Search

In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery.We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo.The simulation studyconfirmedthat LDS could localize the heat distributionbetween the electrode and the outer arterial wall. In the animal study, we could maximize nerve denervation by the localizing ablation energy within the renal nerves and achieve nerve denaturationand decrease in neural density by 20.78% (P0.001), while maintaining a constant tip temperature of 65 °C for the duration of 70 s treatment. The study confirmed intact lumen artery through histological analysis and acute reduction in systolic blood pressure by 9.55 mmHg (p0.001) Conclusion: The LDS presented here has potential to effectively and safely ablate the renal nerves, independent of anatomical variation and nerve distribution, to control hypertension in real clinical conditions.LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.

Catheter-based renal denervation (RDN) was introduced to treat resistant hypertension. However, the reduction in blood pressure after the RDN was modest. Catheter-based RDN was performed only at main renal arteries, except for accessory and branch arteries due to the diameter being too small for the catheter to approach. Here, we retrospectively analyzed the anatomy of diverse renal arteries via 64-channel multi-detector computed tomography angiograms of 314 consecutive donors who underwent living donor nephrectomy from January 2012 to July 2017. Occurrence rates of one or more accessory renal arteries in donors were 25.3% and 19.4% on the left and right sides, respectively. Early branching rates before 25 mm from the aorta to the right and left renal arteries were 13.7% and 10.5%, respectively. Overall, 63.1% and 78.3% of donors had no accessory artery bilaterally and no branched renal artery, respectively. As a result, 47.1% had only main renal arteries without an accessory artery and early-branching artery. Approximately half of the donors had multiple small renal arteries bilaterally, for which catheter-based denervation may not be suitable. Thus, preoperative computed tomography angiography requires careful attention to patient selection, and there is a need for improved methods for denervation at various renal arteries.

Background and ObjectiveTo compare the incidence of febrile urinary tract infection (UTI) and bacterial identification between patients with orthotopic neobladder (ONB) and ileal conduit (IC). Materials and MethodsData of 164 patients who underwent radical cystectomy with ONB and IC for bladder cancer between January 2009 and January 2018 at our institution were analyzed. Febrile UTI observed was listed and subsequently compared. Incidence of febrile UTI, clinicopathological characteristics, and microorganisms identified were reported at 3 months interval; and preoperative predictors of febrile UTI were evaluated with Cox regression analysis. Patients were divided into ONB and IC. ResultsThe study cohort included 52 patients with ONB and 112 patients with IC. Febrile UTI was diagnosed in 49 (29.9%) patients. Compared to IC group, ONB group had significantly higher incidence of young age (p=0.00), lower cancer stage (p=0.013), longer hospital stay (p=0.049), longer operation time (p=0.00), and higher incidence of febrile UTI within the first 3 months after surgery (p=0.006). On univariable and multivariable analysis, factors associated with significantly increased febrile UTI risk were diabetes (odds ratio [OR]: 4.52; p=0.002) and ONB diversion (OR: 1.27; p=0.031). Forty-four (89.8%) patients were culture positive. However, significant difference in microorganisms was not detected between patients who under-went ONB or IC diversion. ConclusionDiabetes and ONB diversion were associated with higher risk symptomatic UTI following radical cystectomy.

The current results show that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are co-prevalent conditions. The objective of this study was to determine which LUTS among seven items on the International Prostate Symptom Scores (IPSS) were related to ED in the general population. The Korean Internet Sexuality Survey was performed in 2006 and 2016. We sent emails and surveyed the panelists registered at an Internet survey agency. The inclusion criteria were sexually active men aged between 20 and 69. Data, including the International Index of Erectile Function-5 (IIEF-5) and IPSS scores were extracted from the surveys. Logistic regression analyses were performed to determine the factors related to ‘any degree of ED’ (IIEF-5

