Differentially Expressed mRNA in Streptozotocin-Induced Diabetic Bladder Using RNA Sequencing Analysis / 대한배뇨장애요실금학회지

Purpose@#To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. @*Methods@#An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. @*Results@#The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. @*Conclusions@#Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

Enhanced Hypoxia-Associated Genes in Impaired Contractility From Bladder Outlet Obstruction

Background@#Hypoxia damages the bladder wall and contributes to the initiation of bladder dysfunction. The change of hypoxia is not well known in impaired bladder contractility caused by long-term bladder outlet obstruction (BOO). We aimed to find out whether hypoxia of bladder tissue is present and what signaling mechanisms are involved in the decompensated bladder in BOO. @*Methods@#Twenty 6-week-old female Sprague-Dawley rats were divided into 2 groups, 10 rats each: group 1, sham operation; group 2, BOO for 8 weeks. Eight weeks after the onset of BOO, we did cystometric evaluation and processed polymerase chain reaction (PCR) array for hypoxia pathway using bladder tissues. The PCR array consists of 84 genes known to be involved in the hypoxic response, cell differentiation, and metabolism. We did quantitative PCR (qPCR) and immunohistochemical staining of bladder tissue for hypoxia. @*Results@#Eight genes were at least 2-fold upregulated and 3 genes were at least 2-fold downregulated in BOO group, compared with the sham operation group. The up-regulated genes (fold change) belonging to the hypoxia-inducible factor (HIF) 1 interactor included Cdkn2a (11.0), and the down-regulated genes belonging to HIF and co-transcription factors included Hif3a (−39.6) and Per1 (−5.1) by BOO. Genes influenced each other by means of TGFβ1, TNF, and TP53. @*Conclusion@#Hypoxia genes were increased in impaired contractility because of long-term BOO. The gene expression profiles could explain the molecular mechanisms of hypoxia in impaired contractility because of long-term BOO.

Serotonin Discharge Regulation by Additional Neurotransmitters of Rat Hippocampus Associated With the Continence Central Circuit / 대한배뇨장애요실금학회지

Purpose@#The lower urinary tract is believed to be centrally regulated with the involvement of a range of neurotransmitters. The parasympathetic excitatory input to the urinary bladder is suppressed when the serotonergic system is activated, and thereby voiding is blocked. In healthy people, continence is usually underpinned by hippocampal formation (circuit 3). In order to advance knowledge of how serotoninergic neurons and additional nerve fibers were correlated, the purpose of the present work was to research how the discharge of serotonin from hippocampal slices was affected by different neurotransmitters in rat models. @*Methods@#The adopted procedure involved administration of the central neurotransmitters acetylcholine, norepinephrine, dopamine, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), glycine, and neuropeptide Y as well as monitoring of the alterations in the discharge of [3H]5-hydroxytryptamine (5-HT). Furthermore, to determine whether the effect of the neurotransmitters was influenced by interneuron, tetrodotoxin was also employed. @*Results@#Acetylcholine (10-5M) did not alter [3H]5-HT discharge, whereas more 5-HT was discharged from the hippocampal slices of rats under stimulation by norepinephrine (10-5M) as well as dopamine (10-5M) and tetrodotoxin (10-6M) did not inhibit the discharge. By contrast, tetrodotoxin inhibited the discharge of [3H]5-HT that was exacerbated by NMDA (10-4M). Meanwhile, compared to control, GABA (10-5M), glycine (10-5M), or neuropeptide Y (10-6M) did not alter the [³H]5-HT discharge. @*Conclusions@#From the research findings, it can be concluded that 5-HT discharge from rat hippocampus is enhanced by norepinephrine and dopamine through direct effect on the 5-HT neuronal terminal. By contrast, 5-HT discharge is intensified by NMDA by activating interneurons.

