Herbert Lepor, M.D.

alpha-Blockers for benign prostatic hyperplasia: the new era
Lepor, Herbert; Kazzazi, Amir; Djavan, Bob
2012 Jan;22(1):7-15, Current opinion in urology
PURPOSE OF REVIEW: alpha1-Adrenoceptor blockers are the most frequently prescribed medical therapy in the treatment of lower urinary tract symptom suggestive of benign prostatic hyperplasia (LUTS/BPH). The purpose of this review is to highlight the evolution of adrenoceptor blockers with emphasis on newly approved drugs. RECENT FINDINGS: Over the past years new formulations of several alpha1-adrenoceptor blockers were introduced to the market. Five long-acting alpha1-blockers are currently approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, alfuzosin and silodosin. Silodosin is the only adrenoceptor blocker that exhibits true selectivity for the alpha1-adrenoceptor subtypes. This unique adrenoceptor selectivity profile likely accounts for the very favorable cardiovascular safety profile. SUMMARY: Tamsulosin, alfuzosin slow release and silodosin do not require dose titration. Alfuzosin, terazosin, doxazosin and silodosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. Low incidence of orthostatic hypotension has been reported for silodosin, but abnormal ejaculation is the most commonly reported adverse effect
— id: 145766, year: 2012, vol: 22, page: 7, stat: Journal Article,

Bmp7 Functions via a Polarity Mechanism to Promote Cloacal Septation
Xu, Kun; Wu, Xinyu; Shapiro, Ellen; Huang, Honging; Zhang, Lixia; Hickling, Duane; Deng, Yan; Lee, Peng; Li, Juan; Lepor, Herbert; Grishina, Irina
2012 ;7(1):e29372-e29372, PLoS ONE
BACKGROUND: During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse. CONCLUSION/SIGNIFICANCE: Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations
— id: 149933, year: 2012, vol: 7, page: e29372, stat: Journal Article,

Diagnostic Strategies for Prostate Cancer
Djavan B.; Kazzazi A.; Dulabon L.; Margreiter M.; Farr A.; Handl M.J.; Lepor H.
2011 ;10(3):e26-e37, European Urology Supplements
Context: Prostate cancer (PCa)is the most common malignancy in men in westernized cultures and the incidence of PCa is rapidly rising in low-risk countries due to significant westernization in these populations. Prostate-specific antigen (PSA) is the gold standard for screening of PCa. Means to improve the specificity and sensitivity of this screening method are imperative. Objective: In this article, we review novel blood-, urine-, and tissue-based biomarkers for screening and early diagnosis of PCa. Evidence acquisition: We discuss three studies: the 2001 Tyrol study, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Evidence synthesis: The new molecular forms of PSA, or precursor isoforms (pPSA), are exciting, but further studies are required to validate their clinical application. Measurement of p2PSA, benign PSA (bPSA), and intracellular macrophage PSA (imPSA) proved to be more stable and promising compared to free PSA and serum total PSA, thus improving early diagnosis of PCa, especially in patients with low serum PSA levels. Novel approaches in molecular technology seem to overcome hurdles in detecting PCa cells and markers in urinary samples. Recent results revealed the proteins PCA3 and AMACR to be useful and efficient new tools for PCa detection. PSA density and PSA velocity are certainly superior to a single PSA measurement, and PCa risk calculators may further enhance cancer prediction. Conclusions: The use of PSA has led to overdiagnosis and overtreatment of PCa, resulting in controversy about its use for screening. PSA also has limited accuracy and poor specificity for early detection of PCa. Novel markers for PCa detection, staging, and monitoring are required. The use of prostate-specific antigen (PSA) has led to overdiagnosis and overtreatment of prostate cancer, and PSA has limited accuracy and poor specificity for early detection of prostate cancer. Novel markers for prostate cancer detection, staging, and monitoring are required. 2011
— id: 132895, year: 2011, vol: 10, page: e26, stat: Journal Article,

Indications and Trends in Pelvic Lymph Node Dissection for Prostate Cancer
Djavan B.; Kazzazi A.; Dulabon L.; Momtahen S.; Dianat S.S.; Sand M.; Cheetham P.; Janetschek G.; Lepor H.; Graefen M.
2011 ;10(3):e38-e43, European Urology Supplements
Context: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with clinically localized prostate cancer (PCa) undergoing radical prostatectomy (RP). Objective: The aim of this review is to critically evaluate the current status of PLND in PCa. Evidence acquisition: A review of the literature was performed concerning RP and PLND with respect to oncologic outcome and associated complications. Evidence synthesis: PLND is still the modality of choice for detecting lymph node metastasis in PCa, as current imaging techniques are not accurate enough for detecting nodal metastases. Extended PLND (ePLND) has complications that increase with extent of dissection. Nodal yield at PLND is directly related to the lymph node invasion rate, and greater nodal yield is associated with superior staging accuracy. Conclusions: For patients with high- and intermediate-risk disease, ePLND-at least for external iliac, obturator, and hypogastric lymph nodes-should be performed during RP. However, for patients with low-risk disease, PLND is neither necessary nor recommended, because the chance of metastasis is low. In high-risk patients, the extent of PLND is controversial and should be the subject of more trials to determine long-term therapeutic benefit. Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with clinically localized prostate cancer undergoing radical prostatectomy. In high- and intermediate-risk disease, extended PLND should be performed, at least for specific lymph nodes. However, for patients with low-risk disease, PLND is neither necessary nor recommended because the chance of metastasis is low. 2011
— id: 132896, year: 2011, vol: 10, page: e38, stat: Journal Article,

The short-term use of erythropoetin-stimulating agents: impact on the biochemical recurrence of prostate cancer
Djavan, Bob; Laze, Juliana; Eckersberger, Elisabeth; Finkelstein, Julia; Agalliu, Ilir; Lepor, Herbert
2011 Nov;108(10):1582-1587, BJU international
Study Type - Harm (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Erythropoletin-stimulating agents (ESAs) have been widely prescribed for treating anaemia secondary to advanced maligancies with the objective of reducing the need for red blood cell transfusions and improving the quality of life. However, the risk/benefit of ESAs has recently been questioned and metaanalyses showing that these agents are associated with an increased risk of mortality when chronically administered to patients with advanced/metastatic cancers. In this study we examined the impact of short-term preoperative utilization of ESAs on biochemical recurrence - free survival rates after open radical retropubic prostatectomy (ORRP). OBJECTIVE: * To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival. PATIENTS AND METHODS: * From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. * Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). * Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. * Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment. RESULTS: * A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. * There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. * In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups. CONCLUSIONS: * The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. * The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease
— id: 140519, year: 2011, vol: 108, page: 1582, stat: Journal Article,

Is the apical soft tissue margin a better predictor of biochemical recurrence than the surgical specimen?
Godoy, Guilherme; Tareen, Basir U; Lepor, Herbert
2011 Jul-Aug;29(4):388-392, Urologic oncology
PURPOSE: To identify predictors of apical surgical margin (ASM) and apical soft tissue margin (ASTM), determine if the ASTM is a better predictor of biochemical recurrence (BR) than the ASM, and ascertain the impact of apical biopsies on BR rates. MATERIALS AND METHODS: One thousand three hundred eight consecutive men underwent open radical retropubic prostatectomy (RP) between October 2000 and December 2006. Circumferential biopsies of the ASTM were obtained intraoperatively and submitted for frozen section analysis. Logistic regression models were utilized to identify the factors associated with the presence of positive ASMs and ASTMs. The estimated 5-year risk of BR was calculated by the Kaplan-Meier method. RESULTS: Overall, 43 (3.3%) and 86 (6.6%) of cases exhibited positive ASM and ASTM, respectively. ASM was significantly associated with higher mean serum prostate-specific antigen levels, presence of perineural invasion, and greater volume of tumor in the biopsy specimen. None of these factors were observed to be associated with the presence of cancer in the ASTMs. In the multivariate analysis, only the presence of perineural invasion was a significant independent predictor of ASMs. The estimated 5-year BR rates in the positive ASMs only, ASTMs only, and both positive ASMs and ASTMs groups were 48.6%, 4.7%, and 38.8%, respectively. CONCLUSIONS: A positive ASM was associated with a significantly greater risk of BR compared with a positive ASTM. The very low estimated risk of BR at 5 years in cases with ASTM suggests that performing the ASTM biopsies may increase the cure rates achieved with RP
— id: 138410, year: 2011, vol: 29, page: 388, stat: Journal Article,

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion
Lee P; Li Y; Ligr M; McCarron J; Daniels G; Zhang D; Zhao X; Ye F; Wang J; Liu X; Osman I; Mencher S; Lepor H; Wang LG
2011 Jul 1;17(13):4414-4424, Clinical cancer research
PURPOSE: The development of new effective therapeutic agents with minimal side effects for prostate cancer treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine - Qing Dai (Indigo Naturalis), has been used to treat leukemia for decades. However, the anti-cancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in prostate cancer.EXPERIMENTAL DESIGN: Human prostate cancer cell lines were treated with or without Natura-alpha followed by cell growth and invasion assays measured. The anti-tumor effects of Natura-alpha were examined in nude mice tumor xenograft models, as well as in a patient with advanced hormone refractory metastatic prostate cancer. Signal network proteins targeted by Natura-alpha were analyzed using Proteomic Pathway Array Analysis (PPAA) on xenografts.RESULTS: Natura-alpha inhibited the growth of both androgen-dependent (LNCaP), and androgen-independent (LNCaP-AI, PC-3, and DU145) prostate cancer cells with IC50 between 4 to 10 Mum, also inhibits invasion of androgen-independent prostate cancer cells. Its anti-tumor effects were further evident in vivo tumor reduction in androgen-dependent and -independent nude mice tumor xenograft models as well as reduced tumor volume in the patient with hormone refractory metastatic prostate cancer. PPAA revealed that anti-proliferative and anti-invasive activities of Natura-alpha on prostate cancer might primarily be through its down-regulation of Forkhead box M1 (FOXM1) protein. Forced over-expression of FOXM1 largely reversed the inhibition by Natura-alpha.CONCLUSIONS: Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone sensitive and hormone refractory prostate cancer with minimal side effects
— id: 133174, year: 2011, vol: 17, page: 4414, stat: Journal Article,

Outcomes of extremely low risk prostate cancer following radical prostatectomy
Lee, E W; Laze, J; Lepor, H
2011 Sep;14(3):266-269, Prostate cancer & prostatic diseases
The optimal management of men with very favorable clinicopathological factors who develop biochemical recurrence (BCR) after radical prostatectomy (RP) has not been previously reported. Both local and systemic recurrences are unlikely in this cohort. This study examines their management and outcomes. Between October 2000 to March 2010, 1627 men underwent open RP by a single surgeon. In all, 448 (27.5%) met the following criteria for extremely low risk disease: preoperative PSA level <10 ng ml(-1), clinical stage T1c/T2a, Gleason score </=6, estimated cancer volume in the surgical specimen </=5% and no evidence for positive surgical margin. Undetectable PSA was defined as </=0.04 ng ml(-1). BCR was defined as PSA >/=0.2 ng ml(-1) or initiation of salvage radiation therapy (SRT) for progressively rising PSA. At 54 months mean follow-up (range 3-114 months), 9 (2%) of the 448 men developed BCR. Mean time to BCR was 63 months (range 12-93) and mean PSA doubling time was 15 months (range 6-27). Six underwent SRT, two elected surveillance and one was lost to follow-up. All men undergoing SRT exhibited more than 75% reduction in pre-SRT PSA, indicating the presence of local disease recurrence. All men undergoing SRT maintained PSA levels <0.1 at last follow-up. The BCR of 2% confirmed that we selected a cohort with extremely low risk for BCR after RP. We demonstrated that men fulfilling our criteria who develop BCR all harbor local disease based on favorable response to SRT. These men should be managed with SRT if recurrence is felt to be biologically significant
— id: 136633, year: 2011, vol: 14, page: 266, stat: Journal Article,

Clinical evaluation of a novel method for the measurement of prostate-specific antigen, AccuPSA(TM) , as a predictor of 5-year biochemical recurrence-free survival after radical prostatectomy: results of a pilot study
Lepor H; Cheli CD; Thiel RP; Taneja SS; Laze J; Chan DW; Sokoll LJ; Mangold L; Partin AW
2011 Oct 12;:?-?, BJU international
Study Type - Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Nadir Ultrasensitive PSA levels has some value for predicting BCR following RD. AccuPSA assays lower limit of PSA quantification of <0.01 pg/ml greatly enhances sensitivity and specificity of nadir PSA to predict BCR following RP. Our pilot study shows an AccuPSA of 3 pg/ml has a sensitory and specificity of 100% and 75% respectively for predicting 5 year BCR following RP. OBJECTIVES * To conduct a proof of concept study to evaluate a novel digital single molecule immunoassay (AccuPSA(TM) ) that detects prostate-specific antigen (PSA) a thousandfold more sensitively than current PSA detection methods. * To determine the ability of the AccuPSA(TM) assay to predict 5-year biochemical recurrence (BCR)-free survival after radical prostatectomy (RP). PATIENTS AND METHODS * A total of 31 frozen serum specimens were obtained from specimen logs maintained at New York University Langone Medical Center and the Johns Hopkins University School of Medicine on men who had undergone RP. Those men without evidence of BCR had a minimum of 5 years' PSA follow-up. * In all cases, preoperative and pathological information were available, as was a serum specimen 3-6 months after RP, with a PSA level of <0.1 ng/mL measured by conventional PSA methods at the time of serum collection. * Specimens were tested using the AccuPSA(TM) method. * A Cox proportional hazard model and Kaplan-Meier analysis were used to determine whether AccuPSA(TM) predicted the risk of BCR. RESULTS * Overall, 11/31 (35.5%) men developed BCR. * Mean AccuPSA(TM) nadir levels were significantly different (P < 0.001) between the non-BCR group (2.27 pg/mL) and the BCR group (46.99 pg/mL). * Using a multivariate Cox proportional hazard model, AccuPSA(TM) nadir level was a significant predictor of BCR-free survival (P < 0.01). * Kaplan-Meier analysis of up to 5 years follow-up showed that 100% of men with AccuPSA(TM) nadir values <3 pg/mL did not develop BCR, whereas 62.5% of men with values >3 pg/mL developed BCR (P= 0.00024). * The sensitivity, specificity, positive predictive value and negative predictive value of the AccuPSA(TM) method was 100%, 75%, 69% and 100%, respectively. CONCLUSIONS * AccuPSA(TM) assay predicts 5-year BCR- free survival after RP. * Identifying a reliable predictor of BCR soon after RP has important implications for frequency of PSA testing, selection of candidates for adjuvant therapy, and reassuring a large subset of men that they are not at risk of recurrence. * Larger studies are needed to validate these findings
— id: 139935, year: 2011, vol: , page: ?, stat: Journal Article,

Medical treatment of benign prostatic hyperplasia
Lepor, Herbert
2011 ;13(1):20-33, Reviews in urology
Medical therapy for the treatment of benign prostatic hyperplasia (BPH) became an accepted standard of care in the 1990s following the reports of randomized, double-blind, placebo-controlled studies showing that finasteride, a 5-alpha reductase inhibitor, and terazosin, an alpha-blocker, significantly improved lower urinary tract symptoms and increased peak urinary flow rates in men with BPH. This article reviews novel approaches to the pharmacological treatment of BPH
— id: 136519, year: 2011, vol: 13, page: 20, stat: Journal Article,

Minimally invasive ablative therapies for the treatment of prostate cancer
Lepor, Herbert
2011 ;13(1):61-62, Reviews in urology
— id: 136521, year: 2011, vol: 13, page: 61, stat: Journal Article,

Planum sphenoidale meningioma leading to visual disturbance
Lutwak N.; Dill C.; Wieczorek R.
2011 ;:?-?, BMJ case reports
A 60-year-old male presented with complaints of dizziness, which worsened with fatigue and a sense his balance was 'off'. Initial physical examination was negative and the laboratory testing was unremarkable. Within weeks, the patient developed bilateral visual field deficits. MRI revealed an extra-axial mass which extended into the pituitary fossa and caused compression of the pituitary gland. The pituitary stalk was displaced posteriorly and the optic chiasm was compressed with displacement superiorly and posteriorly. The patient underwent a surgical resection. Diabetes insipidus developed postoperatively requiring a vasopressin drip. He also developed hypopituitarism after the resection with hypothyroidism, hypoadrenalism and hypogonadism. The patient requires testosterone, levothyroxine and hydrocortisone replacement and has mild residual bitemporal hemianopsia.
— id: 138399, year: 2011, vol: , page: ?, stat: Journal Article,

Three-year postoperative ultrasensitive prostate-specific antigen following open radical retropubic prostatectomy is a predictor for delayed biochemical recurrence
Malik, Rena D; Goldberg, Judith D; Hochman, Tsivia; Lepor, Herbert
2011 Sep;60(3):548-553, European urology
BACKGROUND: Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time. OBJECTIVE: To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR. DESIGN, SETTING, AND PARTICIPANTS: There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level >/=0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels >/=0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was </=0.04 (n=765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n=36). MEASUREMENTS: Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level >/=0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up. RESULTS AND LIMITATIONS: The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio chi(2) for full model: 27.03; df=1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained. CONCLUSIONS: Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences
— id: 135557, year: 2011, vol: 60, page: 548, stat: Journal Article,

Post-prostatectomy incontinence during sexual activity: a single center prevalence study
Mitchell, Sarah A; Jain, Rajat K; Laze, Juliana; Lepor, Herbert
2011 Sep;186(3):982-985, Journal of urology
PURPOSE: The prevalence and mechanism of incontinence during sexual activity after radical prostatectomy has not been well described. We determined the prevalence and severity of incontinence during sexual activity with time and the relationship between incontinence during sexual activity and stress urinary incontinence in the absence of sexual activity. MATERIALS AND METHODS: A total of 1,459 men with prostate cancer underwent radical prostatectomy between October 2000 and December 2007, as performed by 1 surgeon. Patients completed UCLA-PCI preoperatively, and 3, 6, 12 and 24 months postoperatively. We analyzed the frequency distribution of incontinence during sexual activity and stress urinary incontinence with time. We also examined the relationship between incontinence during sexual activity and stress urinary incontinence by chi-square analysis. RESULTS: The percent of patients who reported any bother from incontinence during sexual activity was 44.4% at 3 months, which decreased to 36.1% at 24 months. The percent of patients reporting major bother from incontinence during sexual activity was 22.4% and 12.1% at 3 and 24 months, respectively. Bother from incontinence during sexual activity and from stress urinary incontinence were strongly associated at all times (p <0.001). More than half of the men with major bother due to incontinence during sexual activity also reported bother from stress urinary incontinence. However, more than 10% of those with no stress urinary incontinence problem reported major bother from incontinence during sexual activity. CONCLUSIONS: Incontinence during sexual activity is a persistent problem for some men after radical prostatectomy. Significant incontinence during sexual activity may occur in the absence of stress urinary incontinence during nonsexual activities. Effective management of this problem requires further investigation
— id: 136639, year: 2011, vol: 186, page: 982, stat: Journal Article,

Silodosin for Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Results of a Phase II Multicenter, Double-Blind, Placebo Controlled Study
Nickel, J Curtis; O'Leary, Michael P; Lepor, Herbert; Caramelli, Kim E; Thomas, Heather; Hill, Lawrence A; Hoel, Gary E
2011 Jul;186(1):125-131, Journal of urology
PURPOSE: We evaluated the efficacy and safety of 2 doses of silodosin vs placebo in men with moderate to severe abacterial chronic prostatitis/chronic pelvic pain syndrome who had not been treated previously with alpha-blockers for chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: In this multicenter, randomized, double-blind, phase II study, men 18 years old or older with chronic prostatitis/chronic pelvic pain syndrome, a total National Institutes of Health Chronic Prostatitis Symptom Index score of 15 or greater and a National Institutes of Health Chronic Prostatitis Symptom Index pain score of 8 or greater received 4 or 8 mg silodosin, or placebo once daily for 12 weeks. The primary efficacy end point was change from baseline to week 12 in National Institutes of Health Chronic Prostatitis Symptom Index total score. RESULTS: Of 151 patients (mean age 48 years) 52 received 4 mg silodosin, 45 received 8 mg silodosin and 54 received placebo. Silodosin 4 mg was associated with a significant decrease in total National Institutes of Health Chronic Prostatitis Symptom Index score (mean +/- SD change -12.1 +/- 9.3) vs placebo (-8.5 +/- 7.2, p = 0.0224), including a decrease in urinary symptom (-2.2 +/- 2.7, placebo -1.3 +/- 3.0, p = 0.0102) and quality of life (-4.1 +/- 3.1, placebo -2.7 +/- 2.5, p = 0.0099) subscores. The 4 mg dose of silodosin also significantly increased Medical Outcomes Study Short Form 12 physical component scores (4.2 +/- 8.1, placebo 1.7 +/- 9.0, p = 0.0492). During global response assessment 56% of patients receiving 4 mg silodosin vs 29% receiving placebo reported moderate or marked improvement (p = 0.0069). Increasing the dose of silodosin to 8 mg resulted in no incremental treatment effects. CONCLUSIONS: Silodosin 4 mg relieved symptoms and improved quality of life in men with chronic prostatitis/chronic pelvic pain syndrome but its efficacy requires confirmation in additional studies
— id: 135196, year: 2011, vol: 186, page: 125, stat: Journal Article,

Impact of ultrahigh baseline PSA levels on biochemical and clinical outcomes in two Radiation Therapy Oncology Group prostate clinical trials
Rodrigues, George; Bae, Kyounghwa; Roach, Mack; Lawton, Colleen; Donnelly, Bryan; Grignon, David; Hanks, Gerald; Porter, Arthur; Lepor, Herbert; Sandler, Howard
2011 Jun 1;80(2):445-452, International journal of radiation oncology biology physics
PURPOSE: To assess ultrahigh (UH; prostate-specific antigen [PSA] levels >/=50 ng/ml) patient outcomes by comparison to other high-risk patient outcomes and to identify outcome predictors. METHODS AND MATERIALS: Prostate cancer patients (PCP) from two Phase III Radiation Therapy Oncology Group clinical trials (studies 9202 and 9413) were divided into two groups: high-risk patients with and without UH baseline PSA levels. Predictive variables included age, Gleason score, clinical T stage, Karnofsky performance score, and treatment arm. Outcomes included overall survival (OS), distant metastasis (DM), and biochemical failure (BF). Unadjusted and adjusted hazard ratios (HRs) were calculated using either the Cox or Fine and Gray's regression model with associated 95% confidence intervals (CI) and p values. RESULTS: There were 401 patients in the UH PSA group and 1,792 patients in the non-UH PSA PCP group of a total of 2,193 high-risk PCP. PCP with UH PSA were found to have inferior OS (HR, 1.19; 95% CI, 1.02-1.39, p = 0.02), DM (HR, 1.51; 95% CI, 1.19-1.92; p = 0.0006), and BF (HR, 1.50; 95% CI, 1.29-1.73; p < 0.0001) compared to other high-risk PCP. In the UH cohort, PSA level was found to be a significant factor for the risk of DM (HR, 1.01; 95% CI, 1.001-1.02) but not OS and BF. Gleason grades of 8 to 10 were found to consistently predict for poor OS, DM, and BF outcomes (with HR estimates ranging from 1.41-2.36) in both the high-risk cohort and the UH cohort multivariable analyses. CONCLUSIONS: UH PSA levels at diagnosis are related to detrimental changes in OS, DM, and BF. All three outcomes can be modeled by various combinations of all predictive variables tested
— id: 138279, year: 2011, vol: 80, page: 445, stat: Journal Article,

T1 hyperintensity of bladder urine at prostate MRI: frequency and comparison with urinalysis findings
Rosenkrantz, Andrew B; Niver, Benjamin E; Kopec, Martin; Berkman, Douglas S; Lepor, Herbert; Babb, James S; Hecht, Elizabeth M
2011 May-Jun;35(3):203-207, Clinical imaging
OBJECTIVE: The purpose of this study was to assess the possible clinical significance of bladder urine T1 hyperintensity based upon comparison with urinalysis findings, using a cohort of patients who underwent prostate MRI and urinalysis at a similar point in time during preoperative work-up. METHODS: We identified 56 patients who underwent prostatectomy at our institution who obtained prostate MRI and urinalysis within 1 day of each other preoperatively. A control group of 160 consecutive adult men who underwent pelvic MRI during the same time period for other indications was also identified. Two radiologists independently and in consensus reviewed the T1-weighted images to assess the frequency of bladder urine T1 hyperintensity in both groups. The urinalyses in the 56 men undergoing prostatectomy were reviewed, with the results compared between patients with and without bladder urine T1 hyperintensity. RESULTS: Four (7.1%) of 56 men with prostate cancer exhibited T1 hyperintense bladder urine, compared with six (3.8%) of 160 patients exhibiting this finding in the control group (P=.288). Of the four prostate cancer patients with this finding, all exhibited a normal urinalysis. An abnormal urinalysis was identified for four of the prostate cancer patients, all of whom exhibited normal urine T1 signal intensity. CONCLUSION: Bladder urine T1 hyperintensity may be seen occasionally in patients with prostate cancer but is not associated with abnormal urinalysis and therefore should not be regarded as a sign of acute urinary pathology
— id: 131820, year: 2011, vol: 35, page: 203, stat: Journal Article,