Introduction Cavernosal fibrosis is an important pathologic condition leading to erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, diabetes mellitus, castration, cavernosal nerve injury during radical prostatectomy, hypertension, and Peyronie disease. Aims To summarize published studies investigating suppression of cavernosal fibrosis in rat models of ED of various etiologies. Methods A literature search was conducted using PubMed. Relevant studies were identified using search terms such as erectile dysfunction, penis, fibrosis, and rat models. Main Outcome Measures We reviewed representative literature studies on the mechanisms and suppression of cavernosal fibrosis in rat models of ED. Results The underlying mechanisms and potential therapeutic strategies suggested thus far for cavernosal fibrosis in rat models of ED were as follows. For age-related ED involving oxidative stress and tumor growth factor-β1 (TGF-β1)–driven pathways such as RhoA-ROCK1-LIMK2-cofilin or p42-44 and mitogen-activated protein kinase, proposed therapeutic strategies included phosphodiesterase type 5 inhibitors (PDE5Is), kallikrein-kinin system stimulators, and calorie restriction. For diabetes-related ED involving angiotensin-II– and TGF-β1–driven Smad and non-Smad pathways, TGF-β1-Wnt10b, and histone deacetylase (HDAC)-TGF-β1 pathways, positive therapeutic results were obtained with PDE5Is, TGF-β1 antagonists, HDAC inhibitors, antioxidants, sphingosine-1-phosphate receptor modulators (fingolimod), angiotensin-II antagonists, stem cell therapy, and antidiabetic drugs. For cavernosal nerve injury-associated ED involving TGF-β1–driven pathways (Smad or RhoA-ROCK1-LIMK2-cofilin), Sonic hedgehog signaling, angiotensin-II–Smad, and HDAC4–TGF-β1–Smad signaling triggered by cavernosal hypoxia, PDE5Is, angiotensin-II antagonists, stem cell therapy, HDAC inhibitors, Sonic hedgehog administration, ROCK inhibitors, and LIMK2 inhibitors have shown positive results. For testosterone deficiency-associated ED, TGF-β1–driven pathways were found to be responsive to testosterone supplementation. For hypertensive ED, positive therapeutic results were obtained with angiotensin-II antagonists. For Peyronie disease involving TGF-β1 or myostatin signaling, proposed therapeutic strategies included intra-tunical injection of TGF-β receptor inhibitors or adipose tissue-derived stem cells and HDAC2 small hairpin RNA. Conclusion Several signaling pathways appear to be responsible for the development of cavernosal fibrosis related to ED of various etiologies. Some therapeutic success has been achieved in animal models, but further research focusing on mechanism-specific targeted therapies is needed. Cho MC, Song WH, Paick J-S. Suppression of Cavernosal Fibrosis in a Rat Model. Sex Med Rev 2018;6:572–582.

We compared long-term storage symptom outcomes between photoselective laser vaporization of the prostate with a 120 W high performance system and holmium laser enucleation of the prostate. We also determined factors influencing postoperative improvement of storage symptoms in the long term.Included in our study were 266 men, including 165 treated with prostate photoselective laser vaporization using a 120 W high performance system and 101 treated with holmium laser enucleation of the prostate, on whom 60-month followup data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60 months postoperatively using the International Prostate Symptom Score, uroflowmetry and the serum prostate specific antigen level. Postoperative improvement in storage symptoms was defined as a 50% or greater reduction in the subtotal storage symptom score at each followup visit after surgery compared to baseline.Improvements in frequency, urgency, nocturia, subtotal storage symptom scores and the quality of life index were maintained up to 60 months after photoselective laser vaporization or holmium laser enucleation of the prostate. There was no difference in the degree of improvement in storage symptoms or the percent of patients with postoperative improvement in storage symptoms between the 2 groups throughout the long-term followup. However, the holmium laser group showed greater improvement in voiding symptoms and quality of life than the laser vaporization group. On logistic regression analysis a higher baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet Obstruction Index) were the factors influencing the improvement in storage symptoms 5 years after prostate photoselective laser vaporization or holmium laser enucleation.Our serial followup data suggest that storage symptom improvement was maintained throughout the long-term postoperative period for prostate photoselective laser vaporization with a 120 W high performance system and holmium laser enucleation without any difference between the 2 surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI predicted improved storage symptoms in the long term after each surgery.

