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Background VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. Methods Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. Results Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. Conclusions In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Background Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan. Methods The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts. Results Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not. Conclusions HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

A new automated diagnostic program for high-resolution esophageal manometry (HREM) has been developed. This diagnostic program could detect locations of landmarks and could make final diagnoses automatically. However, the accuracy of the program is not known. The aim of this study was to evaluate the accuracy of the automated diagnostic program for HREM. A total of 445 studies were enrolled. An HREM system (Starlet®) was used, and esophageal motility was diagnosed using the Chicago classification v3.0. First, the locations of the upper esophageal sphincter, transition zone, lower esophageal sphincter, esophago-gastric junction, crural diaphragm and stomach were determined, and each swallow was checked manually. Then, the parameters of the Chicago classification were calculated using an analytic program of the Starlet, and diagnoses were made by three experts. Second, all study raw data were analyzed again by the automated diagnostic program. Diagnoses made by the program were compared to those made by experts to evaluate the accuracy of the diagnoses. The new diagnostic program could identify the landmarks of each swallow, calculate the parameters and make a final diagnosis within 10 s. The diagnoses made by the automated diagnostic program were not matched to those made by experts in only 10 studies, and the overall accuracy of the new automated diagnostic program thus reached 97.8% (435/445). The new automated diagnostic program for HREM is clinically useful in terms of high diagnostic accuracy and time-saving.

Helicobacter pylori causes peptic ulcers and accounts for over 90% of gastric cancers; however, eradication rates have been declining due to antimicrobial resistance. Vonoprazan (VPZ), a potassium-competitive acid blocker, produces rapid and profound gastric acid suppression and has shown promising effects in the improvement of H. pylori eradication rates. The efficacy and safety of VPZ-based triple therapy as a first-line regimen for H. pylori eradication and its relationship with clarithromycin (CAM) susceptibility were evaluated. From May 2015 to September 2017, H. pylori-infected patients who underwent esophagogastroduodenoscopy with CAM susceptibility testing were prospectively enrolled. Patients received a 7-day triple therapy regimen (VAC) of VPZ (20 mg), amoxicillin (750 mg), and CAM (200 mg) twice daily. Eradication rates, demographics, CAM susceptibility, and safety profiles were assessed. VAC was administered to 146 patients (median age: 63, range: 22–85 years) (60% of whom were females) who underwent CAM susceptibility testing, and 131 patients underwent 13C-urea breath testing to evaluate eradication success. The prevalence of CAM resistance was 34.2%. The overall eradication rates of VAC in per protocol (PP) and “intention to treat” (ITT) analyses were 90.8% (n = 131) and 81.5% (n = 146), respectively. In PP analysis for CAM susceptibility, the eradication rates of VAC were comparable between CAM-sensitive (91.6%, n = 83) and CAM-resistant (89.4%, n = 47) strains. The corresponding rates from the ITT analysis were 80.0% (n = 95) and 84.0% (n = 50), respectively. No adverse events requiring discontinuation of VAC were observed. CAM-resistant H. pylori was prevalent in one-third of patients in the Tokyo metropolitan area. VPZ-based triple therapy was highly effective and well-tolerated irrespective of CAM susceptibility. Therefore, it could be a valuable first-line treatment regimen for H. pylori infection.

Esophagectomy, even with the progress in surgical technique and perioperative management, is a highly specialized surgery, associated with a high rate of complications. Early recognition and adequate treatment should be a standard of care for the most common postoperative complications: anastomotic leakage, pneumonia, atrial fibrillation, chylothorax, and recurrent laryngeal nerve palsy. Recent progress in endoscopy with vacuum and stent placement, or in radiology with embolization, has changed the management of these complications. The success of nonoperative treatments should be frequently reassessed and reoperation must be proposed in case of failure. We have summarized the clinical signs, diagnostic process, and management of the frequent complications after esophagectomy for esophageal cancer.

Diagnosis using artificial intelligence (AI) with deep learning could be useful in endoscopic examinations. We investigated the ability of AI to detect superficial esophageal squamous cell carcinoma (ESCC) from esophagogastroduodenoscopy (EGD) videos. We retrospectively collected 8428 EGD images of esophageal cancer to develop a convolutional neural network through deep learning. We evaluated the detection accuracy of the AI diagnosing system compared with that of 18 endoscopists. We used 144 EGD videos for the two validation sets. First, we used 64 EGD observation videos of ESCC using both white light imaging (WLI) and narrow-band imaging (NBI). We then evaluated the system using 80 EGD videos from 40 patients (20 with superficial ESCC and 20 with non-ESCC). In the first set, the AI system correctly diagnosed 100% ESCCs. In the second set, it correctly detected 85% (17/20) ESCCs. Of these, 75% (15/20) and 55% (11/22) were detected by WLI and NBI, and the positive predictive value was 36.7%. The endoscopists correctly detected 45% (25-70%) ESCCs. With AI real-time assistance, the sensitivities of the endoscopists were significantly improved without AI assistance (p