Fifth-generation digital immunoassay for prostate-specific antigen by single molecule array technology
Wilson, David H; Hanlon, David W; Provuncher, Gail K; Chang, Lei; Song, Linan; Patel, Purvish P; Ferrell, Evan P; Lepor, Herbert; Partin, Alan W; Chan, Dan W; Sokoll, Lori J; Cheli, Carol D; Thiel, Robert P; Fournier, David R; Duffy, David C
2011 Dec;57(12):1712-1721, Clinical chemistry
BACKGROUND: Measurement of prostate-specific antigen (PSA) in prostate cancer patients following radical prostatectomy (RP) has been hindered by the limit of quantification of available assays. Because radical prostatectomy removes the tissue responsible for PSA production, postsurgical PSA is typically undetectable with current assay methods. Evidence suggests, however, that more sensitive determination of PSA status following RP could improve assessment of patient prognosis and response to treatment and better target secondary therapy for those who may benefit most. We developed an investigational digital immunoassay with a limit of quantification 2 logs lower than current ultrasensitive third-generation PSA assays. METHODS: We developed reagents for a bead-based ELISA for use with high-density arrays of femtoliter-volume wells. Anti-PSA capture beads with immunocomplexes and associated enzyme labels were singulated within the wells of the arrays and interrogated for the presence of enzymatic product. We characterized analytical performance, compared its accuracy with a commercially available test, and analyzed longitudinal serum samples from a pilot study of 33 RP patients. RESULTS: The assay exhibited a functional sensitivity (20% interassay CV) <0.05 pg/mL, total imprecision <10% from 1 to 50 pg/mL, and excellent agreement with the comparator method. All RP samples were well within the assay measurement capability. PSA concentrations following surgery were found to be predictive of prostate cancer recurrence risk over 5 years. CONCLUSIONS: The robust 2-log improvement in limit of quantification relative to current ultrasensitive assays and the validated analytical performance of the assay allow for accurate assessment of PSA status after RP
— id: 149892, year: 2011, vol: 57, page: 1712, stat: Journal Article,

Differentiation of the ductal epithelium and smooth muscle in the prostate gland are regulated by the Notch/PTEN-dependent mechanism
Wu X; Xu K; Zhang L; Deng Y; Lee P; Shapiro E; Monaco M; Makarenkova HP; Li J; Lepor H; Grishina I
2011 Aug 15;356(2):337-349, Developmental biology (Orlando)
We have shown previously that during branching morphogenesis of the mouse prostate gland, Bone morphogenetic protein 7 functions to restrict Notch1-positive progenitor cells to the tips of the prostate buds. Here, we employed prostate-specific murine bi-genic systems to investigate the effects of gain and loss of Notch function during prostate development. We show that Nkx3.1(Cre) and Probasin(Cre) alleles drive expression of Cre recombinase to the prostate epithelium and periepithelial stroma. We investigated the effects of gain of Notch function using the Rosa(NI1C) conditional allele, which carries a constitutively active intracellular domain of Notch1 receptor. We carried out the analysis of loss of Notch function in Nkx3.1(Cre/+);RBP-J(flox/flox) prostates, where RBP-J is a ubiquitous transcriptional mediator of Notch signaling. We found that gain of Notch function resulted in inhibition of the tumor suppressor PTEN, and increase in cell proliferation and progenitor cells in the basal epithelium and smooth muscle compartments. In turn, loss of Notch/RBP-J function resulted in decreased cell proliferation and loss of epithelial and smooth muscle progenitors. Gain of Notch function resulted in an early onset of benign prostate hyperplasia by three months of age. Loss of Notch function also resulted in abnormal differentiation of the prostate epithelium and stroma. In particular, loss of Notch signaling and increase in PTEN promoted a switch from myoblast to fibroblast lineage, and a loss of smooth muscle. In summary, we show that Notch signaling is necessary for terminal differentiation of the prostate epithelium and smooth muscle, and that during normal prostate development Notch/PTEN pathway functions to maintain patterned progenitors in the epithelial and smooth muscle compartments. In addition, we found that both positive and negative modulation of Notch signaling results in abnormal organization of the prostate tissue, and can contribute to prostate disease in the adult organ
— id: 134432, year: 2011, vol: 356, page: 337, stat: Journal Article,

LEF1 Identifies Androgen-Independent Epithelium in the Developing Prostate
Wu, Xinyu; Daniels, Garrett; Shapiro, Ellen; Xu, Kun; Huang, Hongying; Li, Yirong; Logan, Susan; Greco, M Alba; Peng, Yi; Monaco, Marie E; Melamed, Jonathan; Lepor, Herbert; Grishina, Irina; Lee, Peng
2011 Jun;25(6):1018-1026, Molecular endocrinology
Lymphoid enhancer-binding factor (LEF)1 is a major mediator and a target in canonical Wnt/beta-catenin pathway. Interactions between the androgen receptor (AR) and canonical Wnt pathways have been implicated in the development of the genitourinary organs. Here, we investigated the localization and role of LEF1-positive cells during development of the prostate gland in human and in the murine model. We show that during human prostate development, LEF1 is restricted to the basal epithelial layer of the urogenital sinus. During mouse development, Lef1 is also present in the urogenital mesenchyme in addition to the basal epithelial layer of the urogenital sinus. In the course of elongation and branching of the prostatic ducts, Lef1 is localized to the proliferating epithelium at the distal tips of the buds. Notably, during branching morphogenesis, domains of Lef1 and AR are mutually exclusive. We further employed the TOPGAL reporter strain to examine the dynamics of Wnt signaling in the context of prostate regression upon a 7-d treatment with a competitive AR inhibitor, bicalutamide. We found that Wnt/Lef1-positive basal cells are not dependent upon androgen for survival. Furthermore, upon bicalutamide treatment, Wnt/Lef1-positive basal progenitors repopulated the luminal compartment. We conclude that Wnt/Lef1 activity identifies an androgen-independent population of prostate progenitors, which is important for embryonic development and organ maintenance and regeneration in the adult
— id: 132604, year: 2011, vol: 25, page: 1018, stat: Journal Article,

Intraoperative Frozen Section Analysis of Urethral Margin Biopsies During Radical Prostatectomy
Ye H; Kong X; He TW; Jolis T; Choi K; Lepor H; Melamed J
2011 Aug;78(2):399-404, Urology
OBJECTIVES: To evaluate the accuracy and potential clinical value of intraoperative frozen section analysis (FSA) on urethral margin (UM) tissue during radical prostatectomy. Positive surgical margins increase the risk of post-operative cancer recurrence. Positive surgical margins are frequently found at the apex. The utility of intraoperative FSA of the margins is controversial. METHODS: We reviewed a consecutive series of radical prostatectomy cases (n = 1669) performed at our institution, in which UMs were routinely evaluated by intraoperative FSA. RESULTS: The submitted UM tissue contained cancer glands in 111 cases (6.7%). On FSA, the pathologists detected cancer in 55 cases (3.3%), missed cancer in 38 (2.3%), and reported atypical glands in 18 (1.1%). FSA of the UMs had a sensitivity of 59.1%, specificity of 99.8%, and positive and negative predictive value of 94.8% and 97.6%, respectively. The low sensitivity resulted from a substantial false-negative rate (n = 38), which was largely attributed to limited sampling on FSA (n = 31). Of the 55 patients (3.3%) whose positive UMs were detected by FSA, 20 (1.2%) had cancer-free margins after tissue re-excision. A positive final UM was associated with greater biochemical recurrence (P = .0073). However, the few patients limited the statistical analysis of the benefit of margin conversion through tissue re-excision (P = .35). CONCLUSIONS: Although experienced pathologists can evaluate the UMs on FSA with good accuracy, FSA has a relatively low sensitivity. Our data have indicated a low yield and a questionable value of routine FSA during radical prostatectomy
— id: 134890, year: 2011, vol: 78, page: 399, stat: Journal Article,

Patient centered outcomes in prostate cancer treatment: predictors of satisfaction up to 2 years after open radical retropubic prostatectomy
Abraham, Nitya E; Makarov, Danil V; Laze, Juliana; Stefanovics, Elina; Desai, Rani; Lepor, Herbert
2010 Nov;184(5):1977-1981, Journal of urology
PURPOSE: Few groups have examined satisfaction after prostate cancer treatment. We determined 1) predictors of satisfaction between 3 months and 2 years after open radical retropubic prostatectomy, and 2) whether these factors are time dependent. MATERIALS AND METHODS: This prospective cohort study included 1,542 men who underwent radical retropubic prostatectomy from October 2000 to July 2008. The primary outcome was satisfaction self-assessed at 3, 6, 12 and 24 months. We used multivariate logistic regression and repeated measures analysis to determine predictors of satisfaction, adjusting for demographic and clinical characteristics. RESULTS: Median followup was 24 months. About 93% of the men were satisfied. On multivariate analysis men were significantly less satisfied at 3 months when the urinary catheter was indwelling for 3 weeks or greater (OR 0.23, 95% CI 0.10-0.54), or they required intervention for anastomotic stricture (OR 0.23, 95% CI 0.11-0.49) or experienced 4-point or greater worsening in American Urological Association symptom score (OR 0.26, 95% CI 0.13-0.49). At 6 months worsening urinary function (OR 0.34, 95% CI 0.13-0.88) and biochemical failure (OR 0.15, 95% CI 0.05-0.43) were significantly associated with satisfaction. Worsening sexual function became significant at 12 and 24 months. These associations were confirmed on repeated measures analysis. CONCLUSIONS: Most men were satisfied after radical retropubic prostatectomy. Satisfaction determinants showed a nonsignificant trend toward time dependence. Postoperative factors, such as the duration of indwelling Foley catheterization, were associated with short-term satisfaction while sexual and urinary function, and biochemical failure were associated with long-term satisfaction. Based on high satisfaction rates open radical retropubic prostatectomy is an excellent treatment for prostate cancer
— id: 113746, year: 2010, vol: 184, page: 1977, stat: Journal Article,

Oncologic, Functional, and Cost Analysis of Open, Laparoscopic, and Robotic Radical Prostatectomy
Djavan, B; Eckersberger, E; Finkelstein, J; Sadri, H; Farr, A; Apolikhin, O; Lepor, H
2010 APR ;9(3):371-378, European Urology Supplements
Context: Although open radical retropubic prostatectomy (ORRP) remains the gold standard, the past years have seen a rise in both laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP), and many patients seem to prefer the so-called minimally invasive procedures despite insufficient data demonstrating superiority over the established standard (ORRP). Objective: This article seeks to review the most recent data on a variety of aspects of the different techniques for performing prostatectomies, such as cost, oncologic outcomes, continence, quality of life, and marketing and propaganda as well as the learning curve for each. Evidence acquisition: A search of the most recent literature was performed using PubMed, and data from lectures and presentations given at international conferences were used. Evidence synthesis: The review showed that, overall, LRP and RARP outcomes have not proved superior to ORRP outcomes or resulted in anticipated benefits to patients. In addition, current data seem to suggest that results of any of the procedures depend more on the surgeon's ability than on the approach, with rates of blood loss, positive surgical margins, incontinence, and erectile dysfunction varying widely from surgeon to surgeon with all three techniques. The aggressive marketing associated with RARP has also led to significantly higher rates of dissatisfaction and regret in patients. Conclusions: Considering the evidence, ORRP remains the gold standard in radical prostatectomies. Moreover, although the differences among major outcomes are minor and associated with shorter lengths of stay, the costs associated with LRP and RARP are significantly higher than with ORRP. In the absence of solid scientific evidence, patient education, and counselling are crucial parts of the decision-making process, during which patients will opt for one treatment over another. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved
— id: 109137, year: 2010, vol: 9, page: 371, stat: Journal Article,

Benign prostatic hyperplasia: current clinical practice
Djavan, Bob; Eckersberger, Elisabeth; Finkelstein, Julia; Espinosa, Geovanni; Sadri, Helen; Brandner, Roland; Shah, Ojas; Lepor, Herbert
2010 Sep;37(3):583-97, ix, Primary care
Benign prostatic hyperplasia (BPH) is the most common benign adenoma in men, affecting nearly all of them. BPH represents a clinically significant cause of bladder outflow obstruction in up to 40% of men. The growing frequency of diagnosis is due to increasing life expectancy and a trend toward seeking medical advice at earlier stages of the disease. The last decade has witnessed a significant shift in emphasis in the management of BPH, with medical therapies and, to a lesser extent, minimally invasive therapies becoming the predominant active therapy choices. The development of effective therapies such as alpha-adrenergic blockers and 5-alpha-reductase inhibitors and the possibility of their combined use represent the most significant advance in the treatment of BPH
— id: 111970, year: 2010, vol: 37, page: 583, stat: Journal Article,

Prostate-specific antigen testing and prostate cancer screening
Djavan, Bob; Eckersberger, Elisabeth; Finkelstein, Julia; Sadri, Helen; Taneja, Samir S; Lepor, Herbert
2010 Sep;37(3):441-59, vii, Primary care
Prostate specific antigen (PSA) screening is an integral part of current screening for prostate cancer. Together with digital rectal examinations, it is recommended annually by the American Cancer Society. PSA screening has resulted in a significant stage migration in the past decades. Different forms of PSA, including free PSA, volume adjusted, complexed, intact, or pro-PSA, are being used in the screening process. Other aspects of the screening process include age at diagnosis, survival, overdiagnosis, and overtreatment. Recent studies have cast doubt on whether PSA screening positively affects mortality and how the quality of life of patients may be affected by screening. Future considerations include the need for more longitudinal studies as well as further study of the PSA components that may become more relevant in the future
— id: 111969, year: 2010, vol: 37, page: 441, stat: Journal Article,

Durability and retreatment rates of minimal invasive treatments of benign prostatic hyperplasia: a cross-analysis of the literature
Djavan, Bob; Eckersberger, Elisabeth; Handl, Markus Johannes; Brandner, Roland; Sadri, Helen; Lepor, Herbert
2010 Aug;17(4):5249-5254, Canadian journal of urology
BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold standard of the treatment of benign prostatic hyperplasia (BPH). In recent years there has been a significant shift in the treatment of BPH and guidelines emphasize minimally invasive surgery as a new treatment option. Minimal invasive technologies (MITs), such as transurethral microwave thermotherapy (TUMT), laser ablations, transurethral needle ablation (TUNA) have emerged as an alternative to the TURP. OBJECTIVES: To assess the retreatment rates of the most commonly used minimal invasive techniques. SEARCH STRATEGY: Durability articles were selected by using defined search terms using PubMed as search engine. RESULTS: Comparing to the overall retreatment rates of MITs the results show that TUMT, holmium laser enucleation of the prostate (HoLEP) and contact laser vaporization (CLV) are among the treatments with the lowest retreatment rates. Studies show no significant differences in retreatment rates between TUMT and TURP. CONCLUSION: A review of the current literature, long term results and retreatment rates of MITs shows large variability in outcomes and retreatment rates. The true definition of a MIT remains unclear. High energy TUMT deserves reconsideration in clinical practices, due to low retreatment rates and the low need of anesthetics
— id: 115329, year: 2010, vol: 17, page: 5249, stat: Journal Article,

Uro-oncological controversies in euro-oncology: highlights from the European association of urology section of oncological urology, january 15-17, 2010, vienna, austria
Eckersberger, Elisabeth; Lepor, Herbert; Sadri, Helen; Farr, Alexander; Margreiter, Markus; Harik, Mike; Djavan, Bob
2010 Spring;12(2-3):e125-e128, Reviews in urology
— id: 112057, year: 2010, vol: 12, page: e125, stat: Journal Article,

Open Versus Laparoscopic Versus Robot-Assisted Laparoscopic Prostatectomy: The European and US Experience
Finkelstein, Julia; Eckersberger, Elisabeth; Sadri, Helen; Taneja, Samir S; Lepor, Herbert; Djavan, Bob
2010 Winter;12(1):35-43, Reviews in urology
Open radical prostatectomy (ORP) is the reference standard for the surgical management of localized prostate cancer. With wider availability of minimally invasive radical prostatectomy techniques, there is a debate regarding the standard treatment of the management of localized prostate cancer. Therefore, we reviewed the current status of laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALRP) as compared with ORP. Because no prospective, randomized trials comparing the different techniques have been performed, outcomes must be assessed from published series by centers that focus on ORP, LRP, and RALRP. Aside from reducing the amount of blood loss, current data suggest that the most significant outcomes (cure, continence, and potency) are no better with LRP or RALRP than with conventional ORP. Therefore, in experienced hands, ORP remains the gold standard procedure. However, there is a trend toward consistently better outcomes following RALRP in comparison with LRP. In the end, individual patient outcomes can be maximized by choosing the best modality based on the patient's comorbid medical conditions, cancer characteristics, and surgeon experience. Future studies are needed to further investigate long-term cancer control as well as functional outcomes for RALRP series
— id: 109532, year: 2010, vol: 12, page: 35, stat: Journal Article,

COMPARISON OF POSITIVE SURGICAL MARGINS IN PATIENTS WITH PATHOLOGIC T3 DISEASE UNDERGOING ROBOTIC ASSISTED LAPAROSCOPIC PROSTATECTOMY OR OPEN RADICAL RETROPUBIC PROSTATECTOMY
Jain, R.; Berkman, D. S.; Taneja, S. S.; Huang, W. C.; Lepor, H.; Stifelman, M.
2010 SEP ;24(1):A45-A46, Journal of endourology
— id: 124116, year: 2010, vol: 24, page: A45, stat: Journal Article,

The Preoperative Use of Erythropoietin Stimulating Proteins Prior to Radical Prostatectomy Is Not Associated With Increased Cardiovascular or Thromboembolic Morbidity or Mortality REPLY
Lepor, H
2010 JUN ;75(6):1430-1430, Urology
— id: 110124, year: 2010, vol: 75, page: 1430, stat: Journal Article,

Editorial comment
Lepor, Herbert
2010 Oct;76(4):933-933, Urology
— id: 113809, year: 2010, vol: 76, page: 933, stat: Journal Article,

Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability
Lepor, Herbert; Hill, Lawrence A
2010 Dec;30(12):1303-1312, Pharmacotherapy
Abstract Relief of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms by alpha-blockers (alpha1-adrenoceptor antagonists) is mediated primarily through the blockade of alpha(1A)-receptors, leading to relaxation of smooth muscle in the prostate and bladder neck. Early alpha-blockers that were nonselective for adrenoceptor subtypes have been associated with blood pressure-related adverse effects, such as orthostatic hypotension, that may be attributed at least in part to the blockade of alpha(1B)-adrenoceptors in arterial vessels. Silodosin, a novel alpha-blocker with exceptionally high selectivity for alpha(1A-) versus alpha(1B)-adrenoceptors, was recently approved in the United States for the treatment of urinary symptoms related to BPH. The unique receptor selectivity profile likely accounts for some of the desirable clinical features of the drug. Silodosin possesses an excellent cardiac- and blood pressure-related safety profile, and data have demonstrated that it does not promote QT-interval prolongation. Therapeutic doses of silodosin are safe for men with mild-to-moderate liver dysfunction; dosage adjustment is recommended in those with moderate renal impairment. The drug should not be taken with potent cytochrome P450 3A4 inhibitors. Silodosin may be especially beneficial in patients who need to maximize cardiovascular tolerability
— id: 114854, year: 2010, vol: 30, page: 1303, stat: Journal Article,

The preoperative use of erythropoietin stimulating proteins prior to radical prostatectomy is not associated with increased cardiovascular or thromboembolic morbidity or mortality
Lepor, Herbert; Lipkin, Michael; Slova, Denisa
2010 Jun;75(6):1424-1428, Urology
OBJECTIVES: To critically examine the cardiovascular and thromboembolic risks associated with erythropoietin stimulating proteins (ESPs) in men with normal hemoglobin levels undergoing open radical retropubic prostatectomy. METHODS: Between October 1, 2000, through December 31, 2006, a total of 1308 men underwent open radial retropubic prostatectomy by a single surgeon. Of these men, 1095 received preoperative ESPs. Hematocrit levels measured at baseline, immediately before anesthesia induction and at hospital discharge, were prospectively entered into a database. Thromboembolic and cardiovascular complications were prospectively captured during the hospitalization and after surgery. RESULTS: The mean Delta preoperative hematocrit level was 5.9 g/dL. The pre-anesthesia induction hematocrit level was 49.2%. Hospital discharge hematocrit level was 33.6 g/dL. The overall risk of cardiovascular and thromboembolic complications in men receiving ESP were 0.55% and 0.45%, respectively. The risk of cardiovascular and thromboembolic complications were independent of the Delta in preoperative hematocrit or the absolute level of the pre-anesthesia induction hematocrit. CONCLUSIONS: ESPs represent a safe and effective preoperative blood management strategy for men undergoing open radical retropubic prostatectomy
— id: 112482, year: 2010, vol: 75, page: 1424, stat: Journal Article,

Neurovascular bundle resection: does it improve the margins?
Lepor, Herbert; Tareen, Basir
2010 Mar-Apr;28(2):215-218, Urologic oncology
Prior to the description of the anatomic nerve sparing radical prostatectomy, most men were rendered impotent following radical perineal or retropubic prostatectomies. The fact that these 'erection' nerves were localized outside the prostate suggested the feasibility of totally eradicating localized prostate cancer with preservation of erectile function in selected cases. All of these studies collectively suggest that unilateral excision of neurovascular bundles will compromise potency rates in between 15% to 20% of cases. It seems logical to report the risk of extracapsular extension independently for the two sides of the prostate, especially since independent decisions are made relative to the nerve sparing status of the different sides. Extracapsular extension is a risk factor for positive surgical margins. Positive surgical margins represent an independent risk factor for biochemical recurrence following radical prostatectomy. The surgeon is left with the dilemma of whether to maximize potency at the risk of compromising cancer control. In cases with a 30% risk of side specific extracapsular extension, using the above assumption, the risk of developing a positive surgical margin and biochemical recurrence is only 4.7% and 2%, respectively
— id: 108432, year: 2010, vol: 28, page: 215, stat: Journal Article,

The effect of local compression and topical epinephrine on perioperative bleeding and degree of urinary extravasation on postoperative cystogram following radical retropubic prostatectomy
Malik, Rena; Laze, Juliana; Lepor, Herbert
2010 Aug;17(4):5272-5277, Canadian journal of urology
OBJECTIVE: To evaluate the efficacy of local compression and topical epinephrine in controlling perioperative bleeding during open radical retropubic prostatectomy (ORRP) and its impact on the degree of urinary extravasation on initial postoperative cystogram. METHODS: Between September 2005 to March 2009, 476 men underwent ORRP performed by a single surgeon. Group 1 (n = 200) underwent ORRP between September 2005 and November 2006 without pelvic compression; Group 2 (n = 76) underwent ORRP between November 2006 and May 2007 and a dry laparotomy pad was positioned in the pelvis immediately prior to abdominal wound closure; Group 3 (n = 200) underwent ORRP between May 2007 and March 2009 with a epinephrine soaked laparotomy pad positioned in the pelvis prior to abdominal wound closure. Hematocrit values were obtained prior to anesthesia induction, upon arrival in the recovery room and at hospital discharge in order to estimate intraoperative and postoperative bleeding. The number of allogenic and autologous units transfused was recorded. The utility of compressing the pelvis with a pad was examined by comparing estimated postoperative bleeding between Group 1 versus Groups 2 and 3 and the hemostatic utility of soaking the pad in epinephrine was examined by comparing Group 2 versus 3. Systolic and diastolic blood pressure and pulse measurements were obtained at baseline and 5 and 10 minutes after introducing the epinephrine pad. The relationship between estimated blood loss and degree of extravasation on initial postoperative cystogram was investigated. RESULTS: Estimated intraoperative, postoperative and total blood loss (mean change in Hct) was 12.2, 2.3, 14.2, in Group 1, 10.0, 1.5, 11.1 in Group 2, and 10.8, 2.1, and 12.6 in Group 3. Estimated intraoperative and total blood loss was significantly less in the men treated with a compression pad (Groups 2 and 3) versus no pad (Group 1). There were no significant differences in number of patients transfused, the number of units transfused or the degree of extravasation on postoperative cystograms between Group 1 versus Group 2 and 3 or Group 2 versus 3. However, postoperative bleeding was significantly less in Group 2 compared to Group 3. Mean systolic and diastolic blood pressure and pulse values were unchanged from baseline after epinephrine use. CONCLUSIONS: Local compression of the pelvis with or without epinephrine prior to abdominal wound closure does not appear to have beneficial effects on reducing postoperative bleeding and decreasing the degree of urinary extravasation on cystogram following ORRP. While the use of topical epinephrine appears to be safe and relatively inexpensive, at the concentrations used in our study it does not appear to facilitate postoperative hemostasis
— id: 115328, year: 2010, vol: 17, page: 5272, stat: Journal Article,

