Testosterone Therapy for Late-Onset Hypogonadism Improves Erectile Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Randomized controlled trials (RCTs) of testosterone therapy (TTh) for late-onset hypogonadism are systematically reviewed and a meta-analysis to assess the efficacy of TTh in improving erectile function is performed. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched to identify RCTs published from 2007. RCTs that assessed erectile function using the erectile function domain of the International Index of Erectile Function (IIEF-EFD) were included in the meta-analysis. RESULTS: The systematic review included 18 RCTs and the meta-analysis included 6 studies that enrolled a total of 1,458 patients. The overall meta-analysis revealed that the IIEF-EFD score was significantly improved in the TTh group compared with the placebo group (mean difference 1.86; 95% confidence interval 1.01-2.72; p < 0.0001). Compared with patients receiving placebo, there was a significant improvement in the IIEF-EFD of patients who received TTh using testosterone gel, those who received TTh for over 30 weeks, and those without diabetes mellitus or metabolic syndrome. CONCLUSION: TTh achieved a significant improvement in the IIEF-EFD score of hypogonadal men compared with placebo, especially in those who received testosterone gel, were treated for over 30 weeks, and had no comorbidities.

[Efficacy of Neoadjuvant Endocrine Therapy for Prostate Ductal Carcinoma with Large Multiple Cysts Prior to Robot-Assisted Laparoscopic Radical Prostatectomy].

A 71-year-old man with gross hematuria and urinary retention showed a 7×8 cm polycystic mass compressing the prostate on the right ventral side on pelvic magnetic resonance imaging (MRI). The prostate specific antigen (PSA) level was 6.47 ng/ml. Prostate biopsy histopathology was consistent with prostate ductal carcinoma. Considering the difficulty of surgical therapy, endocrine therapy was undertaken prior to surgery for seven months. Almost all of the cyst disappeared ; robot-assisted laparoscopic radical prostatectomy was then successfully performed. Prostate ductal carcinoma is a relatively rare pathology for which radical prostatectomy plays an important role if the disease is localized. However, when ductal carcinoma involves large cysts, surgical treatment may be difficult. This report discusses the usefulness of neoadjuvant endocrine therapy to reduce the size of the cystic lesions.

Successful Ultra-Minimally Invasive Endoscopic Intrarenal Surgery for 2-Year-Old Boy with Bilateral Cystine Kidney Stones Over 2 cm.

Background: Treatment of upper urinary tract stones measuring >2 cm in children aged <3 years is challenging. Although adult-sized instruments are usually available, in pediatric populations such instruments seem unreasonable and unfit for children with small kidneys and narrow ureters. We use ultra-miniaturized endoscopes and instruments to reduce the damage to normal tissues in pediatric patients. Case Presentation: We treated a 2-year-old boy with >2-cm bilateral cystine kidney stones. We decided to perform retrograde intrarenal surgery using an ultrathin (4.5F) semi-rigid ureteroscope for the right kidney stone (2.0 × 1.2 cm) in the lithotomy position and super ultra-minimally invasive endoscopy combined with intrarenal surgery with a percutaneous 8.5F to 9.5F tract sheath for the left kidney stone (3.5 × 2.4 cm) under the Barts modified Valdivia position. These procedures were successful for the bilateral kidney stones. Postoperatively, the patient was stone-free without major complications. Conclusion: We believe that ultra-minimally invasive endoscopic intrarenal surgery is safe and efficient in pediatric patients. Furthermore, the Barts modified Valdivia position was safely utilized in our 2-year-old patient with multiple large kidney stones.

[Late Relapse of Testicular Cancer at the Pelvis with Elevated AFP Levels : A Case Report].

We report a patient with seminoma which recurred as late relapse at the pelvis with elevated alphafetoprotein (AFP) levels. A 40-year-old man presented with a left testicular tumor and subsequently underwent high orchiectomy in 2006. Pathological findings showed that the tumor was a seminoma with invasion into the tunica albuginea (pT2N0M0). Seven years after surgery, computed tomography showed a 12×8.7 mm, well-circumscribed, pelvic cystic tumor, and AFP and human chorionic gonadotropin levels were elevated. He was clinically diagnosed with recurrent testicular cancer. Despite the fact that the patient had four courses of bleomycin, etoposide, and cisplatin (BEP), the tumor enlarged and AFP levels were still elevated. Therefore, we performed open excision of the pelvic tumor. Judging from the pathological report, we made the final diagnosis of mature cystic teratoma. The patient was free of recurrence or metastasis within 48 months of follow-up.

Comparison of Silodosin Monotherapy vs Silodosin With Tadalafil Add-on Therapy in Patients With Benign Prostatic Hyperplasia.

