- Email: [email protected]
923 THE CDC HORMONE STANDARDIZATION PROGRAM: TESTOSTERONE
Vol. 185, No. 4S, Supplement, Monday, May 16, 2011
ED. Exclusion criteria were radical pelvic surgery, pelvic irradiation, or incomplete clinical data. Average age of first ED diagnosis for cases was 73.4 years. Logistic regression identified independent genetic predictors of ED. Additional analyses included Cox proportional hazard regression defining time as age of study subjects and censored event as first report or treatment for ED. RESULTS: Data from 327 Caucasian, non-Hispanic ED cases and 318 controls from the ACT Cohort Study were analyzed. Unadjusted logistic regression analyses and Cox regression analysis failed to identify any genome-wide significant SNPs. The strongest association from the Cox regression analysis was with SNPs on chromosome 14 near gene ADCK1 (p⫽4.32 E-06, HRR⫽1.67, 95% CI: 1.34 –2.08) and chromosome 21 near HLCS (p⫽4.37 E-06, HRR⫽1.54, 95% CI:1.28 –1.86). Additional analysis was performed adjusting for smoking, diabetes and hypertension, which are risk factors ED, also found the strongest association for SNPs on chromosome 14 (p-1.10 E-06, HHR⫽1.74, 95% CI:1.39 –2.17). CONCLUSIONS: Results from the time to ED analyses, suggest SNPs on chromosome 14 and 21 may be associated with ED risk. Further studies in different cohorts of men will be needed to confirm these results as well as molecular studies confirming expression of relevant genetic markers in susceptible tissues. Source of Funding: Northwest Institute of Genetic Medicine Resource Access Grant
921 INCIDENT HYPERTENSION AND RISK OF SUBSEQUENT ERECTILE DYSFUNCTION IN MEN WITH TYPE 1 DIABETES James Hotaling*, Seattle, WA; Aruna Sarma, Rodney Dunn, Ann Arbor, MI; Jeremy Soule, Charleston, SC; Ian DeBoer, Thomas Walsh, Seattle, WA; Patricia Cleary, Rockville, MD; Patrick Heagerty, Hunter Wessells, Seattle, WA; _ DCCT/EDIC Study Group, Bethesda, MD INTRODUCTION AND OBJECTIVES: To determine how the development of hypertension modulates the risk of incident erectile dysfunction (ED) over time in men with type I diabetes (T1D). METHODS: The study cohort consisted of men enrolled in years 1–13 of the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, the observational follow up of participants of the Diabetes Control and Complications Trial (DCCT). Erectile dysfunction was assessed yearly with a single question querying presence/absence of impotence. Incident hypertension was defined to occur when any of the following criteria were met on 2 consecutive occasions: SBP of 140 mmHg or higher, DBP of 90 mmHg or higher, or use of antihypertensive medications to treat high blood pressure. Cox proportional hazards models estimated the risk of incident ED associated with prior development of hypertension after adjustment for age, prior DCCT assignment to intensive or conventional glycemic treatment, and hemoglobin A1c (HbA1c) levels over time. RESULTS: Of the 761 male subjects with a mean age of 35 years at DCCT closeout, 315 (41%) reported history of impotence at any point during the 13 years of follow-up. The median age of onset of ED was 50 years. The cumulative incidence of hypertension over the 13 years of EDIC was 48%. Incident hypertension was associated with a 1.6 times greater risk of subsequent ED (p⫽0.001) after adjustment for age, DCCT treatment arm and mean HbA1c levels during the DCCT and EDIC. Hazard ratios for age and diabetes variables are included in the table below. CONCLUSIONS: We found an association between incident hypertension and development of subsequent ED in men with T1D that is independent of age and glycemic control. Although analyses are required to control for potential confounding effects of antihypertensive medications, these data suggest that the potential pathophysiological impact of hypertension on diabetes associated ED requires further investigation.