Optimizing the detection of subclinical inguinal hernias in men undergoing open radical retropubic prostatectomy
Marien, Tracy; Taouli, Bachir; Telegrafi, Shpetim; Babb, James; Lepor, Herbert
2010 Nov;106(10):1468-72, BJU international
Study Type - Diagnostic (exploratory cohort)Level of Evidence 2b OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and up-standing ultrasonography (USUS) for the detection of inguinal hernias (IHs) before open radical retropubic prostatectomy (ORRP) and to assess factors associated with the presence of IHs in these men. PATIENTS AND METHODS: From 1 July 2007 to 1 February 2009, 164 men underwent preoperative evaluation for ORRP by one surgeon. Of these men 113 (69%) were evaluated for IHs by physical examination (PE), USUS and MRI. In all 226 groins were examined. Any IH diagnosed by any method was considered a true positive. The sensitivity, negative predictive value (NPV), and concordance were calculated for the three diagnostic methods. Possible predictive factors of IHs were evaluated. RESULTS: Of the 226 groins evaluated, 72 (32%) IHs were diagnosed. USUS had the greatest sensitivity (69.4%) and the highest NPV (87.5%). MRI had fair agreement with PE and USUS, while USUS and PE had moderate agreement with each other. No factor was associated with an increased likelihood of preoperative diagnosis of IH. CONCLUSIONS: This study was limited by the lack of a reference standard to diagnose IH. USUS was the most sensitive method for the detection of IH. We recommend that all men undergoing ORRP should be evaluated for IHs by PE and at least one imaging method and that IHs be repaired at the time of ORRP, obviating the need for a second surgical procedure
— id: 114043, year: 2010, vol: 106, page: 1468, stat: Journal Article,

Recovery of erectile function after nerve sparing radical prostatectomy and penile rehabilitation with nightly intraurethral alprostadil versus sildenafil citrate
McCullough, Andrew R; Hellstrom, Wayne G; Wang, Run; Lepor, Herbert; Wagner, Kristofer R; Engel, Jason D
2010 Jun;183(6):2451-2456, Journal of urology
PURPOSE: To our knowledge we report the first large, randomized, prospective penile rehabilitation clinical trial to compare the effectiveness of nightly intraurethral alprostadil vs sildenafil citrate after nerve sparing prostatectomy. MATERIALS AND METHODS: We performed a prospective, randomized, open label, multicenter American study in men with normal erectile function who underwent bilateral nerve sparing radical prostatectomy. The International Index of Erectile Function erectile function domain was the primary end point. Subjects initiated nightly treatment within 1 month of surgery with intraurethral alprostadil or oral sildenafil citrate (50 mg) for 9 months. After 1-month washout and before sexual activity subjects self-administered sildenafil citrate (100 mg) for a total of 6 attempts in 1 month. Secondary end points were the global assessment question, sexual encounter profile, Erectile Dysfunction Inventory of Treatment Satisfaction and measured stretched penile length. RESULTS: Of 139 men who started intraurethral alprostadil and 73 who started sildenafil citrate, 97 and 59, respectively, completed the trial. There were no statistically significant differences in International Index of Erectile Function erectile function domain and intercourse success rates to intraurethral alprostadil. The global assessment question was significantly better only at 6 months for intraurethral alprostadil (p <0.028). At completion there were no differences between treatments for any of the end points. CONCLUSIONS: This is the first study to directly compare the ability of alprostadil and a phosphodiesterase-5 inhibitor to enhance penile recovery subsequent to bilateral nerve sparing radical prostatectomy. The use of nightly subtherapeutic intraurethral alprostadil is well tolerated after radical prostatectomy. The benefit to return of erectile function of nightly sildenafil citrate and subtherapeutic intraurethral alprostadil appears to be comparable within the first year of surgery
— id: 109674, year: 2010, vol: 183, page: 2451, stat: Journal Article,

Effects of the selective alpha 1a-adrenoceptor antagonist silodosin on ECGs of healthy men in a randomized, double-blind, placebo- and moxifloxacin-controlled study
Morganroth, J; Lepor, H; Hill, L A; Volinn, W; Hoel, G
2010 May;87(5):609-613, Clinical pharmacology & therapeutics
In order to determine the effects of therapeutic and supratherapeutic doses of silodosin on QT interval, healthy men (N = 186; aged 18-45 years) were randomized to receive silodosin (8 or 24 mg) or placebo for 5 days or moxifloxacin 400 mg (positive control, known to prolong QT) once on day 5. At baseline and on day 5, five ECGs were recorded 0.25 h before dosing and 1, 1.5, 2, 3, 4, 6, 8, 10, and 23.5 h after dosing. Adjusted mean differences (analysis of covariance) between silodosin and placebo in the change in individual heart rate-corrected QTc (QTcI) from baseline to day 5 were <5 ms at all times (all 90% confidence interval (CI) upper limits <10 ms). The QTcI difference for moxifloxacin compared with placebo often exceeded 5 ms, establishing assay sensitivity. For silodosin, no statistically or clinically significant correlation was seen between plasma concentration and QTcI, and no clinically important effects on heart rate, PR segment, QRS complex, or morphologic ECG data were observed
— id: 134362, year: 2010, vol: 87, page: 609, stat: Journal Article,

Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy
Mufarrij, Patrick; Sankin, Alex; Godoy, Guilherme; Lepor, Herbert
2010 Sep;76(3):689-692, Urology
OBJECTIVES: To examine the pathologic findings and biochemical recurrence rates for a consecutive cohort of candidates for active surveillance who underwent radical prostatectomy. The role of active surveillance for the treatment of low-risk prostate cancer is highly controversial. METHODS: Between October 2000 and February 2008, a single surgeon performed 1565 open radical retropubic prostatectomies for clinically localized prostate cancer. Cases were selected for extraction if they fulfilled 1 of 2 published criteria for active surveillance in our prospective longitudinal outcomes database. A retrospective review of the prospectively collected database was executed to elucidate the outcomes of candidates for active surveillance who underwent radical retropubic prostatectomy. Gleason score, pathologic stage, and surgical margins were prospectively captured in our database. The 5-year, biochemical-free survival rates were estimated using Kaplan-Meier analysis plots. RESULTS: Overall, 45.9%-47.2% of cases were pathologically upgraded to a Gleason score >/= 7. Moreover, 12.3%-13.1% of cases were found to have a primary Gleason pattern of 4 or 5. Extracapsular extension (pT3a disease) was observed in 7.8%-10.9% of cases. A total of 28.8%-32.2% of cases had an estimated percentage of cancer volume in the surgical specimen exceeding 20%. The 5-year biochemical-free survival was estimated to be 83.2%-92.9%. CONCLUSIONS: Our pathologic findings and risk of biochemical recurrence after open radical prostatectomy questions the wisdom of active surveillance in men with low-risk disease who have 'long' life expectancies
— id: 112424, year: 2010, vol: 76, page: 689, stat: Journal Article,

Reply
Mufarrij, Patrick; Sankin, Alex; Godoy, Guilherme; Lepor, Herbert
2010 Sep;76(3):693-694, Urology
— id: 112433, year: 2010, vol: 76, page: 693, stat: Journal Article,

Para-anastomotic haematoma volume predicts the presence of anastomotic extravasation after radical retropubic prostatectomy
O'Malley, Rebecca L; Telegrafi, Shpetim; Laze, Juliana; Lepor, Herbert
2010 Jan 1;105(1):34-36, BJU international
Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE To determine the mechanism for delayed healing of the urinary anastomosis after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS The volumes of the para-anastomotic haematoma (PHV) and anastomotic extravasation were measured by ultrasonography in 95 men after RRP. The performance characteristics of PHV for predicting urinary extravasation were ascertained and compared with that of postoperative blood loss, measured as the difference between the haematocrit immediately after RRP and that at discharge. RESULTS The sensitivity and specificity of PHV for predicting urinary extravasation at a threshold of 37 mL was 100% and 96%, respectively. PHV was superior to postoperative blood loss in predicting anastomotic extravasation, as shown by an area under the receiver operating curve of 0.99 vs 0.91, respectively. CONCLUSIONS Our findings provide compelling evidence that delayed healing of the anastomosis after RRP is due to distraction forces secondary to a pelvic haematoma. The accuracy of PHV as a predictor of anastomotic extravasation suggests that this measurement might replace cystography for assessing anastomotic integrity after RRP
— id: 106590, year: 2010, vol: 105, page: 34, stat: Journal Article,

Baseline serum testosterone in men treated with androgen deprivation therapy and radiotherapy for localized prostate cancer
Roach, Mack 3rd; Bae, Kyounghwa; Lawton, Colleen; Donnelly, B J; Grignon, David; Hanks, Gerald E; Porter, Arthur; Lepor, Herbert; Venketesan, Varagur; Sandler, Howard
2010 Dec 1;78(5):1314-1322, International journal of radiation oncology biology physics
INTRODUCTION: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forego testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. METHODS AND MATERIALS: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) </=16.5th percentile of BST (</=248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and </=33rd percentile (>248 ng/dL but </=314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and </=67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. >/=70), prostate-specific antigen (PSA; <10 vs. 10 </= PSA <20 vs. 20 </=), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). RESULTS: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. CONCLUSIONS: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer
— id: 115330, year: 2010, vol: 78, page: 1314, stat: Journal Article,

RELATIONSHIP BETWEEN SILODOSIN-INDUCED URODYNAMIC AND SYMPTOMATIC IMPROVEMENT AND RETROGRADE EJACULATION (RE) IN MEN WITH BENIGN PROSTATIC HYPERPLASIA (BPH)
Roehrborn, CG; Lepor, H; Kaplan, SA; Hill, LA; Volinn, W; Hoel, G
2010 MAR ;7(6):14-14, Journal of sexual medicine
— id: 110150, year: 2010, vol: 7, page: 14, stat: Journal Article,

Transperineal sonocystography: new standard for assessing anastomotic leaks after radical prostatectomy
Telegrafi, Shpetim; Ito, Timothy; Kozirovsky, Mariana; Laze, Juliana; Lepor, Herbert
2010 Jan;29(1):71-77, Journal of ultrasound in medicine
OBJECTIVE: Fluorocystography (FC) is the reference standard for assessing the integrity of the vesicourethral anastomosis after radical prostatectomy (RP). We describe a new technique, transperineal sonocystography (TPSC), as a cost-effective alternative and more informative than FC. METHODS: Between May 1, 2007, and October 1, 2008, 175 consecutive men underwent open or robotically assisted RP. Before Foley catheter removal, all men underwent both TPSC and FC, which were performed and interpreted by a single radiologist. Transperineal sonocystography was performed first with real-time imaging after gravity filling of the bladder with 150 mL of normal saline. Extravasation of saline was calculated by computer software after outlining the observed pooling of extravasated saline in the transverse and longitudinal views. Fluorocystography was performed after TPSC using our standard protocol, with qualitative classification of anastomotic leaks as none, slight, moderate, or severe. RESULTS: The mean extravasation volume +/- SEM was 16.3 +/- 2.9 mL. Of the 175 patients, 142 (81.2%) showed no anastomotic leaks on TPSC. Of the remaining 33 patients (18.8%), TPSC identified 20 (11.4%), 13 (7.4%), and 0 patients with slight, moderate, and severe leaks, respectively. Excellent concordance was shown between TPSC and FC. CONCLUSIONS: Transperineal sonocystography was equivalent to FC in detecting anastomotic leaks after RP. It provides a safe, inexpensive, and effective alternative to traditional FC for evaluating the integrity of the vesicourethral anastomosis after RP
— id: 111630, year: 2010, vol: 29, page: 71, stat: Journal Article,

Gene polymorphisms and prostate cancer: the evidence
Dianat, Seyed S; Margreiter, Markus; Eckersberger, Elisabeth; Finkelstein, Julia; Kuehas, Franklin; Herwig, Ralf; Ayati, Mohsen; Lepor, Herbert; Djavan, Bob
2009 Dec;104(11):1560-1572, BJU international
OBJECTIVE: Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome-wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression. MATERIALS AND METHODS: We performed a PubMed search using several key words such as prostate cancer, names of important genes with critical function, and polymorphisms. Then, we reviewed retrieved articles as well as relevant articles from 1997 to 2009. RESULTS: There are conflicting results of studies on some gene polymorphisms in association with prostate cancer. Most of the inconsistent results have been reported in studies investigating the vitamin D receptor gene polymorphism in association with prostate cancer. Genes related to angiogenesis and cell adhesion genes are more promising. Following results of future studies, the use of antibodies blocking over-expressed genes or proteins may be supported in patients with prostate cancer. CONCLUSIONS: The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome-wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors
— id: 115331, year: 2009, vol: 104, page: 1560, stat: Journal Article,

Complex Mechanisms in Prostatic Inflammatory Response
Djavan, Bob; Eckersberger, Elisabeth; Espinosa, Geovanni; Kramer, Gero; Handisurya, Alessandra; Lee, Chung; Marberger, Michael; Lepor, Herbert; Steiner, Georg E.
2009 DEC ;8(13):872-878, European Urology Supplements
Context: The immunology of the prostate has developed into a new field of research in urology. The leukocyte population increases are not yet fully understood, but it has been demonstrated that most resected prostate tissue shows signs of inflammatory response. Objective: This article reviews recent findings and discusses the complex mechanisms involved in the prostatic inflammatory response and the immunologic functions of the prostate, and the roles the prostatic inflammatory response in the cause of prostate disease such as benign prostatic hyperplasia (BPH). Evidence acquisition: We performed a search of the medical literature with PubMed, using keywords such as prostate cancer, inflammation of the prostate, leukocytes, estrogen, and cytokine and genetic expression of inflammation. Articles and data were reviewed as to their relevance, and inclusion and exclusion criteria were determined prospectively. Evidence synthesis: Evidence showing that inflammation of the prostate plays a role in prostate cancer (PCa) is mounting. Different types of inflammation exist and are distinguished according to the distribution and location of leukocytes and the histology of the surrounding tissue. Most resected prostate tissue shows signs of inflammatory response, and a relationship between T-cell infiltration and stromal proliferation can be found. Evidence for the importance of estrogen and proinflammatory cytokine interleukin (IL; IL-6, IL-8, IL-15, IL-17) also can be found. Early stages of investigation of the immunologic function of the prostate show that both prostatic epithelial and stromal cells express members of the toll-like receptor family and are therefore capable of recognizing foreign incoming antigens. Conclusions: Although this area of study is new, the immunology and inflammatory responses of the prostate are seen as important components of further study of prostate diseases such as PCa and BPH. Data supporting the role of immunology and activated leukocytes in malignant cells are also an important finding and can possibly lead to new knowledge about malignant cells. (C) 2009 Published by Elsevier B. V. on behalf of European Association of Urology
— id: 141042, year: 2009, vol: 8, page: 872, stat: Journal Article,

Screening for Prostate Cancer: A Review of the ERSPC and PLCO Trials
Eckersberger, Elisabeth; Finkelstein, Julia; Sadri, Helen; Margreiter, Markus; Taneja, Samir S; Lepor, Herbert; Djavan, Bob
2009 Summer;11(3):127-133, Reviews in urology
The advent of prostate-specific antigen (PSA) testing in the early 1980s revolutionized the diagnosis of prostate cancer. As a result of PSA testing, there has been a surge in the number of prostate cancer diagnoses. This review examines the results of 2 recent landmark trials that studied the effect of screening on prostate cancer mortality: the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
— id: 108182, year: 2009, vol: 11, page: 127, stat: Journal Article,

Changes in continence and erectile function between 2 and 4 years after radical prostatectomy
Glickman, Leonard; Godoy, Guilherme; Lepor, Herbert
2009 Feb;181(2):731-735, Journal of urology
PURPOSE: There is a paucity of information on changes in continence and erectile function beyond 2 years after radical prostatectomy. We prospectively examined changes in continence and erectile function between 2 and 4 years after radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and August 2003, 731 consecutive men underwent open retropubic radical prostatectomy for clinically localized prostate cancer. Preoperative and postoperative continence, and erectile function were ascertained using the UCLA Prostate Cancer Index. The 48-month prospective self-assessment followup questionnaire captured changes in urinary control and erectile function between 24 and 48 months, including marked, moderate or slight improvement, no change or worsening. RESULTS: Overall between 24 and 48 months after radical prostatectomy 23.4% and 42.3% of men showed any degree of improvement in continence and erectile function, and 12.2% and 19.8% showed marked and moderate improvement in continence and erectile function, respectively. The probability of experiencing any qualitative improvement in urinary continence was not significantly different in men who were continent or incontinent at 24 months. The likelihood of experiencing any qualitative improvement in erectile function was significantly greater in men who were potent at 24 months compared to those who were impotent. CONCLUSIONS: Our study provides compelling evidence that clinically significant improvements in urinary control and erectile function occur beyond 2 years after radical prostatectomy. These qualitative improvements are greatest for erectile function in men who were potent at 2 years. Therefore, men should not be counseled that maximal urinary continence or erectile function are achieved by 24 months after radical prostatectomy
— id: 92181, year: 2009, vol: 181, page: 731, stat: Journal Article,

Does benign prostatic tissue contribute to measurable PSA levels after radical prostatectomy?
Godoy, Guilherme; Tareen, Basir U; Lepor, Herbert
2009 Jul;74(1):167-170, Urology
OBJECTIVES: To provide insights into the likelihood that benign prostatic tissue represents a source of measurable prostate-specific antigen (PSA) after radical prostatectomy. METHODS: From October 2000 to December 2006, 1308 consecutive men underwent open radical retropubic prostatectomy by a single surgeon. Of these 1308 men, 331 (25.3%) met our criteria for having 'extremely' low-risk disease as determined by the preoperative and pathologic factors, including a preoperative PSA level <10 ng/mL, clinical Stage T1c or T2a, a Gleason score of < or =6, an estimated cancer volume in the specimen of <5%, and no evidence of positive surgical margins. This cohort was selected because any measurable PSA level would be highly suspicious for a benign origin. Undetectable PSA was defined as a PSA level of < or =0.04 ng/mL. A measurable PSA level included values between 0.05 and 0.14 ng/mL on > or =2 consecutive measurements 6 months apart. Biochemical recurrence was defined as 3 consecutively increasing PSA levels with a peak level of > or =0.15 ng/mL. RESULTS: At 3 months to 6 years of follow-up (mean 36.2 months), 0.6% and 0.3% of patients had developed a measurable PSA level or biochemical recurrence, respectively. The single patient with biochemical recurrence responded to salvage radiotherapy, strongly suggesting a malignant etiology for the recurrence. CONCLUSIONS: A measurable PSA level or biochemical recurrence was an extraordinarily rare event in our select group of patients with extremely low-risk disease. These results provide compelling evidence that retained benign prostatic elements are an unlikely source of elevated PSA levels in men who have undergone radical prostatectomy
— id: 100602, year: 2009, vol: 74, page: 167, stat: Journal Article,

Site of positive surgical margins influences biochemical recurrence after radical prostatectomy
Godoy, Guilherme; Tareen, Basir U; Lepor, Herbert
2009 Dec;104(11):1610-1614, BJU international
OBJECTIVE: To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates. PATIENTS AND METHODS: The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate-specific antigen (PSA) level rises with the peak level >or=0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5-year risk of BCR was calculated using the Kaplan-Meier method. RESULTS: In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5-year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5-year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex approximately posterior. CONCLUSIONS: About half of the men with PSMs in the RP surgical specimen in our prospective series did not develop BCR. The risk of BCR was dependent on the site and not the number of PSMs. Adjuvant therapy should be considered in cases with anterior and basilar PSMs due to the very high risk of BCR
— id: 106088, year: 2009, vol: 104, page: 1610, stat: Journal Article,

Deficiency of pRb family proteins and p53 in invasive urothelial tumorigenesis
He, Feng; Mo, Lan; Zheng, Xiao-Yong; Hu, Changkun; Lepor, Herbert; Lee, Eva Y-H P; Sun, Tung-Tien; Wu, Xue-Ru
2009 Dec 15;69(24):9413-9421, Cancer research
Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression
— id: 105925, year: 2009, vol: 69, page: 9413, stat: Journal Article,

Skin preparation for the prevention of surgical site infection: which agent is best?
Hemani, Micah L; Lepor, Herbert
2009 Fall;11(4):190-195, Reviews in urology
Procedural and surgical site infections create difficult and complex clinical scenarios. A source for pathogens is often thought to be the skin surface, making skin preparation at the time of the procedure critical. The most common skin preparation agents used today include products containing iodophors or chlorhexidine gluconate. Agents are further classified by whether they are aqueous-based or alcohol-based solutions. Traditional aqueous-based iodophors, such as povidone-iodine, are one of the few products that can be safely used on mucous membrane surfaces. Alcohol-based solutions are quick, sustained, and durable, with broader spectrum antimicrobial activity. These agents seem ideal for longer open surgeries with the potential for irrigation or surgical spillage, such as cystoprostatectomy, radical prostatectomy, and retroperitoneal lymph node dissection
— id: 106508, year: 2009, vol: 11, page: 190, stat: Journal Article,

Reply
Lepor H.
2009 ;103(9):1292-1293, BJU international
— id: 97871, year: 2009, vol: 103, page: 1292, stat: Journal Article,

Advances in the medical treatment of benign prostatic hyperplasia
Lepor, Herbert
2009 Fall;11(4):181-184, Reviews in urology
— id: 106507, year: 2009, vol: 11, page: 181, stat: Journal Article,

Pathophysiology of benign prostatic hyperplasia: insights from medical therapy for the disease
Lepor, Herbert
2009 Fall;11(Suppl 1):S9-S13, Reviews in urology
The medical treatment of benign prostatic hyperplasia (BPH) has its roots in the early 1970s. During this era, the first clinical trials investigating alpha-blockade and androgen deprivation therapy were reported for men with clinical BPH. The observation that clinical BPH was improved following administration of both alpha-blockers and androgen deprivation therapy supported the evolving paradigm that clinical BPH resulted from dynamic and static pathways. During the past several decades, the evolution of alpha-blockers for the treatment of BPH has been impacted by innovations targeted to simplify the administration and improve tolerability while maintaining their effectiveness
— id: 106514, year: 2009, vol: 11, page: S9, stat: Journal Article,

Status of radical prostatectomy in 2009: is there medical evidence to justify the robotic approach?
Lepor, Herbert
2009 Spring;11(2):61-70, Reviews in urology
This article presents the evolution of open radical retropubic prostatectomy (ORRP) into a minimally invasive procedure and reviews the literature to provide a legitimate comparison between ORRP and robotic-assisted laparoscopic radical retropubic prostatectomy (RALRP). The article is limited to manuscripts cited in the peer-reviewed literature, and an effort was made to identify those articles that fulfilled the highest level of medical evidence. In centers of excellence, ORRP is performed with no mortality, extraordinarily low technical and medical complications (1%), the rare need for blood transfusions, 1- to 2-day hospital stays, urinary catheters that are routinely removed in a week, the majority of men returning to work in 2 weeks, and up to 97% of men regaining urinary continence. Return of potency remains a challenge, especially for older men with marginal erections. RALRP is now the most common approach for the surgical removal of the malignant prostate. A critical review of the literature fails to support the marketing claims that RALRP is associated with shorter hospitalization, less pain, better cosmetics, shorter catheter time, lower transfusion rates, or improved continence and potency rates. The highest level of medical evidence suggests that RALRP may significantly compromise oncologic outcomes and that men undergoing this approach have higher regret rates than men undergoing ORRP
— id: 101644, year: 2009, vol: 11, page: 61, stat: Journal Article,

Factors Predicting Preservation of Erectile Function in Men Undergoing Open Radical Retropubic Prostatectomy
Marien, Tracy; Sankin, Alex; Lepor, Herbert
2009 Apr;181(4):1817-1822, Journal of urology
PURPOSE: The development of erectile dysfunction represents a major concern for potent men with localized prostate cancer undergoing open radical retropubic prostatectomy. We identified factors predicting the preservation of erectile function in men undergoing open radical retropubic prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2005 a total of 1,110 men underwent open radical retropubic prostatectomy by a single surgeon. The UCLA-PCI was self-administered at baseline, and at 3, 6, 12 and 24 months postoperatively. The 728 (66%) men who responded that they engaged in sexual intercourse with or without taking phosphodiesterase type 5 inhibitors in the month before surgery and who were not dependent on intracavernous injections, intraurethral suppositories, vacuum devices or penile prostheses were considered potent. Followup was available for 659 men. Of the evaluable men 25 received salvage radiation therapy, adjuvant chemotherapy or hormonal therapy and were excluded from the study. Univariate and multivariate analyses using a logistic regression model were used to identify factors predicting the preservation of potency. RESULTS: Age, coronary artery disease, diabetes mellitus, quality of preoperative erections, frequency of intercourse, hypertension, neurovascular bundle preservation and the use of phosphodiesterase type 5 inhibitors preoperatively predicted the preservation of potency. On multivariate analysis age, no history of diabetes mellitus and nerve sparing were independent predictors of the preservation of potency. CONCLUSIONS: We identified many factors that were predictors of the preservation of potency after open radical retropubic prostatectomy. Only age, no history of diabetes mellitus and neurovascular bundle preservation were independent predictors. These parameters should be considered when counseling surgical candidates so that erectile function expectations are realistic
— id: 95826, year: 2009, vol: 181, page: 1817, stat: Journal Article,

Side-specific factors associated with extracapsular extension and seminal vesicular invasion in men undergoing open radical retropubic prostatectomy
Sankin, A; Tareen, B; Lepor, H
2009 ;12(2):204-208, Prostate cancer & prostatic diseases
This study provides further insights into those preoperative parameters that predict side-specific risk of pathological stage in men undergoing radical prostatectomy (RP). The transrectal ultrasound-guided tissue biopsy cores obtained from the right and left sides of the prostate were collected in separate jars and examined independently according to the side of origin in 1250 men with clinically localized prostate cancer who underwent RP. The side-specific biopsy specimens were examined for Gleason score, number of positive cores, percentage of positive cores, percent tumor volume in the biopsy specimens and the presence of perineural invasion. All of the surgical specimens were processed and analyzed by pathologists at NYUMC using a standardized protocol. The surgical specimens were examined for side-specific extracapsular extension (ECE) and seminal vesicle invasion (SVI). Using a univariate analysis, age, serum prostate-specific antigen (PSA), prostate volume, clinical stage, Gleason score, number of positive biopsies, percent positive biopsy cores, percent volume of prostate cancer in cores and perineural invasion were all significant predictors of both ECE and SVI. A multivariate analysis was performed to determine the independent predictors of ECE and SVI. Serum PSA, biopsy Gleason score, percent volume of biopsy cores with cancer and perineural invasion were independent predictors of side-specific ECE. Age, serum PSA, Gleason score and prostate volume were independent predictors of side-specific SVI. Our study identified previously unrecognized independent predictors of side-specific ECE and SVI. Our study also provides evidence that the independent predictors of ECE and SVI are different
— id: 98890, year: 2009, vol: 12, page: 204, stat: Journal Article,

