Tae Nam Kim

Treatment Strategy for Non-Responders to PDE5 Inhibitors

Currently, phosphodiesterase type 5 (PDE5) inhibitors are the initial treatment option for erectile dysfunction. The reported efficacy of PDE5 inhibitors is about 70%, although it is significantly lower in difficult-to-treat subpopulations. Treatment failures might be due to the severity of the underlying pathophysiology, improper use of medication, unrealistic patient expectations, difficult relationship dynamics, severe performance anxiety, and other psychological problems. Physicians must address these issues to identify true treatment failures attributable to the drugs. This article discusses factors that might affect the response to PDE5 inhibitors and develops a strategy to maximize the overall efficacy of PDE5 inhibitors in initial non-responders to PDE5 inhibitors.

Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study

Introduction Although dapoxetine is the only oral pharmacologic agent approved for the treatment of premature ejaculation (PE) and is very effective, the discontinuation rate is high. Aim To assess the discontinuation rate of patients with PE and the reasons for discontinuation in real-world practice. Methods In total, 182 consecutive patients were enrolled. Type of PE, self-estimated intravaginal ejaculation latency time, and medical history were evaluated in all patients who also completed the erectile function domain of the International Index of Erectile Function (IIEF). Visits were scheduled 1, 3, 6, 12, and 24 months after initiation of therapy; treatment status and the reasons for discontinuation in those who did discontinue were checked. The relations of discontinuation rates were compared with various parameters and the time to discontinuation after treatment commencement. Results Of all patients, 9.9% continued treatment to 2 years. The cumulative discontinuation rates at 1, 3, 6, 12, and 24 months were 26.4%, 61.6%, 79.1%, 87.3%, and 90.1%, respectively. Moreover, 79.1% of all patients discontinued treatment within 6 months. After 12 months, the discontinuation rate decreased sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE was not curable and that dapoxetine was required every time sexual intercourse was contemplated (25%), side effects (11.6%), perceived poor efficacy (9.8%), a search for other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs lifelong PE), with intravaginal ejaculation latency time longer than 2 minutes before treatment, on phosphodiesterase type 5 inhibitors, and with IIEF erectile function scores lower than 26 tended to discontinue early and thus exhibited high dropout rates. Conclusion The treatment discontinuation rate of dapoxetine was very high. The main reasons for discontinuation were the cost and disappointment that treatment was required every time adequate sexual function was required. Park HJ, Park NC, Kim TN, et al. Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study. Sex Med 2017;5:e99–e105.

Penile Traumatic Neuroma: A Late Complication of Penile Dorsal Neurotomy to Treat Premature Ejaculation

Introduction Traumatic neuroma is a reactive process caused by the regeneration of an injured nerve that usually forms a nodular proliferation of small nerve bundles. Penile traumatic neuroma is rare; only a few cases related to circumcision have been reported. Aim To report on a case of traumatic neuroma in the penis after selective dorsal neurotomy (SDN) to treat premature ejaculation. Methods The penile traumatic neuroma was successfully removed by excision and confirmed by histopathology. Results A 55-year-old man who had had several painless, slow-growing nodules on his penis for 2 years presented to our hospital. He had no history of genital trauma, urinary tract infection, or penile surgery, except SDN to treat premature ejaculation. The nodules were excised and the final diagnosis was traumatic neuroma. No recurrence has been detected during 1 year of follow-up. Conclusion The main complications of SDN are recurrence of premature ejaculation, pain or paresthesia on the glans penis, and erectile dysfunction. However, no traumatic neuroma has been reported as a complication. We report that a traumatic neuroma can occur after SDN.

Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers

To determine whether bilateral seminal vesicle invasion is associated with worse biochemical recurrence‐free survival than unilateral seminal vesicle invasion after radical prostatectomy.

Penile Glans Necrosis Developing after Internal Pudendal Arterial Embolization: A Case Report

Penile glans ischemia or necrosis developing after internal pudendal arterial embolization is very rare; no relevantreport has yet appeared. A 53-year-old male who visited our emergency room because of massive urethral bleedingwas diagnosed with an internal pudendal artery-urethral fistula; he underwent selective embolization of the internalpudendal artery. However, unexpected penile glans ischemic necrosis developed after embolization. We successfullytreated the patients with intravenous infusion of alprostadil, oral pentoxifylline and tadalafil.

