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PD25-10 CHARACTERIZATION OF FIBRILLAR COLLAGENS AND EXTRACELLULAR MATRIX OF GLANDULAR BENIGN PROSTATIC HYPERPLASIA NODULES
THE JOURNAL OF UROLOGYâ
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
12 weeks. We assessed its impact and the severity of LUTS/BPH using the International Prostate Symptom Score (IPSS) and BPH Impact Index (BII) and IPSS quality-of-life (IPSS-QoL) subscores. Safety was assessed using treatment-emergent adverse events. RESULTS: The severity of LUTS/BPH was similar in the men with and without hypogonadism. Tadalafil significantly reduced LUTS/ BPH from baseline in both groups (IPSS e5.4 vs. e5.1, both p < 0.05; IPSS voiding subscore e3.4 vs. e3.4, both p < 0.05; IPSS storage subscore e2.0 vs. e1.7, both p < 0.05; without and with hypogonadism, respectively). Tadalafil also significantly improved the quality of life from baseline in both groups (IPSS-QoL e1.0 vs. e0.7, BII e1.3 vs. e1.2; both p < 0.05, without and with hypogonadism, respectively). Comparing the groups, the magnitude was significantly larger for the IPSS storage subscore and IPSS-QoL in men without hypogonadism. Tadalafil was safe and well tolerated. CONCLUSIONS: Tadalafil 5 mg once daily improved LUTS/ BPH in men with and without hypogonadism. However, the changes from baseline were more prominent in men without hypogonadism. Source of Funding: none
PD25-09 NON ALCOHOLIC FATTY LIVER DISEASE IS AN INDEPENDENT PREDICTOR OF MODERATE-SEVERE LOWER URINARY TRACT SYMPTOMS IN METABOLIC SYNDROME PATIENTS: RESULTS FROM A CROSS-SECTIONAL STUDY Giorgio Ivan Russo*, Sebastiano Cimino, Vincenzo Favilla, , Salvatore Privitera, Tommaso Castelli, Sandro La Eugenia Fragala Vignera, Rosita Condorelli, Aldo E. Calogero, Giuseppe Morgia, Catania, Italy INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is accepted as the hepatic component of metabolic syndrome and has gained great importance in recent years. This study aimed to investigate the association between NAFLD, BPH-related LUTS and to evaluate its role as an independent worse prognostic factor. METHODS: Between January 2010 to January 2012, 544 consecutive patients with BPH related LUTS were enrolled in this cross-sectional study. LUTS were evaluated by the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation criteria. The presence of NAFLD was assessed by ultrasonography performed by a blinded radiologist and using the hepatic steatosis index (HSI). It was calculated through this formula: 8 ALT/AST ratio+ BMI (+2, if DM;+2, if female). A value of HSI greater than 0.36 was set to predict the presence of NAFLD (ROC¼ 0.81). Continuous variables are presented as means standard deviations and differences between groups were tested by T-student, Mann-Whitney, ANOVA and post-hoc Bonferroni tests. For all statistical comparisons significance was considered as p <0.05. RESULTS: Median age was 65.83 (IQ: 22.84-78.70), median IPSS was 16.5 (IQ: 0-28) and median was IIEF-EF 20 (IQ: 1-30). Of all subjects, 152 (27.9%) had mild LUTS, 248 (45.6%) had moderate LUTS and 144 (26.5%) had severe LUTS. MetS was diagnosed in 264 (48.5%) subjects while IR in 104 (19.1%). NAFLD was diagnosed in 206 (37.86%) subjects and 240 (44.1%) had the HSI > 0.36. Subjects with HSI > 0.36 had higher IPSS (16.63 vs. 12.84, p<0.01), IPSSstorage (6.73 vs. 4.87, p<0.01), IPSS-voiding (9.87 vs. 8.11, p<0.01), homa-index (2.57 vs. 1.47, p<0.05) and lower age (61.44 vs. 64, p<0.01) PSA (2.50 vs. 4.76, p<0.05) and TT (4.58 vs. 5.30, p<0.01). We found significant differences in terms of HSI between severe LUTS patients as compared to those with moderate LUTS (37.62 vs. 36.07, p<0.01) and to those with mild LUTS (37.62 vs. 34.69, p<0.01). At logistic regression analysis, HSI > 0.36 was an independent predictor of moderate-severe LUTS after adjusting for the presence of MetS criteria (OR ¼ 2.92, p<0.01). Finally, subjects with MetS and HSI