Can contemporary transrectal prostate biopsy accurately select candidates for hemi-ablative focal therapy of prostate cancer?
Tareen, Basir; Godoy, Guilherme; Sankin, Alex; Temkin, Steve; Lepor, Herbert; Taneja, Samir S
2009 Jul;104(2):195-199, BJU international
OBJECTIVE To determine if biopsy characteristics can be used to identify men with unilateral prostate cancer on radical prostatectomy (RP) pathological specimens, thereby selecting candidates for hemi-ablative focal therapy. PATIENTS AND METHODS Of 1458 men who had RP from January 2000 to June 2007, we identified 590 of 880 evaluable patients with unilateral disease on their preoperative biopsy. Charts were reviewed to record preoperative prostate-specific antigen (PSA) level, high-grade prostatic intraepithelial neoplasia (HGPIN), clinical stage, Gleason score, perineural invasion (PNI), prostate volume, number of positive cores, and percentage of positive cores. Final surgical pathology was evaluated for unilateral cancer. Univariate analysis was used (logistic regression method) to identify independent predictors of unilateral disease on the RP specimen. A subset analysis was done in men with low-risk disease, defined as clinical stage T1C, Gleason score <7 and a PSA level of <10 ng/mL. RESULTS Of 590 men with unilateral disease on biopsy, 163 (27.3%) had unilateral disease on the RP specimen. Pathological features, including HGPIN (P = 0.714), Gleason score (P > 0.608), PNI (P = 0.714), number of positive cores (P = 0.076), percentage of cores positive (P = 0.056), prostate volume (P = 0.285), and PSA level (P = 0.062) did not improve the prediction of unilateral disease. When men with unilateral cancer were further stratified to include only those with low-risk disease, 28.4% had unilateral disease on the RP specimen. None of the biopsy or clinical features evaluated were predictors of unilateral disease on the RP specimen. CONCLUSION Unilateral prostate cancer on biopsy predicts unilateral disease on RP pathology in only 27.6% of cases. The predictive ability is not improved by adding biopsy and clinical characteristics. Additional methods are needed to accurately identify men appropriate for focal therapy
— id: 94941, year: 2009, vol: 104, page: 195, stat: Journal Article,

Laterality alone should not drive selection of candidates for hemi-ablative focal therapy
Tareen, Basir; Godoy, Guilherme; Sankin, Alex; Temkin, Steve; Lepor, Herbert; Taneja, Samir S
2009 Mar;181(3):1082-1089, Journal of urology
PURPOSE: Because many investigators have suggested that ideal candidates for focal therapy are those with unilateral prostate cancer, we evaluated whether these men are at decreased risk for adverse pathological and oncological outcomes. MATERIALS AND METHODS: We reviewed the charts of 1,458 consecutive patients who underwent open radical prostatectomy, as performed by a single surgeon. Patients were divided into 311 with unilateral (group 1) and 1,147 with bilateral (group 2) disease on final surgical pathology. They were also substratified by clinical risk into low risk (prostate specific antigen less than 10 ng/ml, clinical stage less than T2b or Gleason score less than 7) and high risk groups. The groups were compared with respect to extracapsular extension, seminal vesical invasion, percent of tumor involvement, pathological Gleason score and biochemical recurrence. RESULTS: Compared to patients with bilateral disease those with unilateral disease had a lower rate of extracapsular extension (p = 0.004), seminal vesical invasion (p = 0.003), greater than 10% tumor involvement (p <0.001) and Gleason score 7 or greater (p <0.001). At a median followup of 36 months 8.3% and 16.7% of the men in groups 1 and 2, respectively, experienced biochemical recurrence (p = 0.001). Low risk disease was more prevalent in those with unilateral disease than in those with bilateral disease. Of men with low risk disease the risk of adverse pathological features/biochemical recurrence did not differ between groups 1 and 2. CONCLUSIONS: Although men with unilateral prostate cancer have more favorable oncological outcomes than those with bilateral prostate cancer, this appears to be due to the higher prevalence of low risk disease. While focality/laterality may direct the method of subtotal gland treatment, clinical risk features may be adequate to select candidates for focal therapy
— id: 94942, year: 2009, vol: 181, page: 1082, stat: Journal Article,

Appropriate candidates for hemiablative focal therapy are infrequently encountered among men selected for radical prostatectomy in contemporary cohort
Tareen, Basir; Sankin, Alex; Godoy, Guilherme; Temkin, Steve; Lepor, Herbert; Taneja, Samir S
2009 Feb;73(2):351-354, Urology
OBJECTIVES: To assess the prevalence and pathologic features of men with unilateral prostate cancer at radical prostatectomy (RP), because it has recently been proposed that men with small-volume, well-differentiated, unilateral prostate cancer can be treated with focal therapy. METHODS: The records of 1467 consecutive men who underwent open RP by a single surgeon from January 2000 to June 2007 were reviewed after institutional review board approval. The RP pathologic reports were analyzed to determine the frequency of unilateral or bilateral disease, surgical margin status, presence of extracapsular extension, seminal vesicle invasion, Gleason score, percentage of tumor involvement (PTI), prostate-specific antigen (PSA) level, and prostate volume. Logistic regression analysis was performed to analyze the relationship between these factors and the detection of unilateral disease. RESULTS: Unilateral cancer was identified in 313 of 1467 patients (21.3%). Of these patients, 206 had a PTI of < or = 5%, 40 had a PTI of 5%-10%, 8 had a PTI of 10%-15%, and 40 had a PTI > 15%. The factors significantly associated with unilateral disease on univariate analysis were PTI, PSA level, pathologic Gleason score, seminal vesicle invasion, and extracapsular extension. The PSA level and seminal vesicle invasion remained significant predictors on multivariate analysis. Overall, 163 men (11.1%) had unilateral, low-risk disease (defined as a PSA level < 10 ng/mL, Gleason score < 7, and PTI < 10%). CONCLUSIONS: Although candidates for focal therapy exist among men undergoing RP within a contemporary cohort, they represent a small minority. Before proceeding with focal therapy, the urology community must identify accurate methods of candidate selection
— id: 93566, year: 2009, vol: 73, page: 351, stat: Journal Article,

Vascular targeted photodynamic therapy for localized prostate cancer
Lepor, Herbert
2008 Fall;10(4):254-261, Reviews in urology
Survival for men diagnosed with prostate cancer directly depends on the stage and grade of the disease at diagnosis. Prostate cancer screening has greatly increased the ability to diagnose small and low-grade cancers that are amenable to cure. However, widespread prostate-specific antigen screening exposes many men with low-risk cancers to unnecessary complications associated with treatment for localized disease without any survival advantage. One challenge for urological surgeons is to develop effective treatment options for low-risk disease that are associated with fewer complications. Minimally invasive ablative treatments for localized prostate cancer are under development and may represent a preferred option for men with low-risk disease who want to balance the risks and benefits of treatment. Vascular targeted photodynamic therapy (VTP) is a novel technique that is being developed for treating prostate cancer. Recent advances in photodynamic therapy have led to the development of photosynthesizers that are retained by the vascular system, which provides the opportunity to selectively ablate the prostate with minimal collateral damage to other structures. The rapid clearance of these new agents negates the need to avoid exposure to sunlight for long periods. Presented herein are the rationale and preliminary data for VTP for localized prostate cancer
— id: 95827, year: 2008, vol: 10, page: 254, stat: Journal Article,

Transabdominal sonocystography: a novel technique to assess vesicourethral extravasation following radical prostatectomy
Lepor, Herbert; Kozirovsky, Mariana; Laze, Juliana; Telegrafi, Shpetim
2008 Dec;180(6):2459-2462, Journal of urology
PURPOSE: We describe our new technique of transabdominal sonocystography in men following radical prostatectomy. MATERIALS AND METHODS: From May 2007 to January 2008, 75 men underwent gravity transabdominal sonocystography and fluorocystography 8 days following open radical retropubic prostatectomy. Bladder volume after the instillation of 150 cc saline was determined by measuring bladder height, width and length in the longitudinal and transverse planes. Extravasation volume was calculated by subtracting the calculated bladder volume after filling from a volume of 165 ml, which represents the instilled saline volume of 150 ml plus 15 ml in the urinary catheter balloon. Extravasation was then qualitatively graded as none, slight, moderate or severe after instilling 150 cc contrast medium into the bladder. RESULTS: The correlation between fluorocystography and transabdominal sonocystography was ascertained by determining the mean extravasation volume corresponding to the qualitatively graded categories of extravasation determined fluoroscopically. Mean extravasation volume in cases with no, slight and moderate extravasation on fluoroscopic cystography was -3.72, 6.51 and 46.0 ml, respectively. At an extravasation volume of 20 ml the sensitivity and specificity of transabdominal sonography to differentiate no or slight vs moderate or severe fluoroscopic extravasation was 100%. CONCLUSIONS: The advantages of transabdominal sonocystography over fluorocystography are lower cost, lack of radiation exposure and the ability to perform the procedure at most urological outpatient facilities. Therefore, transabdominal sonocystography represents a good alternative to fluorocystography for assessing the integrity of the vesicourethral anastomosis following open radical retropubic prostatectomy
— id: 93381, year: 2008, vol: 180, page: 2459, stat: Journal Article,

The QT Interval and Selection of Alpha-Blockers for Benign Prostatic Hyperplasia
Lepor, Herbert; Lepor, Norman E; Hill, Lawrence A; Trohman, Richard G
2008 Spring;10(2):85-91, Reviews in urology
The QT interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. Drug-induced long QT syndrome is characterized by acquired, corrected QT (QTc) interval prolongation that is associated with increased risk of torsade de pointes. Every physician must recognize if the drugs he or she prescribes prolongs the QTc interval, especially if the drug is prescribed for a chronic condition in older patients who are on polypharmacy. The evolution of alpha-blockers for the treatment of benign prostatic hyperplasia has allowed the development of drugs that are easier to administer and better tolerated. Because alpha-blockers generally have equivalent efficacy, this class of drugs is typically differentiated by safety and side effects. Studies suggest that alpha-blockers may vary in regard to their effect on the QT interval, and, therefore, on their predisposition to cause potentially life-threatening ventricular arrhythmias
— id: 95829, year: 2008, vol: 10, page: 85, stat: Journal Article,

Penile Rehabilitation Postprostatectomy: Is There a Role for MUSE?
Lepor, Herbert; McCullough, Andrew
2008 Winter;10(1):1-5, Reviews in urology
— id: 95830, year: 2008, vol: 10, page: 1, stat: Journal Article,

Renewing intimacy: advances in treating erectile dysfunction postprostatectomy
Lepor, Herbert; McCullough, Andrew; Engel, Jason D
2008 Fall;10(4):245-253, Reviews in urology
— id: 95828, year: 2008, vol: 10, page: 245, stat: Journal Article,

Stromal AR inhibition of prostate cancer growth and invasion by stromal AR and association with androgen independent disease
Li, Y; Li, CX; Melamed, J; Walden, P; Peng, Y; Lepor, H; Garabedian, MJ; Lee, P
2008 ;179(4):187-187, Journal of urology
— id: 104578, year: 2008, vol: 179, page: 187, stat: Journal Article,

Does a nerve-sparing technique or potency affect continence after open radical retropubic prostatectomy?
Marien, Tracy P; Lepor, Herbert
2008 Dec;102(11):1581-1584, BJU international
OBJECTIVE: To characterize the effect of preserving the neurovascular bundle (NVB) and of potency on urinary continence after open radical retropubic prostatectomy (ORRP). PATIENTS AND METHODS: Between October 2000 to September 2005, 1110 consecutive continent men had ORRP by one surgeon. The University of California Los Angeles Prostate Cancer Index was self-administered at baseline and 3, 6, 12, and 24 months after ORRP. Men were considered continent if they responded that they had total urinary control or had occasional urinary leakage. Men were considered potent if they engaged in sexual intercourse with or without the use of phosphodiesterase inhibitors at least once in the month before or after ORRP. Of the 1110 men, 728 (66%) were potent and continent at baseline. Men undergoing adjuvant hormonal therapy, radiation therapy or chemotherapy were excluded. The potency status was evaluated in 610 men at 24 months after ORRP, and the number of NVBs preserved was recorded at the time of ORRP. RESULTS: Of men who were potent at baseline and had bilateral vs unilateral nerve sparing, 96% and 99% were continent at 24 months, respectively (P = 0.50). Of the men who were potent and impotent at 24 months, 98% and 96% were continent at 24 months, respectively (P = 0.25). Continence did not depend on whether men regained potency or whether they had a bilateral or a unilateral nerve-sparing procedure. CONCLUSION: Our observation that only 60% of men undergoing bilateral nerve-sparing ORRP regain potency suggests that the NVBs are often inadvertently injured, despite efforts to preserve them. We feel that potency status is the best indicator of the true extent of NVB preservation. That men undergoing bilateral vs unilateral nerve-sparing procedures, and that potent vs impotent men at 24 months have similar continence rates, provides compelling evidence that nerve-sparing is not associated with better continence. Based on these findings, NVBs should not be preserved in men with baseline erectile dysfunction, with the expectation of improving continence
— id: 91443, year: 2008, vol: 102, page: 1581, stat: Journal Article,

Management of localized prostate cancer and an incidental ureteral duplication with upper pole ectopic ureter inserting into the prostatic urethra
Marien, Tracy P; Shapiro, Ellen; Melamed, Jonathan; Taouli, Bachir; Stifelman, Michael D; Lepor, Herbert
2008 Fall;10(4):297-303, Reviews in urology
Ectopic ureters are rare congenital malformations of the renal system that most commonly present in females. It is extremely rare to encounter an ectopic ureter in an older man undergoing radical prostatectomy. We report herein a case of a 66-year-old man with prostate cancer and a complete duplication of the left renal collecting system, with an upper pole ectopic ureter and associated normal functioning renal parenchyma entering into the prostatic urethra. This anomaly was incidentally discovered on preoperative magnetic resonance imaging of the prostate. Open radical retropubic prostatectomy and a left ureteroureterostomy were performed
— id: 94870, year: 2008, vol: 10, page: 297, stat: Journal Article,

Prostate-specific antigen doubling time is a reliable predictor of imageable metastases in men with biochemical recurrence after radical retropubic prostatectomy
Perlmutter, Mark A; Lepor, Herbert
2008 Mar;71(3):501-505, Urology
OBJECTIVES: To examine the incidence of imageable metastases at the time of biochemical recurrence after radical prostatectomy and to determine whether prostate-specific antigen doubling time (PSADT) reliably predicts these imageable metastases. METHODS: Between October 2000 and October 2005, 1112 men underwent open radical retropubic prostatectomy by a single surgeon. All men were advised to undergo bone scintigraphy and an abdominal/pelvic imaging study at the time of biochemical recurrence. We ascertained the sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months to predict the presence of imageable metastases. RESULTS: Seventy-four (6.7%) men developed a biochemical recurrence and imageable metastases were demonstrable in 7 cases. Imageable metastases were identified in 11.3% and 7.5% of men undergoing bone scans and abdominal/pelvic imaging, respectively. Extracapsular extension, and older age positive surgical margins, and PSADT were associated with a significantly greater risk of exhibiting imageable metastases. The sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months for predicting imageable metastasis were 100%, 98.0%, 87.5%, and 100%, respectively. CONCLUSIONS: A relatively small proportion of men at the time of developing biochemical recurrence after radical prostatectomy exhibit imageable metastasis. The 100% sensitivity and negative predictive value of a PSADT cut-point of 3 months strongly suggests that PSADT can be used as an excellent proxy for imageable metastasis. Omitting routine bone scintigraphy and body imaging at the time of biochemical recurrence minimizes the costs, inconvenience, and anxiety associated with these studies
— id: 79156, year: 2008, vol: 71, page: 501, stat: Journal Article,

Phase I/II study of biweekly paclitaxel and radiation in androgen-ablated locally advanced prostate cancer
Sanfilippo, Nicholas J; Taneja, Samir S; Chachoua, Abraham; Lepor, Herbert; Formenti, Silvia C
2008 Jun 20;26(18):2973-2978, Journal of clinical oncology
PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent paclitaxel and radiation therapy (RT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had T2-4 tumors with Gleason scores greater than 7 and/or PSA levels greater than 10 ng/mL and/or had tumors with pathologic stage TxN1. Hormonal ablation was initiated 3 months before RT and was given for 9 months. RT was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m(2)). The whole pelvis was irradiated to 39.6 Gy. The radiation dose was escalated as follows: 63 Gy, 66.6 Gy, 70.2 Gy, and 73.8 Gy. The last RT dose level was fixed at 73.8 Gy. RESULTs: Between January 2000 and October 2006, 22 patients were enrolled. The median age was 59 years (range, 48 to 72 years); the median PSA level was 22.4 ng/mL (range, 2.8 to 113 ng/mL). The number of patients per stage was as follows: three with T1, eight with T2, 11 with T3, and five with pN1 = 5. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol then was amended to treat the prostate volume first followed by the whole pelvis. No grade 3 toxicities were observed at 70.2 Gy. One patient experienced grade 3 diarrhea at 73.8 Gy. Five additional patients were treated to 73.8 Gy without grade 3 toxicity, which established the MTD for combined paclitaxel and RT at 73.8 Gy. At 38 months median follow-up (range, 9 to 87 months), 21 (95%) of 22 patients are alive. Six (27%) of 22 experienced recurrence. CONCLUSION: Concurrent biweekly paclitaxel with RT is feasible, with an MTD of 73.8 Gy. Recovery of gonadal function occurs in the majority of patients. These results encourage testing in a phase III setting
— id: 79569, year: 2008, vol: 26, page: 2973, stat: Journal Article,

Comparison of pathologic and oncologic outcomes of radical retro pubic prostatectomy among men with unilateral vs. bilateral prostate cancer: Implications for focal therapy
Tareen, B; Sankin, A; Godoy, G; Temkin, S; Lepor, H; Taneja, SS
2008 MAR ;7(3):169-169, European Urology Supplements
— id: 76435, year: 2008, vol: 7, page: 169, stat: Journal Article,

Does open radical retropubic prostatectomy decrease the risk of acute urinary retention?
Tareen, Basir; Godoy, Guilherme; Laze, Juliana; Lepor, Herbert
2008 Oct;72(4):821-824, Urology
OBJECTIVES: Development of acute urinary retention (AUR) is common in the aging male. The pathophysiology of AUR is attributed primarily to prostatic obstruction. The objective of this study was to evaluate the risk of AUR in men after open radical prostatectomy (ORRP). METHODS: A questionnaire asking whether a urinary catheter had been inserted after its initial removal was sent to 1361 men who underwent ORRP by a single surgeon (HL) between October 2000 and January 2007. Follow-up ranged from 12 to 84 months (mean, 48 months). For those who responded that a catheter had been reinserted, a follow-up question inquired specifically when this event occurred. The reason for postprostatectomy catheter reinsertion was determined via phone interview. RESULTS: A total of 952 men (69.9% response rate) mailed a completed questionnaire to our database manager. No men underwent catheter reinsertion owing to spontaneous AUR. Ninety-two men (9.7%) answered 'yes' to requiring catheter insertion postprostatectomy. The reasons for recatheterization were an intermittent catheterization regimen after dilation of an anastomotic stricture or meatal stenosis (n = 68), AUR immediately after initial catheter removal (n = 14), and elective reasons (n = 10). All urethral strictures were dilated within the first year after surgery and no patient with stricture presented with AUR. CONCLUSIONS: The risk of spontaneous AUR after 1 month of catheter removal after ORRP is 0%. We believe that this is an important unrecognized clinical benefit of ORRP, especially in men with moderate to severe lower urinart tract symptoms or enlarged prostates, who are at higher risk for AUR
— id: 93331, year: 2008, vol: 72, page: 821, stat: Journal Article,

Do biopsy characteristics predict unilateral prostate cancer on radical prostatectomy?
Tareen, U; Sankin, A; Temkin, S; Godoy, G; Lepor, H; Taneja, S
2008 MAR ;7(3):252-252, European Urology Supplements
— id: 76440, year: 2008, vol: 7, page: 252, stat: Journal Article,

Predictors of prostate cancer in the transition zone: Results of a multicenter trial
Djavan, Bob; Rocco, Bernardo; Brausi, Maurizio; Zlotta, Alexandre R.; Ravery, Vincent; Hammerer, Peter; Anagnostou, Theodore; Naegele, Ralph; Margreiter, Markus; Harik, Mike; Lepor, Herbert; Marberger, Michael
2007 APR ;177(4):646-646, Journal of urology
— id: 141018, year: 2007, vol: 177, page: 646, stat: Journal Article,

Persistent uroplakin expression in advanced urothelial carcinomas: implications in urothelial tumor progression and clinical outcome
Huang, Hong-Ying; Shariat, Shahrokh F; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru
2007 Nov;38(11):1703-1713, Human pathology
As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathologic parameter, the tumor's biological behavior, or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or nontumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63 of 74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104 of 202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33 of 50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including microluminal, basal-laminal, cytoplasmic, or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression, or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence, and bladder cancer-specific mortality (P = .042, P = .035, P = .023, and P = .022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27, and cyclin D1, thus excluding a functional link between these 2 groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and -negative carcinomas have different clonal origins or may be derived from different cancer stem cells
— id: 73404, year: 2007, vol: 38, page: 1703, stat: Journal Article,

The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia
Johnson, Theodore M 2nd; Burrows, Pamela K; Kusek, John W; Nyberg, Leroy M; Tenover, J Lisa; Lepor, Herbert; Roehrborn, Claus G
2007 Nov;178(5):2045-2050, Journal of urology
PURPOSE: We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. RESULTS: Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at 1 year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p <0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p <0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p <0.05). CONCLUSIONS: Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride
— id: 95833, year: 2007, vol: 178, page: 2045, stat: Journal Article,

Spontaneous renal artery dissection
Kanofsky, Jamie A; Lepor, Herbert
2007 Summer;9(3):156-160, Reviews in urology
Spontaneous renal artery dissection (SRAD) is a rare event, and thus may be a challenge for physicians to diagnose and treat. We report a case of SRAD in a healthy 56-year-old male who presented with flank pain, fever, and elevated white blood cell count. The patient was initially diagnosed with nephrolithiasis versus pyelonephritis and was admitted for observation. Multiple imaging modalities, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI) with gadolinium, CT angiogram, and intraoperative angiogram, were used to make the final diagnosis of SRAD. The patient was treated with endovascular stent placement and is currently free of pain with normal laboratory values and blood pressure
— id: 95832, year: 2007, vol: 9, page: 156, stat: Journal Article,

Alpha blockers for the treatment of benign prostatic hyperplasia
Lepor, Herbert
2007 Fall;9(4):181-190, Reviews in urology
The evolution of alpha blocker therapy for benign prostatic hyperplasia (BPH) has focused on improving convenience and tolerability. Indications for treating BPH include reversing signs and symptoms or preventing progression of the disease. The indication that most commonly drives the need for intervention is relief of lower urinary tract symptoms (LUTS) with the intent of improving quality of life. Alpha blockers are the most effective, least costly, and best tolerated of the drugs for relieving LUTS. Four long-acting alpha 1 blockers are approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, and alfuzosin. All are well tolerated and have comparable dose-dependent effectiveness. Tamsulosin and alfuzosin SR do not require dose titration. Alfuzosin, terazosin, and doxazosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size
— id: 95831, year: 2007, vol: 9, page: 181, stat: Journal Article,

Inguinal hernias in men undergoing open radical retropubic prostatectomy
Lepor, Herbert; Robbins, David
2007 Nov;70(5):961-964, Urology
OBJECTIVES: To determine the incidence of inguinal hernias in men undergoing open radical retropubic prostatectomy (RRP). METHODS: The incidence of preoperative and postprostatectomy inguinal hernias were determined by a retrospective chart review and questionnaire survey of 1130 consecutive men who underwent open RRP by a single surgeon from October 2000 to October 2005. A preoperative inguinal hernia was diagnosed by the physical examination or abdominal computed tomography findings. The incidence of new postoperative hernias was ascertained by the patients' responses to a survey indicating the development of a new groin bulge or hernia. RESULTS: Of the 1130 patients, 146 (13%) had a preoperative inguinal hernia. Increasing age and lower body mass index were significantly associated with the detection of a preoperative inguinal hernia. The sensitivity of detecting an inguinal hernia by physical examination and routine abdominal computed tomography preoperatively was 96.3% and 42.5%, respectively. Also, 8% of men developed a new hernia. CONCLUSIONS: Although abdominal computed tomography can identify inguinal hernias in men undergoing open RRP, the test's sensitivity is inferior to that of a simple physical examination. All candidates for open RRP should undergo a careful physical examination to identify asymptomatic inguinal hernias. Our findings suggest that the previously reported high incidence of symptomatic inguinal hernias that developed after open RRP can be explained by a failure to diagnose preexisting inguinal hernias and the development of new hernias
— id: 75488, year: 2007, vol: 70, page: 961, stat: Journal Article,

