Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Atrial Fibrillation is Associated with Femoropopliteal Totally Occlusive In-Stent Restenosis: A Single-Center, Retrospective, Observational Study.

INTRODUCTION: The proportion of patients with comorbid atrial fibrillation (AF) and peripheral artery disease (PAD) has increased in this era. This study aimed to assess the relationship between AF and totally occlusive in-stent restenosis (ISR) in femoropopliteal (FP) lesions. METHODS: In this study, 363 patients (461 stents) who underwent endovascular therapy with de novo stent implantation in our hospital between April 2007 and December 2016 were retrospectively evaluated. The patients were divided into two groups according to the AF status (AF group, 61 patients; sinus group, 302 patients). The primary endpoint was the incidence of totally occlusive ISR within 3 years. The secondary endpoint was the incidence of acute limb ischemia (ALI) due to FP stent occlusion. RESULTS: Baseline characteristics were similar, except for higher age and a lower prevalence of dyslipidemia in the AF group. The incidence of a totally occlusive ISR was higher in the AF group than in the sinus group (29.5% vs. 14.6%, p=0.004). A multiple Cox regression model suggested that presence of AF (hazard ratio, 2.10) and CTO lesion (hazard ratio, 1.97) which were the independent predictors of a totally occlusive ISR within 3 years. The incidence of ALI was significantly higher in the AF group than in the sinus group (3.9% vs. 0%, p=0.0001). In the AF group, the introduction of an anticoagulant did not prevent the occurrence of totally occlusive ISR (p=0.71) for ALI (p=0.79). CONCLUSIONS: AF is independently associated with totally occlusive ISR of FP stents; however, anticoagulant use does not prevent stent occlusion.

Efficacy and Feasibility of Magnifying Blue Laser Imaging without Biopsy Confirmation for the Diagnosis of the Demarcation of Gastric Tumors: A Randomized Controlled Study.

BACKGROUND: Accurate diagnosis of the demarcation line (DL) of gastric tumors is essential for curative complete resection by endoscopic submucosal dissection (ESD). It is controversial to perform only magnifying endoscopy for diagnosing the DL of gastric tumors prior to ESD. This study aimed to evaluate the diagnostic accuracy for the DL of gastric adenomas and well-differentiated adenocarcinomas using only magnifying blue laser imaging (M-BLI) compared with that using both M-BLI and biopsy confirmation. METHODS: In this prospective, single-center study, 96 well-differentiated adenocarcinomas and 32 gastric adenomas were enrolled between July 2015 and December 2016. A total of 122 lesions with a clear DL on M-BLI were randomly allocated to undergo M-BLI only (the M-BLI group) or M-BLI with biopsy confirmation (the M-BLI-BC group), performed as biopsies in 4 directions from noncancerous tissues ≈ 5 mm outside the lesion before ESD. The primary end point was to clarify the noninferiority of M-BLI without biopsy confirmation compared with that with biopsy confirmation, in terms of the diagnostic accuracy and complete resection. RESULTS: There were no significant differences in sex, median age, color, circumference, macroscopic type, biopsy-based diagnosis, and Helicobacter pylori infection between the 2 groups. The diagnostic accuracy for the DL was 100 and 95.0% and the complete resection was 100 and 100% in the M-BLI and M-BLI-BC groups, respectively. CONCLUSION: The diagnostic ability of M-BLI is excellent in diagnosing the demarcation of gastric adenoma and well-differentiated adenocarcinoma. Biopsy confirmation is not needed for these lesions with a clear DL by M-BLI.

Effects of Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment on Postoperative Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matching Analysis.