Liberation of Serotonin Is Not Unaffected by Acetylcholine in Rat Hippocampus / 대한배뇨장애요실금학회지

Purpose@#Raised cerebral titers of acetylcholine have notable links with storage symptomatology related to lower urinary tract symptoms. The hippocampus contributes to the normal control of continence in the majority of instances (circuit 3). Owing to synaptic connections with other nerve cells, acetylcholine affects the micturition pathway via the liberation of additional cerebral neurotransmitters. Despite the fact that cerebral serotonin is a key inhibitor of reflex bladder muscle contractions, the influence of acetylcholine on its liberation is poorly delineated. The current research was conducted in order to explore the role of acetylcholine in serotonin liberation from sections of rat hippocampus in order to improve the comprehension of the relationship between cholinergic and serotonergic neurons. @*Methods@#Hippocampal sections from 6 mature male Sprague-Dawley rats were equilibrated over a 30-minute period in standard incubation medium so as to facilitate [3H]5-hydroxytryptamine (5-HT) uptake. The cerebral neurotransmitter, acetylcholine, was applied to the sections. Aliquots of drained medium solution were utilized in order to quantify the radioactivity associated with [3H]5-HT liberation; any alterations in this parameter were noted. @*Results@#When judged against the controls, [3H]5-HT liberation from the hippocampal sections remained unaltered following the administration of acetylcholine, implying that this agent has no inhibitory action on this process. @*Conclusions@#Serotonin liberation from murine hippocampal sections is unaffected by acetylcholine. It is postulated that the bladder micturition reflex responds to acetylcholine through its immediate cholinergic activity rather than by its influence on serotonin release. These pathways are a promising target for the design of de novo therapeutic agents.

Time Trends for Prostate Cancer Incidence from 2003 to 2013 in South Korea: An Age-Period-Cohort Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis. @*Materials and Methods@#Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence. @*Results@#Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort. @*Conclusion@#PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

Trends in Prostate Cancer Prevalence and Radical Prostatectomy Rate according to Age Structural Changes in South Korea between 2005 and 2015

PURPOSE: Radical prostatectomy (RP) is one of main treatments for prostate cancer (Pca). The prevalence of Pca has been decreasing in recent reports. However, no study has reported trends in Pca prevalence or RP rate according to age structural changes. The objective of this study was to investigate trends in Pca prevalence and frequency of RP according to age structural change. MATERIALS AND METHODS: We evaluated trends in Pca prevalence and RP rate using National Health Insurance Data from 2005 to 2015. Relationships for Pca prevalence and RP rate with age structural change were also determined. Primary outcomes included trends in Pca prevalence and RP rates according to age groups, comparing those before and after 2011. RESULTS: Pca prevalence tended to increase before 2011 and decreased after 2011 in persons in the 60-years age group. RP rate increased pattern before 2011 and decreased after 2011 in age groups of 50s, 60s, and over 70s. Pca prevalence and age structural change showed a significantly positive relationship in all age groups, except for the age group under 40 years. RP rate and age structural change also showed a significantly positive relationship in all age groups. CONCLUSION: Age structural change can affect the decreasing trend in Pca prevalence and RP rate in South Korea. Future studies are needed to validate this result.

Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study

PURPOSE: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.

Current status of stem cell therapy in urology

No abstract available.

Geographic Distribution of Urologists in Korea, 2007 to 2012

The adequacy of the urologist work force in Korea has never been investigated. This study investigated the geographic distribution of urologists in Korea. County level data from the National Health Insurance Service and National Statistical Office was analyzed in this ecological study. Urologist density was defined by the number of urologists per 100,000 individuals. National patterns of urologist density were mapped graphically at the county level using GIS software. To control the time sequence, regression analysis with fitted line plot was conducted. The difference of distribution of urologist density was analyzed by ANCOVA. Urologists density showed an uneven distribution according to county characteristics (metropolitan cities vs. nonmetropolitan cities vs. rural areas; mean square=102.329, P<0.001) and also according to year (mean square=9.747, P=0.048). Regression analysis between metropolitan and non-metropolitan cities showed significant difference in the change of urologists per year (P=0.019). Metropolitan cities vs. rural areas and non-metropolitan cities vs. rural areas showed no differences. Among the factors, the presence of training hospitals was the affecting factor for the uneven distribution of urologist density (P<0.001).Uneven distribution of urologists in Korea likely originated from the relatively low urologist density in rural areas. However, considering the time sequencing data from 2007 to 2012, there was a difference between the increase of urologist density in metropolitan and non-metropolitan cities.

Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1x10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.