Hyperactivation of Ha-ras oncogene, but not Ink4a/Arf deficiency, triggers bladder tumorigenesis
Mo, Lan; Zheng, Xiaoyong; Huang, Hong-Ying; Shapiro, Ellen; Lepor, Herbert; Cordon-Cardo, Carlos; Sun, Tung-Tien; Wu, Xue-Ru
2007 Feb 1;117(2):314-325, Journal of clinical investigation
Although ras is a potent mitogenic oncogene, its tumorigenicity depends on cellular context and cooperative events. Here we show that low-level expression of a constitutively active Ha-ras in mouse urothelium induces simple urothelial hyperplasia that is resistant to progression to full-fledged bladder tumors even in the absence of Ink4a/Arf. In stark contrast, doubling of the gene dosage of the activated Ha-ras triggered early-onset, rapidly growing, and 100% penetrant tumors throughout the urinary tract. Tumor initiation required superseding a rate-limiting step between simple and nodular hyperplasia, the latter of which is marked by the emergence of mesenchymal components and the coactivation of AKT and STAT pathways as well as PTEN inactivation. These results indicate that overactivation of Ha-ras is both necessary and sufficient to induce bladder tumors along a low-grade, noninvasive papillary pathway, and they shed light on the recent findings that ras activation, via point mutation, overexpression, or intensified signaling from FGF receptor 3, occurs in 70%-90% of these tumors in humans. Our results highlight the critical importance of the dosage/strength of Ha-ras activation in dictating its tumorigenicity - a mechanism of oncogene activation not fully appreciated to date. Finally, our results have clinical implications, as inhibiting ras and/or its downstream effectors, such as AKT and STAT3/5, could provide alternative means to treat low-grade, superficial papillary bladder tumors, the most common tumor in the urinary system
— id: 70641, year: 2007, vol: 117, page: 314, stat: Journal Article,

Androgen deprivation therapy in the treatment of advanced prostate cancer
Perlmutter, Mark A; Lepor, Herbert
2007 ;9 Suppl 1:S3-S8, Reviews in urology
This article reviews the issues and controversies relevant to the treatment of advanced prostate cancer with androgen deprivation therapy. Initially, diethylstilbestrol was used for achieving androgen deprivation, but was replaced by luteinizing hormone-releasing hormone (LHRH). Adverse events associated with LHRH agonists include the flare phenomenon, hot flashes, loss of libido, erectile dysfunction, depression, muscle wasting, anemia, and osteoporosis. Intermittent therapy has been advocated to reduce morbidity of treatment. The addition of an antiandrogen provides maximum androgen blockade. There remains controversy regarding the timing of the addition of an antiandrogen. Secondary hormonal therapies include antiandrogens, adrenal androgen inhibitors, and estrogens
— id: 105902, year: 2007, vol: 9 Suppl 1, page: S3, stat: Journal Article,

Phase I study of bi-weekly paclitasel and definitive radiation in androgen ablated locally advanced prostate cancer
Sanfilippo, NJ; Taneja, SS; Chachoua, A; Lepor, H; Formenti, SC
2007 JAN ;69(3):S112-S113, International journal of radiation oncology biology physics
— id: 87193, year: 2007, vol: 69, page: S112, stat: Journal Article,

The short-term and long-term effects of radical prostatectomy on lower urinary tract symptoms
Slova, Denisa; Lepor, Herbert
2007 Dec;178(6):2397-2400, Journal of urology
PURPOSE: We determined the long-term effect of radical prostatectomy on lower urinary tract symptoms. MATERIALS AND METHODS: Between October 1, 2000 and January 30, 2003, 587 men underwent open radical retropubic prostatectomy. Of these men 453 completed the American Urological Association symptom index at baseline, and 12 and 48 months. Mean changes in American Urological Association total, voiding and storage symptom scores were ascertained between baseline and 12 months (short term), baseline and 48 months (long term), and between 12 and 48 months (natural history of lower urinary tract symptoms without a prostate). Symptom scores were ascertained independently for men with baseline mild vs moderate/severe lower urinary tract symptoms. RESULTS: Clinically and statistically significant short-term and long-term improvements were observed in mean American Urological Association total, storage and voiding symptom scores for men presenting with moderate/severe lower urinary tract symptoms. The previously reported progression of lower urinary tract symptoms in the general population of men older than 40 years was not observed in our patients with an absent prostate. CONCLUSIONS: The current study provides compelling evidence that radical prostatectomy prevents the progression of lower urinary tract symptoms in men with and without baseline clinically significant lower urinary tract symptoms. This beneficial effect of radical prostatectomy on the natural history of lower urinary tract symptoms should be considered when weighing the risks and benefit of the treatment option for localized prostate cancer
— id: 75457, year: 2007, vol: 178, page: 2397, stat: Journal Article,

Postoperative blood loss predicts the development of urinary extravasation on cystogram following radical retropubic prostatectomy
Fenig, David M; Slova, Denisa; Lepor, Herbert
2006 Jan;175(1):146-150, Journal of urology
PURPOSE: We determined if the degree of postoperative bleeding predicts the extent of urinary extravasation on initial postoperative cystogram. MATERIALS AND METHODS: Between October 2000 to June 2004, 879 men underwent radical retropubic prostatectomy performed by a single surgeon. Of these men 97% underwent the initial postoperative cystogram 3 to 8 days following radical prostatectomy. Postoperative bleeding was expressed as the absolute change in hematocrit between hematocrit values measured immediately upon arrival into the recovery room and hospital discharge. Three hematocrit points were added to the change in postoperative hematocrit for every unit of blood transfused postoperatively. The relationship between the change in postoperative hematocrit and the extent of extravasation was examined. RESULTS: None, mild, moderate and marked extravasation was observed on the initial cystogram in 82.7%, 7.9%, 8.8% and 0.6% of cases, respectively. A significant relationship was observed between changes in postoperative hematocrit and the extent of extravasation on initial cystography (p <0.001). Postoperative changes in absolute hematocrit points of less than 2, 2 to 6 and greater than 6 identified clinically meaningful risk groups for urinary extravasation. The degree of extravasation was not significantly related to risk of anastomotic stricture or urinary incontinence. CONCLUSIONS: The extent of postoperative bleeding predicts the extent of urinary extravasation on initial cystography. It may be a useful measurement for identifying men who can safely undergo early catheter removal without cystography
— id: 62643, year: 2006, vol: 175, page: 146, stat: Journal Article,

Proximal prostatic stem cells are programmed to regenerate a proximal-distal ductal axis
Goto, Ken; Salm, Sarah N; Coetzee, Sandra; Xiong, Xiaozhong; Burger, Patricia E; Shapiro, Ellen; Lepor, Herbert; Moscatelli, David; Wilson, E Lynette
2006 Aug;24(8):1859-1868, Stem cells
Prostate carcinoma and benign prostatic hypertrophy may both originate in stem cells, highlighting the importance of the characterization of these cells. The prostate gland contains a network of ducts each of which consists of a proximal (adjacent to the urethra), an intermediate, and a distal region. Here, we report that two populations of cells capable of regenerating prostatic tissue in an in vivo prostate reconstitution assay are present in different regions of prostatic ducts. The first population (with considerable growth potential) resides in the proximal region of ducts and in the urethra, and the survival of these cells does not require the presence of androgens. The second population (with more limited growth potential) is found in the remaining ductal regions and requires androgen for survival. In addition, we find that primitive proximal prostate cells that are able to regenerate functional prostatic tissue in vivo are also programmed to re-establish a proximal-distal ductal axis. Similar to their localization in the intact prostate, cells with the highest regenerative capacity are found in the proximal region of prostatic ducts formed in an in vivo prostate reconstitution assay. The primitive proximal cells can be passaged through four generations of subrenal capsule grafts. Together, these novel findings illustrate features of primitive prostate cells that may have implications for the development of therapies for treating proliferative prostatic diseases
— id: 72058, year: 2006, vol: 24, page: 1859, stat: Journal Article,

Factors predisposing to the development of anastomotic strictures in a single-surgeon series of radical retropubic prostatectomies
Huang, George; Lepor, Herbert
2006 Feb;97(2):255-258, BJU international
OBJECTIVE: To determine the rate of anastomotic stricture (AS) after radical retropubic prostatectomy (RRP) performed by one experienced surgeon, and to identify factors predisposing to its formation. PATIENTS AND METHODS: In all, 708 men were prospectively monitored for the development of AS after RRP. Potential risk factors for AS were analysed. RESULTS: There were no significant differences in age, Gleason score, nerve-sparing status, intraoperative blood loss, degree of extravasation on initial cystography, or duration of the indwelling urinary catheter between men who developed AS and men who did not. The mean postoperative blood loss was significantly higher in men who developed AS. The incidence of AS was also significantly higher in men whose bladder necks were reconstructed more narrowly. CONCLUSION: The amount of bleeding and the calibre of the reconstructed bladder neck were significantly associated with AS formation after RRP. The development of a haematoma from bleeding might explain the increased likelihood of AS. The mechanism of AS formation is unrelated to the degree of urinary extravasation on cystography, providing that a urinary catheter is left indwelling until extravasation resolves
— id: 62644, year: 2006, vol: 97, page: 255, stat: Journal Article,

Open versus robotic radical prostatectomy
Lepor, H
2006 MAR-APR ;24(2):91-93, Urologic oncology
— id: 62893, year: 2006, vol: 24, page: 91, stat: Journal Article,

Insights into the natural history and treatment of benign prostatic hyperplasia
Lepor, Herbert
2006 Mar;175(3 Pt 1):815-816, Journal of urology
— id: 115350, year: 2006, vol: 175, page: 815, stat: Journal Article,

The evolution of alpha-blockers for the treatment of benign prostatic hyperplasia
Lepor, Herbert
2006 ;8 Suppl 4:S3-S9, Reviews in urology
Alpha-blockers have been evaluated for the treatment of benign prostatic hyperplasia (BPH) for 30 years, from early trials with the nonselective alpha-inhibitor phenoxybenzamine to short-acting (prazosin) then long-acting (terazosin, doxazosin, tamsulosin, alfuzosin) selective alpha(1)-antagonists. All of the alpha-blockers evaluated have demonstrated comparable effectiveness, and the evolution of alpha-blocker therapy for BPH has therefore focused primarily on improving convenience and tolerability. Although all of the long-acting alpha(1)-blockers are well tolerated, only tamsulosin and alfuzosin SR are administered without the requirement for dose titration. Alfuzosin has the additional advantage over tamsulosin of a lower incidence of ejaculatory dysfunction. Studies of subtype-selective alpha(1)-antagonists have not demonstrated superior efficacy or improved tolerability over the existing long-acting alpha(1)-blockers
— id: 105900, year: 2006, vol: 8 Suppl 4, page: S3, stat: Journal Article,

The role of gonadotropin-releasing hormone antagonists for the treatment of benign prostatic hyperplasia
Lepor, Herbert
2006 Fall;8(4):183-189, Reviews in urology
Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men
— id: 115332, year: 2006, vol: 8, page: 183, stat: Journal Article,

Spontaneous retroperitoneal hemorrhage caused by segmental arterial mediolysis
Phillips, Courtney K; Lepor, Herbert
2006 Winter;8(1):36-40, Reviews in urology
Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal hemorrhage can be caused by tumors, such as renal cell carcinoma and angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is segmental arterial mediolysis. Although computed tomography is used for the diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires angiography, with pathologic confirmation for a definitive diagnosis
— id: 115349, year: 2006, vol: 8, page: 36, stat: Journal Article,

Time to return to work and physical activity following open radical retropubic prostatectomy
Sultan, Raymond; Slova, Denisa; Thiel, Bob; Lepor, Herbert
2006 Oct;176(4 Pt 1):1420-1423, Journal of urology
PURPOSE: We identified factors that predict return to part-time and full-time work and resumption of unlimited physical activity following open radical retropubic prostatectomy. MATERIALS AND METHODS: Between July 1, 2002 and February 28, 2005, 537 men with clinically localized prostate cancer underwent open radical retropubic prostatectomy, as performed by a single surgeon. Intraoperative, perioperative and postoperative parameters were recorded in real time and entered into a database. An assessment was made 1 and 3 months postoperatively regarding time to return to work and unrestricted physical activity. RESULTS: Of the men 50% returned to part-time and full-time work, and unrestricted activity within 14, 21 and 30 days after discharge home, respectively. Patient age and hematocrit at hospital discharge significantly predicted return to part-time and full-time work, and unlimited physical activity. The number of days that the urinary catheter was indwelling was also associated with return to part-time work. Occupation (blue vs white collar) and marital status were also associated with return to full-time work. In the multivariate model a unit increase in hematocrit decreased the time to return to part-time and full-time work, and unrestricted physical activity by 0.50, 0.60 and 0.59 days, respectively. Men with discharge hematocrit greater than 32% were 1.57 (p = 0.059), 1.65 (p = 0.041) and 2.03 (p = 0.002) times more likely to return to part-time and full-time work, and unlimited activity before 14, 21 and 30 days, respectively. Overall models were developed that accounted for 9.4%, 14.0% and 4.0% of the time to return to part-time work, full-time work and unrestricted physical activity, respectively. CONCLUSIONS: Efforts to increase discharge hematocrit by minimizing intraoperative blood loss or using preoperative blood management strategies and earlier removal of the urinary catheter have a favorable impact on the return to work and physical activity
— id: 68988, year: 2006, vol: 176, page: 1420, stat: Journal Article,

Reoperation versus observation in men with major bleeding after radical retropubic prostatectomy
Kaufman, Jeremy D; Lepor, Herbert
2005 Sep;66(3):561-565, Urology
OBJECTIVES: To compare the postoperative and quality-of-life outcomes for men experiencing major bleeding after radical retropubic prostatectomy that was managed with reoperation or observation. METHODS: A total of 916 men underwent radical retropubic prostatectomy by a single surgeon between October 2000 and August 2004. Of the 916 men, 15 (1.6%) experienced major bleeding, defined as the transfusion of 3 U or more of allogeneic blood within the first 36 hours after radical prostatectomy. The outcomes were compared between the 5 men undergoing reoperation (group 1) and the 10 men whose bleeding was managed with observation (group 2). RESULTS: The mean total number of allogeneic blood units transfused was significantly greater in group 1 (7.4 U) than in group 2 (4.1 U; P = 0.002). Group 1 also experienced a significantly longer hospital stay (4.6 versus 2.6 days). Those men undergoing reoperation had a significantly lower probability of moderate to severe extravasation on initial cystogram compared with group 2 (0% versus 70%). In addition, the urinary catheter was indwelling for a shorter interval (9.6 versus 23.5 days). We also found a suggestion of better continence in group 1. CONCLUSIONS: Reoperation for major bleeding after radical retropubic prostatectomy facilitates both healing of the vesicourethral anastomosis and removal of the urinary catheter
— id: 115351, year: 2005, vol: 66, page: 561, stat: Journal Article,

A review of surgical techniques for radical prostatectomy
Lepor, Herbert
2005 ;7 Suppl 2:S11-S17, Reviews in urology
Since the early 20th century, radical prostatectomy has been used in the treatment of prostate cancer. However, before the widespread acceptance of prostate-specific antigen screening, the majority of cancers were clinically advanced and not amenable to cure, so relatively few men were candidates for this procedure. Modern advances have contributed dramatically to the reduction of complications and morbidity associated with radical prostatectomy. As a result, the procedure has become the most common treatment selected by men with localized prostate cancer. This article reviews several issues regarding radical prostatectomy, including surgical techniques, cancer control, intraoperative localization of the cavernous nerves, patient selection, and laparoscopic versus robotic approaches
— id: 115338, year: 2005, vol: 7 Suppl 2, page: S11, stat: Journal Article,

Comparison of single-agent androgen suppression for advanced prostate cancer
Lepor, Herbert
2005 ;7 Suppl 5:S3-S12, Reviews in urology
Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for achieving androgen suppression in men with advanced prostate cancer. The GnRH agonists that have been developed and marketed for prostate cancer are leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few randomized studies directly comparing these single-agent therapies; however, the literature and the data on file with the Food and Drug Administration suggest that triptorelin may be more reliable than leuprolide in maintaining castration levels of serum testosterone. The clinical significance of this benefit remains to be proven
— id: 115340, year: 2005, vol: 7 Suppl 5, page: S3, stat: Journal Article,

Managing and preventing acute urinary retention
Lepor, Herbert
2005 ;7 Suppl 8:S26-S33, Reviews in urology
Acute urinary retention (AUR), an uncomfortable and potentially dangerous condition, often occurs in men who have benign prostatic hyperplasia. Although the reported incidence of AUR varies in the literature, there are a number of events that are known to precipitate episodes of AUR, including ingestion of certain agents, infection, general anesthesia, and performance of various diagnostic genitourinary procedures. Because it is preferable to avoid the need for catheterization (and the associated risks) in men at high risk for AUR, certain measures have been studied as means to prevent AUR episodes. Specifically, alpha-blockers and 5-alpha-reductase inhibitors have been shown to reduce the incidence of initial and subsequent AUR episodes in certain at-risk men
— id: 115339, year: 2005, vol: 7 Suppl 8, page: S26, stat: Journal Article,

Open versus laparoscopic radical prostatectomy
Lepor, Herbert
2005 Summer;7(3):115-127, Reviews in urology
Expert laparoscopic surgeons have demonstrated that laparoscopic radical prostatectomy with or without robotic assistance can be performed with excellent results. There is no evidence that laparoscopic radical prostatectomy with or without robotic assistance offers any clinically relevant advantage over open radical prostatectomy. Laparoscopic radical prostatectomy with or without robotic assistance requires a significant learning curve, is a longer surgical procedure, carries greater costs, and requires an expanded operating room team. The literature suggests that laparoscopic radical prostatectomy is associated with more intraoperative complications and higher positive surgical margins. The lesser amount of postoperative bleeding associated with laparoscopic radical prostatectomy is not clinically relevant. Laparoscopic radical prostatectomy is not associated with less pain and does not facilitate earlier urinary catheter removal. The best way to improve overall outcomes after radical prostatectomy is to direct patients to expert open or laparoscopic surgeons
— id: 115343, year: 2005, vol: 7, page: 115, stat: Journal Article,

Pathophysiology of benign prostatic hyperplasia in the aging male population
Lepor, Herbert
2005 ;7 Suppl 4:S3-S12, Reviews in urology
Nearly all men will develop histological benign prostatic hyperplasia by the age of 80, but the degree of prostatic enlargement resulting from the hyperplasia is highly variable. Historically, it has often been assumed that the pathophysiology of lower urinary tract symptoms (LUTS) in men is the result of bladder outlet obstruction associated with prostatic enlargement. The observation that prostatic enlargement, bladder outlet obstruction, and LUTS are all age-dependent has been interpreted to indicate that these phenomena were causally related, but there is insufficient evidence for this. Undoubtedly, some men' prostatic enlargement causes obstruction and symptoms. Based upon the available data, however, this subset appears to be extremely small. Because of the many urological and nonurological conditions that cause LUTS and age-dependent changes in bladder and neurological function, it is unlikely that there exists a single dominant etiology for the aging male population. If this is the case, then the optimal management of LUTS will require different and possibly combination therapies
— id: 115334, year: 2005, vol: 7 Suppl 4, page: S3, stat: Journal Article,

Pathophysiology of lower urinary tract symptoms in the aging male population
Lepor, Herbert
2005 ;7 Suppl 7:S3-S11, Reviews in urology
Nearly all men will develop histological benign prostatic hyperplasia by the age of 80, but the degree of prostatic enlargement resulting from the hyperplasia is highly variable. Historically, it has often been assumed that the pathophysiology of lower urinary tract symptoms (LUTS) in men is the result of bladder outlet obstruction associated with prostatic enlargement. The observation that prostatic enlargement, bladder outlet obstruction, and LUTS are all age-dependent has been interpreted to indicate that these phenomena were causally related, but there is insufficient evidence for this. Undoubtedly, some men's prostatic enlargement causes obstruction and symptoms. Based on the available data, however, this subset appears to be extremely small. Because of the many urological and nonurological conditions that cause LUTS and age-dependent changes in bladder and neurological function, it is unlikely that there exists a single dominant etiology for the aging male population. If this is the case, then the optimal management of LUTS will require different and possibly combination therapies
— id: 115333, year: 2005, vol: 7 Suppl 7, page: S3, stat: Journal Article,

Prostatic intraepithelial neoplasia in a 53-year-old man
Lepor, Herbert
2005 Spring;7(2):105-109, Reviews in urology
— id: 115344, year: 2005, vol: 7, page: 105, stat: Journal Article,

Prostate-specific antigen velocity accurately predicts response to salvage radiotherapy in men with biochemical relapse after radical prostatectomy
Patel, Rupa; Lepor, Herbert; Thiel, Robert P; Taneja, Samir S
2005 May;65(5):942-946, Urology
OBJECTIVES: To determine whether prostate-specific antigen (PSA) velocity (PSAV), used as a selection criterion for salvage radiotherapy (RT) after radical prostatectomy (RP), predicts the likelihood of response to RT in men with biochemical relapse. METHODS: We retrospectively reviewed the records of 48 patients who had undergone salvage RT for biochemical relapse after RP. All men were followed up with serial PSA measurements for a minimum of 6 months from their initial PSA recurrence, and RT was only offered to those patients with a serum PSA level remaining at less than 1.0 ng/mL. The response to RT was defined as maintenance of a PSA level of less than 0.1 ng/mL. The pathologic and clinical parameters, including PSAV, were examined to determine their individual ability to predict the response to RT. RESULTS: Of the 48 patients, 30 had maintained a PSA level of less than 0.1 ng/mL at a median follow-up of 16 months. The PSAV was strongly predictive of the likelihood of a response to salvage RT. The median relapse-free survival time for patients with a PSAV of less than 0.035 ng/mL/mo was 28 months compared with 16 months for patients with a PSAV greater than 0.035 ng/mL/mo. All other parameters tested, including Gleason score, seminal vesicle invasion, extracapsular extension, and margin status, were not predictive of the likelihood of a response to RT. CONCLUSIONS: In the present study, PSAV accurately predicted the likelihood of response to salvage RT in men with biochemical relapse after RP. No other pathologic parameters predicted the likelihood of response to RT. Using PSAV as a sole selection criterion for salvage RT after RP may allow improvement in the historically low rates of durable response
— id: 56091, year: 2005, vol: 65, page: 942, stat: Journal Article,

Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy
Shen, Samson; Lepor, Herbert; Yaffee, Robert; Taneja, Samir S
2005 Mar;173(3):777-780, Journal of urology
PURPOSE: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. RESULTS: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p <0.01), 0.02 (p <0.025) or 0.04 or greater ng/ml (p <0.01). Multivariate logistic regression analysis showed that a nadir of 0.01 (p <0.05), 0.02 (p <0.05) and 0.04 or greater ng/ml (p <0.01) independently predicted an increased risk of biochemical relapse compared to a nadir of less than 0.01 ng/ml. CONCLUSIONS: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies
— id: 56092, year: 2005, vol: 173, page: 777, stat: Journal Article,

Outcomes for men younger than 50 years undergoing radical prostatectomy
Twiss, Christian; Slova, Denisa; Lepor, Herbert
2005 Jul;66(1):141-146, Urology
OBJECTIVES: To compare the surgical outcomes after radical prostatectomy between men younger than 50 years and men 50 years old or older. METHODS: Between October 1, 2000 and December 31, 2003, 790 men underwent open radical retropubic prostatectomy by a single surgeon. The intraoperative, perioperative, and postoperative parameters were recorded in real time and entered into a database. The outcomes were compared for 66 men younger than 50 years of age (group 1) versus 724 men who were 50 years old or older (group 2). RESULTS: The pathologic stage, percentage of cancer in the surgical specimen, positive surgical margin rate, and Gleason score were not significantly different among the two age groups. No significant difference was found in the risk factors for prostate cancer between groups 1 and 2 (33.3% versus 28.9%, respectively; P = 0.63). The operative complications were exceedingly low in both groups. Of the men in groups 1 and 2, 93.3% and 97.1% achieved continence, respectively (P = 0.26). Of the potent men at baseline who underwent bilateral nerve-sparing prostatectomy, 100% of men in group 1 versus 81.4% in group 2 (P = 0.02) were having erections adequate for intercourse with or without phosphodiesterase-5 inhibitors or intracavernous injection therapy, as determined by direct patient interview. Of the men who underwent bilateral nerve-sparing radical retropubic prostatectomy, 78.3% of group 1 versus 62.6% of group 2 (P = 0.14) were potent with or without phosphodiesterase-5 inhibitors. CONCLUSIONS: The preoperative and pathologic predictors of organ-confined disease and biochemical recurrence were similar in both age groups. The results of this study have demonstrated that radical retropubic prostatectomy can be performed with good results and low complication rates in men with localized prostate cancer who are younger than 50 years of age
— id: 115352, year: 2005, vol: 66, page: 141, stat: Journal Article,

