Seol Ho Choo

Role of multiparametric 3.0‐Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance

To evaluate predictors of more aggressive disease and the role of multiparametric 3.0‐T magnetic resonance imaging (MRI) in selecting patients with prostate cancer for active surveillance (AS).

Small tumour size is associated with new-onset chronic kidney disease after radical nephrectomy in patients with renal cell carcinoma

BACKGROUND To investigate the impact of tumour size on postoperative glomerular filtration rate (GFR) in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). METHODS We retrospectively identified 1371 patients who underwent RN between 1995 and 2010. Serum creatinine levels were measured preoperatively, within 7days of RN, at 3months, 1 and 3years. We divided patients into three groups based on tumour size: A: ⩽4cm, B: 4-7cm, C: >7cm. The changes in GFR were compared and multivariate logistic regression was used to analyse the predictive value of tumour size for new-onset chronic kidney disease (CKD, GFR<60mL/min/1.73m(2)). RESULTS The preoperative GFR was significantly different among the three groups (A: 83.0, B: 82.0, C: 79.4ml/min/1.73m(2), P=0.040). The decrease in GFR from preoperative to within 7days was greater in group A than in groups B and C (28.2 versus 24.2 versus 18.5ml/min/1.73m(2), P<0.001). The GFR at 1year postoperative was lower in group A than in group C (58.4 versus 61.5ml/min/1.73m(2), P=0.009), in contrast to preoperative GFR. The incidence of GFR decrease >30% was higher in Group A than in Groups B and C at 1year (52.4% versus 41.5% versus 33.7%, P<0.001). On multivariate analysis Groups A and B had a 2.37-fold (95% confidence interval (CI) 1.56-3.60, P<0.001) and 2.24-fold (95% CI 1.49-3.38, P<0.001) higher risk of new-onset CKD compared with Group C. CONCLUSIONS Small tumour size is associated with CKD after RN. Partial nephrectomy should be considered in patients with tumour size 7cm or less.

Pathological upgrading and upstaging of patients eligible for active surveillance according to currently used protocols

To investigate the ability of six contemporary active surveillance protocols to appropriately select active surveillance candidates among Korean men who underwent radical prostatectomy.

Effect of the Novel BKCa Channel Opener LDD175 on the Modulation of Corporal Smooth Muscle Tone

INTRODUCTION The BKCa channel has been reported to play an important role in erectile function. Recently, novel BKCa channel activator, LDD175, was introduced. AIM This study aims to investigate whether LDD175 relaxes corporal smooth muscle (CSM) via BKCa channel activation. METHODS After isolation of CSM strip from a male rabbit model, contraction studies using organ bath was performed. Isolating human tissue and cell cultures, electrophysiological studies were done via whole-cell patch-clamp recording. MAIN OUTCOME MEASURES Vasodilatory effects of LDD175 were evaluated by cumulative addition ranging from 10(-7) to 10(-4) M in corpus cavernosal strips after precontraction with 10(-5) M phenylephrine via organ bath system. Using cultured human CSM cells, patch-clamp recording was performed. Erectile function was measured by in vivo rat cavernous nerve stimulation. RESULTS LDD175 caused an endothelium-independent relaxation of corporal tissues, and this effect was abolished by pretreatment with iberiotoxin. The relaxation effect of 10(-4) M LDD175 was greater than that of 10(-6) M udenafil (54.0 ± 3.1% vs. 34.5 ± 3.9%, P < 0.05); 10(-5) M LDD175 with 10(-6) M udenafil caused a greater relaxation effect on strips than 10(-5) M LDD175 or 10(-6) M udenafil alone (50.7%, 34.1%, vs. 20.7%, respectively, P < 0.001). In patch-clamp recordings, LDD175 increased K(+) currents in a dose-dependent manner, and washout of LDD175 or the addition of iberiotoxin fully reversed the increase. Intravenous LDD175 improved erectile function measured by area under the curve (AUC) of the intracavernosal pressure (ICP)/arterial blood pressure (ABP) ratio (1,612.1 ± 135.6 vs. 1,093.7 ± 123.1, P < 0.05). There was no difference between 10 mg/kg LDD175 and 1 mg/kg udenafil regarding maximal ICP, maximal ICP/ABP ratio, and the AUC of the ICP/ABP ratio (P > 0.05). CONCLUSIONS LDD175 leads to an endothelium-independent relaxation of erectile tissue, primarily through the opening of BKCa channels. The results suggest that LDD175 might be a new candidate treatment for erectile dysfunction.