Background and Objective: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proinflammatory cytokines in microglial cells and monocytes. However, it is unclear whether 1,25(OH)2D3 inhibits proinflammatory cytokines in muscle cells. This study was conducted to investigate whether 1,25(OH)2D3 inhibits the production of proinflammatory cytokines, resulting in inhibition of the protein expression of E3 ubiquitin ligases and muscle protein loss. Materials and Methods: C2C12 myoblasts were proliferated in Dulbecco’s modified Eagle medium (DMEM) containing 10% fetal bovine serum, and myoblasts were differentiated into myotubes in DMEM containing 2% horse serum. Myotubes were treated with 1,25(OH)2D3 for 24 h, followed by lipopolysaccharide (LPS) stimulation for 48 h. Results: Interleukin (IL)-6 protein concentrations were higher in the culture supernatant following LPS stimulation compared to that without LPS stimulation (p < 0.001). However, the IL-6 concentration was significantly lower in C2C12 myotubes following 1,25(OH)2D3 treatment than in C2C12 myotubes without 1,25(OH)2D3 treatment (p < 0.001). The myosin heavy chain (MHC), muscle atrophy F-box, and muscle ring-finger protein-1 protein levels did not significantly differ (P = 0.324, 0.552, and 0.352, respectively). We could not compare tumor necrosis factor α (TNFα) protein levels because they were below the limit of detection of our assay in many supernatant samples, including in LPS-stimulated samples. Conclusions: 1,25(OH)2D3 inhibited increases in IL-6 protein concentrations in muscle cells stimulated by LPS, suggesting that 1,25(OH)2D3 inhibits inflammation in muscle cells. The findings suggest that 1,25(OH)2D3 can prevent or improve sarcopenia, which is associated with IL-6. The TNFα protein content could not be measured, and MHC was not decreased despite LPS stimulation of C2C12 myotubes. Further studies are needed to examine the effects of higher doses of LPS stimulation on muscle cells and use more sensitive methods for measuring TNFα protein to investigate the preventive effects of 1,25(OH)2D3 on increased TNFα and muscle proteolysis.

Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer.

This work summarizes new and emerging metrics and tools in esophageal function testing and their potential clinical impact. Because the diagnostic sensitivity and reliability of conventional impedance-pH variables are suboptimal, several novel impedance parameters, such as the postreflux swallow-induced peristaltic wave index and the mean nocturnal baseline impedance, as well as mucosal impedance, are entering a validation stage prior to general clinical use. The accurate diagnosis of behavioral disorders in patients with rumination syndrome and supragastric belching using ambulatory multiple intraluminal impedance-pH can lead directly to behavioral interventions in patients with refractory gastroesophageal reflux disease (GERD). New provocative measures, such as multiple rapid swallows and the rapid drink challenge, have been developed to overcome the limitations of standard high-resolution esophageal manometry, aiming at further clarifying esophageal dysmotility. Furthermore, the current diagnostic and therapeutic challenges in patients with esophageal involvement in Sjogren's syndrome and scleroderma, who tend to have severe forms of GERD, are entering a new investigative and clinical phase.

This study aimed to characterize the effect of different running modes on serum irisin concentrations in rats. A total of 18, 10-week-old rats were divided into three groups; control group, 16° uphill running group (concentric exercise; CON) and, -16° downhill running group (eccentric exercise; ECC). The running group's rats ran on the inclined treadmill at 16 m/min, for a total of 90 min. Blood was drawn from the rats, 48 h after running, after which the rats were anesthetized. The serum concentrations of irisin were measured using enzyme-linked immunosorbent assays. Vastus intermedius was collected for immunohistochemical analysis. After multiple comparisons, the ECC showed a significantly high serum irisin concentration (ECC: 28.42 ± 6.31 ng/ml, CON: 21.27 ± 3.03 ng/ml) and a larger irisin antibody reactive cross-sectional area in vastus intermedius compared to the CON (

BACKGROUND There are no reports to prove the repeatability of gastric transit time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE). OBJECTIVE To clarify the repeatability and factors that affect GTT/SBTT in CE. METHODS We analyzed the data of 150 healthy subjects from our previous randomized controlled trial that compared small intestinal injuries between two 14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole. Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In addition, the associations of pre-treatment CE SBTT with physical factors, post-treatment CE SBTT and the presence of small intestinal mucosal injuries were analyzed. RESULTS Analyses of 148 subjects pre-treatment CE and 146 subjects post-treatment CE were performed. There were no significant differences between mean GTT and SBTT before and after treatment. Both GTT (𝜌 = 0.22, p < 0.01) and SBTT (𝜌 = 0.47, p < 0.0001) showed positive correlations between pre- and post-treatment CE. In pre-treatment CE, physical factors and the presence of small intestinal mucosal injury had no associations with SBTT. CONCLUSIONS Moderate correlation in SBTT and slight correlation in GTT were shown on repeated CE. The factors affecting SBTT were not clarified in this analysis.