An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida
Xiao, Chuan-Guo; Du, Mao-Xin; Li, Bing; Liu, Zhao; Chen, Ming; Chen, Zhao-Hui; Cheng, Ping; Xue, Xiao-Nan; Shapiro, Ellen; Lepor, Herbert
2005 Jun;173(6):2112-2116, Journal of urology
PURPOSE: Neurogenic bladder is a major problem for children with spina bifida. Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic. We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying. We report our experience with this procedure in 20 children with spina bifida. MATERIALS AND METHODS: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis. The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration. All patients underwent urodynamic evaluation before and after surgery. RESULTS: Preoperative urodynamic studies revealed 2 types of bladder dysfunction- areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence. Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding. In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any improvement. CONCLUSIONS: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida
— id: 89516, year: 2005, vol: 173, page: 2112, stat: Journal Article,

"A randomized, controlled 6-Mo intervention with soy protein isolate in men with biochemical recurrence after radical prostatectomy"
Bosland, MC; Zeleniuch-Jacquotte, A; Melamed, J; Lepor, H; Taneja, SS; Schmoll, J; Watanabe, H; Levinson, B; Randolph, C; Walden, PD
2004 MAY ;134(5):1259S-1259S, Journal of nutrition
— id: 46488, year: 2004, vol: 134, page: 1259S, stat: Journal Article,

Contemporary management of prostate cancer with lethal potential - The Davis/Shaves/Schellhammer article reviewed
Lepor, H
2004 JUN ;18(7):829-830, Oncology
— id: 64621, year: 2004, vol: 18, page: 829, stat: Journal Article,

Evaluating men with benign prostatic hyperplasia
Lepor, Herbert
2004 ;6 Suppl 1:S8-S15, Reviews in urology
The clinical manifestations of benign prostatic hyperplasia (BPH) include lower urinary tract symptoms (LUTS), poor bladder emptying, urinary retention, detrusor instability, urinary tract infection, hematuria, and renal insufficiency. However, the majority of men with BPH present with LUTS only. Because LUTS can indicate a variety of conditions, evaluation of symptomatic men must first aim to identify or exclude BPH and, if present, assess its severity. It is important to assess symptom severity at baseline and during follow-up, using the American Urological Association Symptom Index or the International Prostate Symptom Score. Further testing can then be tailored to narrow the diagnosis and guide treatment decisions. Factors such as patient age and concomitant malignancy will also affect management, but the main goal of treatment remains the improvement of quality of life for the patient
— id: 115342, year: 2004, vol: 6 Suppl 1, page: S8, stat: Journal Article,

Management of clinically localized prostate cancer
Lepor, Herbert
2004 ;6 Suppl 2:S3-S12, Reviews in urology
Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer
— id: 115341, year: 2004, vol: 6 Suppl 2, page: S3, stat: Journal Article,

Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia
Lepor, Herbert
2004 ;6 Suppl 9:S3-S10, Reviews in urology
The pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia (BPH) are incompletely understood; however, the development of reliable instruments to measure symptom severity, prostatic enlargement, and bladder outlet obstruction has allowed major advances in their elucidation. The development of lower urinary tract symptoms (LUTS) in the aging male is influenced to some degree by the severity of bladder outlet obstruction and prostatic enlargement. Although the development of LUTS, bladder outlet obstruction, and BPH are age-dependent, they are not necessarily causally related; there are many other factors involved in the pathophysiology of LUTS. The clinically important parameters of disease progression in men with moderate to severe LUTS and low peak flow rates are symptom progression and the development of acute urinary retention (AUR). The risk of AUR is related to both baseline serum prostate-specific antigen level and prostate volume. In men with moderate prostate enlargement, the risk of AUR appears to be high enough to justify intervention with a 5alpha-reductase inhibitor in order to reduce this risk
— id: 115337, year: 2004, vol: 6 Suppl 9, page: S3, stat: Journal Article,

Radical prostatectomy: status and opportunities for improving outcomes
Lepor, Herbert
2004 ;22(3):435-444, Cancer investigation
— id: 46080, year: 2004, vol: 22, page: 435, stat: Journal Article,

Role of intraoperative biopsies during radical retropubic prostatectomy
Lepor, Herbert; Kaci, Ledia
2004 Mar;63(3):499-502, Urology
OBJECTIVES: To determine the value of intraoperative biopsy during radical retropubic prostatectomy. METHODS: Between October 2000 and August 2002, 500 men with clinically localized prostate cancer underwent radical retropubic prostatectomy by a single surgeon. A 2 to 3-mm circumferential biopsy was routinely obtained from the apical and bladder neck soft-tissue margin and submitted for frozen section examination. In selective cases suspicious for capsular incision, a biopsy was sent from what was believed to be the contiguous neurovascular bundle/lateral pedicle. RESULTS: Prostate cancer was observed in 4.5%, 0.8%, and 1.6% of the intraoperative biopsies sent from the apical, bladder neck, and neurovascular bundle/lateral pedicle soft-tissue margins, respectively. Patient age, Gleason score, perineural invasion on diagnostic prostate biopsy, and clinical stage were not associated with prostate cancer at the apical soft-tissue margin. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the surgical specimen to predict cancer in the apical soft-tissue margin was 57.7%, 98.2%, 62%, 97.7%, and 96%, respectively. Intraoperative biopsy of the apical soft-tissue margin reduced the positive margin rate by 3.8%. CONCLUSIONS: The yield of intraoperative biopsy of the bladder neck and neurovascular bundle/lateral pedicle is too low to justify it in routine practice. Biopsy of the apical soft tissue should be routinely performed to reduce the positive surgical margin rate
— id: 44931, year: 2004, vol: 63, page: 499, stat: Journal Article,

The impact of open radical retropubic prostatectomy on continence and lower urinary tract symptoms: a prospective assessment using validated self-administered outcome instruments
Lepor, Herbert; Kaci, Ledia
2004 Mar;171(3):1216-1219, Journal of urology
PURPOSE: We determined the impact of radical retropubic prostatectomy on continence and lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Between October 2000 and August 2002, 500 men with clinically localized prostate cancer underwent radical retropubic prostatectomy by a single surgeon, and completed the UCLA Prostate Cancer Index and American Urological Association (AUA) symptom index at baseline, 3, 6, 12 and 24 months after radical prostatectomy. Univariate analysis was performed to identify factors predisposing the early return of continence. RESULTS: A total of 100%, 98.3%, 97.1%, 94.2% and 98.6% of patients filled out the UCLA Prostate Cancer Index and AUA symptom index at baseline, and 3, 6, 12 and 24 months, respectively. Based on protective pad requirement or frequency of incontinence 100%, 90.9%, 87.2%, 92.1% and 98.5% vs 98.8%, 80.6%, 91.2%, 95.2% and 98.5% of men were continent at baseline, 3, 6, 12 and 24 months after surgery, respectively. Age, severity of lower urinary tract symptoms, Gleason score, nerve sparing status, blood loss or presence of benign prostatic tissue in the apical soft tissue margin did not predict early return of continence. All of the individual urinary symptoms captured by the AUA symptom score showed significant improvement after radical retropubic prostatectomy. Radical prostatectomy was associated with a mean 5.4 unit decrease in AUA symptom score (40% decrease) in men with baseline moderate/severe LUTS (AUA symptom score 8 or greater). CONCLUSIONS: The majority of men regain continence after radical retropubic prostatectomy and maximal continence is achieved by 24 months. No factors were identified that predicted early return of continence in our cohort of men undergoing radical prostatectomy. Radical prostatectomy has a clinically significant impact on improving LUTS
— id: 42593, year: 2004, vol: 171, page: 1216, stat: Journal Article,

Continence following radical retropubic prostatectomy using self-reporting instruments
Lepor, Herbert; Kaci, Ledia; Xue, Xiaonan
2004 Mar;171(3):1212-1215, Journal of urology
PURPOSE: We performed a global self-assessment of continence following radical retropubic prostatectomy (RRP) and determined how this global self-assessment of continence correlates with commonly used definitions of continence. MATERIALS AND METHODS: Between October 2000 and February 2002 all men who underwent RRP were encouraged to complete the University of California-Los Angeles Prostate Cancer Index 3, 6, 12 and 24 months postoperatively. Beginning October 2002 a single question capturing the patient global self-assessment of continence status was added to the postoperative continence assessment. The study design was cross-sectional since only continence surveys submitted between October 2002 through February 2003 were evaluated. Sensitivity, specificity and kappa coefficient was determined for the relationship between the patient global assessment of continence vs the definition of continence based on pad requirement, problem due to incontinence and frequency of incontinence. RESULTS: Continence progressively improved 3 to 24 months following RRP for all continence outcomes. At 24 months following RRP 97.1% of men considered themselves continent, while 97.1%, 94.1% and 97.1% were considered continent using continence definitions, including the requirement of no or 1 pad in a 24-hour interval, no or slight bother due to incontinence and total control or occasional dribbling, respectively. Our 3 definitions of continence derived from responses to the University of California-Los Angeles Prostate Cancer Index had excellent agreement with patient global self-assessment of continence (kappa coefficients between 0.76 and 0.83). CONCLUSIONS: The majority of men achieve continence without invasive intervention following RRP. Final continence status should be ascertained at 24 months. The patient global assessment of continence provides face validity for other definitions of continence based on responses to validated self-administered questionnaires
— id: 42594, year: 2004, vol: 171, page: 1212, stat: Journal Article,

Impact of fusion of indium-111 capromab pendetide volume data sets with those from MRI or CT in patients with recurrent prostate cancer
Schettino, Chris J; Kramer, Elissa L; Noz, Marilyn E; Taneja, Samir; Padmanabhan, Priya; Lepor, Herbert
2004 Aug;183(2):519-524, American journal of roentgenology
OBJECTIVE: Our goal was to evaluate the impact of image fusion on the interpretation of indium-111 Prosta-Scint SPECT scans. MATERIALS AND METHODS: Sixty-seven consecutive patients referred for rising prostate-specific antigen (PSA) levels after initial therapy for primary prostate cancer underwent SPECT 96 hr after infusion of (111)In Prosta-Scint, with simultaneous technetium-99m blood pool imaging. Volume data sets from the SPECT scans were then fused with those from CT and MR images of the pelvis using a 3D landmark-based warping program. The SPECT scans were initially interpreted without benefit of MRI or CT fusion. The fused Prosta-Scint MRI-CT volumes were reevaluated by a nuclear radiologist and an MRI radiologist. Independent reviews before and after fusion were available in these patients. Validation of results after fusion was performed through correlation with PSA changes after radiation therapy. RESULTS: Six patients with sites that could not be evaluated and three without their original Prosta-Scint scanning reports were excluded; thus, 58 patients were studied clinically. Seventy-four of 161 prefusion-positive sites were found to be negative after fusion. These 74 sites subsequently were identified primarily as showing bowel, vessel, or marrow uptake after fusion. In two patients, nodal disease was identified although the review before perfusion indicated none. Twenty-five patients previously thought to have nodal disease appeared to have only local disease after fusion. After local radiation therapy, PSA levels decreased in 12 of 25 patients, increased in five, and were unavailable in eight. CONCLUSION: Although Prosta-Scint SPECT alone can help in the proper management of recurrent prostate cancer, fusion with MRI-CT of the pelvis can improve the specificity of the examination
— id: 43816, year: 2004, vol: 183, page: 519, stat: Journal Article,

THE PROSTATIC UTRICLE IS NOT A MULLERIAN DUCT REMNANT: IMMUNOHISTOCHEMICAL EVIDENCE FOR A DISTINCT UROGENITAL SINUS ORIGIN
Shapiro, Ellen; Huang, Hongying; McFadden, Deborah E; Masch, Rachel J; Ng, Eliza; Lepor, Herbert; Wu, Xue-Ru
2004 Oct;172(4, Part 2 Of 2):1753-1756, Journal of urology
PURPOSE:: The embryological origin of the utricle is thought to be a remnant of the fused caudal ends of the mullerian ducts (MDs). Others propose that the urogenital sinus (UGS) contributes either partially or totally to the development of this structure. Using immunohistochemical probes, we provide strong evidence that the utricle is of UGS origin only. MATERIALS AND METHODS:: Human fetal prostates, gestational ages 9 to 24 weeks, were serially cross-sectioned. Representative sections were stained with antibodies to p63 (basal cell marker), vimentin (mesoderm marker), uroplakins (marker for urothelium) Pax-2 (expressed in ductal and mesenchyme of urogenital system including the MDs and wolffian ducts) and Ki67 (proliferation). Apoptosis was detected with the TUNEL assay. RESULTS:: By 9 weeks there was weak expression of p63 in the basal layer of the UGS. At 11 weeks there was increased staining of p63 in the UGS and some p63 staining of the fused MDs, which expressed Pax-2 at this time. At 14 to 15 weeks as the MDs were undergoing apoptosis, there was an ingrowth of uroplakin-expressing UGS epithelium into the periurethral stroma, which formed a plate of p63 positive cells just beneath the UGS that was Ki67 positive. The remaining caudal MD epithelium was p63 negative and expressed vimentin and Pax-2. By 17 weeks the plate of p63 positive cells elongated forming the utricle that remained p63 positive but Pax-2 and vimentin negative. CONCLUSIONS:: We show that the utricle forms as an ingrowth of specialized cells from the dorsal wall of the UGS as the caudal MDs regress
— id: 44930, year: 2004, vol: 172, page: 1753, stat: Journal Article,

Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial
Bautista, Oliver M; Kusek, John W; Nyberg, Leroy M; McConnell, John D; Bain, Raymond P; Miller, Gary; Crawford, E David; Kaplan, Steven A; Sihelnik, Stephen A; Brawer, Michael K; Lepor, Hebert
2003 Apr;24(2):224-243, Controlled clinical trials
Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of benign prostatic hyperplasia (BPH). Taken as monotherapy, alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms. Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery. Direct comparison of the alpha-blocker terazosin with finasteride has been done, but only for a period of 1 year. The Medical Therapy of Prostatic Symptoms (MTOPS) trial is a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride, whether taken as a monotherapy or in combination, in preventing or delaying the progression of BPH. We describe in this paper the design of the MTOPS trial, the concept of BPH progression, the definition and methods of determining the primary outcome events and the proposed statistical analysis methods. A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of randomized participants. Volunteers among randomized participants are to undergo a biopsy of the prostate at predetermined time points during the trial. Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH
— id: 44936, year: 2003, vol: 24, page: 224, stat: Journal Article,

A randomized, controlled six-month intervention study soy protein isolate in men with biochemical recurrence after radical prostatectomy
Bosland, MC; Zeleniuch-Jacquotte, A; Melamed, J; Lepor, H; Taneja, SS; Schmoll, J; Watanabe, H; Levinson, B; Walden, PD
2003 NOV ;12(11):1327S-1328S, Cancer epidemiology biomarkers & prevention
— id: 55376, year: 2003, vol: 12, page: 1327S, stat: Journal Article,

Influence of body weight and prostate volume on intraoperative, perioperative, and postoperative outcomes after radical retropubic prostatectomy
Hsu, Elias I; Hong, Eugene K; Lepor, Herbert
2003 Mar;61(3):601-606, Urology
OBJECTIVES: To determine the influence of body weight and prostate volume on surgical outcomes after radical retropubic prostatectomy. METHODS: Between January 1994 and July 2000, 1024 men underwent radical retropubic prostatectomy by a single surgeon. Information was collected on body weight, prostate volume, operative time, estimated blood loss, allogenic transfusion rate, intraoperative complications, perioperative complications, postoperative complications, surgical margin status, and length of hospital stay. Postoperative continence and erectile function were assessed from self-administered questionnaires. RESULTS: Body weight was not significantly related to operative time (P = 0.09), estimated blood loss (P = 0.12), allogenic transfusion rate (P = 0.49), intraoperative complications (P = 0.37), perioperative complications (P = 0.84), postoperative complications (P = 0.44), positive margin rate (P = 0.07), length of hospital stay (P = 0.27), postoperative continence (P = 0.72), or postoperative erectile function (P = 0.92). The prostate volume was significantly and directly related to the estimated blood loss (P = 0.02), allogenic transfusion rate (P = 0.01), and length of hospital stay (P = 0.01). The prostate volume was significantly and inversely related to the positive surgical margin rate (P = 0.03). The prostate volume was not significantly related to the operative time (P = 0.12), intraoperative complications (P = 0.68), perioperative complications (P = 0.73), postoperative complications (P = 0.14), postoperative continence (P = 0.23), or postoperative erectile function (P = 0.90). CONCLUSIONS: No clinically relevant risks were associated with increasing body weight. Intraoperative bleeding resulting in higher transfusion rates represented the only clinically significant outcome that was adversely impacted by prostate volume. In the hands of experienced surgeons, radical retropubic prostatectomy can be performed in heavy men and in men with large prostates with excellent outcomes
— id: 39271, year: 2003, vol: 61, page: 601, stat: Journal Article,

Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs Cooperative Study Trial
Johnson, Theodore M 2nd; Jones, Karen; Williford, William O; Kutner, Michael H; Issa, Muta M; Lepor, Herbert
2003 Jul;170(1):145-148, Journal of urology
PURPOSE: We evaluate the efficacy of medical therapy on nocturia in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a secondary analysis of data from the VA Cooperative Study Program Trial in which 1,229 men with BPH 45 to 80 years old were randomly assigned to receive terazosin, finasteride, combination or placebo. RESULTS: The 1,078 men who completed 12 months of the trial are included in this study. Of those men 1,040 (96.5%) had at least 1 episode of nocturia at baseline and 38 (3.5%) had less than 1 episode (baseline nocturia is an average of 2 measures). Of those 1,040 men 788 (75.8%) had 2 or more nocturia episodes. Overall, nocturia decreased from a baseline mean of 2.5 to 1.8, 2.1, 2.0 and 2.1 episodes in the terazosin, finasteride, combination and placebo groups, respectively. Of men with 2 or more episodes of nocturia 50% reduction in nocturia was seen in 39%, 25%, 32% and 22% in the terazosin, finasteride, combination and placebo groups, respectively. Changes in nocturia were correlated with changes in reported bother from nocturia (Pearson correlation 0.48), BPH impact index (0.32) and overall satisfaction with urinary symptoms (0.33). CONCLUSIONS: Terazosin and combination therapy reduced nocturia in men with BPH, yet the net advantage of terazosin over placebo was a net reduction of 0.3 nocturia episode. For a person to reach a 50% or greater reduction in nocturia, the advantage of terazosin over placebo was 17 percentage points. Changes in nocturia had a moderate impact on symptom specific quality of life measures
— id: 44935, year: 2003, vol: 170, page: 145, stat: Journal Article,

Landmark studies impacting the medical management of benign prostatic hyperplasia
Lepor, Herbert
2003 ;5 Suppl 4:S34-S41, Reviews in urology
The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over the past 10 years. Phase 3 studies of the safety and effectiveness of alpha-blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg, finasteride) for the treatment of BPH began to appear in the literature in 1992. This article reviews the results of landmark studies of these agents, either separately as monotherapy or as combined therapy, for the treatment of BPH. The relationship between prostate size and lower urinary tract symptoms (LUTS) is discussed. Although prostate volume is not as strongly correlated with these symptoms as was once believed, it has been shown to be an important predictor of risk for developing acute urinary retention. alpha-Blockers represent an effective treatment for LUTS independent of prostate volume; the clinical benefit of finasteride for LUTS is limited primarily to men with large prostates. Finasteride decreases the risk of progression to acute urinary retention and the requirement for surgical intervention; this benefit is greatest in men with enlarged prostates
— id: 115336, year: 2003, vol: 5 Suppl 4, page: S34, stat: Journal Article,

Landmark studies impacting the medical management of benign prostatic hyperplasia
Lepor, Herbert
2003 ;5 Suppl 5:S28-S35, Reviews in urology
The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over the past 10 years. Phase 3 studies of the safety and effectiveness of alpha-blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg, finasteride) for the treatment of BPH began to appear in the literature in 1992. This article reviews the results of landmark studies of these agents, either separately as monotherapy or as combined therapy, for the treatment of BPH. The relationship between prostate size and lower urinary tract symptoms (LUTS) is discussed. Although prostate volume is not as strongly correlated with these symptoms as was once believed, it has been shown to be an important predictor of risk for developing acute urinary retention. alpha-Blockers represent an effective treatment for LUTS independent of prostate volume; the clinical benefit of finasteride for LUTS is limited primarily to men with large prostates. Finasteride decreases the risk of progression to acute urinary retention and the requirement for surgical intervention; this benefit is greatest in men with enlarged prostates
— id: 115335, year: 2003, vol: 5 Suppl 5, page: S28, stat: Journal Article,

Practical considerations in radical retropubic prostatectomy
Lepor, Herbert
2003 May;30(2):363-368, Urologic clinics of North America
Overall, in the hands of an experienced surgeon, the outcomes following radical prostatectomy are excellent. Attention to patient selection, preoperative management, surgical technique, and postoperative management are essential factors contributing to favorable outcomes for men with a biologically significant cancer and 10-year life expectancy. For these men, radical prostatectomy represents the optimal management based on cure, morbidity, and quality of life
— id: 39233, year: 2003, vol: 30, page: 363, stat: Journal Article,

Surgical, Pharmacological, and Technological Advances in Adult and Pediatric Urology-State of the Art: Highlights of the 8th Annual NYU Department of Urology Post-Graduate Course December 6-8, 2001, New York, NY
Lepor, Herbert
2003 Winter;5(1):29-39, Reviews in urology
— id: 115348, year: 2003, vol: 5, page: 29, stat: Journal Article,

Contemporary evaluation of operative parameters and complications related to open radical retropubic prostatectomy
Lepor, Herbert; Kaci, Ledia
2003 Oct;62(4):702-706, Urology
OBJECTIVES: To determine the impact of recent advances in surgical technique, management, and early detection on outcome after open radical retropubic prostatectomy. METHODS: Between October 2000 and August 2002, 500 men with clinically localized prostate cancer underwent radical retropubic prostatectomy by a single surgeon (H.L.). One of the unique aspects of this prospective outcomes analysis was that both data acquisition and entry were conducted totally independent of the primary surgeon. RESULTS: The mean operative and prostatectomy time was 142.9 and 65.2 minutes, respectively. A single ureteral injury was the only intraoperative complication. The overall incidence of pulmonary embolus and/or deep vein thrombosis was 0.4%. The overall risk of allogeneic transfusion was 4.6%. The mean length of hospital stay was 2.11 +/- 0.04 days. Of the catheters, 83.6% were removed by postoperative day 8. The positive surgical margin rate was 8%. CONCLUSIONS: In the hands of experienced surgeons, outcomes after open radical prostatectomy are excellent. Laparoscopic and robotic prostatectomy must be compared with concurrent experiences with open radical prostatectomy
— id: 39034, year: 2003, vol: 62, page: 702, stat: Journal Article,

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia
McConnell, John D; Roehrborn, Claus G; Bautista, Oliver M; Andriole, Gerald L Jr; Dixon, Christopher M; Kusek, John W; Lepor, Herbert; McVary, Kevin T; Nyberg, Leroy M Jr; Clarke, Harry S; Crawford, E David; Diokno, Ananias; Foley, John P; Foster, Harris E; Jacobs, Stephen C; Kaplan, Steven A; Kreder, Karl J; Lieber, Michael M; Lucia, M Scott; Miller, Gary J; Menon, Mani; Milam, Douglas F; Ramsdell, Joe W; Schenkman, Noah S; Slawin, Kevin M; Smith, Joseph A
2003 Dec 18;349(25):2387-2398, New England journal of medicine
BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy
— id: 42894, year: 2003, vol: 349, page: 2387, stat: Journal Article,

Volume indexes of total, free, and complexed prostate-specific antigen enhance prediction of extraprostatic disease extension in men with nonpalpable prostate cancer
Naya, Yoshio; Fritsche, Herbert A; Cheli, Carol D; Stamey, Thomas A; Bartsch, Georg; Brawer, Michael K; Childs, Stacy; Taneja, Samir S; Lepor, Herbert; Partin, Alan W; Sokoll, Lori J; Chan, Daniel W; Babaian, Richard J
2003 Dec;62(6):1058-1062, Urology
OBJECTIVES: To analyze the ability of volume-adjusted total, complexed, and free prostate-specific antigen (PSA) to predict organ-confined cancer at radical prostatectomy in patients with nonpalpable disease. METHODS: Collected sera were assayed for total PSA (tPSA), complexed PSA (cPSA), and free PSA (fPSA) in 78 men who underwent radical prostatectomy with nonpalpable prostate cancer. The pathologic results (organ-confined versus extraprostatic extension [EPE]), tPSA, cPSA, fPSA/tPSA ratio, cPSA/tPSA ratio, fPSA/cPSA ratio, tPSA density (tPSAD), cPSA density (cPSAD), and fPSA density (fPSAD) were compared by the Mann-Whitney U test and receiver operating characteristic curves. RESULTS: Fifteen men (19.2%) had pathologic EPE. After stratifying the patients on the basis of the Beckman tPSA, the cPSAD, tPSAD, and fPSAD were significant predictors of EPE when comparing their respective medians in individuals with tPSA greater than 4.0 ng/mL. Statistically significant differences were noted between patients with and without EPE for tPSAD (P = 0.0015), cPSAD (P = 0.0018), and fPSAD (P = 0.0022), but not for the fPSA/tPSA, cPSA/tPSA, and fPSA/cPSA ratios. The area under the receiver operating characteristic curve was similar for tPSA (0.539) and cPSA (0.542), as it was for tPSAD (0.708), cPSAD (0.700), and fPSAD (0.731). The specificity and diagnostic accuracy of tPSAD, cPSAD, and fPSAD were significantly greater than those of tPSA and cPSA (specificity P <0.001; diagnostic accuracy P <0.05). CONCLUSIONS: In men with nonpalpable prostate cancer, the density parameters of tPSA, cPSA, and fPSA performed equivalently and appeared to enhance the predictability of EPE
— id: 44933, year: 2003, vol: 62, page: 1058, stat: Journal Article,