e729
> 0.36 had 2.0 fold the risk of having moderate-severe LUTS than those with only MetS. CONCLUSIONS: Our data provided new insight about the association between hepatic steatosis, metabolic syndrome and LUTS. Subjects with NAFLD should be considered as a new population at risk of having moderate-severe LUTS. Source of Funding: none
PD25-10 CHARACTERIZATION OF FIBRILLAR COLLAGENS AND EXTRACELLULAR MATRIX OF GLANDULAR BENIGN PROSTATIC HYPERPLASIA NODULES Tyler Bauman*, Madison, WI; Tristan Nicholson, Rochester, NY; Brett Becker, Wei Huang, William Ricke, Madison, WI INTRODUCTION AND OBJECTIVES: Recent studies have associated prostatic fibrosis with lower urinary tract symptoms (LUTS) independent of hyperplasia, indicating that fibrosis may be important in evaluating benign prostatic hyperplasia (BPH). However, collagen and extracellular matrix (ECM) composition within the normal and hyperplastic prostate have not previously been characterized. The purpose of this study was to evaluate collagen and ECM in normal prostate tissue and in glandular BPH, as well as the effects of therapies on these parameters. METHODS: Fibrillar collagen and ECM were assessed in prostate tissues stained for picrosirius red (PSR) and Masson’s trichrome (MTC), respectively, using a tissue microarray (TMA) with glandular BPH tissue from patients with LUTS and normal prostate tissue from prostatectomy specimens. Additional tissues from BPH patients who underwent transurethral resection of the prostate (TURP) were assessed from patients treated with 5a-reductase inhibitors (5aRIs) (n ¼ 22) a-blockers (n ¼ 38). Images were acquired and tissues were quantified in ImageJ. RESULTS: Total collagen staining, quantified by birefringence of PSR-stained tissues viewed under circularly polarized light, was similar in normal prostate tissue (n ¼ 48) and glandular BPH (n ¼ 23) (125.9 4.9 vs. 111.9 5.1; p ¼ 0.08). Differences of collagen bundle size were also assessed and no differences were observed. No differences were observed in the quantity of ECM in normal and BPH tissue quantified with MTC (12.97 1.03 vs. 10.20 1.24; p ¼ 0.11). Collagen staining intensity was not associated with age (p ¼ 0.63). In tissues from TURP specimens, treatment with 5a-RIs (p ¼ 0.71) or a-blockers (p ¼ 0.69) had no effect on total collagen staining (n ¼ 47). Collagen staining was not associated with age (p ¼ 0.61), pre-TURP prostate-specific antigen (p ¼ 0.87), pre-TURP AUA symptom index (p ¼ 0.11), or pre-TURP post-void residual (p ¼ 0.67). CONCLUSIONS: The association between fibrosis and LUTS that has been demonstrated in previous studies cannot be explained by increased fibrillar collagen or extracellular matrix deposition in glandular BPH nodules. If fibrosis is associated with BPH/LUTS, it is likely affecting collagen and ECM deposition within the periurethral tissue independent of nodular BPH. Source of Funding: R01CA123199, T32GM07356, F30DK093173.