THE JOURNAL OF UROLOGY姞
Incident Hypertension
Hazard Ratios for Risk of ED HR 1.6
e369
p-value 0.001
DCCT Treatment Arm
1.0
0.8
DCCT Mean HbA1c
1.1
0.2
EDIC Mean HbA1c
1.4
Age
1.1
Source of Funding: NIH, NIDDK
922 DOES THE NEED FOR A REPLACEMENT INFLATABLE PENILE PROSTHESIS LEAD TO DECREASED PATIENT SATISFACTION? Arthur Caire*, Aaron Boonjindasup, Brian Richardson, Wayne Hellstrom, New Orleans, LA INTRODUCTION AND OBJECTIVES: To analyze the reason for replacement and overall satisfaction of a cohort who underwent surgical replacement of an inflatable penile prosthesis (IPP). METHODS: A cohort of 105 patients who underwent IPP placement from 2005 to 2007 was retrieved from the prosthesis database. Approximately 21.9% (23) underwent replacement of their prosthesis due to complications and were further analyzed. Reason for removal was stratified into infectious and non-infectious (erosion, non-functional, and patient discomfort). Age, race (African American vs nonAfrican American), smoking history, hypertension, diabetes, coronary artery disease, and hyperlipidemia were stratified by reason for removal. Finally we contacted patient’s via telephone and recorded subjective satisfaction with their IPP. RESULTS: The reason for removal was most commonly due to a non-functional (47.8%) IPP, followed by infection (30.4%), erosion (17.4%), and patient discomfort (4.3%). Age and race did not show a significant difference when analyzing reason for replacement (p⬎0.05). Patients who were smokers (p⫽0.907) had hypertension (p⫽0.554), diabetes (p⫽0.591), or hyperlipidemia (p⫽0.219) did not have significantly higher infection rates. Approximately 58.3% were satisfied with their prosthesis, 75% would have the surgery performed again, and 91.7% would still recommend prosthesis surgery. CONCLUSIONS: Device malfunction was the primary reason for replacement/removal at our institution. Despite the complication of prosthesis removal, the majority of patients were still satisfied with their prosthesis, would have the surgery performed again, and would recommend prosthesis surgery to a friend. Source of Funding: None
923 THE CDC HORMONE STANDARDIZATION PROGRAM: TESTOSTERONE Julianne Botelho*, Hubert Vesper, Atlanta, GA INTRODUCTION AND OBJECTIVES: Testosterone assays are widely used in patient care and research. However, deficiencies in these assays limit their broad and effective implementation and create challenges for patients whose medical care relies upon its accurate measurement. Furthermore, the translation of research findings into information useful for patient care, such as new evidence-based clinical guidelines, is not possible unless both research and clinical assays produce measurements that are comparable and transferable from research setting to patient care. To overcome these problems and limitations in testosterone testing, the American Urology Association, as well as other clinical and research organizations, stated the need for standardizing testosterone measurements. This need and suggested actions have been formulated in a recently published consensus document (J. Clin. Endocrinol. Metab. 2010 95: 4542– 4548). METHODS: To address this need, CDC started a project to standardize testosterone testing. As part of this effort, the CDC has worked with researchers to develop and implement a standardization program for laboratories and assay manufacturers. The CDC Hormone
e370
THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4S, Supplement, Monday, May 16, 2011
Standardization (HoSt) Program is providing participants with matrixbased “secondary” reference materials in the form of non-pooled sera from single donors. Values obtained from participants are used for bias assessment as described in CLSI guideline EP9-A2 “Method comparison and Bias Estimation using Patient Samples” and for establishing traceability and standardization to the CDC laboratory. An overall mean bias, 6.4%, based on the data published by Westgard (www.Westgard. com) is used in the final assessment. Laboratories and assay manufacturers that meet certain performance criteria for testosterone measurements assessed in for challenges