The O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically useful indicator of treatment outcome in patients with interstitial cystitis/bladder pain syndrome with Hunner lesions: A post hoc analysis of the Japanese phase III trial of KRP-116D, 50% dimethyl sulfoxide solution.

OBJECTIVES: To evaluate the efficacy of intravesical KRP-116D, 50% dimethyl sulfoxide solution, in interstitial cystitis/bladder pain syndrome patients with Hunner lesions (Hunner-type interstitial cystitis), and to evaluate the correlations between efficacy variables and global response assessment to determine what constitutes a minimal clinically important change. METHODS: We performed a post hoc analysis of the Japanese phase III trial of KRP-116D. Changes at Week 12 from baseline in objective and subjective outcomes were compared between the KRP-116D and placebo groups in Hunner-type interstitial cystitis or non-Hunner-type interstitial cystitis patients. Correlations between efficacy variables at Week 12 and global response assessment were analyzed. Area under the receiver operating characteristic curve and the cut-off value of efficacy valuables were calculated to determine clinically meaningful changes. RESULTS: The effectiveness of intravesical treatment with KRP-116D was demonstrated in Hunner-type interstitial cystitis, but not in non-Hunner-type interstitial cystitis patients. Global response assessment was closely correlated with subjective outcomes including O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, and a numeric rating scale for bladder pain, but was less correlated with voiding variables including micturition frequency, voided volume, and maximum voided volume. In the receiver operating characteristic curve analyses, the cut-off value for the O'Leary-Sant Interstitial Cystitis Symptom Index was -5 (sensitivity 81.3%, specificity 83.3%). CONCLUSIONS: Clinical benefit of intravesical KRP-116D in Hunner-type interstitial cystitis patients was confirmed in this post hoc analysis. A five-point reduction in O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically meaningful indicator for assessing patient satisfaction with KRP-116D treatment in patients with Hunner-type interstitial cystitis.

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.

Quantitative T1 mapping of the substantia nigra using phase-sensitive inversion recovery sequence at 3.0-T: a healthy volunteer study.

BACKGROUND: Quantitative evaluation of degeneration of the substantia nigra (SN) is important for early, pre-symptomatic diagnosis of Parkinson's disease (PD). Accordingly, a clinically feasible imaging and quantification technique are needed. PURPOSE: To investigate the T1 value of the SN in healthy individuals from phase-sensitive inversion recovery (PSIR) images and to clarify its correlation with the SN characteristics on neuromelanin (NM) images to identify an imaging biomarker for early diagnosis of PD. MATERIAL AND METHODS: T1-weighted and NM images of the SN from 32 healthy volunteers were obtained using PSIR and turbo spin-echo sequences. The contrast between the SN and cerebral peduncle (CP) and area of the SN were measured; the T1 values of the SN from PSIR images and relationships between the T1 value and age/SN area were evaluated. RESULTS: There was a significant negative correlation between age and the SN area obtained using PSIR imaging. The SN area on PSIR images (104.9 ± 20.9 mm2) was significantly larger than that on NM images (72.1 ± 14.9 mm2). There was a significant negative correlation between the SN area and the T1 value of the SN obtained from PSIR images. CONCLUSION: In healthy adults, the area and T1 value of the SN measured on PSIR images were different from those obtained from NM images. This suggests that PSIR imaging may help in the assessment of SN degeneration.

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.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Clinical guidelines for interstitial cystitis/bladder pain syndrome.

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.

Blue laser imaging-bright improves the real-time detection rate of early gastric cancer: a randomized controlled study.

BACKGROUND AND AIMS: Blue laser imaging-bright (BLI-bright) has shown promise as a more useful tool for detection of early gastric cancer (EGC) than white-light imaging (WLI). However, the diagnostic performance of BLI-bright in the detection of EGC has not been investigated. We aimed to compare real-time detection rates of WLI with that of BLI-bright for EGC. METHODS: This was a prospective, randomized, controlled study in 2 Japanese academic centers. We investigated 629 patients undergoing follow-up endoscopy for atrophic gastritis with intestinal metaplasia or surveillance after endoscopic resection of EGC. Patients were randomly assigned to receive primary WLI followed by BLI-bright or primary BLI-bright followed by WLI. The real-time detection rates of EGC were compared between primary WLI and primary BLI-bright. RESULTS: There were 298 patients in each group. The real-time detection rate of EGC with primary BLI-bright was significantly greater than that with primary WLI (93.1% vs 50.0%; P = .001). Primary BLI-bright had a significantly greater ability to detect EGCs in patients with a history of endoscopic resection for EGC, no Helicobacter pylori infection in the stomach after eradication therapy, lesions with an open-type atrophic border, lesions in the lower third of the stomach, depressed-type lesions, small lesions measuring <10 mm and 10 to 20 mm in diameter, reddish lesions, well-differentiated adenocarcinomas, and lesions with a depth of invasion of T1a. CONCLUSIONS: BLI-bright has a higher real-time detection rate for EGC than WLI. BLI-bright should be performed during surveillance endoscopy in patients at high risk for EGC. (Clinical trial registration number: UMIN000011324.).