BACKGROUND: Management of antithrombotic agents during endoscopic treatment changed after the publishing of -Japan Gastroenterological Endoscopy Society guidelines for gastroenterological endoscopy in antithrombotic drug users (GL-2012). OBJECTIVES: We aimed to evaluate the effect of implementing antithrombotic agent management guidelines (GL-2012) on postoperative bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and on the prevention of thromboembolic events. METHODS: A total of 1,264 patients who underwent ESD for EGC at Kyoto Prefectural University Hospital between June 2002 and March 2017 were enrolled and divided into 2 groups: 621 patients before the publication of GL-2012 (Pre-GL group) and 643 patients after (Post-GL group). Relationships between postoperative bleeding and various clinicopathological factors in each group were investigated through propensity score-matching analysis. RESULTS: In the Pre-GL group, antihypertensive agent use (p < 0.01) and upper third of the stomach (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 4.6, 95% CI 1.6-12.8) and upper third of the stomach (OR 4.9, 95% CI 1.8-13.4) were significantly related to postoperative bleeding in multivariate analysis. In the Post-GL group, antihypertensive agent use (p < 0.01), dual antiplatelet agents use (p < 0.01), anticoagulant agents use (p < 0.01), and heparin replacement therapy (p < 0.01) were significantly related to postoperative bleeding in univariate analysis. Antihypertensive agent use (OR 3.4, 95% CI 1.1-9.6), dual antiplatelet agents (OR 12.3, 95% CI 2.4-63.0), and heparin replacement therapy (OR 10.2, 95% CI 2.5-41.5) were significantly related to postoperative bleeding in multivariate analysis. CONCLUSIONS: The adherence to GL-2012 might reduce risk of thromboembolic events. On the other hand, dual antiplatelet agents therapy and heparin replacement therapy were the new independent risk factors for ESD postoperative bleeding in EGC after GL-2012. Especially as for heparin replacement therapy, uninterrupted warfarin or a temporary short interruption of direct oral anticoagulants without heparin replacement therapy might be recommended rather than heparin replacement therapy.

Diagnostic Ability of Magnifying Blue Light Imaging with a Light Emitting Diode Light Source for Early Gastric Cancer: A Prospective Comparative Study.

INTRODUCTION: An innovative endoscopic system using 4-color light-emitting diodes (LED) was released between 2016 and 2017 in locations that had not approved laser endoscopes for use, including the United States and Europe. OBJECTIVE: This study compared the diagnostic efficacy between magnifying blue light imaging with an LED light source (LED-BLI) and magnifying blue laser imaging with a laser light source (Laser-BLI) for early gastric cancer (EGC). METHODS: In this prospective, single-center, noninferiority study, 80 gastric lesions were evaluated between January 2017 and July 2017. The magnifying findings of gastric lesions - including the demarcation line (DL), microvascular pattern (MVP), and microsurface pattern (MSP) - were evaluated using Laser-BLI and LED-BLI according to the vessel plus surface classification system (VSCS). The primary end point was to determine whether the diagnostic accuracy of LED-BLI for EGC was noninferior to that of conventional Laser-BLI. RESULTS: Overall, we evaluated 79 gastric lesions histopathologically diagnosed as adenocarcinomas from the specimens obtained via endoscopic submucosal dissection. A DL was observed by Laser-BLI and LED-BLI in 98.7% (78/79) and 96.2% (76/79) of EGCs, respectively. The MVP observed using Laser-BLI and LED-BLI was irregular in 92.4% (73/79) and 89.9% (71/79), respectively. The MSP observed using Laser-BLI and LED-BLI was irregular in 83.5% (66/79) and 82.2% (65/79), respectively. According to the VSCS, diagnosable cancers were found in 94.9% (75/79) and 93.7% (74/79) of cases when using Laser-BLI and LED-BLI, respectively (p = 0.73; difference ratio, 1.2%; 95% CI -8.5 to 6.0%). CONCLUSIONS: LED-BLI could accurately visualize the DL, MVP, and MSP of EGCs and was not inferior to Laser-BLI. Therefore, LED-BLI can be used to diagnose EGC accurately according to the VSCS-based diagnosis criteria.

Diagnostic performance of magnifying blue laser imaging versus magnifying narrow-band imaging for identifying the depth of invasion of superficial esophageal squamous cell carcinoma.