over 1 year will be considered standardized. RESULTS: Currently 14 participants are enrolled which include clinical, academic, and pharmaceutical laboratories as well as immunoassay manufactures. CONCLUSIONS: The CDC Hormone Standardization Program is working towards providing accurate and reliable results for optimal patient care. Further, CDC works with the AUA and other organizations to provide information to physicians, researchers and laboratories to help in the selection, use and interpretation of data obtained from testosterone measurements. Source of Funding: Funding for this project is provided through the CDC Foundation by Solvay Pharmaceutical, now part of Abbott Laboratories, the Division of Laboratory Sciences at the National Center for Environmental Health and the Division of Cancer Prevention and Control at the National Center for Chronic Disease Prevention and Health Promotion
924 CHANGES IN THE PLASMA PROTEOME OF PATIENTS WITH ERECTILE DYSFUNCTION AND DIABETES MELLITUS AFTER VARDENAFIL TREATMENT
Source of Funding: None
Luis San Jose*, Carlos Olivier, Isabel Galante, Petra Mateos Caceres, Pedro Lanzat, Estela Mahillo, Pablo Rodriguez, Carlos Macaya, Angel Silmi, Antonio Lopez-Farre, Madrid, Spain INTRODUCTION AND OBJECTIVES: Erectile Dysfunction (ED) is associated with atherosclerosis and its associated risk factors, such as dyslipidemia, hypertension and diabetes, which is characterized by an enhanced pro-inflammatory status. It is known that ED seems to be mediated by damage to the endothelium. Some studies have shown that vardenafil may act on the vascular endothelium by modifying vessels atherosclerosis. However, its effect on systemic inflammation remains unclear. OBJECTIVE: To determine changes in the plasma proteome of mainly proteins associated with inflammation and atherogenesis in diabetic patients with ED after vardenafil administration. METHODS: 17 patients with ED (IIEF-EF 8.9⫾0.7) and diabetes were enrolled and 20 mg vardenafil once or twice a week was administered during 12 weeks. Plasma obtained from each patient was used to perform two dimensional electrophoresis and mass spectrometry analysis. RESULTS: After vardenafil administration, IIEF-EF score was significatively improved (18.3⫾2.0 p⬍0.05). The protein level of fibrinogen gamma chain isotype three was significatively reduced after vardenafil treatment (p⬍0.05) (Figure 2) as well as fibrinogen fragment-D (p⬍0.05)In addition, the expression of three haptoglobin isotypes and two ␣1-antitripsin isotypes (figure 1), other two important inflammatory-related proteins, were significatively downexpressed after vardenafil treatment (p⬍0.05). No differences were observed in the expression of five apolipoprotein-AI isotypes and apolipoprotein-AIV after vardenafil treatment. CONCLUSIONS: Vardenafil treatment significatively reduced circulating plasma levels of different biomarkers mainly associated with inflammation and atherogenesis. These results may suggest that vardenafil plays an anti-inflammatory and protective effect of atherogenesis in diabetic patients with ED.
Technology & Instruments: Robotics/Laparoscopy Moderated Poster 31 Monday, May 16, 2011
10:30 AM-12:30 PM
925 SUPRAPUBIC VS. URETHRAL CATHETER DRAINAGE FOLLOWING ROBOT ASSISTED RADICAL PROSTATECTOMY: A MATCHED ANALYSIS Jesse Sammon, Quoc-Dien Trinh*, Sumit De, Sanjeev Kaul, Shyam Sukumar, Mireya Diaz, Mani Menon, Detroit, MI INTRODUCTION AND OBJECTIVES: Patients undergoing radical prostatectomy traditionally require urethral catheterization for adequate bladder drainage in the postoperative period. However, many patients have significant discomfort from the urethral catheter. In this matched analysis, we compare the rate of bladder neck contracture, operative time, estimated blood loss, length of stay and complications of 195 patients undergoing RARP with exclusive suprapubic tube placement with a minimum 1 year follow-up vs. 195 matched controls undergoing RARP with urethral catheter. METHODS: Between October 2008 and October 2009, 302 patients underwent RARP with suprapubic drainage. One hundredninety-five patients possessed all follow-up data required for proper matching. Patients were matched with 195 controls of similar age, clinical stage, Gleason score, Charlson Comorbidity Index, BMI, prostate mass and prior urologic surgery status. RESULTS: Mean follow-up was 500.7 days for suprapubic tube cases vs. 677.9 days for matched urethral catheter controls. There was no incidence of bladder neck contracture in the cases group and a
