1 Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi, Taiwan, ROC
2 Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial Hospital, Chia-Yi, Taiwan, ROC
3 Department of Nursing, Chang Gung University of Science and Technology, Chia-Yi, Taiwan, ROC
BACKGROUND: The mechanism of non-bacterial chronic prostatitis (CP / CPPS) has long been investigated but remains unclear. Under the hypothesis that abnormal response of innate immunity may be a cause of CP/CPPS, this study evaluated inflammasome, as part of innate immunity, and its effects on persist inflammation and CP/CPPS.
METHODS: Carrageenan was used to induce CP/CPPS in a rat animal model. After confirming tactile hyper-algesia in the rats, their local prostate inflammation status, and inflammasome expression were determined. The amount of inflammasome and its downstream protein was checked, along with prostate localization. Chlorogenic acid (CHA), an active ingredient of Chinese herbal remedy for CP/CPPS treatment, was used as treatment.
RESULTS: The rats had CP/CPPS once scrotal static tactile allodynia developed and CHA treatment relieved the scrotal hypersensitivity. Downstream inflammasome proteins like IL1ß and caspase 1 increased within the prostate and decreased with CHA treatment. Inflammasome, NALP1 but not NALP3, was significantly increased in the prostate glandular endothelial cells. Treatment with CHA also changed the distribution pattern of NALPI in the prostate.
CONCLUSIONS: There is a close relationship between activation of inflammasome and patho-physiologic changes of CP/CPSS in rats. Increased inflammasome may be a possible mechanism of CP/CPPS and clinically active regimen may inhibit the inflammasome-related pathway. This provides a new therapeutic rationale and
友華論文獎臨床組 第一名
Diurnal Temperature Change is Associated with Testicular Torsion – A Nationwide, Population Based Study in Taiwan
Jeng-Sheng Chen, Yung-Ming Lin, Wen-Horng Yang Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Purpose: We investigated the association between climatic variables and testicular torsion in Taiwanese males.
Materials and Methods: Using the Taiwan Longitudinal Health Insurance Database, we reviewed the files of patients who were diagnosed with testicular torsion and underwent orchiectomy or orchiopexy between January 1996 and December 2008. Children younger than 1 year were excluded from the study. Climatic data were provided by the Taiwan Central Weather Bureau and included ambient temperature, relative humidity, diurnal temperature change and barometric pressure. Patients with acute appendicitis who underwent appendectomy were chosen as the control group. Climatic variables in relation to testicular torsion were analyzed using the Mann-Whitney U test and chi-square test, and seasonal climatic variations using the Kruskal-Wallis H test. Relative risk was calculated to compare the incidence of testicular torsion for diurnal temperature changes.
Results: A total of 65 patients with a mean age of 16.2 years presented with testicular torsion and were treated surgically. Four children younger than 1 year were excluded, and thus the study population consisted of 61 patients. The estimated incidence of testicular torsion was 2.58 per 100,000 person-years. There were no special climatic conditions on days of admission. However, 73.7% of the patients had testicular torsion when the diurnal temperature change was 6C or greater. Compared to the torsion rate for diurnal temperature changes less than 6C, the relative risk of testicular torsion at 6C or greater was 1.8 (p = 0.05). Average seasonal diurnal temperature change in the 2 days before hospitalization showed increases in all seasons except spring, which fluctuated.
Conclusions: Diurnal temperature change was associated with testicular torsion and may be an etiological climatic factor affecting this condition. This is the first known study to demonstrate an association between diurnal temperature change and testicular torsion.
友華論文獎臨床組 第二名
Clinical Characteristics and Reproductive Outcomes in Infertile Men with Testicular Early and Late Maturation Arrest
aDepartment of Urology, bGraduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
† These authors contributed equally to this work. Correspondence
Yung Ming Lin, MD, Department of Urology, College of Medicine, National Cheng Kung University and Hospital, 138, Sheng Li Road, Tainan, Taiwan
Objective: To compare the clinical characteristics and reproductive outcomes of non-obstructive azoospermic men with uniform early and late maturation arrest (MA).