Background We developed a predictive model of long-term gastrointestinal (GI) bleeding risk in patients receiving oral anticoagulants and compared it with the HAS-BLED score. Methods We periodically followed a cohort of 508 patients taking oral anticoagulants (66 direct oral anticoagulants users and 442 warfarin users). Absence of GI bleeding at an initial examination, and any subsequent GI bleeding, were confirmed endoscopically. The bleeding model was developed by multivariate survival analysis and evaluated by Harrell's c-index. Results During a median follow-up of 31.4 months, 42 GI bleeds (8.3%) occurred; 42.8% in the upper GI tract, 50.0% in the lower GI tract, and 7.1% in the middle GI tract. The cumulative 5- and 10-year probability of GI bleeding was 12.6% and 18.5%, respectively. Patients who bled had a significantly higher cumulative incidence of all-cause mortality (hazard ratio 2.9, p

ObjectiveTo compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.DesignUsing the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.ResultsIn the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.ConclusionThe risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.

We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0–60 min), late period (60–120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying.

We examined the effect of 1α-hydroxyvitamin D3 [1α(OH)D3] on mice in the forced swimming test. Intragastric administration of 1.0 μg/kg of 1α(OH)D3 reduced immobility time in the forced swimming test. At all concentrations tested (0.5, 1.0, 2.0 μg/kg), 1α(OH)D3 had no effect on locomotor activity, compared with controls. These results suggest that 1α(OH)D3 may have antidepressant-like activity.

It remains unclear whether type of antiplatelet (AP) therapy, AP combination therapy, and AP continuing or switching strategy affect the risk of post-polypectomy bleeding (PPB). In this study, we sought to elucidate this risk. We analyzed 1050 patients who underwent colonoscopic polypectomy: 525 AP users and 525 controls matched for age, sex, comorbidities, concomitant non-steroidal anti-inflammatory drugs use, and polyp characteristics who did not receive antithrombotics. PPB risk was evaluated by AP number, type, and continuing or switching strategies during the peri-endoscopic period. In multivariate analysis, bleeding risk increased significantly as the number of AP agents used increased (monotherapy, adjusted odds ratio [aOR], 3.7; dual antiplatelet therapy (DAPT), 4.6; triple antiplatelet therapy (TAPT), 11.1) compared with controls. With monotherapy, significantly increased PPB risk was found for aspirin (aOR 4.3), thienopyridine (aOR 6.3), and cilostazol (aOR 5.9), but not for eicosapentaenoic acid or other APs (beraprost, limaprost, sarpogrelate, dilazep, or dipyridamole). With DAPT, significantly increased PPB risk was found for combination aspirin plus cilostazol, but not aspirin plus other APs. Bleeding rates for continuing monotherapy were 4.3% for aspirin and 0% for thienopyridine, cilostazol, and other APs, respectively. Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at

Serological evidence of the epidemiological trends in Entamoeba histolytica infection is scarce, especially in nonendemic countries. We aimed to determine the antibody-positive rates over a 10-year period, and compare the trends between human immunodeficiency virus (HIV)–infected and –noninfected patients. We reviewed 3,514 patients who underwent antibody testing during the study periods, which were divided into five annual categories: 2004–2005, 2006–2007, 2008–2009, 2010–2011, and 2012–2013. Anti-E. histolytica antibody was assessed by indirect immunofluorescence assay. The antibody-positive rate increased yearly from 2004–2005 to 2012–2013 (P < 0.001), although there was no increase in the annual number of antibody tests. This trend was seen among males (18.6–28.3%; P < 0.01), females (5.4–28.2%; P < 0.01), HIV-infected patients (18.4–26.9%; P < 0.001), and non-HIV-infected patients (14.6–36.8%; P < 0.001), and HIV-infected men who have sex with men (19.4–29.1%; P < 0.001). Among antibody-positive patients, there was a significant increase in the proportion of patients with high (≥ 1,600) titers (0.7–12.9%; P < 0.001), whereas this trend was not seen in patients with low (100) or intermediate (200–800) titers (P = 0.282 and 0.409, respectively). This large hospital-based study demonstrated that positive anti-E. histolytica antibody rates increased over 10 years, even though the annual number of antibody tests remained constant. Moreover, this trend was identified in non-high-risk patients (females and non-HIV-infected patients) as well as in high-risk patients. The proportion of patients with high antibody titers significantly increased among the antibody-positive patients.