ED. Exclusion criteria were radical pelvic surgery, pelvic irradiation, or incomplete clinical data. Average age of first ED diagnosis for cases was 73.4 years. Logistic regression identified independent genetic predictors of ED. Additional analyses included Cox proportional hazard regression defining time as age of study subjects and censored event as first report or treatment for ED. RESULTS: Data from 327 Caucasian, non-Hispanic ED cases and 318 controls from the ACT Cohort Study were analyzed. Unadjusted logistic regression analyses and Cox regression analysis failed to identify any genome-wide significant SNPs. The strongest association from the Cox regression analysis was with SNPs on chromosome 14 near gene ADCK1 (p⫽4.32 E-06, HRR⫽1.67, 95% CI: 1.34 –2.08) and chromosome 21 near HLCS (p⫽4.37 E-06, HRR⫽1.54, 95% CI:1.28 –1.86). Additional analysis was performed adjusting for smoking, diabetes and hypertension, which are risk factors ED, also found the strongest association for SNPs on chromosome 14 (p-1.10 E-06, HHR⫽1.74, 95% CI:1.39 –2.17). CONCLUSIONS: Results from the time to ED analyses, suggest SNPs on chromosome 14 and 21 may be associated with ED risk. Further studies in different cohorts of men will be needed to confirm these results as well as molecular studies confirming expression of relevant genetic markers in susceptible tissues. Source of Funding: Northwest Institute of Genetic Medicine Resource Access Grant
921 INCIDENT HYPERTENSION AND RISK OF SUBSEQUENT ERECTILE DYSFUNCTION IN MEN WITH TYPE 1 DIABETES James Hotaling*, Seattle, WA; Aruna Sarma, Rodney Dunn, Ann Arbor, MI; Jeremy Soule, Charleston, SC; Ian DeBoer, Thomas Walsh, Seattle, WA; Patricia Cleary, Rockville, MD; Patrick Heagerty, Hunter Wessells, Seattle, WA; _ DCCT/EDIC Study Group, Bethesda, MD INTRODUCTION AND OBJECTIVES: To determine how the development of hypertension modulates the risk of incident erectile dysfunction (ED) over time in men with type I diabetes (T1D). METHODS: The study cohort consisted of men enrolled in years 1–13 of the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, the observational follow up of participants of the Diabetes Control and Complications Trial (DCCT). Erectile dysfunction was assessed yearly with a single question querying presence/absence of impotence. Incident hypertension was defined to occur when any of the following criteria were met on 2 consecutive occasions: SBP of 140 mmHg or higher, DBP of 90 mmHg or higher, or use of antihypertensive medications to treat high blood pressure. Cox proportional hazards models estimated the risk of incident ED associated with prior development of hypertension after adjustment for age, prior DCCT assignment to intensive or conventional glycemic treatment, and hemoglobin A1c (HbA1c) levels over time. RESULTS: Of the 761 male subjects with a mean age of 35 years at DCCT closeout, 315 (41%) reported history of impotence at any point during the 13 years of follow-up. The median age of onset of ED was 50 years. The cumulative incidence of hypertension over the 13 years of EDIC was 48%. Incident hypertension was associated with a 1.6 times greater risk of subsequent ED (p⫽0.001) after adjustment for age, DCCT treatment arm and mean HbA1c levels during the DCCT and EDIC. Hazard ratios for age and diabetes variables are included in the table below. CONCLUSIONS: We found an association between incident hypertension and development of subsequent ED in men with T1D that is independent of age and glycemic control. Although analyses are required to control for potential confounding effects of antihypertensive medications, these data suggest that the potential pathophysiological impact of hypertension on diabetes associated ED requires further investigation.