Prostate cancer: radical prostatectomy
Nelson, Joel B; Lepor, Herbert
2003 Nov;30(4):703-23, viii, Urologic clinics of North America
Today, more men than ever before are being followed after radical prostatectomy. Prognosis and follow-up should be based on the pathologic specimen. Measurable prostate-specific antigen (PSA) after surgery defines failure, with time to detectable PSA and rate of PSA rise being useful prognostic factors. The natural history of untreated biochemical failure is protracted, a fact to be considered in discussions of adjuvant treatment. Early in disease recurrence, imaging studies to locate residual disease rarely are useful clinically. Both adjuvant and salvage radiation to the prostate bed have benefits and risks, but neither is superior in overall prostate cancer survival. The timing of hormone therapy remains largely empiric. The promise of effective cytotoxic chemotherapy still is greater than its actual benefits, although novel cytostatic agents are being developed. The future management of this disease will improve with better molecular definition of risk and therapeutic response
— id: 44932, year: 2003, vol: 30, page: 703, stat: Journal Article,

Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial
Partin, Alan W; Brawer, Michael K; Bartsch, Georg; Horninger, Wolfgang; Taneja, Samir S; Lepor, Herbert; Babaian, Richard; Childs, Stacy J; Stamey, Thomas; Fritsche, Herbert A; Sokoll, Lori; Chan, Daniel W; Thiel, Robert P; Cheli, Carol D
2003 Nov;170(5):1787-1791, Journal of urology
PURPOSE: Complexed (c) prostate specific antigen (PSA) has been shown to enhance specificity for prostate cancer (CaP) detection over total PSA (tPSA), although a large multi-institutional prospective evaluation was required to confirm these findings. We compared the clinical performance of cPSA with tPSA as a first line test for CaP detection and secondarily to determine if PSA ratios, namely percent free PSA (fPSA) and percent cPSA, can provide further enhancement in diagnostic performance over cPSA or tPSA. MATERIALS AND METHODS: Consecutive men scheduled for initial biopsy of the prostate were enrolled prospectively at each of 7 university centers and community based urology practices. Serum was collected and tested with the Immuno 1 (Bayer Diagnostics, Tarrytown, New York), tPSA and cPSA, and Access (Beckman, Inc., San Diego, California) fPSA and tPSA methods. RESULTS: A total of 831 patients were evaluated, of whom 313 (37.5%) were diagnosed with CaP. ROC curve analysis performed from the results of all samples and those within the clinically relevant cPSA ranges of 1.5 to 3.2, 1.5 to 5.1, 1.5 to 8.3 and 3.2 to 8.3 ng/ml (tPSA 2 to 4, 2 to 6, 2 to 10 and 4 to 10 ng/ml, respectively) indicated a significant improvement in the AUC ROC curve for cPSA compared with tPSA (p < or =0.001). Using cutoff points that provide a sensitivity of 80% to 95% for CaP detection within the 1.5 to 8.3 ng/ml cPSA range cPSA provided a statistically significant enhancement in specificity over tPSA of 6.2% to 7.9%. Within the cPSA range of 1.5 to 3.2 ng/ml using a cutoff point of 2.5 ng/ml for tPSA and 2.2 ng/ml for cPSA provided a specificity of 21.2% and 35%, respectively, and 85% sensitivity for CaP detection. PSA ratios provided no further enhancement in specificity over cPSA within these ranges. CONCLUSIONS: The use of cPSA as a single test provided improved specificity over tPSA. Percent fPSA and percent cPSA offered little to no additional benefit in the differentiation of benign and malignant disease at clinically relevant cPSA concentrations
— id: 44934, year: 2003, vol: 170, page: 1787, stat: Journal Article,

Tamsulosin reduces the incidence of acute urinary retention following early removal of the urinary catheter after radical retropubic prostatectomy
Patel, Rupa; Fiske, Joshua; Lepor, Herbert
2003 Aug;62(2):287-291, Urology
OBJECTIVES: To determine the efficacy of tamsulosin in preventing acute urinary retention following early catheter removal after radical retropubic prostatectomy. METHODS: Between February 2000 and October 2000, cystography was performed on postoperative day 7 after radical retropubic prostatectomy by a single surgeon (group 1). Between September 2001 and August 2002, cystography was performed on postoperative day 8 after radical retropubic prostatectomy by the same surgeon (group 2). The protocol for performing cystography and assessment of extravasation was similar for both groups. Tamsulosin 0.4 mg was administered 3 days before and 4 days after cystography for all men in group 2. RESULTS: Of 179 cystograms in group 1, 135 (75%) revealed no extravasation, and the catheters were removed in 130 of these cases. Of 246 cystograms in group 2, 230 (93.5%) revealed no extravasation, and the catheters were removed in 229 of these cases. A significantly greater proportion of men in group 2 had no extravasation (P = 0.0007). The incidence of acute urinary retention in groups 1 and 2 was 10% and 2.6%, respectively (P = 0.0018). The incidence of anastomotic stricture was not significantly different between the two groups. CONCLUSIONS: Our data strongly suggest that tamsulosin significantly reduces the risk of acute urinary retention after attempts at early catheter removal following radical retropubic prostatectomy. Therefore, we recommend administering a 7-day course of tamsulosin therapy when attempting to remove the urinary catheter before postoperative day 8
— id: 39122, year: 2003, vol: 62, page: 287, stat: Journal Article,

Removal of urinary catheter on postoperative day 3 or 4 after radical retropubic prostatectomy
Patel, Rupa; Lepor, Herbert
2003 Jan;61(1):156-160, Urology
OBJECTIVES: To determine the feasibility and safety of removing the urinary catheter on postoperative day (POD) 3 or 4 after radical retropubic prostatectomy (RRP). METHODS: Between January 2001 and August 2001, gravity cystography was performed on POD 3 or 4 after RRP by a single surgeon (H.L.) on 151 men. The urinary catheter was removed on POD 3 or 4 providing no extravasation was evident on cystography. Urinary catheters were replaced over a guidewire placed into the bladder under flexible cystoscopic guidance in cases of acute urinary retention (AUR). Continence was assessed at 3 months after RRP. RESULTS: Of the 151 cystograms performed on POD 3 or 4, 116 (76.8%) revealed no evidence of extravasation. The indwelling catheters were removed in 114 of these cases (98.3%). Twenty-two (19.3%) of the 114 men whose catheters were removed on POD 3 or 4 developed AUR within 48 hours of catheter removal, requiring catheter replacement. Two of these patients required repeated surgery secondary to complications related to AUR. At 3 months after RRP, 75% of the men whose catheters were removed on POD 3 or 4 required no pads or a single pad during a 24-hour interval, and 77.6% reported none or slight bother from incontinence. Of the 37 men whose catheters were removed on POD 7 or later, 1 patient (2.7%) developed AUR, and the catheter was replaced without complications. At 3 months after RRP, 65.7% of men whose catheters were removed on POD 7 or later required no pads or a single pad during a 24-hour interval, and 71.4% reported none or slight bother from incontinence. The incidence of anastomotic stricture in men whose catheters were removed on POD 3 or 4 and POD 7 or later was 12.1% and 22.6%, respectively. CONCLUSIONS: Most men will have a watertight anastomosis on POD 3 or 4 after RRP. Early catheter removal does not have a negative impact on continence or the rate of anastomotic strictures. Because of the high incidence of AUR, requiring replacement of the urinary catheter, and the potential for disruption of the anastomosis or bladder neck reconstruction, we currently recommend delaying catheter removal until POD 7 or later
— id: 39319, year: 2003, vol: 61, page: 156, stat: Journal Article,

The New York University nerve sparing algorithm decreases the rate of positive surgical margins following radical retropubic prostatectomy
Shah, Ojas; Robbins, David A; Melamed, Jonathan; Lepor, Herbert
2003 Jun;169(6):2147-2152, Journal of urology
PURPOSE: We developed an algorithm that prospectively defines when to excise the neurovascular bundles during radical retropubic prostatectomy with the goal of maximizing the performance of nerve sparing procedures while minimizing positive surgical margins. MATERIALS AND METHODS: From January 1 to December 31, 2000 a single surgeon performed 272 radical retropubic prostatectomies and 263 were performed from January 1 to December 31, 2001. A single pathologist analyzed all specimens with positive margins. There were no prospectively defined criteria to guide decisions regarding excision of the neurovascular bundles in the 2000 study cohort. Gleason score, percent tumor volume and perineural invasion were independently analyzed in the biopsy specimens according to the site of origin (right versus left side) for the 2001 group only. The ipsilateral neurovascular bundle was excised for Gleason 6 or less tumors when there were 50% or greater tumor volume in the biopsy specimen and perineural invasion, for Gleason 7 tumors when there was 30% or greater tumor volume, or perineural invasion and for Gleason 8 to 10 tumors when there was 10% or greater tumor volume, or perineural invasion. RESULTS: There were no statistically significant differences between the 2000 and 2001 groups in regard to preoperative prostate specific antigen, clinical and pathological stage, biopsy Gleason score and percent tumor volume in the surgical specimen. There was a statistically significant decrease in the incidence of positive margins between the 2000 and 2001 groups (14% versus 8%, p = 0.027). The lower positive margin rate was not achieved because of a tendency to excise more neurovascular bundles since a significantly greater percent of neurovascular bundles was preserved in the 2001 group. The sensitivity, specificity, positive and negative predictive values, and accuracy of our algorithm were 18%, 93%, 28%, 89% and 84%, respectively. In sides of the prostate with extraprostatic extension ipsilateral wide excision of the neurovascular bundle was associated with positive margins in 33% of cases compared with 22% when the neurovascular bundle was preserved (p = 0.42). CONCLUSIONS: The New York University nerve sparing algorithm prospectively defines when to excise the neurovascular bundle based on Gleason score, perineural invasion and tumor volume in the biopsy specimen. Use of this algorithm decreases positive surgical margin rates, while significantly increasing the preservation of neurovascular bundles
— id: 37582, year: 2003, vol: 169, page: 2147, stat: Journal Article,

Stromal/epithelial interactions of murine prostatic cell lines in vivo: a model for benign prostatic hyperplasia and the effect of doxazosin on tissue size
Takao, Tetsuya; Tsujimura, Akira; Coetzee, Sandra; Salm, Sarah N; Lepor, Herbert; Shapiro, Ellen; Moscatelli, David; Wilson, E Lynette
2003 Jan 1;54(1):17-24, Prostate
BACKGROUND: One of the major constraints in elucidating the mechanisms involved in the etiology of benign prostatic hyperplasia (BPH) is the lack of suitable model systems that are readily manipulable in vitro and in vivo. To address this issue, we have used murine prostatic cell lines to establish a novel in vivo model for studying prostatic cell interactions. METHODS: Luminal, basal, and smooth muscle (SM) cell lines were inoculated alone or in combinations under the renal capsule of intact or castrated male mice, and the growth and composition of prostatic tissue in the absence or presence of doxazosin was determined. RESULTS: Both the luminal and basal cell lines reconstituted prostatic tissue if co-inoculated under the renal capsule with normal SM cells, whereas none of the lines formed significant tissue when inoculated alone. Luminal cells produced and secreted prostatic secretory products. The growth of prostatic tissue formed from co-inoculation of basal and SM cells was androgen responsive. In addition, a significant reduction in prostatic tissue was noted in animals treated with doxazosin. CONCLUSION: We have established an in vivo model that uses prostatic epithelial and SM cell lines for investigating cellular interactions between epithelial and SM cells that regulate prostatic growth and function. This model will be useful for delineating the mechanisms by which prostatic cells interact and in determining the efficacy of new approaches aimed at interfering with prostatic stromal/epithelial interactions that result in abnormal cellular proliferation
— id: 35189, year: 2003, vol: 54, page: 17, stat: Journal Article,

Complexed PSA for early detection of prostate cancer in men with serum PSA values of 2-4 ng/mL
Cheli, CD; Horninger, W; Babaian, R; Fritsche, H; Taneja, S; Lepor, H; Sokoll, L; Chan, D; Childs, S
2002 Jun;48(6):A41-, Clinical chemistry
— id: 30703, year: 2002, vol: 48, page: A41, stat: Journal Article,

Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter
Horninger, Wolfgang; Cheli, Carol D; Babaian, Richard J; Fritsche, Herbert A; Lepor, Herbert; Taneja, Samir S; Childs, Stacy; Stamey, Thomas A; Sokoll, Lori J; Chan, Daniel W; Brawer, Michael K; Partin, Alan W; Bartsch, Georg
2002 Oct;60(4 Suppl 1):31-35, Urology
Complexed PSA (cPSA) has been shown to improve specificity in the detection of prostate cancer over that of total PSA (tPSA) testing in men with tPSA values greater than the cutoff value of 4.0 ng/mL. However, recent studies have reported a 25% incidence of prostate cancer in men with tPSA values in the 2.5- to 4.0-ng/mL range. We performed a multicenter study of cPSA in a population of men who underwent prostate biopsies because of elevated PSA levels or abnormal digital rectal examination (DRE). As part of this study, we sought to assess the clinical value of cPSA in comparison to tPSA, the free/tPSA ratio (f/tPSA) and the complexed/tPSA ratio (c/tPSA) in early detection of prostate cancer in men with tPSA values in the range of 2 to 4 ng/mL. The study was performed at 7 centers. Sera were drawn from men who underwent biopsy procedures consisting of >10 prostate tissue cores. Receiver operating characteristic (ROC) analysis was performed from the results of patients with tPSA values in the range of 2 to 4 ng/mL, including men with suspicious as well as unremarkable findings on DRE. Sera were collected and tested with the Bayer tPSA and cPSA assay and the Beckman free PSA and tPSA assays. ROC analysis was performed for all samples in the 2- to 4-ng/mL PSA range. At biopsy, 158 men had no evidence of malignancy and 57 (26.5%) were diagnosed with prostate cancer. ROC analysis indicated that the area under the curve (AUC) for cPSA was 0.64, which was statistically significantly greater than that achieved for tPSA (AUC, 0.57; P <0.0001). The AUC for f/tPSA and c/tPSA were 0.60 and 0.63, respectively, which was not statistically significantly different from that of tPSA or cPSA (P >or=0.252). A cutpoint of 2.5 ng/mL for tPSA and 2.1 ng/mL for cPSA provided a specificity of 20.3% and 34.2%, respectively, and sensitivity levels of 86%. Using cutpoints of 25% for f/tPSA and 74% for c/tPSA provided a specificity of 11.0% and 21.5%, respectively, and sensitivity levels of 97%. In all, >92% of the cancers treated with radical prostatectomy were organ confined, and the histologic grading of the tumors ranged from moderately to poorly differentiated with Gleason scores from 5 to 9. These data confirm that there is a high incidence of clinically significant prostate cancer in men with tPSA levels <4.0 ng/mL. Measurement of cPSA proved useful in stratifying men with tPSA values in the 2- to 4-ng/mL range into high- and low-risk groups for prostate cancer. The use of cPSA as a single test was found to enhance detection of prostate cancer over that of testing with tPSA and PSA ratios in men with tPSA values in the range of 2 to 4 ng/mL
— id: 68185, year: 2002, vol: 60, page: 31, stat: Journal Article,

Followup interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels
Lefkowitz, Gary K; Taneja, Samir S; Brown, Jordan; Melamed, Jonathan; Lepor, Herbert
2002 Oct;168(4 Pt 1):1415-1418, Journal of urology
PURPOSE: Repeat biopsy has been advocated following the diagnosis of high grade prostatic intraepithelial neoplasia to exclude coexisting prostate cancer. We further define the natural history of high grade prostatic intraepithelial neoplasia by determining the incidence of prostate cancer 3 years following diagnosis. MATERIALS AND METHODS: A total of 31 men underwent followup interval biopsy 3 years after high grade prostatic intraepithelial neoplasia diagnosis in 1996 to 1997, regardless of change in serum prostate specific antigen (PSA) or digital rectal examination findings. A single pathologist reviewed all biopsy specimens. All men had a minimum of 12 biopsy cores taken at the time of diagnosis. RESULTS: A 3-year followup interval biopsy eight (25.8%) men had prostate cancer, 11 (35.5%) had high grade prostatic intraepithelial neoplasia only and 12 (38.7%) had no disease. Mean serum PSA at diagnosis and before the followup biopsy was 6.88 and 9.69 ng./dl., respectively (p = 0.008). Of the men 48% had less than a 1.0 unit increase in serum PSA. Upon univariate regression analysis change in serum PSA was not associated with the detection of prostate cancer (p >0.10). All 4 patients who subsequently underwent radical prostatectomy had organ confined disease. CONCLUSIONS: In a high proportion of men with high grade prostatic intraepithelial neoplasia prostate cancer will develop in a 3-year interval. Our findings support the concept that high grade prostatic intraepithelial neoplasia is a precursor to prostate cancer and that repeat biopsy at a delayed interval is recommended regardless of changes in PSA
— id: 68187, year: 2002, vol: 168, page: 1415, stat: Journal Article,

Assessing quality of life following radiotherapy
Lepor, Herbert
2002 Summer;4(3):160-161, Reviews in urology
— id: 115345, year: 2002, vol: 4, page: 160, stat: Journal Article,

Selecting treatment for high-risk, localized prostate cancer: the case for radical prostatectomy
Lepor, Herbert
2002 Summer;4(3):147-152, Reviews in urology
The most common treatment options for men with clinically localized prostate cancer include radical prostatectomy and radiation therapy. The choice between these options is often controversial, and selecting the optimal treatment poses a great challenge for patients and physicians. Factors important to the decision include age and life expectancy of the patient, the natural history of the prostate cancer, how curable the disease is, and the morbidity of treatment. Use of these criteria to select treatment for a healthy, 70-year-old man presenting with a nonpalpable tumor, stage T1c disease, serum prostate-specific antigen of 12 ng/mL, and an adenocarcinoma with a Gleason score of 8 that is present in 2 of 12 biopsy cores would lead to the choice of radical prostatectomy over radiation therapy. Data show that such a patient has a life expectancy of more than 12.3 years if the prostate cancer can be cured and a high probability of dying from the disease if it is not cured. Data further show that radical prostatectomy in such a patient would confer a survival advantage over radiation therapy without resulting in greater complications or reduction in quality of life
— id: 115346, year: 2002, vol: 4, page: 147, stat: Journal Article,

Surgical, Pharmacological, and Technological Advances in Adult and Pediatric Urology - State of the Art: Highlights of the 7th Annual NYU Department of Urology Postgraduate Course December 7-9, 2000, New York, NY
Lepor, Herbert
2002 Winter;4(1):24-33, Reviews in urology
— id: 115347, year: 2002, vol: 4, page: 24, stat: Journal Article,

Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP
McCullough, A; Woo, K; Telegrafi, S; Lepor, H
2002 Dec;14(6):462-465, International journal of impotence research
Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency. doi:10.1038/sj.ijir.3900909
— id: 33138, year: 2002, vol: 14, page: 462, stat: Journal Article,

Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?
Naya, Yoshio; Stamey, Thomas A; Cheli, Carol D; Partin, Alan W; Sokoll, Lori J; Chan, Daniel W; Brawer, Michael K; Taneja, Samir S; Lepor, Herbert; Bartsch, Georg; Childs, Stacy; Fritsche, Herbert A; Babaian, Richard J
2002 Oct;60(4 Suppl 1):36-41, Urology
We assessed whether volume-based complexed prostate-specific antigen (cPSA) indices could enhance prostate cancer detection in men with serum total PSA (tPSA) between 2.5 and 10.0 ng/mL. Between December 1998 and April 2000, cPSA assay was measured in 480 men who underwent transrectal ultrasound-guided prostate biopsies at 7 institutions. We compared the usefulness of cPSA and its indices with the ratio of free PSA (fPSA) to tPSA (percent fPSA) for early detection of prostate cancer. Overall, 168 men (35%) had cancer. In the 341 men with tPSA between 4.01 and 10.0 ng/mL at approximately 90% sensitivity and areas under the receiver operating characteristics curve, the performances of volume-based parameters were significantly better (P <0.05) than those of tPSA and cPSA. In the 139 men with tPSA between 2.5 and 4.0 ng/mL, at 90% sensitivity, the specificity of the ratio of cPSA to tPSA (percent cPSA) was best, followed by cPSA density (cPSAD). In the 101 men with the history of a previous prostate biopsy, at approximately 90% sensitivity, the specificity of cPSAD was significantly better than those of tPSA and percent fPSA (P <0.05). In the 371 men with a total prostate volume of >or=30 cm(3) at approximately 90% sensitivity, the specificity of the cPSAD was significantly better than that of tPSA, percent fPSA, and cPSA (P <0.05). In the 109 men with a total prostate volume of <30 cm(3), at 90% sensitivity the specificity of cPSA and cPSAD was better than that of percent fPSA. In conclusion, volume-based cPSA can modestly enhance the performance of cPSA
— id: 68184, year: 2002, vol: 60, page: 36, stat: Journal Article,

Complexed prostate-specific antigen as a staging tool: results based on a multicenter prospective evaluation of complexed prostate-specific antigen in cancer diagnosis
Taneja, Samir S; Hsu, Elias I; Cheli, Carol D; Walden, Paul; Bartsch, Georg; Horninger, Wolfgang; Babaian, Richard J; Fritsche, Herbert A; Childs, Stacy; Stamey, Thomas A; Sokoll, Lori J; Chan, Daniel W; Brawer, Michael K; Partin, Alan W; Lepor, Herbert
2002 Oct;60(4 Suppl 1):10-17, Urology
Within a 7-site prospective evaluation of the Bayer complexed prostate-specific antigen PSA (cPSA) assay, we analyzed the ability of cPSA to predict extracapsular extension (ECE) before radical prostatectomy. Included in this analysis were 152 men diagnosed with cancer, who subsequently underwent radical prostatectomy. Sera were tested with the Bayer total PSA (tPSA) and cPSA assays, and the Beckman free PSA (fPSA) and tPSA assays. Treating surgical pathology result as a binary variable (organ confined vs ECE), mean tPSA, cPSA, fPSA/tPSA (f/tPSA) ratios, tPSA density (tPSAD), and cPSA density (cPSAD) were compared by receiver operating characteristic (ROC) curves and univariate analysis. In all, 28 men (18.4%) had pathologically identified ECE. Between those with and without ECE, significant differences were observed for tPSA (P = 0.0127), cPSA (P = 0.0120), tPSAD (P = 0.0001), and cPSAD (P = 0.0002), but not f/tPSA (P = 0.3774) or c/tPSA (P = 0.2882). All tested parameters except f/tPSA (P = 0.376) and c/tPSA (P = 0.288) predicted ECE (P <0.05) by logistic regression. The ROC area under the curve (AUC) was identical for tPSA and cPSA (0.621) and for tPSAD (0.692) and cPSAD (0.691). Kendall-tau correlation coefficients also demonstrated the strongest correlation with ECE for cPSAD and tPSAD. Either alone or as a tPSAD calculation, cPSA carries equivalent staging ability to tPSA. The use of f/tPSA appears to be less effective in staging than either cPSA or tPSA, whereas the use of either cPSAD or tPSAD provides maximal staging accuracy. Therefore, cPSA could be applied as an accurate predictor of ECE independently or in a nomogram along with other predictive variables
— id: 68186, year: 2002, vol: 60, page: 10, stat: Journal Article,

Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis
Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E Lynette
2002 Jun 24;157(7):1257-1265, Journal of cell biology
Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation
— id: 32485, year: 2002, vol: 157, page: 1257, stat: Journal Article,

Isolation of mouse THP gene promoter and demonstration of its kidney-specific activity in transgenic mice
Zhu, Xinhua; Cheng, Jin; Gao, Jing; Lepor, Herbert; Zhang, Zhong-Ting; Pak, Joanne; Wu, Xue-Ru
2002 Apr;282(4):F608-F617, American journal of physiology. Renal physiology
Tamm-Horsfall protein (THP), the most abundant urinary protein synthesized by the kidney epithelial cells, is believed to play important and diverse roles in the urinary system, including renal water balance, immunosuppression, urinary stone formation, and inhibition of bacterial adhesion. In the present study, we describe the isolation of a 9.3-kb, 5'-region of the mouse THP gene and show the highly conserved nature of its proximal 589-bp, 5'-flanking sequence with that in rats, cattle, and humans. We also demonstrate using the transgenic mouse approach that a 3.0-kb, proximal 5'-flanking sequence is sufficient to drive the kidney-specific expression of a heterologous reporter gene. Within the kidney, transgene expression was confined to the renal tubules that endogenously expressed the THP protein, which suggests specific transgene activity in the thick ascending limb of the loop of Henle and early distal convoluted tubules. Our results establish the kidney- and nephron-segment-specific expression of the mouse THP gene. The availability of the mouse THP gene promoter that functions in vivo should facilitate additional studies of the molecular mechanisms of kidney-specific gene regulation and should provide new molecular tools for better understanding renal physiology and disease through nephron-specific gene targeting
— id: 39700, year: 2002, vol: 282, page: F608, stat: Journal Article,