Exciting new developments—pharmacologic, endoscopic, and surgical—have arisen for the treatment of many esophageal diseases. Refractory gastroesophageal reflux disease presents a therapeutic challenge, and several new options have been proposed to overcome an insufficient effectiveness of proton pump inhibitors. In patients with distal esophageal spasm, drugs and endoscopic treatments are the current mainstays of the therapeutic approach. Treatment with proton pump inhibitors (or antireflux surgery) should be considered in patients with Barrett's esophagus, since a recent meta-analysis demonstrated a 71% reduction in risk of neoplastic progression. Endoscopic resection combined with radiofrequency ablation is the standard of care in patients with early esophageal adenocarcinoma. Mucosal squamous cancer may also be treated endoscopically, preferably with endoscopic submucosal dissection. Patients with upper esophageal cancer often refrain from surgery. Robot-assisted, thoracolaparoscopic, minimally invasive esophagectomy may be an appropriate option for these patients, as the robot facilitates a good overview of the upper mediastinum. Induction chemoradiotherapy is currently considered as standard treatment for patients with advanced squamous cell carcinoma, while the role of neoadjuvant therapy for adenocarcinoma remains controversial. A system for defining and recording perioperative complications associated with esophagectomy has been recently developed and may help to find predictors of mortality and morbidity.

AIM To elucidate the rates of recurrence and mortality in acute esophageal variceal bleeding and the associated risk factors. METHODS A cohort of 174 patients emergently hospitalized for esophageal variceal bleeding was analyzed. All patients underwent endoscopic variceal ligation within 3 h of arrival. Comorbidities, vital signs, drug use, laboratory data, etiology, endoscopic findings, transfusion requirement, and follow-up endoscopy were assessed. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS Rebleeding was identified in 49 patients with a mean follow-up of 18 months. The cumulative rebleeding rate at 1 month, 1 year, and 5 years was 10.2%, 30.0%, and 51.0%, respectively. In multivariate analysis, independent risk factors for rebleeding were child-Pugh class C (HR 1.94; P = 0.027), alcoholic liver cirrhosis (HR 2.32; P = 0.01), and no follow-up endoscopy (HR 13.3; P

Background & Aims We investigated the safety and effectiveness of early colonoscopy (performed within 24 hours of hospital admission) for acute lower gastrointestinal bleeding (LGIB) vs elective colonoscopy (performed 24 hours after admission). Methods We conducted a retrospective study by using a database of endoscopies performed at the National Center for Global Health and Medicine in Tokyo, Japan from January 2009 through December 2014. We analyzed data from 538 patients emergently hospitalized for acute LGIB. We used propensity score matching to adjust for differences between patients who underwent early colonoscopy vs elective colonoscopy. Outcomes included rates of adverse events during bowel preparation and colonoscopy procedures, stigmata of recent hemorrhage, endoscopic therapy, blood transfusion requirement, 30-day rebleeding and mortality, and length of hospital stay. Results We selected 163 pairs of patients for analysis on the basis of propensity matching. We observed no significant differences between the early and elective colonoscopy groups in bowel preparation–related rates of adverse events (1.8% vs 1.2%, P = .652), colonoscopy-related rates of adverse events (none in either group), blood transfusion requirement (27.6% vs 27.6%, P = 1.000), or mortality (1.2% vs 0, P = .156). The early colonoscopy group had higher rates than the elective group for stigmata of recent hemorrhage (26.4% vs 9.2%, P P P P = .048), and rebleeding (13.5% vs 7.4%, P = .070). Patients in the early colonoscopy group stayed in the hospital for a shorter mean time (10 days) than patients in the elective colonoscopy group (13 days) ( P Conclusions Early colonoscopy for patients with acute LGIB is safe, allows for endoscopic therapy because it identifies the bleeding source, and reduces hospital stay. However, compared with elective colonoscopy, early colonoscopy does not reduce mortality and may increase the risk for rebleeding.

Esophageal diseases, both benign and malignant, impose an increasing burden to global health. In the West, gastroesophageal reflux disease (GERD) and Barrett's esophagus are increasing in prevalence and impact. In the East, squamous esophageal cancer remains a large burden, but increasingly, precancerous lesions related to GERD are recognized. We review the various advanced endoscopic techniques that have been developed to improve the accuracy of endoscopic identification of esophageal disease. These techniques are designed to increase the sensitivity of detecting disease and high-risk lesions, enable targeted biopsies, decrease total number of biopsies and costs for surveillance, but also guide therapy in real-time. After proper clinical validation, the widespread use of these technologies will lead to improved outcomes, mostly in cancer prevention.