R01DK093690,
PD25-11 IGF1 EXPRESSION AND ITS RELATIONSHIP WITH OTHERS GROWTH FACTORS IN THE PATHOGENESIS OF BENIGN PROSTATIC HYPERPLASIA Karlo Biolo*, Porto Alegre, Brazil; Sabrina T. Reis, Ricardo Kirihara, Nayara Viana, Fabio Oliveira, Katia R. Leite, Miguel Srougi, Alberto A. Antunes, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Patients with peripheral insulin resistance appear to be at an increased risk of prostate
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
12 weeks. We assessed its impact and the severity of LUTS/BPH using the International Prostate Symptom Score (IPSS) and BPH Impact Index (BII) and IPSS quality-of-life (IPSS-QoL) subscores. Safety was assessed using treatment-emergent adverse events. RESULTS: The severity of LUTS/BPH was similar in the men with and without hypogonadism. Tadalafil significantly reduced LUTS/ BPH from baseline in both groups (IPSS e5.4 vs. e5.1, both p < 0.05; IPSS voiding subscore e3.4 vs. e3.4, both p < 0.05; IPSS storage subscore e2.0 vs. e1.7, both p < 0.05; without and with hypogonadism, respectively). Tadalafil also significantly improved the quality of life from baseline in both groups (IPSS-QoL e1.0 vs. e0.7, BII e1.3 vs. e1.2; both p < 0.05, without and with hypogonadism, respectively). Comparing the groups, the magnitude was significantly larger for the IPSS storage subscore and IPSS-QoL in men without hypogonadism. Tadalafil was safe and well tolerated. CONCLUSIONS: Tadalafil 5 mg once daily improved LUTS/ BPH in men with and without hypogonadism. However, the changes from baseline were more prominent in men without hypogonadism. Source of Funding: none
PD25-09 NON ALCOHOLIC FATTY LIVER DISEASE IS AN INDEPENDENT PREDICTOR OF MODERATE-SEVERE LOWER URINARY TRACT SYMPTOMS IN METABOLIC SYNDROME PATIENTS: RESULTS FROM A CROSS-SECTIONAL STUDY Giorgio Ivan Russo*, Sebastiano Cimino, Vincenzo Favilla, , Salvatore Privitera, Tommaso Castelli, Sandro La Eugenia Fragala Vignera, Rosita Condorelli, Aldo E. Calogero, Giuseppe Morgia, Catania, Italy INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is accepted as the hepatic component of metabolic syndrome and has gained great importance in recent years. This study aimed to investigate the association between NAFLD, BPH-related LUTS and to evaluate its role as an independent worse prognostic factor. METHODS: Between January 2010 to January 2012, 544 consecutive patients with BPH related LUTS were enrolled in this cross-sectional study. LUTS were evaluated by the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation criteria. The presence of NAFLD was assessed by ultrasonography performed by a blinded radiologist and using the hepatic steatosis index (HSI). It was calculated through this formula: 8 ALT/AST ratio+ BMI (+2, if DM;+2, if female). A value of HSI greater than 0.36 was set to predict the presence of NAFLD (ROC¼ 0.81). Continuous variables are presented as means standard deviations and differences between groups were tested by T-student, Mann-Whitney, ANOVA and post-hoc Bonferroni tests. For all statistical comparisons significance was considered as p <0.05. RESULTS: Median age was 65.83 (IQ: 22.84-78.70), median IPSS was 16.5 (IQ: 0-28) and median was IIEF-EF 20 (IQ: 1-30). Of all subjects, 152 (27.9%) had mild LUTS, 248 (45.6%) had moderate LUTS and 144 (26.5%) had severe LUTS. MetS was diagnosed in 264 (48.5%) subjects while IR in 104 (19.1%). NAFLD was diagnosed in 206 (37.86%) subjects and 240 (44.1%) had the HSI > 0.36. Subjects with HSI > 0.36 had higher IPSS (16.63 vs. 12.84, p<0.01), IPSSstorage (6.73 vs. 4.87, p<0.01), IPSS-voiding (9.87 vs. 8.11, p<0.01), homa-index (2.57 vs. 1.47, p<0.05) and lower age (61.44 vs. 64, p<0.01) PSA (2.50 vs. 4.76, p<0.05) and TT (4.58 vs. 5.30, p<0.01). We found significant differences in terms of HSI between severe LUTS patients as compared to those with moderate LUTS (37.62 vs. 36.07, p<0.01) and to those with mild LUTS (37.62 vs. 34.69, p<0.01). At logistic regression analysis, HSI > 0.36 was an independent predictor of moderate-severe LUTS after adjusting for the presence of MetS criteria (OR ¼ 2.92, p<0.01). Finally, subjects with MetS and HSI
