Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis.

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88-1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding.

A Case of Superficial Primary Malignant Melanoma of the Esophagus Detected and Treated at Stage 0.

The patient was a 79-year-old male. At three years and eight months after his initial presentation, upper gastrointestinal endoscopy revealed a black-flattened elevated lesion in the middle third of the esophagus, which was diagnosed as malignant melanoma on biopsy. No lymph node or distant metastasis was found. A diagnosis of cT1bN0M0 Stage I was thus made. We performed a robot-assisted, minimally invasive esophagectomy and D2 dissection. The postoperative diagnosis was pT1a (MM), N0, M0, vascular invasion+, stage 0. The patient was recurrence-free for 14 months after surgery. We presume that an aggressive biopsy diagnosis is important for the early detection of malignant melanoma.

Usefulness of argon plasma coagulation for bleeding around hepaticojejunal anastomosis.

Ectopic varices due to extrahepatic portal vein obstruction (EHO) after hepaticojejunostomy have been previously reported. However, few case reports have described angiodysplasia-like lesions due to EHO around the hepaticojejunal anastomosis because they comprise small vessels in the mucosal surface and cannot be detected by contrast-enhanced computed tomography. Physicians need to insert the endoscope into the long afferent limb to diagnose angiodysplasia-like lesions around the hepaticojejunal anastomosis. Some reports have described that endoscopy stops bleeding from angiodysplasia-like lesions around the hepaticojejunal anastomosis; however, a standard methodology remains to be established. We present three cases of bleeding from an angiodysplasia-like lesion around the hepaticojejunal anastomosis that were successfully treated using argon plasma coagulation (APC) with balloon-assisted enteroscopy. Although one patient died owing to cancer progression 3 months after APC hemostasis, the hemostatic effect persisted for >2 years in the remaining two patients. These results suggest that APC is a good treatment option to stop bleeding from angiodysplasia-like lesions at hepaticojejunal anastomosis.

Percutaneous transhepatic obliteration-related procedures for isolated gastric varices: experience of three cases.

Percutaneous transhepatic obliteration (PTO) can facilitate antegrade embolization of variceal veins. We herein report three patients who underwent percutaneous transhepatic sclerotherapy (PTS) or percutaneous transportal outflow-vessel-occluded sclerotherapy (PTOS) for isolated gastric varices. PTS was performed in Cases 1 and 2, and PTOS was performed in Case 3. Technical success was achieved in all patients without a decline in liver function; however, lack of a therapeutic benefit with rupture of esophageal varices occurred in Case 3. Case 3 had a history of pylorus gastrectomy plus Billroth-I reconstruction for gastric cancer and multiple feeding veins existed. PTO-related procedures are good treatment options for isolated gastric varices, but clinicians should be aware of the risk of treatment failure, especially the cases which have multiple feeding veins.

Relationships of Dietary Habits and Physical Activity Status with Non-Alcoholic Fatty Liver Disease Featuring Advanced Fibrosis.

(1) Aim: Hepatic fibrosis is a prognostic factor for disease progression in non-alcoholic fatty liver disease (NAFLD). We aimed to determine the relationships between diet, physical activity, and the progression of liver fibrosis. (2) Methods: The 349 participants were categorized by their FibroScan-aspartate aminotransferase score, and they completed a questionnaire regarding their diet and physical activity. (3) Results: There were 233 patients in the negative-on-screening group, 78 in the gray zone group, and 38 in the positive-on-screening group. The frequencies of consumption of soybeans and soybean products and of light-colored vegetables were lower in the positive group; whereas the frequencies of consumption of snack food and fried sweets, jelly and pudding, fried food, and butter, lard, and beef tallow were higher. The odds ratios for the fibrosis progression in patients who consumed fried food ≥4 times/week was 2.21. The positive group also showed lower physical activity level (PAL) and exercise (Ex, metabolic equivalents for tasks (METs)/hour/week). The patients who undertook Ex at >7.5 had an odds ratio of 0.21 for the fibrosis progression. (4) Conclusion: High consumption of fried food and low Ex are risk factors for the fibrosis progression in NAFLD.