To determine the cumulative incidence, disease-specific mortality, and all-cause mortality of pancreatic cancer (PC) in patients with intraductal papillary mucinous neoplasms (IPMNs) and to identify imaging findings that are associated with these outcomes.This retrospective study had institutional review board approval, and the need to obtain patient consent was waived. Data from an electronic database were analyzed and supplemented by chart reviews for 285 patients with nonresected IPMNs who were periodically followed up with imaging (1273 multidetector computed tomography and 750 magnetic resonance cholangiopancreatography examinations). The Kaplan-Meier method was used to estimate the cumulative development of PC, PC mortality, and all-cause mortality (factors were compared by using the log-rank test).Over a median imaging follow-up period of 39 months, 12 (4.2%) of 285 patients developed PC; the cumulative 5-year PC incidence was 3.9% for branch duct (BD)-IPMNs, 45.5% for main duct (MD)-IPMNs (P.01), 7.7% for cysts 30 mm or larger, and 5.3% for cysts smaller than 30 mm (P = .82). Over a median survival follow-up period of 47.5 months, seven (2.5%) of 285 patients died of PC and 14 (4.9%) patients died of other causes. Cumulative 5-year PC mortality was 2.1% for BD-IPMNs, 18.5% for MD-IPMNs (P.01), 2.6% for cysts 30 mm or larger, and 2.8% for cysts smaller than 30 mm (P = .90). Cumulative 5-year all-cause mortality was 5.5% for BD-IPMNs, 18.5% for MD-IPMNs (P.01), 12.5% for cysts 30 mm or larger, and 5.9% for cysts smaller than 30 mm (P = .89).Five-year PC development, disease-specific mortality, and all-cause mortality were approximately 4%, 2%, and 6% for BD-IPMNs and 46%, 19%, and 19% for MD-IPMNs, respectively. The presence of an MD-IPMN, but not cyst size, was significantly associated with PC development and subsequent mortality.

The ratio of the number of patients with non-alcoholic steatohepatitis (NASH) to the total number of patients with liver dysfunction has increased in many countries around the world. Liver dysfunction is also caused by multiple blood transfusions in patients with leukemia and other hematological diseases, with liver dysfunction often accompanied by secondary hemochromatosis. This study describes a 25-year-old man with secondary hemochromatosis combined with NASH. Magnetic resonance imaging was useful for visualizing the distributions of both iron and fat in the liver of this patient in order to make a differential diagnosis and to evaluate the effect of treatment.

Background/Aim: We evaluated the efficacy of vonoprazan (VPZ), a novel potassium-competitive acid blocker, in patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD), exhibiting continued pathological esophageal acid exposure (EAE). Methods: Despite ≥8 weeks of appropriate PPI therapy, patients with ­persistent reflux symptoms and pathological EAE times (EAETs ≥4%) were invited to switch to VPZ treatment. After an 8-week-course of once-daily VPZ (20 mg), multichannel intraluminal impedance-pH (MII-pH) monitoring was repeated to compare gastric acid exposure times (GAETs), EAETs, and other reflux parameters relative to the baseline values. Before each MII-pH study, reflux symptom severities were scored using the Gastrointestinal Symptom Rating Scale; erosive esophagitis and fasting plasma gastrin levels were also assessed. Results: From among the 124 patients undergoing MII-pH monitoring, 13 patients (median age, 69 years; females, 64%) were monitored at baseline (while on PPI therapy) and after VPZ therapy. The median GAET associated with VPZ treatment (23.8%) was less than that for PPI treatment (41.1%; p = 0.01), including both daytime and nighttime measurements. VPZ therapy resulted in better median EAET values (4.5%) than did PPI therapy (10.6%) during the 24-h monitoring period (p = 0.055). EAE normalization was achieved in 46% of VPZ-treated patients and was associated with complete gastric acid suppression (p = 0.005). After switching to VPZ, reflux symptoms (p < 0.01) and erosive esophagitis (p = 0.01) improved. Conclusion: In patients with PPI-refractory GERD, VPZ provides more potent gastric acid suppression, more effective EAE control, enhanced symptom improvement, and better esophagitis healing than PPIs.

Large bowel preparation may cause a substantial change in the gut microbiota and metabolites. Here, we included a bowel prep group and a no-procedure control group and evaluated the effects of bowel prep on the stability of the gut microbiome and metabolome as well as on recovery. Gut microbiota and metabolome compositions were analyzed by 16S rRNA sequencing and capillary electrophoresis time-of-flight mass spectrometry, respectively. Analysis of coefficients at the genus and species level and weighted UniFrac distance showed that, compared with controls, microbiota composition was significantly reduced immediately after the prep but not at 14 days after it. For the gut metabolome profiles, correlation coefficients between before and immediately after the prep were significantly lower than those between before and 14 days after prep and were not significantly different compared with those for between-subject differences. Thirty-two metabolites were significantly changed before and immediately after the prep, but these metabolites recovered within 14 days. In conclusion, bowel preparation has a profound effect on the gut microbiome and metabolome, but the overall composition recovers to baseline within 14 days. To properly conduct studies of the human gut microbiome and metabolome, fecal sampling should be avoided immediately after bowel prep.

