Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

Objective To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.Design A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.Results The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.Conclusion The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg)

Role of surgical resection in adult urological soft tissue sarcoma: 25-Year experience

金沢大学附属病院泌尿器科The effect of chelating ligands on iron (Fe) uptake and growth of radish (Raphanus sativus L.) was investigated. The ethylenediaminetetraacetic acid (EDTA) increased 55Fe uptake in roots of radish though its subsequent translocation from roots to shoots and leaves did not increase. About 70%-80% of the total 55Fe was distributed in the roots while about 5%-15% and 11%-17% were in shoots and leaves, respectively. The EDTA increased iron uptake into the roots of radish, but not in the above ground parts of the plant. The growth of radish (Raphanus sativus L.) decreased drastically in alkaline condition (pH > 9), even though the concentration of iron was sufficient in the growth medium. The growth of radish was enhanced successfully by the addition of hydroxyiminodisuccinic acid (HIDS) and EDTA. This might be because HIDS and EDTA solubilize iron from its precipitation with hydroxides at higher pH, and increase iron bioavailability. The influence of EDTA and HIDS on radish growth was comparable. Increase of radish growth by ethylenediaminedisuccinic acid (EDDS) and methylglicinediacetic acid (MGDA) was less than those by EDTA and HIDS. Considering the reproducibility of the radish growth (biomass production) at pH 10, HIDS is supposed to be more effective compared to EDTA. © Taylor & Francis Group, LLC

Urodynamic evaluation before and immediately after robot-assisted radical prostatectomy

Objective To evaluate continence status and mechanism of urinary incontinence immediately after robot-assisted radical prostatectomy (RARP) by performing urodynamic evaluation. Methods A total of 87 patients with localized prostate cancer who underwent RARP were included. Filling cystometry, urethral pressure profilometry, and abdominal leak point pressure (ALPP) tests were performed before and immediately after RARP. Results The mean urine loss ratio (ULR), calculated by dividing the total urine volume by the weight of urine loss after RARP, was 17.8%. Nerve-sparing (NS) surgery significantly affected ULR compared with non-NS surgery. In the comparison between preoperative and postoperative results, the mean maximal cystometric capacity (MCC) and maximal closure urethral pressure (MUCP) decreased from 341 mL and 84.6 cm H 2O to 250 mL and 35.6 cm H2O, respectively. No urine leakage was observed in ALPP test preoperatively; however, urine leakage was observed postoperatively in 75 patients (86%), with a mean ALPP of 47.7 cm H2O. Multivariate analysis revealed that MCC, MUCP, and ALPP after RARP were predictive factors for ULR. Linear correlations were found between ULR and MUCP and between ULR and ALPP after RARP. NS status and MUCP after RARP (r = 0.247; P =.021) and the ALPP (r = 0.254; P =.018) were significantly correlated. Conclusion In urodynamic evaluation immediately after RARP, MCC, MUCP, and ALPP were found to predictive factors for urinary incontinence. The NS procedure contributed to continence status after RARP. © 2014 Elsevier Inc

Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis

金沢大学附属病院泌尿器科Study Type - Prognosis (case series) Level of Evidence4 What\u27s known on the subject? and What does the study add? Bone turnover markers such as BAP and 1CTP in patients with SRE or metastatic bone progression were significantly higher at later phase after starting treatment with zoledronic acid compared with those without SRE or progression. However, there are no evident biomarkers predicting SRE or survival at an early phase after starting zoledronic acid treatment. The increase in serum 1CTP and BAP levels at an early phase after starting zoledronic acid treatment predicts short SRE-free survival and overall survival. The measurement of bone turnover markers may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan. OBJECTIVE: To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal-related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS: In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. Serum C-terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate-specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS: SRE-free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION: The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.発行後1年より最終稿

Cardiovascular and respiratory effects of the degree of head-down angle during robot-assisted laparoscopic radical prostatectomy

Background: Robot-assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis. Methods: Forty-seven ASA physical status 1 and 2 patients underwent open retropubic radical prostatectomy (RRP) or RALP. Patients receiving RALP were randomized to undergo the operation in the 20°, 25° or 30° Trendelenburg position. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end-tidal CO2 pressure (PetCO2), tidal volume (Vt), peak inspiratory pressure (PIP) and dynamic compliance (Cdyn) were recorded during the operation. Results: Angle of head-down tilt was significantly correlated with MAP, PIP and Cdyn, but not with HR, RR or PetCO2. MAP decreased gradually over time in each group in the Trendelenburg position with pneumoperitoneum. As the angle of head-down tilt became stronger, MAP, RR, PetCO2 and PIP tended to increase and Cdyn tended to decrease. Conclusions: This study demonstrated that the degree of the head-down angle at RALP affected the cardiovascular and respiratory parameters. Pneumoperitoneum with head-down position in RALP influenced the cardiovascular and respiratory system to a greater extent than RRP, and these effects were stronger with deeper head-down angle. © 2013 John Wiley & Sons, Ltd