Effects of Schisandra chinensis extract on the relaxation of isolated human prostate tissue and smooth muscle cell

ETHNOPHARMACOLOGICAL RELEVANCE Schisandra chinensis has been commonly used as a traditional herbal medicine to treat various diseases including body weakness, dysentery, impotence, enuresis and frequent urination in many countries including Korea, China and Russia. Benign prostate hyperplasia is a common disease for the elderly men and it induces lower urinary tract symptoms which hinder general activity and quality of life. We evaluated the therapeutic potential of Schisandra chinensis extract (SCE) in benign prostate hyperplasia using human prostate tissue. MATERIALS AND METHODS Schisandra chinensis fruit was collected and extracted with ethanol. Human prostate tissues were obtained from 14 prostate cancer patients. Macroscopically normal tissue was excised from the transition zone and the periurethral regions. Isolated prostate tissue strips were mounted in an organ-bath system, and the relaxation effect of SCE was evaluated by cumulative addition to prostate strips pre-contracted with 10(-5)M norepinephrine. The effect of tamsulosin was compared, and the additive effect was evaluated. Electrophysiological studies using cultured human prostate smooth muscle cells (HPrSMC) were conducted. RESULTS Cumulative dosing of SCE induced concentration-dependent relaxation in contracted prostate tissue (n=18, P<0.05). Simultaneous dosing of SCE and tamsulosin showed an additive relaxation effect. The relaxation effect of SCE was abolished by inhibition of K+ channels by pre-treatment with tetraethylammonium. In HPrSMC, extracellular application of 100 μg/mL SCE significantly increased outward currents, and this effect was significantly attenuated by treatment with 100 nM Iberiotoxin. CONCLUSIONS SCE showed a dose dependent relaxation effect on human prostate tissue as well as an additive effect with tamsulosin. The relaxation effects of SCE on HPrSMC were, in part, due to the activation of K+ channels.

Incidence and management of extended-spectrum beta-lactamase and quinolone-resistant Escherichia coli infections after prostate biopsy.

OBJECTIVE To provide an overview of the incidence, bacteriologic characteristics, and antimicrobial resistance in acute prostatitis after transrectal ultrasonography (TRUS)-guided prostate biopsy. MATERIALS AND METHODS We reviewed the medical records of 9568 patients who underwent TRUS-guided biopsy between March 1995 and May 2013. These patients received oral quinolone and/or cephalosporin and intramuscular aminoglycoside as antibiotic prophylaxis. In patients with acute prostatitis, blood and urine cultures were obtained on hospital admission. The incidences of acute prostatitis and antimicrobial resistance were examined according to time period. RESULTS A total of 11,345 cases of TRUS-guided biopsy were performed for 9568 patients. Acute prostatitis developed in 103 patients (0.91%). In 63 patients, the causative organism was isolated from blood and/or urine culture. The most frequent etiologic organism was Escherichia coli, which was present in 47 of 49 patients (95.9%) in blood and from 39 of 41 patients (95.1%) in urine. Extended-spectrum beta-lactamase (ESBL)-producing E coli were detected continuously since 2008 and found in 10 patients (21.3%) in blood and 8 patients (20.5%) in urine. Forty-four patients (93.6%) in blood and 36 patients (92.3%) in urine of the positive cultures and all cases with ESBL-producing E coli infection showed resistance to quinolone. ESBL-producing E coli were susceptible to imipenem, amikacin, and cefoxitin. CONCLUSION In the treatment of acute prostatitis after TRUS-guided biopsy, quinolone is not an effective antimicrobial of choice. We should take into account antimicrobial-resistant patterns because of the high prevalence of quinolone resistance and emergence of an ESBL-producing strain.

Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes

In recent reports, an association between altered TRPC channel function and the development of various diabetic complications has drawn the attention of many investigators. The aim of this study was to investigate the expression of TRPC4 channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the association between erectile dysfunction (ED) and altered TRPC4 channel function. The expression of TRPC4 in the penile tissue of human, normal and diabetic rat was investigated using RT‐PCR, western blotting and immunohistochemistry (IHC). In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was conducted. In vivo pelvic nerve stimulation was performed to measure erectile function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM tissues was confirmed by RT‐PCR, western blot and IHC. In the diabetic rat, the expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly increased compared to control rats (p < 0.05). The change in TRPC4 expression in the diabetic rats was higher than those of the other TRPC subunits (p < 0.05). The IHC showed that only TRPC4 expression had a higher intensity in the diabetes compared to normal rats (p < 0.05). Gene transfection with TRPC4DN into the diabetic rats restored erectile function to levels similar to that of normal controls. Gene expression of TRPC4DN in CSM tissue was confirmed by RT‐PCR 2 weeks after transfection. This study demonstrated that TRPC4 channel expression increased in the penile CSM cells of diabetic rats. The down‐regulation of TRPC4 with DN form restored erectile function in the diabetic rats. The alteration of TRPC4 channel is one of pathophysiology of ED and could be a target for drug development for ED.