Identifying the depth of invasion (DOI) of superficial esophageal squamous cell carcinoma (SESCC) is crucial to determine the indication for endoscopic resection. This retrospective, single-center study aimed to evaluate the diagnostic efficacy of magnifying blue laser imaging (M-BLI) compared with white-light imaging (WLI) or magnifying narrow-band imaging (M-NBI) for identifying the DOI of SESCC. A total of 160 consecutive patients with SESCCs who underwent endoscopic submucosal dissection were enrolled in this study. Still images of the lesion were obtained using WLI, M-BLI and M-NBI prior to endoscopic submucosal dissection. Three endoscopists retrospectively evaluated the DOI using WLI according to non-magnifying findings and using M-BLI and M-NBI images according to the magnifying endoscopic classification of the Japan Esophageal Society. The diagnostic accuracy of each modality was compared using the chi-square test. The DOIs in 160 SESCCs evaluated pathologically were as follows: invasion to the epithelium or lamina propria mucosa in 130, invasion to the lamina muscularis mucosa or submucosa to a depth ≤ 200 µm in 18, and invasion to the submucosa to a depth > 200 µm in 12. The overall diagnostic accuracy rates of WLI, M-BLI, M-NBI, WLI with M-BLI (WLI + M-BLI), and WLI with M-NBI (WLI + M-NBI) were 86.9, 91.2, 90.6, 95.6 and 94.4%, respectively. Significant differences were found between WLI and WLI + M-BLI or WLI + M-NBI (P = 0.006 and P = 0.021, respectively). The concordance of intrapapillary capillary loops between M-BLI and M-NBI was 91.2%. The kappa coefficients for interobserver variability of the three endoscopists for M-BLI and M-NBI were 0.728/0.649/0.792 and 0.729/0.666/0.791, respectively, while those for intraobserver variability were 0.919/0.746/0.778 and 0.736/0.720/0.745, respectively. Similar to M-NBI, M-BLI was useful in predicting the DOI of SESCCs.

Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. METHODS: We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. RESULTS: The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. CONCLUSIONS: The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.

Promotion of wound healing by acetate in murine colonic epithelial cell via c-Jun N-terminal kinase activation.

BACKGROUND AND AIM: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. METHODS: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. RESULTS: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. CONCLUSIONS: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.

Mucosa-Associated Microbiota in the Gastrointestinal Tract of Healthy Japanese Subjects.

BACKGROUND: The importance of microbiota infiltrating the gut mucus layer has been reported in the pathogenesis of various gastrointestinal and systemic diseases. However, little is known about the mucosa-associated microbiota (MAM) in healthy subjects. The present study aimed to clarify the characteristics of the gastrointestinal MAM from the oral cavity to the rectum in healthy Japanese subjects. METHODS: Seventeen healthy subjects were enrolled. In this study, 5 mucosa samples from the upper gut (intraoral, mid-esophagus, gastric corpus, gastric antrum, and duodenum) and 7 from the lower gut (ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were collected with a brush under endoscopic examination. MAM profiles of each sample were analyzed by 16S-rRNA V3-V4 gene sequences. RESULTS: Collecting mucosa samples by brushing provided sufficient material for MAM profiling without causing adverse effects. The upper and lower gut MAM profiles differed significantly (p < 0.0001). In the upper and lower gut, the intra- and inter-individual MAM profiles were significantly different (p = 0.0008 and p < 0.0001 respectively). CONCLUSIONS: The MAM profiles of the upper and lower gut were significantly different. The inter-individual differences in MAM were remarkable compared to the intra-individual differences.

Massive atonic bleeding during cesarean delivery in a patient with chronic idiopathic intestinal pseudo-obstruction: A case report and literature review.

A 35-year-old primigravid woman with chronic idiopathic intestinal pseudo-obstruction presented to our institution. Except for an enlarged fetal bladder, her pregnancy was almost uneventful until she developed pre-eclampsia requiring emergent cesarean section at 34 weeks gestation. After delivery, intractable uterine atony developed with blood loss reaching 3500 mL within 15 min. Following a B-Lynch suture, the bleeding attenuated but uterine atony persisted; lochia persisted for 3 months post-partum. The infant was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome after birth. The mother's clinical course and previous reports suggested that atonic bleeding was associated with the pathology of chronic idiopathic intestinal pseudo-obstruction; the infant's disease was considered to be maternal-related disease. Clinicians should be vigilant in pregnant patients with chronic idiopathic intestinal pseudo-obstruction especially with these complications.