In this study, we propose a novel laparoscopy-based renal denervation (RDN) system for treating patients with resistant hypertension. In this feasibility study, we investigated whether our proposed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectively and can overcome the depth-related limitations of the previous catheter-based system with less damage to the arterial walls.We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-based RDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF) energy. We evaluated the thermal distribution via simulation study on a numerical model designed using histological data and validated the results by the in vitro study. Finally, to show the effectiveness of this system, we compared the performance of our system with that of catheter-based RDN system through simulations.Simulation results were within the 95% confidence intervals of the in vitro experimental results. The validated results demonstrated that the proposed laparoscopy-based RDN system produces an effective thermal distribution for the removal of renal sympathetic nerves without damaging the arterial wall and addresses the depth limitation of catheter-based RDN system.We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.

Background Many studies on sexual attitudes and behavior have been performed to improve sexual health. Aim To evaluate changing trends in Korean female sexual life and attitudes in an internet-based survey at 10-year intervals. Methods The survey was targeted toward 20- to 59-year-old women who were asked to complete the questionnaire only if they were sexually active. The survey contained 110 questions about demographic statistics, sexual life, and attitudes that were crafted based on the 2004 study. Outcomes Results of the 2004 study vs those of the 2014 study. Results In total, 516 women participated in the study; the questionnaire response rate was 16.0%. The mean frequency of intercourse (FOI) per month was 3.46 ± 2.56 in 2014 vs 5.34 ± 3.84 in 2004. Women in their 20s and 30s in 2014 reported a lower mean FOI than those in 2004. There was no significant difference in the mean FOI in 2004 vs 2014 for women who in their 40s. Risk factors for lower FOI were being older, being single, and having dyspareunia. Most Korean women had positive attitudes toward sex (3.2 ± 0.6 of 5) and considered it as important (3.3 ± 0.7 of 5) as those surveyed in 2004. However, women 20 to 39 years old had less positive attitudes toward sex than in the past decade. Women in their 40s were more active and had more conversations with their partners. Of women using contraceptives, 63.8% were found to use less effective methods, such as intercourse withdrawal and the fertility awareness method. Clinical Implications Assessment of changing trends in Korean female sexual life, attitudes, and contraceptive methods could help to establish proper national sexual education programs and campaigns. Strengths and Limitations This study was not a cohort study, because subjects in the 2014 were not identical to those in the 2004 study. Nevertheless, we applied the same inclusion and exclusion criteria for this internet survey, a suitable tool to evaluate the sex life of women, which is often considered a sensitive and private issue in Asian culture. Conclusions Compared with the 2004 survey, young Korean women had fewer sexual relationships and had a less positive attitude toward sex. In addition, many women used less effective methods of contraception.

This study was conducted to investigate the indicators of recovery in storage symptoms after GreenLight High Performance System photoselective vaporization of the prostate (HPS-PVP) in men with benign prostate hyperplasia.A total of 155 men with a baseline subtotal storage symptom score of international prostate symptom score (sIPSS) greater than or equal to six, who underwent HPS-PVP and were followed up on for as much as 3 years, were included in this retrospective study. Surgical outcomes were evaluated at 1, 3, 6, 12, 24, and 36 months after surgery. Improvement of storage symptoms was defined as a reduction greater than or equal to 30% of sIPSS after surgery compared to the baseline.The mean age was 67.5 ± 7.8 years and the preoperative median prostate-specific antigen, mean total prostate volume, and sIPSS were 1.95 (0.97-5.27) ng/mL, 52.1 ± 32.5 mL, and 9.6 ± 2.6, respectively. The mean improvement rate of sIPSS after 3 years was 34.4%. Age was only associated with an improvement of sIPSS in the multivariate analysis (odds ratio = 0.889, p = 0.008). The mean improvement rates of sIPSS according to age group (65 vs ≥65) were 44.7% and 26.0%, respectively.Age can serve as an independent predictor of storage symptom improvement for as much as 3 years. Therefore, we suggest that older patients who are being considered candidates for surgical treatment should be further evaluated.

INTRODUCTION AND OBJECTIVES:Although machine learning (ML) methods show promising results in diagnostic fields, well-designed logistic regression model provides still more powerful results for dete...

Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 μm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.

This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.