Effects of ethanol on the tonicity of corporal tissue and the intracellular Ca2+ concentration of human corporal smooth muscle cells

Heavy alcohol consumption is associated with an increased risk of erectile dysfunction (ED); however, the acute effects of ethanol (EtOH) on penile tissue are not fully understood. We sought to investigate the effects of EtOH on corporal tissue tonicity, as well as the intracellular Ca(2+) concentration ([Ca(2+)](i)) and potassium channel activity of corporal smooth muscle. Strips of corpus cavernosum (CC) from rabbits were mounted in organ baths for isometric tension studies. Electrical field stimulation (EFS) was applied to strips precontracted with 10 μmol L(-1) phenylephrine as a control. EtOH was then added to the organ bath and incubated before EFS. The [Ca(2+)](i) levels were monitored by the ratio of fura-2 fluorescence intensities using the fura-2 loading method. Single-channel and whole-cell currents were recorded by the conventional patch-clamp technique in short-term cultured smooth muscle cells from human CC tissue. The corpus cavernosal relaxant response of EFS was decreased in proportion to the concentration of EtOH. EtOH induced a sustained increase in [Ca(2+)](i) in a dose-dependent manner, Extracellular application of EtOH significantly increased whole-cell K(+) currents in a concentration-dependent manner (P < 0.05). EtOH also increased the open probability in cell-attached patches; however, in inside-out patches, the application of EtOH to the intracellular aspect of the patches induced slight inhibition of Ca(2+)-activated potassium channel (KCa) activity. EtOH caused a dose-dependent increase in cavernosal tension by alterations to [Ca(2+)](i). Although EtOH did not affect KCa channels directly, it increased the channel activity by increasing [Ca(2+)](i). The increased corpus cavernosal tone caused by EtOH might be one of the mechanisms of ED after heavy drinking.

Comparisons of apomorphine‐induced erection and spontaneous erection in rats by telemetric assessment of intracavernosal pressure

Although there are several methods for assessing erectile function in rats, the standard methods for telemetric monitoring have not been established. Theoretically assessment of spontaneous erection (SE) seems to be a physiologic method but it needs long measuring time and additional efforts. Apomorphine‐induced erection (AIE) is one available and simple method; however, the correlation with SE has not been assessed. We compared erection profiles of AIE and SE in normal and two disease rat models using telemetric assessment of intracavernosal pressure (ICP). Seven‐week‐old male Sprague–Dawley rats were assigned to normal control, diabetes mellitus (DM) and hypercholesterolemia (HC) group. After 19 weeks a telemetric pressure sensor (C40; Data Sciences) was surgically implanted in the corpus cavernosum. One week later, ICP was recorded in freely moving rats after intraperitoneal apomorphine (100 μg/kg) injection (AIE) or during SE. Sexual events were visually identified and recorded. Only the pressure increases that occurred during sexual behavior were analyzed. We compared the erectile profiles such as duration, maximal ICP and the area under the curve (AUC, area under time × ICP curves). Two‐way anova revealed no significant effect of the measuring methods on the mean AUC (F1,43 = 2.756, p‐value = 0.104), but a significant effect of different disease models on mean AUC (two‐way anova: F2,43 = 12.929, p‐value < 0.001) was observed. The mean AUC of normal control rats was significantly higher than that of DM and HC rats (Bonferroni post hoc test: p < 0.001 and p = 0.001, respectively). ICP measurements using a telemetric device showed no significant difference in AUC between AIE and SE. AIE is easy and requires less time than SE measurements. Therefore, AIE could be a useful method to evaluate ICP in rats.

Predictive factors of unfavorable prostate cancer in patients who underwent prostatectomy but eligible for active surveillance

Purpose: To investigate the predictive factors of unfavorable prostate cancer in Korean men who underwent radical prostatectomy but eligible for active surveillance according to Epstein criteria. Methods: We retrospectively reviewed the medical records of 2,036 patients who underwent radical prostatectomy for prostate cancer between 1994 and 2011. Among these, 233 patients were eligible for active surveillance based on Epstein criteria. Unfavorable prostate cancer was defined as pathologic Gleason sum ≥7 or non–organ-confined disease. We investigated pathologic outcomes and predictive factors for unfavorable prostate cancer. Results: Of 233 cases, 91 patients (39.1%) were pathologic Gleason sum ≥7, 11 (4.7%) had extracapsular extension, and three (1.3%) had seminal vesicle invasion. Ninety-eight patients (42.1%) had unfavorable prostate cancer. When comparing clinically insignificant and significant prostate cancer, there were significant differences in mean age (P=0.007), prostate volume (P=0.021), prostate-specific antigen (PSA) density (P=0.03), maximum tumor volume in biopsy core (P<0.001), and rate of two positive cores (P=0.001). On multivariate analysis, age (P=0.015), PSA density (P=0.017) and two positive cores (P=0.001) were independent predictive factors for unfavorable prostate cancer. Conclusions: A significant proportion of patients who were candidates for active surveillance had unfavorable prostate cancer. Age, PSA density, and two positive cores were independent significant predictive factors for unfavorable prostate cancer. These factors should be considered when performing active surveillance.