Efficacy and safety of endoscopic submucosal dissection using a scissors-type knife with prophylactic over-the-scope clip closure for superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND STUDY AIM: This study aimed to assess the safety and feasibility of endoscopic submucosal dissection (ESD) using a scissors-type knife with prophylactic closure using over-the-scope clip (OTSC) for superficial non-ampullary duodenal epithelial tumors (SNADETs). PATIENTS AND METHODS: Consecutive patients who underwent ESD for SNADETs >10 mm between January 2009 and July 2019 were retrospectively enrolled. We performed ESD using either a needle-type knife (Flush Knife-ESD) or a scissors-type knife (Clutch Cutter-ESD). Mucosal defects were prophylactically closed using three methods: conventional clip, laparoscopic closure, or OTSC. RESULTS: A total of 84 lesions were resected using the Flush Knife-ESD and the Clutch Cutter-ESD (37 and 47 patients, respectively), and conventional clip, laparoscopic closure, and OTSC for mucosal defect closure after ESD were applied in 13, 13, and 56 lesions, respectively. The R0 resection rate was significantly higher in the Clutch Cutter-ESD than that in the Flush Knife-ESD (97.9% vs 83.8%, respectively, P = 0.040). The intraoperative perforation rate was significantly lower in the Clutch Cutter-ESD than in the Flush Knife-ESD (0% vs 13.5%, respectively, P = 0.014). Complete closure rates of conventional clip, laparoscopic closure, and OTSC were 76.9%, 92.3%, and 98.2%, respectively (P = 0.021); and delayed perforation rates were 15.4%, 7.7%, and 1.8%, respectively (P = 0.092). CONCLUSIONS: Endoscopic submucosal dissection using a scissors-type knife with prophylactic OTSC closure is safe and feasible for the low-invasive treatment of SNADETs.

Ginsenoside Rb1 promotes intestinal epithelial wound healing through extracellular signal-regulated kinase and Rho signaling.

BACKGROUND AND AIM: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti-inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. METHODS: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound-healing assay. RESULTS: The colon epithelial regeneration ratio in the daikenchuto-treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1-induced enhancement was inhibited by extracellular signal-regulated kinase and Rho inhibitors. CONCLUSIONS: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease.

Efficacy of Magnifying Narrow Band Imaging for Delineating Horizontal Margins of Early Gastric Cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the diagnostic accuracy of magnifying narrow-band imaging (M-NBI) with histopathological confirmation in identifying the demarcation line (DL) of early gastric cancer (EGC). METHODS: EGCs resected by endoscopic submucosal dissection after identifying the DL using M-NBI following histopathological confirmation were included. After determining the DL for the entire EGC lesion using M-NBI, at least 4 biopsies were taken from non-cancerous tissues outside the EGC lesion for histopathological confirmation. RESULTS: A total of 330 EGCs were analyzed in this study. The rate of biopsy-negative and negative horizontal margin were 96.7% (319/330) and 97.9% (323/330) in EGC respectively. Tumors larger than 20 mm showed a higher risk for showing remnant cancer cells on biopsies taken outside the DL. Risk factors for a positive horizontal resection margin were tumor size > 20 mm and moderately or poorly differentiated adenocarcinomas. CONCLUSION: The assessment of demarcation of EGC using M-NBI was excellent in well-differentiated (WD) adenocarcinoma and lesions below 20 mm in size. However, histopathological confirmation is needed to assess the demarcation of non-WD adenocarcinomas and EGC over 20 mm in size.