GAG replenishment therapy for bladder pain syndrome/interstitial cystitis.

AIMS: To present a rationale for the inclusion of urothelial coating dysfunction in the etipathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) and the preclinical and clinical evidence in support of glycosaminoglycan (GAG) replenishment therapy in the treatment of BPS/IC, supplemented by the clinical experience of medical experts in the field and patient advocates attending a symposium on GAG replenishment at ESSIC'17, the annual Meeting of the International Society for the Study of Bladder Pain Syndrome, held in Budapest, Hungary in 2017. RESULTS: The urothelial GAG layer has a primary role in providing a permeability barrier to prevent penetration of urinary toxins and pathogens into the bladder wall. Disruption of the GAG layer contributes to the development of BPS/IC. The evidence shows that replenishment of GAGs can restore the GAG layer in BPS/IC, reducing inflammation, pain, and other symptoms. CONCLUSIONS: Although data from large randomized controlled studies are limited, long clinical observation and the experience of clinicians and patients support the beneficial effects of intravesical GAG replenishment therapy for providing symptomatic relief for patients with BPS/IC.

History of gastroesophageal reflux disease in patients with suspected coronary artery disease.

It is well known that patients with gastroesophageal reflux disease (GERD) experience GERD-related chest pain, but little is known about the relationship between GERD and coronary artery disease (CAD). We evaluated medical history of GERD in patients with suspected CAD and its association with types of CAD. We enrolled 236 patients who underwent coronary angiography (CAG). We assessed past medical history of each patient, making note of esophageal or stomach diseases such as GERD including reflux esophagitis and non-erosive reflux disease. The patients were divided into the following three subgroups based on the CAG results. Group I, patients with o-CAD (> 50% stenosis with ischemic findings, n = 141); Group II, patients with vasospastic angina (VSA, with positive spasm provocation test without organic coronary stenosis, n = 52); and Group III, patients without organic coronary stenosis or VSA (n = 43). Group I included more men than women (p < 0.001) and the frequencies of smoking, lipid disorders, and diabetes mellitus in this group were higher than those in the other groups (p < 0.01). The frequency of medical history of GERD was significantly higher in Group II (21%) than in Group I (3%) or Group III (7%, p < 0.0001). Logistic regression analysis showed that a medical history of GERD (OR 7.8; p < 0.01) was one of the factors associated with the presence of VSA. Our findings showed that a medical history of GERD was frequently observed in approximately one-fifth of patients with VSA, indicating that VSA may be present in patients with chest pain and a medical history of GERD.

Suplatast tosilate in patients with interstitial cystitis: Efficacy and treatment possibilities, with suggestions for future assessments.

OBJECTIVE: Suplatast tosilate, a Th2 cytokine inhibitor, was predicted to relieve interstitial cystitis symptoms. Four studies with suplatast tosilate in Japanese interstitial cystitis patients have been conducted: a single-arm clinical study, a phase II dose-ranging trial, a phase III trial with placebo, and a second phase PIII trial with placebo. Treatment efficacy was observed in the first two studies; however, in the phase PIII trials, no significant difference in interstitial cystitis symptom score changes was observed between suplatast tosilate and placebo. We summarized these four studies to investigate factors causing the difference in observed efficacy. METHODS: Placebo effects in the first two studies and differences regarding study design between the four studies were considered to be possible factors. Therefore, placebo effects were investigated by comparing interstitial cystitis symptom score changes, and the study designs were compared to investigate the effects on observed efficacy. RESULTS: Interstitial cystitis symptom score changes in the phase PII treatment groups increased in a dose-dependent manner and showed an almost linear relationship with interstitial cystitis symptom score changes observed in placebo groups of 2 phase PIII studies. A major difference regarding the phase PIII study design was the use of diagnostic hydrodistention. Diagnostic hydrodistention and its washout period were applied only in the phase PIII trials. CONCLUSIONS: Comparison of interstitial cystitis symptom score changes suggested that the placebo effect was very small. Use of diagnostic hydrodistention was considered to be a major difference in the population characteristics of the studies and may have resulted in different observed efficacies. Diagnostic hydrodistention, which potentially influences the treatment effect, is probably not essential for trials of suplatast in interstitial cystitis patients.