Prevention of non-alcoholic steatohepatitis by long-term exercise via the induction of phenotypic changes in Kupffer cells of hyperphagic obese mice.

Exercise ameliorates nonalcoholic fatty liver disease (NAFLD) by inducing phenotypic changes in Kupffer cells (KCs). p62/Sqstm1-knockout (p62-KO) mice develop NAFLD alongside hyperphagia-induced obesity. We evaluated (1) the effects of long-term exercise on the foreign-body phagocytic capacity of KCs, their surface marker expression, and the production of steroid hormones in p62-KO mice; and (2) whether long-term exercise prevented the development of non-alcoholic steatohepatitis (NASH) in p62-KO mice fed a high-fat diet (HFD). In experiment 1, 30-week-old male p62-KO mice were allocated to resting (p62-KO-Rest) or exercise (p62-KO-Ex) groups, and the latter performed long-term exercise over 4 weeks. Then, the phenotype of their KCs was compared to that of p62-KO-Rest and wild-type (WT) mice. In experiment 2, 5-week-old male p62-KO mice that were fed a HFD performed long-term exercise over 12 weeks. In experiment 1, the phagocytic capacity of KCs and the proportion of CD68-positive cells were lower in the p62-KO-Rest group than in the WT group, but they increased with long-term exercise. The percentage of CD11b-positive KCs was higher in the p62-KO-Rest group than in the WT group, but lower in the p62-KO-Ex group. The circulating dehydroepiandrosterone (DHEA) concentration was higher in p62-KO-Ex mice than in p62-KO-Rest mice. In experiment 2, the body mass and composition of the p62-KO-Rest and p62-KO-Ex groups were similar, but the hepatomegaly, hepatic inflammation, and fibrosis were less marked in p62-KO-Ex mice. The DHEA concentration was higher in p62-KO-Ex mice than in WT or p62-KO-Rest mice. Thus, long-term exercise restores the impaired phagocytic capacity of KCs in NAFLD obese mice, potentially through greater DHEA production, and prevents the development of NASH by ameliorating hepatic inflammation and fibrogenesis. These results suggest a molecular mechanism for the beneficial effect of exercise in the management of patients with NAFLD.

Effects of Exercise on the Oral Microbiota and Saliva of Patients with Non-Alcoholic Fatty Liver Disease.

Exercise can be hypothesized to play an important role in non-alcoholic fatty liver disease (NAFLD) treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n = 49) or dietary restriction (n = 21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and, measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher, and that of Prevotella (-28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound in children.

Gastrointestinal endoscopy is fundamental to diagnostic and therapeutic procedures in pediatric gastroenterology. In the decades since endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) for hepatobiliary and pancreatic disease were introduced into clinical practice, there has been increasing interest in these procedures, and practice guidelines and position papers that clearly define the role of ERCP and EUS in children have been published. Based on the distinction of endoscopy between children and adults, this review focuses on the current state of ERCP and EUS procedures in children, including the types of endoscopes used in children, general anesthesia and radiation exposure, biliary and pancreatic indications, considerations of education and training for ERCP and EUS procedures in children, and expectations for development of endoscopes for children.

A Durable Response after the Discontinuation of Nivolumab in an Advanced Gastric Cancer Patient.

A durable response after the discontinuation of immune checkpoint-inhibitor therapy has previously been reported in several cancers. We herein describe a patient with gastric cancer who maintained a durable response after the discontinuation of nivolumab. A 65-year-old man was treated with nivolumab as a sixth-line therapy for recurrent gastric cancer. After four cycles of nivolumab therapy, he showed a partial response. But the treatment was discontinued when two immune-related adverse events occurred after six cycles. Disease regression was sustained for approximately 2 years, without the re-administration of nivolumab. The characteristics leading to such responses are unclear, and further studies are warranted in this regard.

Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry.

The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged ≥75 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI-). Risk scores for stroke (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI- group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; P <0.0001) and had significantly higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores (P <0.0001 for each) as well as higher prevalences of several comorbidities. In the PPI+ group, 54.6% of patients did not have gastrointestinal (GI) disorders and were likely prescribed a PPI to prevent GI bleeding events. Most of the patients with a GI disorder in the PPI+ group had reflux esophagitis. Compared with patients not receiving anticoagulants, a significantly higher proportion of patients receiving anticoagulants received PPIs. For patients receiving anticoagulants, antiplatelet drugs, and both drugs, rates of PPI use were 34.1%, 44.1%, and 53.5%, respectively (P <0.01). Although the rate of PPI use was the highest for NVAF patients receiving both antiplatelet and anticoagulants, no clear differences were observed in the anticoagulants used. These data suggest that PPIs were actively prescribed in high-risk cases and may have been used to prevent GI bleeding among elderly NVAF patients receiving antithrombotic drugs. Trial registration: UMIN000024006.

Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial.

INTRODUCTION: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. OBJECTIVE: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. METHODS: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. RESULTS: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. CONCLUSIONS: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

Prediction of true Helicobacter pylori-uninfected status using a combination of age, serum antibody and pepsinogen: Logistic regression analysis.

INTRODUCTION: To prevent gastric cancer, it is important to accurately determine the presence of Helicobacter pylori (HP) infection. However, correctly identifying HP-uninfected individuals is difficult when using the combination of HP antibody and pepsinogen (PG). OBJECTIVE: The aim of this study was to discriminate true HP-uninfected individuals from others without the need for endoscopic examination. METHODS: A total of 684 subjects with no history of HP eradication who underwent a medical checkup at our hospital were enrolled. The "true uninfected individuals" were determined by a negative stool antigen test and no endoscopic findings of HP-associated gastritis. HP antibody was measured by the latex immunoassay method. Logistic regression analysis using a combination of noninvasive parameters was performed to develop a formula for predicting true uninfected individuals. RESULTS: A total of 528 subjects were classified as true uninfected individuals. Logistic regression analysis showed that statistically significant factors for true uninfected individuals were age (p < 0.001), HP antibody (p <0.001), PGI (p <0.001), and PGII (p = 0.012). The areas under the curve (AUCs) for true uninfected individuals were the highest (0.944) upon applying the prediction formula including four parameters: age, HP antibody, PGI, and PGII. Both the sensitivity and the specificity of the four-parameter prediction formula were higher than those of the traditional three-parameter model using HP antibody, PGI, and PGI/II ratio (sensitivity: 93.2% vs. 86.6% and specificity: 88.5% vs. 82.7%). CONCLUSIONS: Our findings suggest that a model with a combination of four noninvasive parameters is useful for predicting true HP-uninfected individuals without the need for endoscopic examination.

The Risks of Exfoliative Esophagitis in Patients with Atrial Fibrillation: A retrospective observational study.