OBJECTIVE: To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil for patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) treated with the α1-adrenoceptor blocker silodosin. MATERIALS AND METHODS: We analyzed 103 patients with LUTS/BPH with an International Prostate Symptom Score (IPSS) of >8 after ≥4 weeks of silodosin treatment from April 2016 through December 2016 at Kori Hospital. The patients subsequently received silodosin 4.0 mg twice daily (monotherapy group) or silodosin 4.0 mg twice daily plus tadalafil 5.0 mg once daily (add-on therapy group) for 8 weeks. We assessed adverse events and evaluated the mean change from baseline to 8 weeks in the IPSS, Overactive Bladder Symptom Score (OABSS), maximum urine flow rate (Qmax), and post-void residual urine volume. RESULTS: Of 103 patients, 101 (98.1%) could continue medical treatment. The IPSS, OABSS, and Qmax showed significantly greater improvement in the add-on therapy than in the monotherapy group (-3.92 vs -1.24, -1.18 vs 0.10, and 1.09 vs -1.04, respectively; all P <.05). Although 4 patients experienced adverse events (add-on therapy: n = 3, 5.7%; monotherapy: n = 1, 2.0%), no significant differences were observed (P = .62). Among patients with overactive bladder (n = 55), the IPSS storage symptom subscore, IPSS urgency subscore, and OABSS urgency subscore showed significantly greater improvement in the add-on therapy than in the monotherapy group (-2.23 vs 0.17, -0.88 vs 0.28, and -1.5 vs -0.48, respectively; all P <.05). CONCLUSION: Add-on therapy with tadalafil may be effective for patients with LUTS/BPH resistant to silodosin monotherapy.

Preoperative Pyuria Is a Poor Prognostic Factor in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Surgery.

INTRODUCTION: The purpose of this study was to determine the prognostic significance of preoperative pyuria in patients with upper urinary tract urothelial carcinoma after surgery. PATIENTS AND METHODS: We retrospectively evaluated data on 157 patients with nonmetastatic upper urinary tract urothelial carcinoma who had undergone surgery at our institution. The associations between clinical features and advanced pathological findings were evaluated using a logistic regression model. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed with the Kaplan-Meier method and Cox regression analysis. The influence of pyuria on the predictive accuracy of the multivariate model was assessed using the concordance index. RESULTS: The median postoperative follow-up among patients who survived was 48.1 months. Preoperative pyuria was significantly correlated with worse RFS, CSS, and OS (P < .001 each). Pyuria was also associated with significantly increased risk of a high pathological T stage (≥ pT3; odds ratio, 2.99; P = .003), high tumor Grade (G3; odds ratio, 2.25; P = .038), and lymphovascular invasion (odds ratio, 2.25; P = .008). Moreover, multivariate Cox regression analyses showed that pyuria was an independent prognostic factor for RFS (hazard ratio, 3.02; P < .001), CSS (hazard ratio, 2.15; P = .043), and OS (hazard ratio, 2.10; P = .019). For CSS, the addition of pyuria to the multivariate model increased its predictive accuracy from 0.87 to 0.90. CONCLUSION: Preoperative pyuria is significantly associated with CSS, OS, and increased risk of locally advanced disease and subsequent disease recurrence in patients with upper urinary tract urothelial carcinoma who undergo surgery.

RNAi targeting embryonic myosin heavy chain isoform inhibited bound thrombin-induced migration of vascular smooth muscle cells.

To investigate the effect of bound thrombin, a complex of alpha-thrombin with fibrin fragments derived from clots, on proliferation and migration of cultured rabbit vascular smooth muscle cells, cell proliferation was measured by WST-1 reagent and migration was evaluated by counting migrated cells through pores of cell culture insert (8 mum size) after 48-hour treatment with bound thrombin (10 U/ml). To examine the role of an embryonic myosin heavy chain isoform (SMemb) in these effects by bound thrombin, the cells were subsequently treated for 48 h with an siRNA expression vector (ORF-2/pSilencer) directed against the open reading frame of SMemb mRNA. SMemb and plasminogen activator inhibitor-1 mRNA expressions were measured by Northern blot analysis. Bound thrombin significantly increased SMemb mRNA expression by 1.4 +/- 0.01-fold and significantly increased plasminogen activator inhibitor-1 mRNA expression by 2.65 +/- 0.69-fold (p < 0.01 vs. PBS treatment for each), which were abolished by treatment with ORF-2/pSilencer. Although bound thrombin had no effect on cell proliferation, bound thrombin significantly increased migration by 1.93 +/- 0.20-fold (p < 0.05). ORF-2/pSilencer treatment significantly reduced the bound thrombin-stimulated migration activity by 1.28 +/- 0.15-fold (p < 0.05). Thus, SMemb plays an important role in bound thrombin-induced cell migration activity of cultured vascular smooth muscle cells.