Treatment of Bladder Dysfunction Using Stem Cell or Tissue Engineering Technique

Tissue engineering and stem cell transplantation are two important options that may help overcome limitations in the current treatment strategy for bladder dysfunction. Stem cell therapy holds great promise for treating pathophysiology, as well as for urological tissue engineering and regeneration. To date, stem cell therapy in urology has mainly focused on oncology and erectile dysfunction. The therapeutic potency of stem cells (SCs) was originally thought to derive from their ability to differentiate into various cell types including smooth muscle. The main mechanisms of SCs in reconstituting or restoring bladder function are migration, differentiation, and paracrine effects. Nowadays, paracrine effects of stem cells are thought to be more prominent because of their stimulating effects on stem cells and adjacent cells. Studies of stem cell therapy for bladder dysfunction have been limited to experimental models and have been less focused on tissue engineering for bladder regeneration. Bladder outlet obstruction is a representative model. Adipose-derived stem cells, bone marrow stem cells (BMSCs), and skeletal muscle-derived stem cells or muscle precursor cells are used for transplantation to treat bladder dysfunction. The aim of this study is to review stem cell therapy and updated tissue regeneration as treatments for bladder dysfunction and to provide the current status of stem cell therapy and tissue engineering for bladder dysfunction including its mechanisms and limitations.

Homogeneity Among the Korean International Prostate Symptom Score Questionnaires Used in Real Practice

PURPOSE: We analyzed whether any problems existed in terms of the homogeneity of the Korean International Prostate Symptom Score (IPSS) questionnaire used in real practice. MATERIALS AND METHODS: Between July 2012 and August 2012, 48 Korean IPSS questionnaires used in real practice were collected. All the items on the questionnaire, including the quality of life (QoL) questions, were compared and we then determined the homogeneity of each question in comparison with the originally validated Korean version of the IPSS from 1996. RESULTS: Only 5 of 48 sources (10.4%) of the Korean IPSS totally corresponded with the original Korean version of the IPSS questionnaire. The consistency rate with the originally validated version was generally low for the answer choice items for each question, ranging from 16.6% for "less than half the time" to 35.4% for "almost always," with the exception of the item "not at all" (100.0%). The consistency rate was 60.4% for question 3 (intermittency) and 18.8% for question 6 (straining). No homogeneity was found in any of the QoL-related questions. The average consistency rate with the originally validated version was 42.2% and ranged from 22.9% for "unhappy" to the highest rate of 95.8% for "mostly satisfied." CONCLUSIONS: Compared with the originally validated Korean version of the IPSS, various Korean IPSS questionnaires used in real practice had significant problems in terms of homogeneity for both the questions and the answer choice items. Efforts are needed to ensure the uniform use of the validated Korean version of the IPSS questionnaire.

Ectopic Prostate Tissue at the Bladder Dome Presenting as a Bladder Tumor

The presence of ectopic prostate tissue in the bladder is common, but the involvement of the bladder dome has rarely been reported. This case report describes a 72-year-old man who presented with gross painless hematuria. Cystoscopy revealed a smooth sessile mass at the dome region of the bladder. A complete transurethral resection of the mass was performed. Histopathological examination of the mass revealed the presence of benign ectopic prostatic tissue.

Metastasis of Renal Cell Carcinoma to the Bladder

Renal cell carcinoma is an uncommon source of bladder metastases. Here we report a case of renal cell carcinoma that metastasized to the bladder. A 73-year-old woman complained of gross hematuria. Abdominopelvic computerized tomography showed a bladder mass and a heterogenous enhancing mass in the lower pole of the left kidney with left vein thrombosis. The pathological analysis of the resected bladder specimen revealed metastatic renal cell carcinoma of the clear cell type.