Efficacy of Clutch Cutter for Standardizing Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matched Analysis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the safety and efficacy of gastric endoscopic submucosal dissection (ESD) using the Clutch Cutter (CC), a scissor-type knife, compared with those of procedures using conventional devices. METHODS: This single-center retrospective study evaluated 237 patients with early gastric cancer: 83 who underwent ESD using the CC group and 154 who underwent ESD using the insulated-tip knife 2 (IT2 group). Clinicopathological features and technical outcomes were compared between the 2 groups using a propensity score-matched analysis. RESULTS: In 61 pairs of matched patients, there was no significant difference in R0 resection, perforation, or postoperative bleeding between the CC and IT2 groups. Comparisons between the 2 groups showed similar treatment outcomes for an expert endoscopist. Nevertheless, there were significant differences between the 2 groups for nonexperts in terms of self-completion (61.7 and 24.5%, respectively, p < 0.001), mean procedure times (45 and 61 min, respectively, p = 0.002), and mean numbers of intraoperative bleeding points and bleeding points requiring hemostatic forceps (3 and 0 vs. 8 and 3, respectively, p < 0.001). CONCLUSION: Better self-completion rates and shorter procedure times were noted for gastric ESD using the CC by nonexperts than for that using IT2, probably due to hemostatic efficacy.

A Rare Case of Fetal Meconium Peritonitis Developing Coagulopathy In utero.

Hydrops fetalis in association with meconium peritonitis is a rare condition, and the mechanism underlying hydropic changes has not been fully recognized. We present a case of fetal meconium peritonitis with hydrops and coagulopathy. Clinically, the cause of fetal disseminated intravascular coagulation is considered to be a consequence of a systematic inflammatory response based on progressive, but mild fetal anemia without other apparent triggers, thrombocytopenia, elevated white blood cell count and serum C reactive-protein, hypoalbuminemia, and increased vascular permeability. The infant was born at 32 weeks of gestation and survived after postnatal multidisciplinary treatment. Our experience suggests that recognition of this rare condition will enable early diagnosis and better clinical management for fetuses with meconium peritonitis.

Transforming growth factor ß1-induced collagen production in myofibroblasts is mediated by reactive oxygen species derived from NADPH oxidase 4.

Intestinal fibrosis with stricture formation is a severe complication of Crohn's disease (CD). Though new therapeutic targets to enable the prevention or treatment of intestinal fibrosis are needed, markers of this condition and the basic mechanisms responsible have not been established. NADPH oxidase (NOX) 4 has already been reported to play a key role in models of fibrogenesis, including that of the lung. However, its importance in intestinal fibrogenesis remains unclear. In this study, we examined the role of NOX4 in collagen production by intestinal myofibroblasts stimulated with transforming growth factor (TGF)-ß1. Using LmcMF cells, an intestinal subepithelial myofibroblast (ISEMF) line, we first examined the induction of collagen production by TGF-ß1. Subsequently, we investigated the role of NOX4 in TGF-ß1-induced collagen I production in these cells using SB525334 (an SMAD2/3 inhibitor), diphenyleneiodonium (an NOX inhibitor), and Nox4 small interfering RNA (siRNA). Production of collagen was assessed with Sirius red staining, and Nox4 expression was measured by quantitative real-time PCR. Reactive oxygen species (ROS) production was determined using DCFDA and fluorescent microscopy. We observed that TGF-ß1 induced collagen production via NOX4 activation and ROS generation in LmcMF cells. Nox4 siRNA and inhibitors of TGF-ß1 receptor and NOX significantly reduced TGF-ß1-induced ROS and collagen production. Thus, in the present study, we revealed that collagen production in ISEMFs is induced via an NOX4-dependent pathway. This work supports a function for NOX4 in intestinal fibrogenesis and identifies it as a potential therapeutic target in recalcitrant fibrotic disorders of CD patients.

Factors associated with emergency cesarean delivery during induction of labor in nulliparous women aged 35 years or older at term.