Most bladder cancer patients present with noninvasive bladder cancer, but 20–40% of patients progress to advanced state with muscle-invasive or metastatic disease (Raghavan, Urol Oncol 21:468–474, 2003). In general, bladder cancer first spreads to lymph nodes and then to distant organs, and invasion of distant organs such as the lung, liver, and bone is a poor prognostic factor for bladder cancer (Loehrer et al., J Clin Oncol 10:1066–1073, 1992). The most common treatment for metastatic bladder cancer is systemic chemotherapy (Loehrer et al., J Clin Oncol 10:1066–1073, 1992). Cisplatin-based chemotherapy was the only treatment approved by the FDA (Vaughn et al., J Clin Oncol 20:937–940, 2002). There is little RCT performed with first-line setting in metastatic bladder cancer. Second-line setting also has few RCTs performed. Although combination chemotherapy has a high initial response rate, the median survival rate for cisplatin-based first-line chemotherapy is 12–15 months, and the 5-year survival rate is about 15% (von der Maase et al., J Clin Oncol 23:4602–4608, 2005; von der Maase et al., J Clin Oncol 19:3068–3077, 2000). In addition, the results of second chemotherapy are limited and have a little evidence that OS and quality of life can be greatly improved based on modest response rates in small, randomized, phase II trials. However, recently, five immunotherapeutic agents (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) have been developed and approved by the FDA. It can be used in the second-line setting as well as the first setting in case of ineligibility to cisplatin. Also, immune checkpoint inhibitor-related biomarker and combined immunotherapy have been actively studied, and research on precision medicine.

One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers. His genomic sequencing analysis of the BRCA genes revealed the same BRCA2 deleterious mutation that his breast cancer-affected nieces carried. Previous studies have suggested that BRCA2-mutated PC is associated with a more aggressive phenotype and poor prognosis. Our experience in the present case also indicated the urgent needs for novel treatment modality and PC screening in this high-risk group of patients.

INTRODUCTION AND OBJECTIVE:To evaluate the prognosis of prostate cancer with various biomarkers in addition to conventional pathologic findings after radical prostatectomy.METHODS:For 594 patients ...

Purpose: This study was conducted to compare the accuracy of bi-parametric magnetic resonance imaging (bpMRI) with high b-value (b=1,000 s/mm2, b1000) diffusion-weighted imaging (DWI) to that of bpMRI with ultra-high b-value (b=1,800 s/mm2, b1800) DWI to detect clinically significant prostate cancer (csPCa). Materials and Methods: A total of 408 patients with suspected PCa were evaluated by bpMRI prior to biopsy. One reader retrospectively reviewed all images for confirmation of Prostate Imaging–Reporting and Data System (PI-RADS) score. Cognitive magnetic resonance/ultrasound fusion target biopsy was done for all visible lesions (PI-RADS 3–5). Systematic biopsy was done for all cases. The csPCa detection rates were compared according to the bpMRI protocol (with/without b1800 DWI) or PI-RADS score. The accuracy of PI-RADS score was estimated using receiver operating characteristics curve. The signal intensity (SI) ratio (visible lesion/surrounding background) was evaluated. Results: Among 164 men confirmed having PCa, 102 had csPCa (Gleason score≥7). Proportions of PI-RADS score 1–2/3/4/5 without b1800 DWI (n=133) and with b1800 DWI (n=275) were 19.5%/57.9%/15.8%/6.8% and 21.1%/48.7%/22.2%/8.0%, respectively. csPCa detection rates with/without b1800 DWI were 27.6%/19.5% (p=0.048), respectively. Areas under the curve of PI-RADS grading with/without b1800 DWI for csPCa detection were 0.885 and 0.705, respectively. The SI ratio in b1800 DWI was higher than that in b1000 DWI (p