Strong Impact of Nocturia on Sleep Quality in Patients with Lower Urinary Tract Symptoms

PURPOSE: Nocturia is a bothersome symptom that impacts sleep quality in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). This study was performed to evaluate the impact of nocturia on sleep quality. MATERIALS AND METHODS: A total of 58 male patients with LUTS/BPH were enrolled. LUTS/BPH patients without nocturia were included in the control group. The inclusion criteria were eight or more points on the International Prostate System Score (IPSS) including more than one episode of nocturia and a prostate volume larger than 20 ml. IPSS, prostate volume, uroflowmetry, and the Pittsburgh Sleep Quality Index (PSQI) from each patient were recorded. RESULTS: Patients with nocturia showed a higher mean global PSQI (8.5+/-0.4) than patients without nocturia (4.82+/-0.4) (p<0.01). Patients with nocturia showed a higher percentage of severe sleep disorders (74.1%) than patients without nocturia (35.3%) (p<0.01). The regression coefficient between the number of episodes of nocturia and mean global PSQI was 0.42 (p<0.01). CONCLUSIONS: Patients with nocturia showed poor sleep quality, and this was related to the number of episodes of nocturia. This suggests that nocturia has a strong impact on sleep quality in patients with LUTS/BPH.

A Case of Tuberculous Prostatitis with Abscess

We present a case of acute prostatitis with abscess. The patient had undergone intravesical bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer. A prostate biopsy demonstrated tuberculous prostatitis with abscess. This case illustrates that when bladder cancer is treated with BCG, a tuberculous prostate abscess can develop.

Skeletal Muscle Metastases from Urothelial Cell Carcinoma

Hematogenous metastasis to skeletal muscle from urothelial carcinoma is extremely rare and metastatic disease to skeletal muscle tends to be found in people with advanced-stage neoplasm. We report in this paper a case of left sartorius muscle metastasis from urothelial cell carcinoma. A left nephroureterectomy with bladder cuff excision was performed and revealed a high-grade papillary transitional cell carcinoma (TCC) of the pelvis. And 6 month later, recurrent bladder cancer was found regular cystoscopy and then treated with transurethral resection of the bladder. After 6 times resection of bladder, an invasion into the bladder muscle layer was found. We recommended additional radical cystectomy to prevent the disease from advancing. However, the patient refused additional surgery. 6 month later, the patient complained of left thigh pain, so ultrasonography-guided biopsy of the nodular mass lesion in the left sartorius muscle was performed. The pathological analysis of the biopsy specimen revealed poorly differentiated metastatic urothelial carcinoma.

Category Migration of Renal Cystic Masses with Use of Gadolinium-Enhanced Magnetic Resonance Imaging

The Bosniak renal cyst classification has been accepted by urologists and radiologists as a way of diagnosing cystic renal masses and determining the management approach. We report two cases of a renal cystic mass that showed a category change from category II on the basis of enhanced computed tomography to category IV after further gadolinium-enhanced magnetic resonance imaging. In both cases, the cysts were later confirmed as kidney cancer by pathology.

Preoperative Clinical Factors for Diagnosis of Incidental Prostate Cancer in the Era of Tissue-Ablative Surgery for Benign Prostatic Hyperplasia: A Korean Multi-Center Review

PURPOSE: To identify potential predictive factors of incidental prostate cancer (IPca) in patients considering tissue-ablation treatment for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From the 11 centers, 1,613 men who underwent transurethral resection of the prostate (TURP) or open prostatectomy were included. Before surgery, prostate biopsy was performed in all patients with prostate-specific antigen (PSA) > or =4.0 ng/ml or with abnormal digital rectal examination (DRE) findings. The patients with prostate cancer preoperatively or with PSA >20 ng/ml were excluded. As predictive factors of IPca, age, body mass index, PSA, DRE, and transrectal ultrasonography (TRUS) findings, including total prostate volume (TPV), transition zone volume (TZV), and the presence of hypoechoic lesions, were reviewed. PSA density (PSAD) and PSAD in the transition zone (PSAD-TZV) were calculated. RESULTS: IPca was diagnosed in 78 patients (4.8%). DRE findings, PSA, and TZV were independent predictive factors in the multivariate analysis. In the receiver operating characteristic curve analysis of PSA, PSAD, and PSAD-TZV, the area under the curve (AUC) was the largest for PSAD-TZV (AUC, 0.685). CONCLUSIONS: IPca was detected in 4.8% of the population studied. In addition to DRE findings, the combination of TZV and PSA can be useful predictive factors of IPca in patients considering tissue-ablation treatment as well as TURP.

Myotonic Dystrophy Type 1 Presenting as Male Infertility

Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia and azoospermia, and increased follicle-stimulating hormone levels. We describe a rare case of DM1 presenting as infertility in a 29-year-old man.