THE JOURNAL OF UROLOGY姞
Incident Hypertension
Hazard Ratios for Risk of ED HR 1.6
e369
p-value 0.001
DCCT Treatment Arm
1.0
0.8
DCCT Mean HbA1c
1.1
0.2
EDIC Mean HbA1c
1.4
Age
1.1
Source of Funding: NIH, NIDDK
922 DOES THE NEED FOR A REPLACEMENT INFLATABLE PENILE PROSTHESIS LEAD TO DECREASED PATIENT SATISFACTION? Arthur Caire*, Aaron Boonjindasup, Brian Richardson, Wayne Hellstrom, New Orleans, LA INTRODUCTION AND OBJECTIVES: To analyze the reason for replacement and overall satisfaction of a cohort who underwent surgical replacement of an inflatable penile prosthesis (IPP). METHODS: A cohort of 105 patients who underwent IPP placement from 2005 to 2007 was retrieved from the prosthesis database. Approximately 21.9% (23) underwent replacement of their prosthesis due to complications and were further analyzed. Reason for removal was stratified into infectious and non-infectious (erosion, non-functional, and patient discomfort). Age, race (African American vs nonAfrican American), smoking history, hypertension, diabetes, coronary artery disease, and hyperlipidemia were stratified by reason for removal. Finally we contacted patient’s via telephone and recorded subjective satisfaction with their IPP. RESULTS: The reason for removal was most commonly due to a non-functional (47.8%) IPP, followed by infection (30.4%), erosion (17.4%), and patient discomfort (4.3%). Age and race did not show a significant difference when analyzing reason for replacement (p⬎0.05). Patients who were smokers (p⫽0.907) had hypertension (p⫽0.554), diabetes (p⫽0.591), or hyperlipidemia (p⫽0.219) did not have significantly higher infection rates. Approximately 58.3% were satisfied with their prosthesis, 75% would have the surgery performed again, and 91.7% would still recommend prosthesis surgery. CONCLUSIONS: Device malfunction was the primary reason for replacement/removal at our institution. Despite the complication of prosthesis removal, the majority of patients were still satisfied with their prosthesis, would have the surgery performed again, and would recommend prosthesis surgery to a friend. Source of Funding: None
923 THE CDC HORMONE STANDARDIZATION PROGRAM: TESTOSTERONE Julianne Botelho*, Hubert Vesper, Atlanta, GA INTRODUCTION AND OBJECTIVES: Testosterone assays are widely used in patient care and research. However, deficiencies in these assays limit their broad and effective implementation and create challenges for patients whose medical care relies upon its accurate measurement. Furthermore, the translation of research findings into information useful for patient care, such as new evidence-based clinical guidelines, is not possible unless both research and clinical assays produce measurements that are comparable and transferable from research setting to patient care. To overcome these problems and limitations in testosterone testing, the American Urology Association, as well as other clinical and research organizations, stated the need for standardizing testosterone measurements. This need and suggested actions have been formulated in a recently published consensus document (J. Clin. Endocrinol. Metab. 2010 95: 4542– 4548). METHODS: To address this need, CDC started a project to standardize testosterone testing. As part of this effort, the CDC has worked with researchers to develop and implement a standardization program for laboratories and assay manufacturers. The CDC Hormone
e370
THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4S, Supplement, Monday, May 16, 2011
Standardization (HoSt) Program is providing participants with matrixbased “secondary” reference materials in the form of non-pooled sera from single donors. Values obtained from participants are used for bias assessment as described in CLSI guideline EP9-A2 “Method comparison and Bias Estimation using Patient Samples” and for establishing traceability and standardization to the CDC laboratory. An overall mean bias, 6.4%, based on the data published by Westgard (www.Westgard. com) is used in the final assessment. Laboratories and assay manufacturers that meet certain performance criteria for testosterone measurements assessed in for challenges over 1 year will be considered standardized. RESULTS: Currently 14 participants are enrolled which include clinical, academic, and pharmaceutical laboratories as well as immunoassay