Introduction Because the prevalence of premature ejaculation (PE) may change with time, few studies have been conducted over a 10-year time interval. Aim A 10-year time interval survey to determine whether there was a change in the prevalence of self-identified PE and PE defined on the basis of an estimated intravaginal ejaculation latency time of Methods We sent an e-mail to the panels registered in the same Internet survey agency in 2006, asking them to participate in a questionnaire-based survey of the same study design. 1,401 participants were enrolled in the 2016 study that included 800 subjects in their 20s–50s. The PE prevalence adjusted for age was evaluated because the proportion of participants per age was different between the 2 surveys. The age-adjusted prevalence of self-identified PE and PE with an estimated intravaginal ejaculation latency time of 3 minutes, which meets the diagnostic criteria for PE set by the International Society for Sexual Medicine (PE), was evaluated. Main Outcome Measures Changes in the overall prevalence of self-identified PE and PE in over a decade were evaluated. Results The overall age-adjusted prevalence of self-identified PE increased from 19.0% in 2006 to 21.6% in 2016; however, the result was not statistically significant (P = .244). The overall age-adjusted prevalence of PE increased from 1.8–4.0% in 2006 and 2016, respectively (P = .012). The risk factors of self-identified PE were few intercourses per month, masturbation, and self-identified erectile dysfunction. In addition, the risk factors of PE were aging, high body mass index, few intercourses per month, and masturbation. Clinical Implication The prevalence of PE has increased over 10 years. However, this increase may be due to sociocultural changes and should be more concerned with these factors. Strength & Limitations This study was the first to conduct a 10-year interval Web-based survey on the prevalence and risk factors of PE. However, this was not a cohort study with the same participants. Conclusion The overall age-adjusted prevalence of PE increased significantly over a decade, and sociocultural factors such as lifestyle were associated with the difference of PE prevalence for 10 years. However, more research is needed to determine how these sociocultural changes affect PE prevalence.

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to non-selective property. Recently, catheter based RDN system using radiofrequency (RF) ablation was developed and considered promising, however, it failed in sham controlled trial. Therefore, there are needs for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instruments for laparoscopic renal denervation (RDN) to treat of resistant hypertension through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN is a new surgical approach to remove renal sympathetic nerves.

Purpose: Although the prevalence of erectile dysfunction (ED) can be affected by social changes, this association has not been well evaluated. We aimed to evaluate the prevalence and risk factors of ED through a 10-year-interval web-based sur-vey using the previous database of same group of panels, with same methodology. Materials and Methods: We sent e-mails and surveyed the panels registered in the Internet survey agency. Results: In total, 900 participants were recruited in 2016. The age-adjusted overall prevalences of self-reported ED (self-ED) and International Index of Erectile Function-5-assessed ED (IIEF-5-ED; score ≤21) in the 2016 study were 3.2% and 44.8%, respectively, which were lower than the prevalences of 8.1% (p=0.036) and 51.4% (p=0.323), respectively, in the 2006 study. The risk factors of IIEF-5-ED in their 20s and 30s in 2016 were psycho-social factors such as depression, low frequency of conversation about sex with sexual partner. The risk factors of IIEF-5-ED in their 40s to 60s in 2016 were organic factors, such as hypertension, diabetes mellitus, smoking, alcohol use, and self-reported premature ejaculation. Conclusions: Although the age-adjusted overall prevalence of self-ED has decreased during a decade, there was no differ-ence in the age-adjusted overall prevalence of IIEF-5-ED. Psycho-social support may be important for young men with ED and overall healthcare can be helpful for elderly men with ED.

