Satoshi Washino

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients

To assess the value of the Prostate Imaging Reporting and Data System (PI‐RADS) scoring system, for prostate multi‐parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate‐specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer.

18F-Fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of idiopathic retroperitoneal fibrosis associated with mediastinal fibrosis

A 68-year-old man was admitted to our hospital with left intermittent claudication. Computed tomography showed soft tissue masses surrounding the left iliac artery and in the bilateral pulmonary hilum, and the first FDG PET showed increased FDG uptake by the lesions. Retroperitoneal fibrosis associated with mediastinal fibrosis was most suspected. An open biopsy of the left peri-iliac masses revealed retroperitoneal fibrosis. Corticosteroid treatment was initiated. The second FDG PET under corticosteroid treatment showed no pathological FDG uptake. The third FDG PET after cessation of corticosteroid treatment showed increased FDG uptake in the mediastinum, and so Sairei-to treatment was initiated. The fourth FDG PET under Sairei-to treatment showed no improvement of the pathological FDG uptake, and so low-dose corticosteroid was re-started in combination with Sairei-to treatment. The fifth FDG PET under Sairei-to and corticosteroid treatment showed no pathological FDG uptake. These FDG PET findings suggest the usefulness of FDG PET for the diagnosis and monitoring of retroperitoneal fibrosis associated with mediastinal fibrosis.

Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

Objective: To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Materials and Methods: Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. Results: A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p < 0.01) and higher grade (p < 0.05). In contrast, serum CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p < 0.01). Patients who were positive for CYFRA 21-1 had significantly worse disease-specific survival (p < 0.0001, log rank test). Conclusion: Serum CYFRA 21-1 seems to be a marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated.

Early prediction of cisplatin-induced nephrotoxicity by urinary vanin-1 in patients with urothelial carcinoma.

Cisplatin is a widely used anticancer drug, but its nephrotoxicity is a serious problem. To examine whether the novel biomarker, urinary vanin-1, could predict reduction in renal function after dosing of cisplatin. We conducted a prospective single-center pilot study of 24 patients with urothelial carcinoma who received cisplatin-based chemotherapy between 2012 and 2015. The primary outcome was a 20% or greater decline in estimated glomerular filtration rate (eGFR) from baseline within the first 6days of cisplatin. Urine concentration of creatinine, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and NAG (N-acetyl-β-d-glucosaminidase) as well as vanin-1 were measured during the perioperative period. During 6days after cisplatin, 37.5% (9/24) of patients showed more than 20% decline in eGFR (baseline, 68.8±11.1mL/min/1.73m(2); on day 6, 51.0±2.5mL/min/1.73m(2)) and this reduction persisted until day 10. Urinary vanin-1, but not KIM-1, NGAL and NAG, significantly elevated early on day 3 after cisplatin, which preceded the elevation of serum creatinine on day 6. Sensitivity and specificity of a cutoff point of urinary vanin-1 (9.31ng/mg Cr) on day 3 were calculated to be 66.7% (95% CI: 0.30-0.93) and 83.3% (95% CI: 0.52-0.97), respectively, for predicting 20% decline in eGFR during 6days after cisplatin. These data suggest that urinary vanin-1 is an early predictive biomarker for decline in eGFR in patients with urothelial carcinoma after dosing of cisplatin.

Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

To compare the efficacy and safety of single half‐dose silodosin and single full‐dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH).

Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice

Interstitial lung disease (ILD) is a well-known adverse effect of mammalian target of rapamycin (mTOR) inhibitors. However, it remains unknown how lung toxicities are induced by mTOR inhibitors. Here, we constructed a mouse model of mTOR inhibitor-induced ILD using temsirolimus and examined the pathogenesis of the disease. Male ICR mice were treated with an intraperitoneal injection of different doses of temsirolimus (3 or 30 mg·kg(-1)·wk(-1)) or vehicle. Temsirolimus treatment increased capillary-alveolar permeability and induced neutrophil infiltration and fibrinous exudate into the alveolar space, indicating alveolar epithelial and/or endothelial injury. It also induced macrophage depletion and the accumulation of excessive surfactant phospholipids and cholesterols. Alveolar macrophage depletion is thought to cause surfactant lipid accumulation. To further examine whether temsirolimus has cytotoxic and/or cytostatic effects on alveolar macrophages and alveolar epithelial cells, we performed in vitro experiments. Temsirolimus inhibited cell proliferation and viability in both alveolar macrophage and alveolar epithelial cells. Temsirolimus treatment caused some signs of pulmonary inflammation, including upregulated expression of several proinflammatory cytokines in both bronchoalveolar lavage cells and lung homogenates, and an increase in lymphocytes in the bronchoalveolar lavage fluid. These findings indicate that temsirolimus has the potential to induce alveolar epithelial injury and to deplete alveolar macrophages followed by surfactant lipid accumulation, resulting in pulmonary inflammation. This is the first study to focus on the pathogenesis of mTOR inhibitor-induced ILD using an animal model.