Clinicopathologic Characteristics and Treatment Outcomes of Penile Cancer

Purpose The aim of this study was to assess the clinicopathologic characteristics of penile cancer, including patterns of therapy, oncologic results, and survival. Materials and Methods Between January 2005 and July 2015, 71 patients at 6 institutions who had undergone penectomy or penile biopsy were enrolled. Their medical records were reviewed to identify the mode of therapy, pathology reports, and cancer-specific survival (CSS) rate. Results Clinicopathologic and outcome information was available for 52 male patients (mean age, 64.3 years; mean follow-up, 61.4 months). At presentation, 17 patients were node-positive, and 4 had metastatic disease. Management was partial penectomy in 34 patients, total penectomy in 12 patients, and chemotherapy or radiotherapy in 6 patients. The pathology reports were squamous cell carcinoma in 50 patients and other types of carcinoma in the remaining 2 patients. Kaplan-Meier survival analysis showed a 5-year CSS rate of 84.0%. In univariate and multivariate analyses, the American Joint Committee on Cancer (AJCC) stage and pathologic grade were associated with survival. Conclusions Partial penectomy was the most common treatment of penile lesions. The oncologic outcomes were good, with a 5-year CSS of 84.0%. The AJCC stage and pathologic grade were independent prognostic factors for survival.

MP09-05 DOES CONCOMITANT TESTOSTERONE REPLACEMENT IMPROVE THE RESPONSE OF TADALAFIL 5 MG ONCE DAILY IN MEN WITH LOWER URINARY TRACT SYMPTOMS?

non inferiority randomized clinical study. Two sided noninferiority test using one-sided of a levle with 95% power assuming an equivalence margin of 0.5 for the IPSS and 0.8 for the peak flow, requiring 300 patients. The sample size was set at 330 (assuming a 10% dropouts) using one-sided of a level of 0.05 with 95% power. The co-primary endpoints of the study were the changes of IPSS and peak flow after 6 months. The secondary endpoint was the reduction of post-void residual (PVR). One tablet of Profluss1 consisted of 320 mg of supercritical CO2 lipidic extract SeR containing 85% of fatty acids sterols, selenium (50mcg) and lycopene (5mg) and distributed by Konpharma Srl (Rome, Italy). The Treatment-related adverse events (TEAEs) were collected. RESULTS: A total of 303 patients concluded the study protocol, 199 in the group A and 104 in the group B. All patients were balanced at baseline and any statistical difference was found when considering age, IPSS, peak flow, prostate volume, PVR and IIEF-5. After 6 months of therapy we observed a decrease in IPSS of -3 (95%CI -4;-3) and of -3 (95%CI -3;-2) in the group A and B respectively (non inferiority test p1⁄40.04), an increase in peak flow of 2 (95%CI 2;4) and of 2 (95% 1;3) in the group A and B respectively (non inferiority test p<0.01) and a decrease in PVR of -12 (95%CI -32;-2) and of -10 (95% -25; -5) in the group A and B respectively (non inferiority test p1⁄40.04). We observed a total of 25 (0.08%) of TEAEs, 5 in the group A (0.02%) and 20 in the group B (0.19%)(p<0.05). CONCLUSIONS: In this phase IV randomized, non-inferiority clinical trial, we demonstrated that treatment with SeR-Se-Ly was not inferior to Tadalafil 5 mg after 6 months in patients affected by LUTS/BPE and in terms of clinical efficacy and furthermore it showed less TEAEs.

MP73-14 CAPABILITY OF ELECTRICAL IMPEDANCE SPECTROSCOPY SENSOR ON A NEEDLE AS A NOVEL TOOL TO ESTIMATE MALIGNANT RENAL TUMOR MARGIN: EX-VIVO DEMARCATION OF TUMOR AND SURGICAL MARGIN

INTRODUCTION AND OBJECTIVES: The combination of the human immunodeficiency virus (HIV) protease inhibitors lopinavir and ritonavir has been a standard regimen used to treat HIV infection. Ritonavir acts as a chemical booster to enhance lopinavir’s activity. Lopinavir has recently been shown to act against cancer by inducing endoplasmic reticulum (ER) stress, and we thought that the combination would kill renal cancer cells by inducing robust ER stress. METHODS: The viability and clonogenicity of renal cancer cells (769-P, 786-O, Caki-2) treated with clinically feasible concentrations of lopinavir (10-40 mM) and/or ritonavir (5-10 mM) were assessed by MTS assay and colony formation assay. Apoptosis was evaluated by annexin-V assay. Cell cycle analysis was done using flow cytometry. Induction of ER stress and the expression of cell-cycle regulators, apoptosis-associated proteins, NOXA, Akt, BCL-2, and survivin were evaluated by western blot analysis. Drug synergism was assessed by the Chou-Talalay method. RESULTS: Lopinavir in combination with ritonavir inhibited renal cancer growth synergistically (combination index <1). The combination also inhibited clonogenic survival of cancer cells significantly (p <0.05). It perturbed the cell cycle by inhibiting the expression of cyclin D1 and cyclin-dependent kinase 4, increasing the cells in the sub-G1 fraction. The combination caused apoptosis synergistically: 10-20 mM lopinavir increased the number of annexin-V positive cells and the expression of cleaved poly(ADP-ribose) polymerase slightly but in combination with 10 mM ritonavir increased both drastically. As expected, the combination induced ER stress evidenced by the increased expression of the ER stress markers glucose-regulated protein 78 and endoplasmic reticulum resident protein 44. Furthermore, increased expression of NOXA confirmed that the combination-induced apoptosis was a result of ER stress. We also found that the combination decreased the expression of the antiapoptotic proteins BCL-2 and survivin by inhibiting the Akt signaling pathway. CONCLUSIONS: The combination of lopinavir and ritonavir induces ER stress and causes renal cancer apoptosis synergistically. Inhibition of the Akt pathway is another important mechanism of its action.