The aging of the population has resulted in atrial fibrillation (AF) becoming increasingly prevalent. Treatment focuses on the prevention of thromboembolism through the use of catheter ablation or drug therapy with anticoagulants, such as warfarin or direct oral anticoagulants (DOACs). Dabigatran-induced exfoliative esophagitis has been reported as a rare side effect of DOACs. Although most cases are mild, some result in severe outcomes. However, the etiology of exfoliative esophagitis remains incompletely understood. The aim of this study is to investigate the etiology of exfoliative esophagitis and identify its risk factors by observational study.The participants were 524 patients using anticoagulants who received catheter ablation for AF and subsequently underwent upper gastrointestinal endoscopy at University of Tsukuba Hospital. Exfoliative esophagitis was noted in 21 (4.0%) patients. Potential risk factors for exfoliative esophagitis were examined retrospectively by comparing patients with and without this condition across the following parameters that were extracted retrospectively from the electronic medical records: physical characteristics, comorbidities, blood-based cardiac markers, echocardiographic and endoscopic findings, and current medications.Regarding physical characteristics, patients with exfoliative esophagitis had significantly higher body weight and BMI. No association was observed between exfoliative esophagitis and comorbidities. Associations were also not found for cardiac markers, echocardiographic findings, or endoscopic findings. In terms of current medications, patients receiving oral dabigatran showed the highest prevalence of exfoliative esophagitis at 8.8% (13/148). The adjusted odds ratio of dabigatran for exfoliative esophagitis was 10.3 by multivariable logistic regression analysis.Obesity and oral dabigatran were found to be significant risk factors for exfoliative esophagitis.

Inflammatory myofibroblastic tumor of ileum with intussusception in adult.

A 62-year-old man was referred to our department with suspected intussusception due to an ileal tumor. Tumor markers including soluble interleukin-2 receptor were not elevated. Contrast-enhanced computed tomography and color Doppler ultrasonography showed a distinct ileal tumor without intratumoral blood flow or surrounding lymphadenopathies. Retrograde single-balloon enteroscopy revealed a submucosal tumor in the ileum that was hard and ulcerated. Partial intestinal resection was performed, and the lesion was diagnosed as an inflammatory myofibroblastic tumor. The patient had no recurrence over 2 years without additional treatment after surgery. This rare tumor should be kept in mind as a cause of ileal intussusception in adult and a multidisciplinary approach is vital to characterize it.

Mediastinal Neuroendocrine Carcinoma Slowly Growing for 8 Years after Surgical Resection of Esophageal Squamous Cell Carcinoma.

A 70-year-old woman was referred to our department due to a solitary mediastinal tumor which gradually grew near the site of anastomosis for 8 years after radical surgery of esophageal squamous cell carcinoma. It was difficult to distinguish the lymph node recurrence of esophageal cancer from another tumor of unknown primary origin. Endoscopic ultrasound-guided fine-needle aspiration was performed, and the tumor was diagnosed to be neuroendocrine carcinoma. She received concurrent chemoradiotherapy with etoposide plus cisplatin. After the completion of chemoradiotherapy, the tumor disappeared. A solitary growing tumor which develops after radical resection of cancer would be better to be examined histologically in order to make an accurate diagnosis and select the most appropriate treatment.

Splenic rupture caused by pancreatic pseudocyst successfully treated by endoscopic ultrasound-guided drainage.

A 43-year-old man was admitted to a local hospital because of acute left abdominal pain. Chronic alcoholic pancreatitis and a 10-cm pancreatic pseudocyst in the tail of the pancreas had been found 5 years previously. He had not stopped drinking alcohol since then. On admission, laboratory tests revealed severe anemia, and contrast-enhanced computed tomography showed extravasation in the pancreatic pseudocyst. The spleen was retracted by the pancreatic pseudocyst, and its configuration was indistinct. The patient was diagnosed with acute bleeding within the pancreatic pseudocyst and splenic rupture. He was transferred to our university hospital on an emergency basis. Abdominal angiography of the splenic artery was immediately performed, but the bleeding point was not found. Although the bleeding stopped spontaneously, an infection of the pancreatic pseudocyst and a splenic hematoma subsequently developed. Endoscopic ultrasound-guided pseudocyst drainage was performed. The infection improved after the drainage, and the size of the pancreatic pseudocyst and splenic hematoma decreased. Five months later, the pancreatic pseudocyst had almost disappeared, and the splenic hematoma was even smaller. We herein report a rare case of splenic rupture caused by a pancreatic pseudocyst. Although the patient's condition became complicated by severe infection, treatment by endoscopic ultrasound-guided drainage was successful.