e729
> 0.36 had 2.0 fold the risk of having moderate-severe LUTS than those with only MetS. CONCLUSIONS: Our data provided new insight about the association between hepatic steatosis, metabolic syndrome and LUTS. Subjects with NAFLD should be considered as a new population at risk of having moderate-severe LUTS. Source of Funding: none
PD25-10 CHARACTERIZATION OF FIBRILLAR COLLAGENS AND EXTRACELLULAR MATRIX OF GLANDULAR BENIGN PROSTATIC HYPERPLASIA NODULES Tyler Bauman*, Madison, WI; Tristan Nicholson, Rochester, NY; Brett Becker, Wei Huang, William Ricke, Madison, WI INTRODUCTION AND OBJECTIVES: Recent studies have associated prostatic fibrosis with lower urinary tract symptoms (LUTS) independent of hyperplasia, indicating that fibrosis may be important in evaluating benign prostatic hyperplasia (BPH). However, collagen and extracellular matrix (ECM) composition within the normal and hyperplastic prostate have not previously been characterized. The purpose of this study was to evaluate collagen and ECM in normal prostate tissue and in glandular BPH, as well as the effects of therapies on these parameters. METHODS: Fibrillar collagen and ECM were assessed in prostate tissues stained for picrosirius red (PSR) and Masson’s trichrome (MTC), respectively, using a tissue microarray (TMA) with glandular BPH tissue from patients with LUTS and normal prostate tissue from prostatectomy specimens. Additional tissues from BPH patients who underwent transurethral resection of the prostate (TURP) were assessed from patients treated with 5a-reductase inhibitors (5aRIs) (n ¼ 22) a-blockers (n ¼ 38). Images were acquired and tissues were quantified in ImageJ. RESULTS: Total collagen staining, quantified by birefringence of PSR-stained tissues viewed under circularly polarized light, was similar in normal prostate tissue (n ¼ 48) and glandular BPH (n ¼ 23) (125.9 4.9 vs. 111.9 5.1; p ¼ 0.08). Differences of collagen bundle size were also assessed and no differences were observed. No differences were observed in the quantity of ECM in normal and BPH tissue quantified with MTC (12.97 1.03 vs. 10.20 1.24; p ¼ 0.11). Collagen staining intensity was not associated with age (p ¼ 0.63). In tissues from TURP specimens, treatment with 5a-RIs (p ¼ 0.71) or a-blockers (p ¼ 0.69) had no effect on total collagen staining (n ¼ 47). Collagen staining was not associated with age (p ¼ 0.61), pre-TURP prostate-specific antigen (p ¼ 0.87), pre-TURP AUA symptom index (p ¼ 0.11), or pre-TURP post-void residual (p ¼ 0.67). CONCLUSIONS: The association between fibrosis and LUTS that has been demonstrated in previous studies cannot be explained by increased fibrillar collagen or extracellular matrix deposition in glandular BPH nodules. If fibrosis is associated with BPH/LUTS, it is likely affecting collagen and ECM deposition within the periurethral tissue independent of nodular BPH. Source of Funding: R01CA123199, T32GM07356, F30DK093173.
R01DK093690,
PD25-11 IGF1 EXPRESSION AND ITS RELATIONSHIP WITH OTHERS GROWTH FACTORS IN THE PATHOGENESIS OF BENIGN PROSTATIC HYPERPLASIA Karlo Biolo*, Porto Alegre, Brazil; Sabrina T. Reis, Ricardo Kirihara, Nayara Viana, Fabio Oliveira, Katia R. Leite, Miguel Srougi, Alberto A. Antunes, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Patients with peripheral insulin resistance appear to be at an increased risk of prostate