Waterjet submucosal dissection of porcine esophagus with the HybridKnife and ERBEJET 2 system: a pilot study

Background and study aims Esophageal endoscopic submucosal dissection (ESD) is technically difficult because of narrow working spaces and ease of perforation due to the lack of serosa. HybridKnife is a recently developed ESD device that is combined with the high pressure waterjet ERBEJET 2 system to lift mucosa. We hypothesized that this waterjet could make submucosal dissection safer and studied this in porcine esophagus.Materials and methods Water pressures of 30 – 70 bar were tested to determine the appropriate pressure for waterjet ESD with HybridKnife (WJ-ESD) in one pig. WJ-ESD safety and completion were compared with those of conventional ESD using DualKnife (C-ESD) as a reference. Each of three virtual esophageal lesions in two pigs were resected alternatively using both methods from the lower to upper esophagus. For WJ-ESD, the submucosa, apart from hard fibrous tissues, was dissected using water pressure alone.Results Using 50 bar of water pressure resulted in the best balance between proper dissection and view-disturbing water backflow. The dissection speeds for the lower, middle, and upper esophagus were 0.2, 0.9, and 0.2 cm2/min in 50 bar WJ-ESD and 1.1, 0.5, and 1.0 cm2/min in C-ESD, respectively. Minor bleeding was frequent in WJ-ESD, but was easily stopped by electrocoagulation with the same needle. No perforation was observed in either procedure. Thermal damage to dissected tissues appeared mild, and the extent of muscle injury was lower for WJ-ESD (4, 6, and 8 %) compared with C-ESD (14, 16, and 7 %).Conclusions WJ-ESD could be completed safely for porcine esophagus with less damage to the muscle layer compared with C-ESD

Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism (s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance. They also showed dysbiosis associated with an increased proportion of gram-negative bacteria species and an increased lipopolysaccharide (LPS) level in feces. Intestinal permeability was elevated in association with both epithelial damage and decreased expression levels of tight junction protein zona occludens-1, and thereby LPS levels were increased in serum. For Kupffer cells, the foreign body phagocytic capacity was decreased in magnetic resonance imaging, and the proportion of M1 cells was increased in DKO mice. In vitro experiments showed that the inflammatory response was accelerated in the p62:Nrf2 double-deficient Kupffer cells when challenged with a low dose of LPS. Diet restriction improved the hepatic conditions of NASH in association with improved dysbiosis and decreased LPS levels. The results suggest that in DKO mice, activation of innate immunity by excessive LPS flux from the intestines, occurring both within and outside the liver, is central to the development of hepatic damage in the form of NASH

Nuclear factor (erythroid derived 2)-like 2 activation increases exercise endurance capacity via redox modulation in skeletal muscles

Sulforaphane (SFN) plays an important role in preventing oxidative stress by activating the nuclear factor (erythroid derived 2)-like 2 (Nrf2) signalling pathway. SFN may improve exercise endurance capacity by counteracting oxidative stress-induced damage during exercise. We assessed running ability based on an exhaustive treadmill test (progressive-continuous all-out) and examined the expression of markers for oxidative stress and muscle damage. Twelve- to 13-week-old Male wild-type mice (Nrf2+/+) and Nrf2-null mice (Nrf2−/−) on C57BL/6J background were intraperitoneally injected with SFN or vehicle prior to the test. The running distance of SFN-injected Nrf2+/+ mice was significantly greater compared with that of uninjected mice. Enhanced running capacity was accompanied by upregulation of Nrf2 signalling and downstream genes. Marker of oxidative stress in SFN-injected Nrf2+/+ mice were lower than those in uninjected mice following the test. SFN produced greater protection against muscle damage during exhaustive exercise conditions in Nrf2+/+ mice than in Nrf2−/− mice. SFN-induced Nrf2 upregulation, and its antioxidative effects, might play critical roles in attenuating muscle fatigue via reduction of oxidative stress caused by exhaustive exercise. This in turn leads to enhanced exercise endurance capacity. These results provide new insights into SFN-induced upregulation of Nrf2 and its role in improving exercise performance

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: A randomised controlled study

金沢大学附属病院泌尿器科Purpose. We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH). Methods. Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment. Results. Forty-six patients (ART group, n=23; control, n=23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7±8.7 vs. 12.5 ± 9.5; p < 0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p < 0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p < 0.05), whereas no significant changes were seen in the controls. Conclusion. ART improved LUTS in hypogonadal men with mild BPH. © 2010 Informa UK, Ltd