AIM: To examine the intrapartum cesarean delivery rate following failure of induction of labor (IOL) as well as risk factors associated with failed IOL among nulliparous women of advanced maternal age (AMA). METHODS: This was a retrospective cohort study conducted at a single perinatal care center. We retrospectively reviewed the medical records of nulliparous AMA women (aged 35 years or older) with singleton vertex pregnancy who underwent IOL at term. Data regarding maternal baseline characteristics and pregnancy course, including complications during pregnancy and maternal status at time of IOL, were collected. Rate of emergency cesarean section (eCS) as well as risk factors associated with failed IOL were investigated by means of logistic regression analysis. RESULTS: Among 234 women included in this study, 103 (44%) had failed IOL and delivered by eCS. Hypertensive disorder during pregnancy (adjusted odds ratio [aOR], 2.01; 95% confidence interval [CI], 1.0-4.12; P = 0.025) and unfavorable cervical status (aOR, 1.92; 95% CI, 1.08-3.41; P = 0.038) were identified as independent risk factors for failed IOL. CONCLUSION: IOL failed in 44% of nulliparous AMA women. Hypertensive disorder and immature cervical status should be considered as independent risk factors for eCS among such women.

Rate of intrapartum cesarean section and related factors in older nulliparous women at term.

AIM: The aim of this study was to determine the effect of maternal age on emergency cesarean section (CS) during labor, and to identify the independent risk factors for emergency CS. METHODS: This was a retrospective cohort study using data from 2009 to 2014 from a tertiary perinatal care center in Japan. Inclusion criteria were maternal age ≥ 35 years, nulliparous singleton pregnancy at term and a cephalic presentation without indication of elective CS at onset of labor. The primary outcome was rate of emergency CS, while independent risk factors were elucidated using multivariate logistic regression analysis. RESULTS: Of 953 women, 199 (20.9%) delivered by emergency CS. Rates of emergency CS were 18.3% (129/706) in women aged 35-39 years and 28.3% (70/247) in those aged ≥ 40 years (P < 0.01). Adjusted odds ratios (95% confidence intervals) of independent risk factors were 1.50 (1.03-2.18) for maternal age ≥ 40 years, 1.51 (1.06-2.17) for body mass index ≥ 25 kg/m2 , 2.22 (1.24-3.98) for hypertensive disorder during pregnancy, 3.43 (1.31-8.95) for large-for-date fetus and 4.64 (3.23-6.69) for induction of labor. CONCLUSIONS: The rate of intrapartum emergency CS in older nulliparous women at term was approximately 21%. Induction of labor should be recognized as a significant factor for emergency CS.

Impact of the Charlson comorbidity index and prognostic nutritional index on prognosis in patients with early gastric cancer after endoscopic submucosal dissection.

BACKGROUND AND AIM: With the aging of society, comorbidities or nutritional status are assessed prior to endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). However, it is uncertain which factors are important for predicting prognosis in EGC patients after ESD. Thus, we aimed to evaluate clinical outcomes of ESD for EGC, with respect to comorbidities or nutritional status. METHODS: We carried out a retrospective study involving 708 EGC in 585 patients who were enrolled between April 2007 and March 2012. They were classified into two groups; an elderly (≥80 years) and non-elderly (<80 years) group. Short- and long-term outcomes were evaluated between the groups. RESULTS: There were no significant differences regarding short-term outcomes. Overall survival (OS) rates in the elderly group were significantly lower than those in the non-elderly group (P = 0.001). OS rates in patients with a low (≤2) Charlson comorbidity index (CCI) were significantly higher than those in patients with a high (≥3) CCI, regardless of age. OS rates in patients with a high (≥47.7) prognostic nutritional index (PNI) were significantly higher than those in patients with a low (<47.7) PNI, regardless of age. In multivariate analysis, an Eastern Cooperative Oncology Group performance status (PS) ≥2 (hazard ratio [HR], 95% confidence interval: 3.23, 1.54-6.75), CCI ≥3 (HR 7.88, 4.50-13.80) and PNI <47.7 (HR 3.44, 2.00-5.90) were significantly associated with OS rate (P < 0.01). CONCLUSION: CCI and PNI can be prognostic indicators for non-elderly and elderly patients with EGC after ESD.

Immunotherapy-responsive Non-paraneoplastic Encephalitis with Antibodies against GAD, LGI1, and GABAA Receptor.

A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis (AE). Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.