Statins and exercise reduce cardiovascular disease incidence. We investigated whether endurance exercise in mice induces mitochondrial adaptation in skeletal muscle and muscle injury during administration of atorvastatin, a member of the statin medication class. Male C57BL mice were assigned to one of three groups: control (Con), statin (Statin), or statin and exercise (Statin + Ex). Atorvastatin was administered, and exercise performed on a treadmill for 8 weeks. The levels of mitochondria-associated proteins, PGC-1α, and respiratory chain complex, (COX) I–V, in the quadriceps femoris, and serum creatine kinase, a muscle injury marker, were measured. PGC-1α and COX I–V were upregulated in the Statin + Ex group compared to those in the Statin and Con groups; serum creatine kinase levels were similar. Endurance training in mice induced mitochondrial adaptation in skeletal muscle without causing muscle injury, during atorvastatin administration.

Background and Aims Very few prospective studies with over 100 samples have evaluated the long-term outcomes of endoscopic therapy for colonic diverticular bleeding (CDB). This study sought to elucidate the recurrent bleeding risk of endoscopic band ligation versus clipping for definitive CDB based on stigmata of recent hemorrhage (SRH). Methods Patients emergently hospitalized for acute lower GI bleeding and examined by high-resolution colonoscopy were enrolled. Better visualization of SRH from a diverticulum was obtained using a water-jet device. Endoscopic band ligation or clipping was performed as first-line treatment, and patients were prospectively followed after discharge. Results No statistical difference was found between the ligation (n = 61) and clipping (n = 47) groups in baseline characteristics or follow-up period. The probability of 1-year recurrent bleeding was 11.5% in the ligation group versus 37.0% in the clipping group (P = .018). No patients required surgery or experienced perforation. One patient in the ligation group experienced diverticulitis the next day. In patients with recurrent bleeding within 7 days, the recurrent bleeding site was the same diverticulum, and ulceration was found in the ligation group on repeat colonoscopy. In patients with recurrent bleeding after 2 months, repeat colonoscopy identified that the recurrent bleeding site was different, and scar formation was seen in the ligation group. The left side of the colon was an independent predictor for recurrent bleeding in the ligation group but not in the clipping group. Conclusions Band ligation for definitive CDB has better outcomes than clipping during long-term follow-up after endoscopic therapy, probably because of complete elimination of the diverticulum. CDB can recur at the same diverticulum in the short term but at a different diverticulum in the long term.

Background It remains unclear whether diverticulosis, absent inflammation, is responsible for chronic bowel symptoms. We examined the association between bowel symptoms and asymptomatic diverticulosis. Method This case-control study included 543 patients with diverticulosis and 1086 age and sex-matched controls (1:2) without diverticulosis on screening colonoscopy. Eleven symptoms (abdominal discomfort, hunger discomfort, borborygmus, abdominal distension, flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were evaluated using a gastrointestinal symptoms rating scale (GSRS) at baseline and second questionnaire. Associations between diverticulosis and symptoms were estimated using odds ratios (ORs) and 95 confidence interval (CI). Results In multivariate analysis, constipation (OR, 0.85 [0.78–0.93]) and hard stools (OR, 0.86 [0.78–0.94]) were negatively associated with diverticulosis. The other nine symptoms showed no association with diverticulosis. Diverticulosis was negatively associated with constipation (OR, 0.93 [0.74–0.93]), hard stools (OR, 0.85 [0.76–0.96]), and incomplete evacuation (OR, 0.88 [0.79–0.99]) in males, and positively associated with diarrhea (OR, 1.39 [1.14–1.69]) and loose stools (OR, 1.28 [1.05–1.55]) in females. No bowel symptoms were positively associated with any of right-sided, left-sided, or bilateral diverticulosis. Test–retest reliability of GSRS (mean interval, 4.4 months) was moderate (Mean Kappa, 0.568) in males and good (Mean Kappa, 0.652) in females. Conclusions This large, colonoscopy-based, case-control study demonstrated that neither constipation nor hard stools were associated with an increased risk of diverticulosis, regardless of diverticulum location. In females, but not males, diarrhea and loose stools were positively associated with diverticulosis. Long-term test–retest reliability suggested that these symptoms remain consistent over a given period.