RNA interference targeting embryonic myosin heavy chain isoform inhibited mRNA expressions of phenotype markers in rabbit cultured vascular smooth muscle cells.

To investigate whether the knockdown of SMemb gene expression induces phenotypic modulation of vascular smooth muscle (VSM) cells toward a contractile type, we constructed a siRNA targeting the 3' untranslated region (UTR) of SMemb gene (SMemb-siRNA). The SMemb-siRNA was introduced into cultured rabbit VSM cells for 48 h at 37 degrees C by the lipofection method. The mRNA expressions were estimated by comparative reverse transcription-polymerase chain reaction (RT-PCR). SMemb-siRNA significantly decreased the ratio of SMemb to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in a dose-dependent manner (P < 0.01): 0 nM, 0.90 +/- 0.08; 100 nM, 0.43 +/- 0.07. Immunofluorescence and immunoblot analyses demonstrated that SMemb-siRNA markedly decreased SMemb protein expression to 56% +/- 7.8% (P < 0.01). Other MHC isoform (SM1 and SM2) mRNA expressions were not changed. The relative mRNA expressions of other phenotype markers (plasminogen activator inhibitor (PAI)-1 and beta-actin) were significantly decreased by SMemb-siRNA to 71% +/- 7.5% and 61% +/- 7.5%, respectively (P < 0.01). Expression of smooth muscle (SM) alpha-actin protein and cell proliferation was not changed by SMemb-siRNA. Thus, SMemb gene might be involved in the transcription of PAI-1 and beta-actin, but not involved in SM alpha-actin and cell proliferation in cultured VSM.

Elevation of intracellular cAMP up-regulated thrombomodulin mRNA in cultured vascular endothelial cells derived from spontaneous type-II diabetes mellitus model rat.

To investigate whether antihemostatic function of vascular endothelial cells (VECs) is changed in type-II diabetic model rats, the mRNA expressions of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), thrombomodulin (TM), PA inhibitor type-1 (PAI-1), and phosphodiesterases (type 3A, 3B, and 4D PDEs) were quantitated by the method of comparative reverse transcriptase-polymerase chain reaction (RT-PCR). VECs from type-II diabetic model Otsuka Long-Evans Tokushima Fatty (OLETF) rats and from its normal counterpart (LETO) rats were cultured for 24 h with dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) or a type-3 PDE inhibitor, cilostazol. Intracellular cAMP concentration was determined by the chemiluminescent enzyme-linked immunosorbent assay (ELISA) system. In cultured VECs from OLETF rats, the basal mRNA expressions of u-PA and TM were significantly decreased as compared to those in cultured VECs from LETO rats. TM mRNA expression in cultured VECs from OLETF rats was increased 2.1-fold at 24 h after treatment with db-cAMP (3 mmol/L). Basal mRNA expressions of type 3A, 3B, and 4D PDEs were significantly higher in VECs from OLETF rats than those from LETO rats. After treatment with cilostazol (30 micromol/L), intracellular cAMP was significantly increased at 60 min and TM mRNA expression was increased 1.5-fold at 24 h. Therefore, elevation of intracellular cAMP by db-cAMP or cilostazol up-regulated TM mRNA expression in cultured VECs from OLETF rats.

Argatroban, specific thrombin inhibitor, induced phenotype change of cultured rabbit vascular smooth muscle cells.

To investigate whether argatroban ((2R,4R)-4-methyl-1-[N(2)-((RS)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid hydrate, a selective thrombin inhibitor, exerts a direct action on phenotype conversion of vascular smooth muscle cells, cultured rabbit aortic vascular smooth muscle cells were employed. Myosin heavy chain isoforms (SM1, SM2, and SMemb) mRNA expressions were evaluated by in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). After the cells were incubated in serum-free medium containing argatroban (10 and 50 microg/ml) and platelet-derived growth factor (PDGF)-BB (10 and 50 ng/ml) for 3 h, total RNA was extracted. In situ hybridization demonstrated that myosin heavy-chain isoform mRNAs were homogenously expressed in argatroban- and PDGF-BB-treated cells. RT-PCR revealed that SM1/SM2 mRNA expressions were not changed with argatroban, while SMemb mRNA expression was increased to 1.6-fold with a statistical significance (P<0.05). Treatment with argatroban (10 and 50 microg/ml) at 24 h did not change SM1/SM2 mRNA expressions. Although SMemb mRNA expression was slightly increased, there was no statistical significance. Other phenotype markers including plasminogen activator inhibitor-1 (PAI-1) and beta-actin mRNAs were also significantly increased by argatroban. In conclusion, argatroban can directly induce phenotype conversion of vascular smooth muscle cells with the resultant up-regulation of SMemb, PAI-1, and beta-actin mRNAs.