α-Lipoic acid protects against arsenic trioxide-induced acute QT prolongation in anesthetized guinea pigs

Clinical use of arsenic trioxide (As₂O₃), which can induce the remission of relapsed or refractory acute promyelocytic leukemia, is often limited because of its cardiotoxicity. Symptoms of cardiotoxicity include acute cardiac conduction disturbances, such as QT prolongation. The present study was undertaken to evaluate the effects of α-lipoic acid (LA) on acute As₂O₃-induced ECG abnormalities (QTc interval prolongation) in anesthetized guinea pigs. Intravenous injection of As₂O₃ in guinea pigs caused QTc interval prolongation, which was significantly attenuated by co-treatment with LA (0.35, 3.5 and 35 mg/kg) in a dose-dependent manner. In isolated guinea pig cardiomyocytes, the decrease in IKs current induced by As₂O3 (1 μM) was rapidly restored to the basal level by the addition of LA (10 μM). Consistent with this finding, the As₂O₃-induced QTc interval prolongation was also improved rapidly by post-treatment with LA in guinea pigs. Electrospray ionization time-of-flight mass spectrometry analysis detected an expected peak of arsenic-LA complex in vitro, indicating that LA and As₂O3 form a new compound in vivo. In addition, pre-treatment with a chelating agent, British anti-Lewisite (BAL, 3.5 or 35 mg/kg), also attenuated the As₂O₃-induced QTc interval prolongation. In this study, co- and post-treatments with LA and pre-treatment with BAL ameliorated As₂O₃-induced acute QT prolongation in anesthetized guinea pigs. Because LA and probably BAL may bind to As₂O₃, these agents may exert protective effects through their chelating activity. Further studies are needed to determine whether LA is beneficial as a prophylactic or rescue agent for acute promyelocytic leukemia patients treated with As₂O₃.

Impact of Androgen Deprivation Therapy on Volume Reduction and Lower Urinary Tract Symptoms in Patients with Prostate Cancer

To evaluate the impact of androgen deprivation therapy (ADT) on prostate volume, lower urinary tract symptoms (LUTS), and LUTS‐related quality of life (QOL) in patients with prostate cancer.

Long-Term Survival after Adrenalectomy for Asynchronous Metastasis of Bladder Cancer to the Bilateral Adrenal Glands

Isolated adrenal metastasis of bladder cancer, particularly the bilateral, is quite rare. Systemic chemotherapy is the treatment of choice for metastatic urothelial carcinoma. However, despite initially promising response rates of approximately 45%–71%, most tumors eventually show progression, and the median survival time following chemotherapy regimen is approximately 14-15 months. Recently, favorable results of surgery for metastatic urothelial carcinoma have been reported. Here, we report a rare case of asynchronous metastasis of bladder cancer to the bilateral adrenal glands with long-term survival after bilateral adrenalectomy. A 69-year-old man underwent radical cystoprostatectomy and ileal conduit urinary diversion for invasive bladder cancer. Ten months later, left adrenalectomy was performed for a left adrenal tumor, revealing metastatic urothelial carcinoma. After adjuvant chemotherapy, a tumor in the right adrenal gland was detected. Right adrenalectomy was done, and the tumor was also found to be metastatic urothelial carcinoma. The patient had an uneventful recovery after starting steroid replacement therapy. Three years later, he was doing well and had no evidence of recurrence. Adrenalectomy for isolated adrenal metastasis of urothelial carcinoma may be a reasonable option, even if such metastases are bilateral.

Early urinary biomarkers of renal tubular damage by a high-salt intake independent of blood pressure in normotensive rats

Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high‐salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high‐salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high‐salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt‐loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin‐1, neutrophil gelatinase‐associated lipocalin (NGAL), and kidney injury molecule‐1 (Kim‐1) were measured. At 17 weeks of age, 8% salt‐loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N‐acetyl‐β‐D‐glucosaminidase (NAG), or Kim‐1 during the study period among the groups, urinary vanin‐1 and NGAL significantly increased in 8% salt‐loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin‐1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high‐salt intake.