Low bladder capacity is an important predictor for comorbidity of interstitial cystitis with Hunner's lesion in patients with refractory chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To evaluate the predictive factors for comorbidity of Hunner-type interstitial cystitis in patients with chronic prostatitis/chronic pelvic pain syndrome using urethrocystoscopy. METHODS: Thirty-two male patients were included in this study. Between April 2012 and April 2016; they were diagnosed with chronic prostatitis/chronic pelvic pain syndrome according to the National Institutes of Health classification. Their symptoms were not improved by 3 months of behavioral and pharmacological therapies. They all underwent narrow band imaging-assisted urethrocystoscopy to assess whether the presence of Hunner's lesions correlated with other variables. RESULTS: Thirteen out of 32 patients (41%) had Hunner's lesions. Of the variables, maximal voided volume per micturition (106 ± 29 mL vs 171 ± 61 mL) and bladder capacity (267 ± 121 mL vs 407 ± 137 mL) were significantly smaller in patients with Hunner's lesions compared to those without. Other variables, apart from age, were not significantly different. Furthermore, patients with voided volume less than 150 mL were more likely to have Hunner's lesions than those with voided volume exceeding 150 mL. CONCLUSIONS: Hunner-type interstitial cystitis is a common comorbidity among patients with refractory chronic prostatitis/chronic pelvic pain syndrome. In cases where voided volume is small, performing narrow band imaging-assisted urethrocystoscopy would be very helpful for detecting bladder mucosal changes such as Hunner's lesions.

The protective effect of orally administered redox nanoparticle on intestinal ischemia-reperfusion injury in mice.

BACKGROUND: Intestinal ischemia-reperfusion (I-R) injury is a serious abdominal condition leading to multiple organ failure with high mortality. However, no reliable treatment is available. A redox nanoparticle (RNPO) was recently developed, and its efficacy for several intestinal inflammatory conditions has been reported. To this end, the aim of this study was to investigate the therapeutic effects of RNPO on intestinal I-R injury in mice. METHODS: Ischemia was induced in the small intestine of C57BL/6 mice by occluding the superior mesenteric artery for 45 min under anesthesia followed by reperfusion for 4 h. Mice were orally administered the vehicle or RNPO 1 h before ischemia. Inflammatory markers such as histological findings, thiobarbituric acid (TBA)-reactive substances as an index of lipid peroxidation, myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and expression of pro-inflammatory cytokine mRNA in the intestinal mucosa were assessed. RESULTS: Induction of I-R caused a significant increase in inflammatory markers (histological scores, TBA-reactive substances, MPO activity, and expression of keratinocyte chemoattractant mRNA). These changes were significantly attenuated in RNPO-treated mice as compared to vehicle-treated mice. CONCLUSION: Orally administered RNPO attenuated intestinal I-R injury in mice in association with reductions in neutrophil infiltration and lipid peroxidation, suggesting the possibly potential of RNPO as a therapeutic agent for intestinal I-R injury.

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.

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.

Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.

Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options.

A Safety and Efficacy Study of Tolvaptan Following Open Heart Surgery in 109 Cases.

This study was conducted to evaluate the safety and efficacy of tolvaptan following open heart surgery.We retrospectively reviewed 109 patients who were administered tolvaptan following open heart surgery between August 2011 and July 2014. We divided the patients according to their urine output index (amount of urine output/body surface area) into tertiles as follows: T1 (low responders; n = 36), T2 (intermediate responders; n = 36), and T3 (high responders; n = 37). No fatal adverse events were observed following tolvaptan administration. The factors that showed a significant difference among the 3 groups were body surface area (BSA) and preoperative body weight. Body weight rapidly decreased and a greater increase in the serum sodium level was observed on day 1 in the T3 group than in the other 2 groups. No decrease in blood pressure and no significant differences in the occurrence of atrial fibrillation were observed among the 3 groups during tolvaptan administration.Tolvaptan can be safely and effectively administered to increase the urine output without adversely affecting the cardiovascular system or renal function following open heart surgery. However, careful attention is required regarding the possibility of a rapid increase in the serum sodium level so it is important to monitor changes in serum Na levels.