Background and Aim Visceral adiposity is a strong determinant of insulin resistance, which decreases cholecystokinin response sensitivity, and increases cholesterol saturation in the gallbladder bile; thus, it potentially relates to gallstone disease development. We aimed to investigate whether visceral fat measured by computed tomography (CT) is a risk factor for gallstone disease. Methods A cohort of 717 participants undergoing CT and ultrasonography was analyzed. The associations between body mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area, and gallstone disease were analyzed adjusted for age, sex, hypertension, diabetes, and dyslipidemia. Results In multivariate analysis, gallstone disease was significantly associated with VAT and SAT areas for both categorical data and trend (P for trend

Differential diagnosis of intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) can be difficult, but many gastroenterologists may only perform biopsy for pathology and their own experience. This study aimed to identify optimal sample collection and pathogen detection methods for diagnosing ITB.A cohort of 182 patients (50 had ITB and 132 had IBD or other colonic diseases) who underwent colonoscopy was analyzed. Sensitivity of acid-fast bacilli (AFB), culture, polymerase chain reaction (PCR), and granuloma pathology on hematoxylin and eosin stain for diagnosing ITB were compared in relation to biopsy, endoscopic aspirated intestinal fluid, or standard stool evaluations. We also evaluated which combination offered the highest yield to diagnose intestinal tuberculosis in addition to granuloma pathology.Between ITB and non-ITB, no significant differences were observed in age, sex, and nationality. In biopsy analysis, sensitivity was as follows: culture (50%), AFB (38%), PCR (25%), granuloma pathology (51%), and caseous granuloma (8.2%), while specificity of granuloma pathology was low (80%), compared to other tests. In intestinal fluid analysis, sensitivity was as follows: culture (46%), AFB (42%), and PCR (35%). In standard stool analysis, sensitivity was as follows: culture (47%), AFB (37%), and PCR (23%). Granuloma pathology plus biopsy culture offered the highest combination sensitivity (77 %), significantly (P 0.01) higher than that for granuloma pathology alone (51%).When encountering suspected intestinal tuberculosis or IBD on colonoscopy, biopsy culture is recommended in addition to pathological assessment of granuloma. This diagnostic strategy will lead to accurate differential diagnosis of colonic disease, facilitating appropriate treatment.

The aim of this study was to identify predictors for the identification of stigmata of recent hemorrhage (SRH) on colonic diverticula.Several factors influence the identification of SRH in the diagnosis of colonic diverticular bleeding.A total of 396 patients hospitalized for lower gastrointestinal bleeding were analyzed. Comorbidities, medications, timing of colonoscopy [24 h (h); urgent, 24 to 48 h,48 h], preparation, expert colonoscopist, use of a cap, use of a water-jet scope, total colonoscopy, and procedure time (over 60 min) were assessed. A multivariable logistic regression model was used to estimate odds ratio (OR) and 95% confidence interval (CI).Two hundred fifteen patients were diagnosed with colonic diverticular bleeding and 37 (17%) were identified with SRH. Urgent colonoscopy (OR, 8.4; 95% CI, 2.3-30; P0.01), expert colonoscopist (OR, 3.0; 95% CI, 1.2-7.3; P=0.02), use of a cap (OR, 3.4; 95% CI, 1.4-8.0; P=0.01), and use of water-jet scope (OR, 5.8; 95% CI, 2.3-15; P0.01) were found to be independent predictive factors for SRH. The accuracy of these factors in combination was 0.90 (95% CI, 0.85-0.96) as measured by area under the receiver operating characteristic curve (ROC-AUC). SRH identification rate was higher in the urgent (22%) than in the 24 to 48 hours (2.9%, P0.01) and48 hours groups (1.0%, P0.01), showing a tendency to decrease with time (P0.01 for trend).Factors of urgent colonoscopy, expert colonoscopist, use of a cap, and use of water-jet scope are useful for identifying SRH diverticula.

Background We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk.

Background This study aimed to evaluate risk factors for resistance to proton-pump inhibitor (PPI) therapy among patients with reflux esophagitis (RE) and nonerosive reflux disease (NERD) in gastroesophageal reflux disease (GERD) using a standardized questionnaire in Japan: the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG).

We compared the clinical efficacy of barium therapy and conservative therapy in preventing recurrence in patients with diverticular bleeding.Previous case reports have indicated that barium impaction therapy provides initial hemostasis for diverticular bleeding and prevention against rebleeding.After spontaneous cessation of bleeding, patients were randomly assigned to conservative treatment (n = 27) or high-dose barium impaction therapy (n = 27). Patients were followed up for 1 year after enrollment of the last patient. The main outcome measure was rebleeding.Median follow-up period was 584.5 days. The probability of rebleeding at 30-day, 180-day, 1-year, and 2-year follow-up in all patients was 3.7%, 14.8%, 28.4%, and 32.7%, respectively. By group, probability at 1 year was 42.5% in the conservative group and 14.8% in the barium group (log-rank test, P = 0.04). After adjustment for a history of hypertension, the hazard ratio of rebleeding in the barium group was 0.34 (95% confidence interval, 0.12-0.98). No complications or laboratory abnormalities due to barium therapy were observed. Compared with the conservative group, the barium group had significantly (P0.05) fewer hospitalizations per patient (1.7 vs 1.2), units of blood transfused (1.9 vs 0.7), colonoscopies (1.4 times vs 1.1 times), and hospital stay days (15 days vs 11 days) during the follow-up period. No patients died and none required angiographic or surgical procedures in either group.High-dose barium impaction therapy was effective in the long-term prevention of recurrent bleeding, and reduced the frequency of rehospitalization and need for blood transfusion and colonoscopic examination. ClinicalTrials.gov Identifier, UMIN 000002832.