Methods: Patients with biopsy-documented uniform MA undergoing testicular sperm retrieval and complete medical records were enrolled in the present study. Their medical history, physical examination findings, testicular volume, serum hormone parameters, genetic anomalies, sperm retrieval, and reproductive outcomes were retrospectively analyzed.
Results: In a cohort of 223 non-obstructive azoospermic men, 34 men with uniform MA (21 early MA and 13 late MA) were identified. There were no significant differences in the age distribution, testicular volume, or hormone parameters between patients with early and late MA. Only 13 (38.2%) patients had a normal serum follicle-stimulating hormone level and normal testicular volume. Patients with early MA had a greater frequency of overall genetic anomalies, and patients with late MA had a greater frequency of previous testicular insults. The sperm retrieval and impregnation rate were non-significantly greater in patients with late MA.
Conclusions: MA has a variety of causes and presents with diverse phenotypes. Not all patients with uniform MA have a normal FSH level or testicular volume. Patients with early MA have a higher incidence of genetic anomalies and are more likely to have worse reproductive outcomes than are patients with late MA.
友華論文獎基礎組 第二名
Metallothionein 3: An Androgen-upregulated Gene Enhances Cell Invasion and Tumorigenesis of Prostate Carcinoma Cells.
BACKGROUND: Metallothioneins (MT1, MT2, MT3, and MT4) are regarded as modulators regulating a number of biological processes including cell proliferation, differentiation, and invasion. We determined the effects of androgen, cadmium, and arsenic on MT1/2 and MT3 in prostate carcinoma cells, and evaluated the functional effects of MT3 on cell proliferation, invasion, and tumorigenesis.
METHODS: We determined the expression of MT1/2 and MT3 in prostate carcinoma cells by immunoblotting assays or real-time reverse transcription-polymerase chain reactions. The effects of ectopic MT3 overexpression or MT3-knockdown on cell proliferation, invasion, and tumorigenesis were determined by (3) H-thymidine incorporation, matrigel invasion, and murine xenograft studies. The effects of androgen, cadmium, and arsenic on target genes were assessed using immunoblotting and reporter assays.
RESULTS: Androgen, cadmium, and arsenic treatments enhanced gene expression of MT1/2 and MT3 in prostate carcinoma LNCaP cells. Results of immunohistochemical staining indicated MT3 overexpression was found predominantly in the nuclear areas of PC-3 cells overexpressing MT3. Overexpression of MT3 significantly increased cell proliferation, invasion, and tumorigenic activities in PC-3 cells in vitro and in vivo. MT3 overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (Ndrg1) and maspin, and attenuated blocking effects of doxorubicin in PC-3 cells on cell proliferation. MT3-knockdown enhanced Ndrg1 and maspin expressions in LNCaP cells.
CONCLUSIONS: The experiments indicate that MT3 is an androgen-upregulated gene, and promotes tumorigenesis of prostate carcinoma cells. The downregulation of Ndrg1 and maspin gene expressions appears to account for the enhancement of proliferative and invasive functions of MT3 in PC-3 cells.
財團法人鳳凰泌尿科學文教基金會論文獎臨床組 第一名
Prediabetes is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome
1 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
2 Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
3 Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
4 Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
5 Health Management Center, National Taiwan University Hospital, Taipei, Taiwan
Objective: The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency.
Methods: This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen’s formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (<300 ng/dL) or free testosterone (<6 ng/dL) in prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS).
Results: Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses.