manufactures. CONCLUSIONS: The CDC Hormone Standardization Program is working towards providing accurate and reliable results for optimal patient care. Further, CDC works with the AUA and other organizations to provide information to physicians, researchers and laboratories to help in the selection, use and interpretation of data obtained from testosterone measurements. Source of Funding: Funding for this project is provided through the CDC Foundation by Solvay Pharmaceutical, now part of Abbott Laboratories, the Division of Laboratory Sciences at the National Center for Environmental Health and the Division of Cancer Prevention and Control at the National Center for Chronic Disease Prevention and Health Promotion
924 CHANGES IN THE PLASMA PROTEOME OF PATIENTS WITH ERECTILE DYSFUNCTION AND DIABETES MELLITUS AFTER VARDENAFIL TREATMENT
Source of Funding: None
Luis San Jose*, Carlos Olivier, Isabel Galante, Petra Mateos Caceres, Pedro Lanzat, Estela Mahillo, Pablo Rodriguez, Carlos Macaya, Angel Silmi, Antonio Lopez-Farre, Madrid, Spain INTRODUCTION AND OBJECTIVES: Erectile Dysfunction (ED) is associated with atherosclerosis and its associated risk factors, such as dyslipidemia, hypertension and diabetes, which is characterized by an enhanced pro-inflammatory status. It is known that ED seems to be mediated by damage to the endothelium. Some studies have shown that vardenafil may act on the vascular endothelium by modifying vessels atherosclerosis. However, its effect on systemic inflammation remains unclear. OBJECTIVE: To determine changes in the plasma proteome of mainly proteins associated with inflammation and atherogenesis in diabetic patients with ED after vardenafil administration. METHODS: 17 patients with ED (IIEF-EF 8.9⫾0.7) and diabetes were enrolled and 20 mg vardenafil once or twice a week was administered during 12 weeks. Plasma obtained from each patient was used to perform two dimensional electrophoresis and mass spectrometry analysis. RESULTS: After vardenafil administration, IIEF-EF score was significatively improved (18.3⫾2.0 p⬍0.05). The protein level of fibrinogen gamma chain isotype three was significatively reduced after vardenafil treatment (p⬍0.05) (Figure 2) as well as fibrinogen fragment-D (p⬍0.05)In addition, the expression of three haptoglobin isotypes and two ␣1-antitripsin isotypes (figure 1), other two important inflammatory-related proteins, were significatively downexpressed after vardenafil treatment (p⬍0.05). No differences were observed in the expression of five apolipoprotein-AI isotypes and apolipoprotein-AIV after vardenafil treatment. CONCLUSIONS: Vardenafil treatment significatively reduced circulating plasma levels of different biomarkers mainly associated with inflammation and atherogenesis. These results may suggest that vardenafil plays an anti-inflammatory and protective effect of atherogenesis in diabetic patients with ED.
Technology & Instruments: Robotics/Laparoscopy Moderated Poster 31 Monday, May 16, 2011
10:30 AM-12:30 PM
925 SUPRAPUBIC VS. URETHRAL CATHETER DRAINAGE FOLLOWING ROBOT ASSISTED RADICAL PROSTATECTOMY: A MATCHED ANALYSIS Jesse Sammon, Quoc-Dien Trinh*, Sumit De, Sanjeev Kaul, Shyam Sukumar, Mireya Diaz, Mani Menon, Detroit, MI INTRODUCTION AND OBJECTIVES: Patients undergoing radical prostatectomy traditionally require urethral catheterization for adequate bladder drainage in the postoperative period. However, many patients have significant discomfort from the urethral catheter. In this matched analysis, we compare the rate of bladder neck contracture, operative time, estimated blood loss, length of stay and complications of 195 patients undergoing RARP with exclusive suprapubic tube placement with a minimum 1 year follow-up vs. 195 matched controls undergoing RARP with urethral catheter. METHODS: Between October 2008 and October 2009, 302 patients underwent RARP with suprapubic drainage. One hundredninety-five patients possessed all follow-up data required for proper matching. Patients were matched with 195 controls of similar age, clinical stage, Gleason score, Charlson Comorbidity Index, BMI, prostate mass and prior urologic surgery status. RESULTS: Mean follow-up was 500.7 days for suprapubic tube cases vs. 677.9 days for matched urethral catheter controls. There was no incidence of bladder neck contracture in the cases group and a