bone marrow function in patients with Graves’ disease. Methods In this retrospective cohort study, we included patients with Graves’ disease who received RAI therapy only once between 2003 and 2019 at Tokyo Women’s Medical University. Blood cell counts at baseline were compared with counts at 1, 2, 4, 12, 24, 48, 144, and 240 weeks after RAI therapy. Moreover, changes in white blood cell (WBC) count and leukopenia at 1 week after RAI treatment were compared by baseline patient characteristics. Results We enrolled 48 patients. Leukopenia was observed in 6 patients at 1 week after RAI treatment, and the overall WBC count significantly decreased (P Conclusion These data showed that RAI treatment induced transient reduction in the WBC count 1 week after treatment, although WBC levels were subsequently restored.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease that presents with bone destruction and pain. Although genetic studies have identified signalling pathways involving CRMO, molecularly targeted drugs remain unavailable. We used an animal model of CRMO as an in vivo screening system for candidate therapeutic agents. A gain-of-function mutation in Fgr, a member of Src family kinases (SFKs), causes peripheral paw inflammation and reduced bone mineral density (BMD) in Ali18 mice. The SFK inhibitor dasatinib was selected for administration to Ali18 mice daily for 2 weeks. Local inflammation and BMD were assessed by clinical scoring and computed tomography, respectively. Pilot studies in a small number of animals showed that dasatinib administration effectively suppressed the early phase of autoinflammation in Ali18 mice. Serial oral gavage of dasatinib to a group of Ali18 mice confirmed significant suppression of paw swelling with no side effects. Histological analysis revealed that abnormal proliferative bone marrow cells and inflammatory infiltration into the skin in the affected area were clearly reduced in the animals with dasatinib administration. Further, trabecular BMD in Ali18 long bones was restored to levels similar to that found in wild type mice. Our results indicate that autoinflammation and related-bone phenotypes were completely suppressed by the dasatinib kinase inhibitor in CRMO model animals. Thus, it is strongly suggested that dasatinib can be used for clinical treatments of CRMO with the combination of molecular diagnosis of the FGR locus. SIGNIFICANCE OF THE STUDY: Autoinflammation and related-bone phenotypes were effectively suppressed by the kinase inhibitor dasatinib in CRMO model animals. In combination with molecular analysis of the FGR locus, dasatinib is a strong candidate for the clinical treatments of CRMO. We propose that the animal model employed in this study can be used to screen this and other potential drugs for CRMO.

Although patients suffering from atrial fibrillation have increased worldwide, detailed information about factors associated with bleeding during direct oral anticoagulant therapy remains insufficient. We studied 1086 patients for whom direct oral anticoagulants were initiated for non-valvular atrial fibrillation between April 2011 and June 2017. Endpoints were clinically relevant bleeding or major adverse cardiac and cerebrovascular events until the end of December 2018. Incidences of bleeding and thrombosis were 4.5 per 100 person-years and 4.7 per 100 person-years, respectively. Most bleeding events represented gastrointestinal bleeding. Multivariate analysis revealed initiation of anticoagulants at ≥ 85 years old as significantly associated with bleeding, particularly gastrointestinal bleeding, but not major cardiac and cerebrovascular events. Other significant factors included chronic kidney disease, low-dose aspirin and nonsteroidal anti-inflammatory drugs. For gastrointestinal bleeding alone, histories of gastrointestinal bleeding and malignancy also showed positive correlations, in addition to the above-mentioned factors. Clinicians should pay greater attention to the risk of gastrointestinal bleeding when considering prescription of anticoagulants to patients ≥ 85 years old with atrial fibrillation.

The diagnostic reference levels (DRLs) are one of several effective tools for optimizing nuclear medicine examinations and reducing patient exposure. With the advances in imaging technology and alterations of examination protocols, the DRLs must be reviewed periodically. The first DRLs in Japan were established in 2015, and since 5 years have passed, it is time to review and revise the DRLs. We conducted a survey to investigate the administered activities of radiopharmaceuticals and the radiation doses of computed tomography (CT) in hybrid CT accompanied by single photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. We distributed a Web-based survey to 915 nuclear medicine facilities throughout Japan and survey responses were provided by 256 nuclear medicine facilities (response rate 28%). We asked for the facility's median actual administered activity and median radiation dose of hybrid CT when SPECT/CT or PET/CT was performed for patients with standard habitus in the standard protocol of the facility for each nuclear medicine examination. We determined the new DRLs based on the 75th percentile referring to the 2015 DRLs, drug package inserts, and updated guidelines. The 2020 DRLs are almost the same as the 2015 DRLs, but for the relatively long-lived radionuclides, the DRLs are set low due to the changes in the Japanese delivery system. There are no items set higher than the previous values. Although the DRLs determined this time are roughly equivalent to the DRLs used in the US, overall they tend to be higher than the European DRLs. The DRLs of the radiation dose of CT in hybrid CT vary widely depending on each imaging site and the purpose of the examination.

Targeted radionuclide therapy with high-dose radioisotopes should be performed in isolation rooms. Patients can be released only after radioactivity remaining in their bodies becomes less than the limits determined by the release criteria in order to secure public protection. Patients are asked to stay in isolation rooms for a few days. Physicians often face difficulties to carry out therapy in patients with limited activities of daily living and those undergoing hemodialysis, and have to avoid therapy in such cases. The Japanese Society of Nuclear Medicine conducted a nationwide survey in order to find out the actual situation. The survey results should reflect future improvement of therapeutic environment in collaborating with related societies and administrative bodies.

A 72-year-old woman had undergone a right mastectomy for breast cancer 3 years earlier. PET/CT revealed a tumor with bony destruction of the skull base and FDG accumulation (SUVmax, 7.86). MRI showed the well-circumscribed tumor in the sphenoid sinus. The possibility of bone metastasis could not be denied. Tumor removal surgery was performed; the tumor was separate from the normal pituitary gland, and an ACTH-producing ectopic pituitary adenoma was diagnosed pathologically.

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.