Conclusions: Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in
財團法人鳳凰泌尿科學文教基金會論文獎臨床組 第二名
The Impact of Metabolic Syndrome on the Responsiveness to α 1-blocker in Men with BPH/LUTS
Yung-Chin Lee, MD, PhD, Chia-Chu Liu, MD, PhD, Chii-Jye Wang, MD, PhD, Wen-Jeng Wu, MD, PhD, Hsin-Chih Yeh, MD, Chun-Nung Huang, MD, PhD, Chun-Hsiung Huang, MD, PhD, Shu-Pin Huang, MD, PhD, Department of Urology, Kaohsiung Medical University Hospital, Department of urology, Faculty of medicine, College of medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Aims: Increasing evidence has proposed the components of metabolic syndrome (MtS) as risk factors for the development of benign prostate hyperplasia (BPH); therefore, it is thought that MtS may play a role in lower urinary tract symptoms related to BPH (BPH/LUTS) etiology. Considering the closed relationships between MtS and BPH/LUTS, it is possible that patients with MtS might have different drug responsiveness in men with BPH/LUTS. We prospectively investigated the impact of MtS on responsiveness to α 1-blocker in men with BPH/LUTS.
Methods: We enrolled a total of 109 patients with a mean (SD) age of 59.8 (9.0) years, having a prostate volume of 20 cm3 or greater with moderate to severe LUTS. All patients received doxazosin-GITS (gastrointestinal therapeutic system) 4 mg once-daily for a 12-week period of treatment. The efficacy measurement was assessed by the changes from baseline in the total IPSS, maximum urinary flow rate and post void residual urine volume. The drug responders were defined as those who had a total IPSS decrease of more than 4 points from baseline after 12 weeks of treatment.
Results: Using multiple logistic regression analysis, our results showed that MtS was an independent factor for drug non-responder (OR=4.26, p=0.002). The rate of drug responder and total IPSS improvements in patients with MtS significantly decreased as the number of MtS components increased (p=0.012 and p=0.026). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor for drug non-responder (OR=3.17, p=0.020).
Conclusion: This study suggested that the presence of MtS had a significantly negative impact on the responsiveness to α1-blocker in men with BPH/LUTS. Our results are important for BPH/LUTS patients who did not initially respond to α1-blocker or who strive to reduce these metabolic risk factors.
財團法人鳳凰泌尿科學文教基金會論文獎臨床組 第二名
Increased Risk of Large Post-void residual Urine and Decreased Long-term Success Rate after Intravesical OnabotulinumtoxinA Injection for Refractory Idiopathic Detrusor Overactivity.
Liao CH, Kuo HC.
PURPOSE: Intravesical injection of onabotulinumtoxinA is effective for idiopathic detrusor overactivity refractory to antimuscarinics. However, safety is a major concern, especially in elderly individuals. We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection for refractory idiopathic detrusor overactivity in the frail elderly population.
MATERIALS AND METHODS: A total of 166 patients with urodynamic idiopathic detrusor overactivity refractory to previous antimuscarinics for more than 3 months received 1 intravesical 100 U onabotulinumtoxinA injection from 2004 to 2009. Frail elderly was defined as age greater than 65 years and 3 or more of certain criteria, including unintentional weight loss, self-reported exhaustion, weakness, slow walking speed and/or low physical activity. Treatment results were assessed by the Patient Perception of Bladder Condition, voiding diary, urodynamic parameters and Kaplan-Meier estimates of survival plots.
RESULTS: We evaluated 61 frail elderly patients, 63 who were elderly without frailty and 42 younger than 65 years. Large post-void residual urine volume (greater than 150 ml) after onabotulinumtoxinA injection was significantly higher in the frail elderly group than in the other groups (60.7% vs 39.7% and 35.7%, respectively, p = 0.018). Urinary retention developed in 7 frail elderly patients (11.5%), 4 (6.3%) who were elderly without frailty and 1 younger patient (2.4%) (p = 0.203). Recovery duration was significantly longer in frail elderly patients. The cumulative success rate was significantly lower in the frail elderly group than in the other 2 groups (p = 0.009).
CONCLUSIONS: Although safety and efficacy were similar between elderly patients without frailty and younger patients, an increased risk of large post-void residual urine volume and a lower long-term success rate in frail elderly patients were noted after intravesical onabotulinumtoxinA injection for refractory idiopathic detrusor overactivity.