Background The cavernosal apoptosis and fibrosis are considered to be important pathophysiologies of post-radical prostatectomy (RP) erectile dysfunction (ED). Recently, we demonstrated that inhibition of LIMK2 alleviate ED through suppression of cavernosal fibrosis in a rat model of cavernous nerve (CN) injury. Also, some previous studies showed that administration of PDE5 inhibitors improved both cavernosal apoptosis and endothelial dysfunction in a rat model of CN injury, leading to improvement of ED. Thus, the aim of this study was to determine whether combined administration of LIMK2 inhibitors and PDE5 inhibitors could restore erectile function by combination of anti-fibrotic effect with suppression of apoptosis or potentiation of endothelial function in a rat model of CN injury. Methods Seventy 12-week-old Sprague-Dawley (SD) rats were distributed equally into five groups: sham surgery (S), CN crush injury (I), CN crush injury treated with daily intraperitoneal administration of 10.0 mg/kg LIMK2 inhibitors (I+L), daily oral administration of 20.0 mg/kg udenafil (I+U), and combined administration of 10.0 mg/kg LIMK2 inhibitors and 20.0 mg/kg udenafil (I+L+U). The I+L, I+U and I+L+U groups was treated for 2 weeks from the following day after surgery. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissue was processed for Masson’s-trichrome staining, immunohistochemical staining to alpha-SMA (smooth muscle actin), TUNEL, Western blot, and double immunofluorescence with antibody to vimentin (a fibroblast marker) and phosphorylated LIMK2. Results The I group showed significantly lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining of alpha-SMA (SM content), higher apoptotic index, lower smooth muscle/collagen ratio, increased amount of fibroblasts positive for phosphorylated LIMK2, decreased Akt or endothelial NO synthase (eNOS) phosphorylation, decreased protein expression of total neuronal nitric oxide synthase (nNOS), increased NOS phosphorylation, increased LIMK2 phosphorylation, compared to the S group. In all of the I+L, I+U and I+L+U groups, the ICP/MAP and AUC/MAP significantly improved, but did not recover to values observed in the S group. The SM content in the I+U and I+L+U groups significantly improved compared to the I group, but did not recover to the control value observed in the S group. The I+L group did not show a significant improvement in the SM content compared to the I group. For the SM/collagen ratio, all of the three treatment groups showed its significant improvement compared to the I group, but it did not recover to the value observed in the S group. According to the TUNEL analysis, apoptotic index in the I+U and I+L+U groups significantly improved compared to the I group, but the I+L group did not show its improvement. The amount of fibroblasts positive for phosphorylated LIMK2 in the I+L and I+L+U groups was normalized, but that in the I+U group was not. According to the densitometry, the Akt and eNOS phosphorylation in the I+U and I+L+U groups significantly improved compared to the I group, but the I+L group did not show its improvement. The LIMK2 phosphorylation in the I+L and I+L+U groups significantly improved compared to the I group, but that in the I+U group did not. The protein expression of total nNOS and dysregulated NOS phosphorylation did not improve in any of the three treatment groups (I+L, I+U and I+L+U). Conclusions Our data indicate that combined treatment with a LIMK2 inhibitor and udenafil can improve erectile function by suppression of cavernosal apoptosis or potentiating endothelial function via alleviating AKT/eNOS pathway and by suppression of cavernosal fibrosis via normalizing LIMK2 phosphorylation, although it does not recover to normal level. Thus, an early combined treatment with LIMK inhibition and PDE5 inhibitors may be helpful to effectively suppress structural alterations of cavernosum after CN injury, leading to alleviation of ED.

Phosphorous (P)-containing titania films were prepared by micro-arc oxidation (MAO) of titanium (Ti) in an electrolyte containing β-glycerol phosphate disodium salt pentahydrate (β-GP, C 3 H 7 Na 2 O 6 P . 5H 2 O), and their apatite inducing ability in a simulated body fluid (SBF) was investigated. Macro-porous titania films were formed, consisting of only anatase phase, and the P content in the films increased up to 8 at.% with an increasing applied voltage. During hydrothermal treatment, the P in the films was diffused out to the surface and hydrolyzed to form the hydrogen phosphate (HPO 4 2− ) group. When immersed in SBF, no apatite was induced in any of the P-containing MAO specimens for up to 28 days. However, after a hydrothermal treatment at 250 °C, apatite was induced on the titania surfaces as early as 9 h immersion, and the entire exposed surface was covered with the apatite globules after 36 h immersion, which was much faster than the apatite induction on Ca-containing titania. The higher apatite-inducing ability of P-containing titania after hydrothermal treatment was believed to be due to the crystal structure (anatase) and presence of HPO 4 2− group on the surface.

Skeletal metastases from renal cell carcinoma (RCC) are common, but its metastasis to the digital extremities is rare. The lesion presents diagnostic and therapeutic challenges because of the mimicry of other benign skeletal diseases resulting in difficulties in prompt recognition of diagnosis. We here report a 62 year-old male patient with RCC metastatic to a metacarpal bone presenting with pain and swelling of left hand after 8 years’ follow-up at stable disease without any recurrences. The pathological cytology from the swelling site revealed findings consistent with metastatic clear cell carcinoma.