MP91-15 CAN CONCOMITANT DUTASTERIDE REDUCE THE EFFECT OF TESTOSTERONE REPLACEMENT THERAPY IN MEN WITH LATE-ONSET HYPOGONADISM? A 24-WEEK, RANDOMIZED, PARALLEL STUDY

INTRODUCTION AND OBJECTIVES: Controversy still exists regarding the efficacy of testosterone replacement therapy (TRT) for symptomatic hypogonadism. A recent multi-site randomized controlled study of men undergoing TRT failed to show an improvement in several symptom domains, among them is vitality. We hypothesized that differences in androgen sensitivity would obscure symptom improvement for a subset of individuals. Androgen sensitivity is related to the number of trinucleotide (CAG) repeats on exon 1 of the androgen receptor (AR) gene. We sought to examine the regulatory role of this genetic polymorphism on the relationship between testosterone and vitality in middle-aged men METHODS: Participants were men from the Vietnam Era Twin Study of Aging (N1⁄4696). Average waking, salivary free-testosterone level was acquired on 3 non-consecutive days. The AR gene CAG repeat length was derived using a combination of PCR fragment analysis and Sanger sequencing. Vitality was evaluated with the SF-36Vitality scale. We tested the interaction between low testosterone (low-T) and CAG repeat length while controlling for age, ethnicity, smoking status, BMI, heart disease, hypertension, diabetes, and the correlated nature of the twin data. Low-T was defined as being 1⁄4 1 SD below the mean for the 3-day average value RESULTS: Mean age of the participants was 56.4 years (SD 1⁄4 2.6) with average CAG repeat length of 22 (range: 8-37). We observed a significant interaction effect between low-T and AR CAG repeat length. In men with a short variant of the AR gene (< 21 repeats), representing greater androgen sensitivity, there was a significant effect of low-T on vitality (p < 0.01). Men with low-T and the short AR gene were on average 10 points lower on the Vitality scale relative to men with normal T and the same genotype. This effect was not observed in men with either medium (21-23 repeats) or long (1⁄4 24 repeats) variants of the AR gene. Without the interaction effect in the model, neither low-T nor the AR gene had a significant effect on vitality CONCLUSIONS: These results demonstrate that the relationship between low-T and vitality is regulated, in part, by variation in the AR gene. The effect of low-T on vitality was observed only when the genetically-determined sensitivity of the androgen receptor is at its greatest. Variations in the AR gene, bestowing differential androgen sensitivity, are potential targets for personalized therapy of hypogonadism. Future studies are needed to determine how genetic information can be used to improve the efficacy of TRT

Clinical outcomes of the sequential use of pazopanib followed by everolimus for the treatment of metastatic renal cell carcinoma: A multicentre study in Korea

INTRODUCTION The aim of this study was to investigate the real-world clinical outcomes of first-line pazopanib and second-line everolimus in Korean patients with metastatic renal cell carcinoma (mRCC). METHODS Data of patients who had mRCC with clear-cell component between 2001 and 2015 at multiple institutions were collected retrospectively. To be included in the analysis, patients had to meet the following criteria: age ≥18 years; received first-line targeted therapy with pazopanib; and received second-line targeted therapy with everolimus. The primary outcomes included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). RESULT A total of 36 patients were included in the analysis. The median followup period was 33.5 months (range 17-49.5). The median PFS was eight months (95% confidence interval [CI] 6.4-9.6) after treatment with pazopanib and three months (95% CI 1.9-4.1) with everolimus. The median OS was 27 months (95% CI 16.6-37.4). The median treatment duration was seven months (range 4.3-10.8) after treatment with pazopanib and 3.5 months (range 3-4) with everolimus. Multivariate analysis revealed that the Heng risk criteria were independently associated with OS (p<0.001). Almost every patient experienced some form of AE, the majority of which were mostly mild or moderate in severity. The most common AEs were diarrhea (50%), hypertension (44.4%), and fatigue (41.7%) after treatment with pazopanib, and anemia (47.2%), stomatitis (41.7%), and fatigue (38.9%) with everolimus. CONCLUSIONS The outcomes for the patients treated with pazopanib followed by everolimus in Korea as observed by us were consistent with those reported by previous studies. The Heng risk criteria were significantly associated with the prognosis of patients with mRCC. AEs were mainly mild to moderate and readily managed.