Background and Aim The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aims to evaluate the risks of PUB from antithrombotic drugs, angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, α-blockers, and β-blockers. Methods This prospective hospital-based case-control study included 230 patients with endoscopically verified PUB and 920 age and sex-matched controls (1:4) without bleeding on screening endoscopy. Adjusted odds ratios (AOR) for the risk of PUB were determined by conditional logistic regression analysis. Results In multivariate analysis, alcohol consumption (AOR, 2.2; P

Background The effect of a combined antithrombotic drug regimen on lower GI bleeding (LGIB) remains unknown. Objective To investigate the risk of LGIB associated with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, thienopyridine (ticlopidine or clopidogrel), or other antiplatelets used. Design Prospective study. Setting Emergency hospital, gastroenterology department. Patients A cohort of 319 patients emergently hospitalized for acute, continuous, or frequent LGIB and 3358 patients with no bleeding on colonoscopy. Main Outcome Measurements Odds ratios (ORs) for the risk of LGIB associated with drug exposure adjusting for age, sex, smoking, alcohol, medications, comorbidities, and GI symptom scores. Results After considering antithrombotic drugs by dividing them into single- and combined-use, single use of nonselective NSAID or cyclooxygenase-2 inhibitor was independently associated with LGIB. The combined use of NSAIDs with low-dose aspirin (OR 4.3) or with other antiplatelets (OR 4.9) was more associated with LGIB than the use of NSAIDs alone (OR 2.3). Use of low-dose aspirin, thienopyridine, or other antiplatelets alone was not significantly associated with LGIB, but combined use of low-dose aspirin with thienopyridine (OR 2.2) or with other antiplatelets (OR 3.6) was associated with LGIB. Combined use of different NSAIDs carried a higher risk than single use (combined use, OR 4.9; single use, OR 2.3). Limitations Single-center study. Conclusion The use of nonselective or selective NSAIDs alone was associated with LGIB. Although antiplatelet use alone was not significantly associated with LGIB, combined use of NSAIDs with antiplatelets or of low-dose aspirin with thienopyridine or with nonthienopyridine antiplatelets was independently associated with LGIB.

We investigated muscle atrophy, major antioxidant enzymes and lipid peroxidation in the extensor digitorum longus (EDL, predominantly fast fibers) and soleus (predominantly slow fibers) muscle of streptozotocin-diabetic rats. Female Wistar rats were divided into a control (n = 5) and streptozotocin-induced diabetic group (n = 5). Eight weeks after diabetes induction the EDL and soleus muscles were removed and catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase activity (SOD), and thiobarbituric acid reactive substances (TBARS) levels measured. The CAT activity increased in both the EDL and soleus muscles of the diabetic rats (p < 0.01), whereas the GPX and SOD activities were increased only in the EDL muscle (p < 0.01 and p < 0.05). The TBARS levels were only increased in the EDL muscle of the diabetic rats (p < 0.01). Both muscles showed significant atrophy but the EDL muscle elicited the greatest atrophy. In conclusion, it appears that adaptive responses to oxidative stress were adequate in the soleus muscle, but not in the EDL muscle, of diabetic rats. Thus fast twitch muscle fibers may be more susceptible to oxidative stress than slow twitch muscle fibers and this may contribute to muscle atrophy under diabetic conditions.

To identify differences in incidence and mortality of pancreatic cancer (PC) between intraductal papillary mucinous neoplasm (IPMN) and non-neoplastic cyst.Patients with pancreatic cyst (n = 526; 263 with IPMN and 263 with non-neoplastic cyst matched for age, sex, and diagnosis year) were periodically followed-up with imaging. Hazard ratio (HR), standardized incidence ratio (SIR), and standardized mortality ratio (SMR) for PC and PC-related mortality were estimated.During a mean follow-up of 57.5 months with 3,376 computed tomography scans and 1,079 magnetic resonance imaging scans, 5-year cumulative PC incidence was 4.0% for IPMN and 0% for non-neoplastic cyst, respectively (HR 5.2; P = 0.031). During a mean follow-up of 73.1 months, 5-year cumulative PC-related mortality was 2.6% for IPMN and 0% for non-neoplastic cyst, respectively (HR 4.5; P = 0.05). Compared with the general population in Japan, patients with IPMN, but not those with non-neoplastic cyst, had significantly increased risks of PC incidence (SIR 22.03) and related mortality (SMR 15.9).During long-term imaging follow-up, patients with IPMN developed PC over time, whereas none of the patients with non-neoplastic cyst developed it within 5 years. Compared with the general population, patients with IPMN, but not those with non-neoplastic cyst, were at risk of PC and related mortality.