Chemoprevention trials in men with prostate-specific antigen failure or at high risk for recurrence after radical prostatectomy: Application to efficacy assessment of soy protein
Bosland MC; Kato I; Melamed J; Taneja S; Lepor H; Torre P; Walden P; Zeleniuch-Jacquotte A; Lumey LH
2001 Apr;57(4 Suppl 1):202-204, Urology
This article discusses the basic elements of chemoprevention trial designs using cohorts of men following radical prostatectomy who either have prostate-specific antigen (PSA) failure indicative of recurrence or are at high risk for recurrence (positive surgical margins, extracapsular extension, seminal vesicle invasion, positive lymph nodes, Gleason score of greater than or equal to 8, preoperative serum PSA less than 20 ng/mL). Two ongoing randomized, double-blind, placebo-controlled clinical trials with soy protein as intervention in these 2 populations are described. In the trial with men at high risk for recurrence, participants started intervention within 4 months after surgery and were followed for up to 2 years; primary endpoints were PSA failure rate and time-to-PSA failure. In the trial with men with PSA failure (PSA 0.1 to 2.0 ng/mL), participants received treatment for 8 months and the primary endpoint is rise in PSA over time. The strengths and limitations of these designs are discussed and interim experience using studies with soy protein as the intervention agent are summarized
— id: 18555, year: 2001, vol: 57, page: 202, stat: Journal Article,

Changes in nocturia from medical treatment of B
Johnson, TM; Jones, K; Williford, WO; Lepor, H; Kutner, MH
2001 APR ;49(4):S137-S138, Journal of the American Geriatrics Society
— id: 55064, year: 2001, vol: 49, page: S137, stat: Journal Article,

Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling?
Lefkowitz GK; Sidhu GS; Torre P; Lepor H; Taneja SS
2001 Dec;58(6):999-1003, Urology
OBJECTIVES: To determine whether repeat biopsy is necessary when the diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is made with a 12-core biopsy. Repeated biopsy has been recommended for individuals with HGPIN noted on sextant prostate biopsy because of the high likelihood of cancer detection. Recently, we have recommended the routine use of 12 cores, rather than 6, to improve cancer detection. METHODS: The charts of all patients undergoing prostate biopsy during a 2-year period at the Manhattan Veterans Administration Medical Center were reviewed. Patients diagnosed with HGPIN on a 12-core biopsy were identified, and those undergoing a repeat 12-core biopsy within 1 year of the initial biopsy were evaluated to determine the rate of cancer detection. RESULTS: A total of 619 men underwent biopsy during the study period. Of 103 men diagnosed with HGPIN, 43 underwent a repeat biopsy within 1 year at the discretion of the managing urologist. The mean age and median prostate-specific antigen level of those undergoing a repeat biopsy was 65.5 years and 5.37 ng/mL, respectively. At the time of the repeat biopsy, 1 patient was found to have cancer (2.3%), 20 had HGPIN (46.5%), 20 had benign pathologic findings (46.5%), and 1 patient (2.3%) had atypical small acinar proliferation. CONCLUSIONS: A repeat biopsy after the diagnosis of HGPIN on 12-core prostate biopsy rarely results in cancer detection. In the absence of other factors increasing the suspicion of cancer, immediate repeat biopsy for HGPIN diagnosed on a 12-core biopsy is unnecessary
— id: 26550, year: 2001, vol: 58, page: 999, stat: Journal Article,

Radical retropubic prostatectomy
Lepor H
2001 Aug;28(3):509-19, viii, Urologic clinics of North America
Historically, radical prostatectomy is a surgical technique associated with significant morbidity. The ability to minimize intraoperative bleeding and preserve continence and potency requires a comprehensive understanding of pelvic anatomy, meticulous surgical technique, and appropriate surgical instruments. The anatomic radical retropubic prostatectomy first described by Walsh in 1982 represents a technique in evolution. The detailed surgical approach for anatomic radical retropubic prostatectomy described in this article represents the author's technique that has been developed after performing over 2,000 radical prostatectomies since 1986. The step by step illustrations and description of technique are designed to aid the urologic surgeon develop an efficient approach to this surgical procedure
— id: 26610, year: 2001, vol: 28, page: 509, stat: Journal Article,

Intraoperative and postoperative complications of radical retropubic prostatectomy in a consecutive series of 1,000 cases
Lepor H; Nieder AM; Ferrandino MN
2001 Nov;166(5):1729-1733, Journal of urology
PURPOSE: We critically examined the intraoperative and postoperative complications associated with radical retropubic prostatectomy in the modern era. MATERIALS AND METHODS: Between April 18, 1994 and July 13, 2000, 1,000 men underwent radical retropubic prostatectomy performed by a single surgeon. The whole inpatient hospital medical record of 909 patients, the outpatient charts of 955 and a self-administered patient survey completed by 679 were reviewed by 2 data managers not involved in surgical management or followup care. In all 1,000 cases at least 1 of the 3 data sources was reviewed. RESULTS: Mean patient age was 60.3 years. In 73%, 99.8% and 95.7% of cases serum prostate specific antigen was 10 ng./ml. or less, disease was clinical stage T1 or T2 and Gleason score was 7 or less, respectively, while 19.9% of pathological specimens showed positive margins. There were 8 intraoperative complications (0.8%). All 5 rectal injuries and the single ureteral injury were detected during the initial surgical procedure and repaired without sequelae. Only 14 men (1.4%) had any other complications during hospitalization. Until postoperative day 30, 4 pulmonary emboli (0.4%) with or without deep vein thrombosis and 5 myocardial infarctions (0.5%) developed. There were no intraoperative or in-hospital postoperative deaths and only 1 postoperative death secondary to myocardial infarction during the initial 30 days. Reexploration was done for hemorrhage and a disrupted anastomosis in 3 and 2 cases, respectively. Mean hospitalization was 2.3 days, 9.7% of patients required allogenic blood transfusion and 15 (1.5%) were rehospitalized. CONCLUSIONS: Our series represents a rigorous assessment of the complications associated with radical retropubic prostatectomy. It shows that in the hands of an experienced urological surgeon, this procedure is associated with minimal intraoperative and postoperative morbidity. Of the patients 98% had no intraoperative or postoperative complications. Our series enables appropriate contemporary comparisons to be made with laparoscopic prostatectomy and radiation therapy. This outcomes analysis implies that radical retropubic prostatectomy cannot be assumed to have greater morbidity than radiation therapy and it sets a high standard for those advocating laparoscopic radical prostatectomy
— id: 26650, year: 2001, vol: 166, page: 1729, stat: Journal Article,

Early removal of urinary catheter after radical retropubic prostatectomy is both feasible and desirable
Lepor H; Nieder AM; Fraiman MC
2001 Sep;58(3):425-429, Urology
OBJECTIVES: To determine the feasibility and desirability of removing the urinary catheter 7 days after radical retropubic prostatectomy. METHODS: Between February 28, 2000 and October 5, 2000, 184 men underwent radical retropubic prostatectomy by a single surgeon. Of these men, 97% underwent gravity cystography under fluoroscopic control on postoperative day (POD) 7. The indwelling urinary catheter was removed on POD 7 if no evidence of extravasation was observed on cystography. Patients completed a self-administered questionnaire at the time of catheter removal to capture the degree of bother from incisional pain and the indwelling urinary catheter during the recovery period. The level of urinary continence was determined at 3 months after radical retropubic prostatectomy. RESULTS: One hundred thirty-five of the cystograms (75%) had no evidence of extravasation. The indwelling catheters were removed in 130 (97%) of 135 cases. The body weight, surgical specimen weight, presence or absence of intraoperative anastomotic extravasation, volume of pelvic drainage recorded from the Hemovac drain, and creatinine level of the pelvic drainage fluids did not predict the finding of extravasation on the POD 7 cystogram. Fifteen percent of the men whose catheters were removed on POD 7 developed acute urinary retention. At 3 months, 72% of men required no or a single protective pad, and 87% indicated they experienced no or slight bother from incontinence. These continence outcomes are comparable with a historical control group by the same surgeon who underwent catheter removal on POD 14. Forty-five percent of the men reported the catheter caused moderate to severe bother, compared with only 19% of men who indicated moderate to severe bother from incisional pain. In retrospect, 95.6% of men indicated willingness to undergo cystography on POD 7 with the intent of early catheter removal. CONCLUSIONS: The results of our study suggest that most men will have no extravasation on a cystogram performed on POD 7 and that removing the catheter at this time in these cases does not increase the risk of complications or compromise overall urinary continence. The urinary catheter is a significant bother and limits physical activity during the postoperative period. Cystography and early removal of the catheter is both feasible and desirable and should be offered to men after radical retropubic prostatectomy
— id: 26619, year: 2001, vol: 58, page: 425, stat: Journal Article,

Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia - Editorial comment
Lepor, H
2001 AUG ;58(2):208-208, Urology
— id: 54945, year: 2001, vol: 58, page: 208, stat: Journal Article,

Radical-prostatectomy - Preface
Lepor, H
2001 AUG ;28(3):XV-XV, Urologic clinics of North America
— id: 54887, year: 2001, vol: 28, page: XV, stat: Journal Article,

Predicting continence following radical prostatectomy
Marsh DW; Lepor H
2001 Jun;2(3):248-252, Current urology reports
Stress urinary incontinence is a recognized complication following radical prostatectomy. Fortunately, in the hands of experienced surgeons, the overwhelming majority of men ultimately regain urinary continence following the procedure. Most men regain urinary continence 3 to 12 months after the prostatectomy. We have developed and validated a continence index that is administered at the time of catheter removal after radical prostatectomy. This index identifies those men who rapidly regain continence and men who will have permanent incontinence after prostatectomy. The study population was stratified into tertile groups based on the continence scores. At 3 months, 96%, 82%, and 68% of men in the highest, mid, and lowest tertile groups reported using no pads or one small pad. Based on these observations, we recommend initiating biofeedback immediately postoperatively in men with continence scores of 14 or less. At 1 year, 100%, 98%, and 87% of the men in the highest, mid, and lowest tertile group reported using no pads or only one small pad. Men who have continence scores greater than 14 can be assured that they will regain urinary continence within 1 year. To our knowledge, this index is the only validated instrument that predicts the return of urinary continence after radical prostatectomy
— id: 32126, year: 2001, vol: 2, page: 248, stat: Journal Article,

Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia
Narayan, P; Lepor, H
2001 MAR ;57(3):466-470, Urology
Objectives. To investigate the long-term efficacy and safety of tamsulosin in patients with benign prostatic hyperplasia and to monitor the increases and decreases in therapeutic response over time. Tamsulosin, a uroselective alpha-adrenergic receptor antagonist for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, targets alpha(1A)-adrenergic receptors of prostatic smooth muscle with greater affinity than the vascular alpha,, receptors. Since the alpha(1A)-adrenoceptor subtype mediates prostatic smooth muscle tension, alpha(1A)-adrenoceptor antagonists may diminish toxicity, with few unwanted effects on blood pressure, while still providing efficacious treatment. Methods. This study extended two 13-week trials and one 40-week extension trial for an additional 64 weeks. On study entry, all patients (n = 949) received 0.4 mg/day tamsulosin. Baseline values were taken from either those of the previous trials for patients who had been treated with tamsulosin or the first visit of this study for patients not previously exposed to the drug. The primary efficacy parameters were the changes in the total American Urological Association (AUA) symptom score, mean peak urinary flow rate (Qmax), and percentage of patients having 25% or greater improvement in the total AUA symptom score and 30% or more improvement in the Qmax. Safety was assessed primarily on the incidence and severity of adverse events and discontinuations due to adverse events. Results. Improvements from baseline were seen in all primary efficacy parameters and were maintained throughout the study. The changes from baseline for the total AUA symptom score and Qmax were statistically significant (P < 0.001) at all 3-month intervals. Tamsulosin was well tolerated, and the incidence of adverse events did not increase over time. The mean sitting vital signs did not vary from baseline or relative to the treatment duration. Conclusions. Tamsulosin was safe and effective in long-term treatment (longer than 1 year) of benign prostatic hyperpasia. UROLOGY 57: 466-470, 2001, (C) 2001, Elsevier Science Inc
— id: 55123, year: 2001, vol: 57, page: 466, stat: Journal Article,

Comparison of two different doses of preoperative recombinant erythropoietin in men undergoing radical retropubic prostatectomy
Nieder AM; Rosenblum N; Lepor H
2001 Apr;57(4):737-741, Urology
OBJECTIVES: To determine whether the response to recombinant erythropoietin is dose dependent in men undergoing radical prostatectomy and to elucidate the relative cost-effectiveness of two dosing regimens. METHODS: A prospective, open-label study comparing the effectiveness, cost, and safety of two different doses of recombinant erythropoietin was performed in men undergoing radical retropubic prostatectomy. The first 100 men received 600 IU/kg (high dose) of epoetin alfa. A second group of 100 men received 300 IU/kg (low dose). All men received two doses of erythropoietin on preoperative days 14 and 7, provided their baseline hematocrit levels were less than 48%. Hematocrit levels were measured at baseline (more than 14 days before surgery), at the time of anesthesia induction, in the recovery room postoperatively, on the first postoperative day, and on the morning of discharge. RESULTS: The mean increase in hematocrit from baseline to induction for the high and low-dose groups was 4.50 and 4.69, respectively (P = 0.7225). Six men (6%) in the high-dose group and seven (7%) in the low-dose group required allogenic blood transfusions. The mean cost of high and low-dose epoetin alfa was $1218 and $656, respectively. The cost per percentage point increase in hematocrit in the low-dose group was significantly less than in the high-dose group. No thromboembolic events occurred in the high or low-dose group. CONCLUSIONS: In men undergoing radical retropubic prostatectomy, the administration of epoetin alfa on preoperative days 14 and 7 was a safe and effective treatment strategy for reducing the risk of allogenic blood transfusions. The 300 IU/kg dosing regimen was significantly more cost effective than the 600 IU/kg dosing regimen
— id: 21198, year: 2001, vol: 57, page: 737, stat: Journal Article,

Anastomotic strictures following radical prostatectomy: insights into incidence, effectiveness of intervention, effect on continence, and factors predisposing to occurrence
Park R; Martin S; Goldberg JD; Lepor H
2001 Apr;57(4):742-746, Urology
OBJECTIVES: To examine the incidence, effectiveness of intervention, effect on continence, and factors predisposing to the occurrence of anastomotic strictures following radical retropubic prostatectomy. METHODS: Between January 1994 and June 1999, 753 radical retropubic prostatectomies were performed by a single surgeon. Anastomotic strictures were managed by dilatation followed by a self-catheterization regimen. Dilatations were repeated unless more than three dilatations were required over a 9-month interval. A control group representing a randomly selected group of men who did not develop anastomotic strictures was identified. The largest width of the midline vertical abdominal scar was measured. RESULTS: Of the 753 radical retropubic prostatectomies, 36 (4.8%) developed an anastomotic stricture. The mean time interval between the surgical procedure and diagnosis of the stricture was 4.22 months. Of the 26 cases of anastomotic strictures with at least 1-year follow-up, 24 (92.3%) were managed successfully by dilatations alone. No baseline characteristics before surgery were associated with the development of a stricture. The maximal scar width was the only factor that was associated with the development of a stricture in this study. Men with a maximal scar of greater than 10 mm were eight times more likely to develop strictures than men with smaller scars. The percentage of men who required protective pads 1 year following radical retropubic prostatectomy in the control and stricture groups was 12.5% and 46.2%, respectively. CONCLUSIONS: Anastomotic strictures are relatively rare following radical prostatectomy and have a negative effect on the development of continence. Most men are successfully managed with dilatations alone. The development of anastomotic strictures in some men appears to be related to a generalized hypertrophic wound-healing mechanism
— id: 21197, year: 2001, vol: 57, page: 742, stat: Journal Article,

Radical retropubic prostatectomy. Preoperative management
Rosenblum N; Lepor H
2001 Aug;28(3):499-507, Urologic clinics of North America
The morbidity of radical prostatectomy is minimized by identifying men who are at significant cardiovascular risk and excluding them from the procedure. Preoperative management designed to minimize surgical and medical complications and exposure to allogenic blood products increases the benefit-to-risk ratio of radical prostatectomy over other treatment options for localized prostate cancer
— id: 26611, year: 2001, vol: 28, page: 499, stat: Journal Article,

Impact of image fusion of In-111 Capromab Pendetide with MR or CT in patients with recurrent prostate CA
Schettino, CJ; Noz, ME; Kramer, E; Taneja, S; Lepor, H
2001 MAY abstract #1224;42(5):294-294, Journal of nuclear medicine
— id: 33363, year: 2001, vol: 42, page: 294, stat: Journal Article,

Analysis of apical soft tissue margins during radical retropubic prostatectomy
Shah O; Melamed J; Lepor H
2001 Jun;165(6 Pt 1):1943-1948, Journal of urology
PURPOSE: We determine the use of information gained with intraoperative biopsy and frozen section analysis of the apical soft tissue margin during nerve sparing radical retropubic prostatectomy. MATERIALS AND METHODS: A separate 2 to 3 mm. circumferential biopsy was obtained from the apical soft tissue margin, and was sent for frozen and permanent section analysis during radical retropubic prostatectomy in 95 men with clinically localized adenocarcinoma of the prostate. A single pathologist examined the surgical and apical soft tissue margin specimens for evidence and extent of benign or malignant prostate tissue. Urinary continence was evaluated at catheter removal and 3 months postoperatively. RESULTS: Of the patients 26% had positive surgical margins, of which 64% were positive apical margins. Permanent section of the apical soft tissue biopsy revealed no prostate in 39%, benign prostate in 54% and prostate cancer in 7% of patients. Because of the frozen section finding of adenocarcinoma in 3 patients, the apical soft tissue margin was further resected until the specimen was negative for malignancy. The apical soft tissue margin was the only positive margin site in 2 of these 3 patients. Positive surgical and apical margins, and percent tumor volumes greater than 26% on prostatectomy specimen had a significantly higher likelihood for positive apical soft tissue margins. The pathological finding of a positive apical margin on the surgical specimen had sensitivity, specificity, and positive and negative predictive values of 57%, 86%, 25% and 96%, respectively, for detecting prostate cancer on the apical soft tissue biopsy. Of the apical soft tissue biopsies 54% contained an element of benign prostatic tissue, although 92% of them contained benign tissue in less than 25% of the total specimen. Mean continence score in the men with and those without benign prostate tissue on apical soft tissue biopsy was 15.6 and 14.4, respectively (p = 0.15). The percent of men who required no protective pads for urinary continence at 3 months was 53% and 65% for those who had no prostate and those who had benign prostate tissue, respectively, in the apical soft tissue margin. CONCLUSIONS: Excising and submitting an additional 2 to 3 mm. of apical soft tissue margin for permanent section analysis after prostate removal during radical prostatectomy represent an effective method for decreasing residual prostate tissue. Attempts at maximizing urethral length when dividing the prostato-urethral junction likely increases the chance of leaving residual prostate without improving continence
— id: 20647, year: 2001, vol: 165, page: 1943, stat: Journal Article,

Volume-specific cutoffs are necessary for reproducible application of prostate-specific antigen density of the transition zone in prostate cancer detection
Taneja SS; Tran K; Lepor H
2001 Aug;58(2):222-227, Urology
OBJECTIVES: To determine the effect of prostate volume on the specificity of prostate-specific antigen density (PSAD) and PSAD of the transition zone (PSA-TZ) in the detection of prostate cancer. METHODS: Between February 1994 and April 1998, transrectal ultrasound-guided prostate needle biopsies were performed in 235 men with serum prostate-specific antigen (PSA) levels between 4.0 and 10.0 ng/mL. The PSAD and PSA-TZ specificities were calculated at 95% sensitivity cutoff levels generated from the whole group, as well as from cohorts stratified by transition zone index or prostate volume. RESULTS: Statistical significance was noted between the benign (n = 176) and prostate cancer (n = 59) groups for all tested PSA parameters. At 95% sensitivity, PSA-TZ carried a specificity of 37.5% compared with 29.6% for PSAD. When applying a single 95% sensitivity cutoff derived from the entire group to individual volume-stratified cohorts, the specificity decreased to 0% in glands less than 30 g in size. A 95% sensitivity PSA-TZ cutoff generated individually for volume-stratified cohorts of glands less than 30, 30 to 40, and 40 to 60 g resulted in more consistent specificity of 28.2%, 35.2%, and 45.7% for each cohort, respectively. CONCLUSIONS: Unlike whole group-derived cutoffs, the use of volume-specific PSA-TZ cutoffs allows consistently high specificity in all volume-stratified cohorts. The discrepancies in the PSA-TZ and PSAD specificities in published reports are likely due to the application of published cutoffs to populations of differing prostate volumes. The use of volume-specific cutoffs results in reproducible specificity in populations with differing prostate volume distribution, and thereby definitively resolves the differences in PSA-TZ specificity reported in published reports
— id: 26709, year: 2001, vol: 58, page: 222, stat: Journal Article,

Efficacy of first-generation Cavermap to verify location and function of cavernous nerves during radical prostatectomy: A multi-institutional evaluation by experienced surgeons
Walsh, PC; Marschke, P; Catalona, WJ; Lepor, H; Martin, S; Myers, RP; Steiner, MS
2001 MAR ;57(3):491-494, Urology
Objectives. To evaluate, using five experienced surgeons, the efficacy of the first-generation Cavermap Surgical Aid to identify the cavernous nerves intraoperatively and to predict the recovery of sexual function. This study was not designed to determine whether this device improves the ability to preserve the nerves or improve outcome. Methods. Fifty men younger than 60 years old (mean age 52.5 years; range 43 to 59) with clinically localized prostate cancer (76% T1c, mean Gleason score 6, prostate-specific antigen level less than 10 ng/mL) underwent nerve-sparing radical prostatectomy (90% bilateral). Intraoperatively, the Cavermap device was used to test for the presence of the cavernous nerves once the neurovascular bundle was identified visually and to determine whether the nerves were intact after the prostate was removed. Erectile function was evaluated using the International Index of Erectile Function; men were considered potent if they were able to achieve unassisted intercourse in at least one half of their attempts. Results. Before the removal of the prostate, the tumescence response to stimulation of the neurovascular bundle was 87.8%; when tissue not containing the neurovascular bundle was stimulated, no tumescence response occurred in 54%. After prostatectomy, a bilateral response to stimulation occurred in 90%, a unilateral response in 5%, and no response in 5%. Postoperatively, 71% of the patients were potent at 12 months. In the patients who demonstrated bilateral stimulation after removal of the prostate, 78% were potent at 12 months. Conclusions. After radical prostatectomy performed by experienced surgeons, patient-reported potency rates in men younger than 60 years of age were high. Cavermap stimulation demonstrated an 87.8% sensitivity and 54% specificity in locating the neurovascular bundle as identified by experienced surgeons. The lack of specificity of this first-generation device limits its application for deciding which structures can be safely preserved or excised. Because virtually ail patients demonstrated a positive response after removal of the prostate, the value of stimulation to predict the recovery of sexual function is yet to be determined. UROLOGY 57: 491-494, 2001. (C) 2001, Elsevier Science Inc
— id: 55124, year: 2001, vol: 57, page: 491, stat: Journal Article,

Filling and voiding symptoms in the American Urological Association symptom index: The value of their distinction in a Veterans Affairs randomized trial of medical therapy in men with a clinical diagnosis of benign prostatic hyperplasia
Barry, MJ; Williford, WO; Fowler, FJ; Jones, KM; Lepor, H
2000 NOV ;164(5):1559-1564, Journal of urology
Purpose: We used data from a large Veterans Affairs trial of medical therapy for men with benign prostatic hyperplasia to evaluate the value of calculating separate filling and voiding subscores of the American Urological Association (AUA) symptom index. Materials and Methods: We performed factor analysis to assess the psychometric validity of separating the 7 items of the AUA symptom index into filling and voiding subsets. To assess the clinical usefulness of calculating these subscores we correlated them against baseline measurements of symptom interference as well as urodynamic and anatomical measures of disease severity, and used them for predicting the response to medical therapy. Results: Factor analysis confirmed the psychometric validity of separating the AUA symptom index into a 3-item filling and a 4-item voiding subscale. However, calculating filling and voiding subscores did not result in differential correlations with measures of disease interference or severity. It also did not enable us to predict a better symptomatic or uroflowmetry response to medical therapy. Conclusions: Calculating separate filling and voiding subscores of the AUA symptom index is psychometrically valid but not clinically useful
— id: 54503, year: 2000, vol: 164, page: 1559, stat: Journal Article,

alpha(1)-Adrenoceptor selectivity and the treatment of benign prostatic hyperplasia and lower urinary tract symptoms
Kirby R; Andersson KE; Lepor H; Steers WD
2000 Aug;3(2):76-83, Prostate cancer & prostatic diseases
The storage (irritative) and voiding (obstructive) symptoms associated with benign prostatic hyperplasia are generally attributed to prostate enlargement and increased prostatic smooth muscle tone mediated by the prevailing alpha(1)-adrenoceptors in the bladder neck and prostate. This results in obstruction and subsequent secondary changes to the bladder. However, there is growing evidence that many of these symptoms may be due to changes in extraprostatic alpha(1)-adrenoceptors, possibly alpha(1D)-adrenoceptors. Findings from the VA cooperative trial challenge the current theory that the common side effects associated with these agents are due to vascular action of alpha(1)-adrenoceptor blockers. Prostate Cancer and Prostatic Diseases (2000) 3, 76-83
— id: 44937, year: 2000, vol: 3, page: 76, stat: Journal Article,

The mechanism of adverse events associated with terazosin: an analysis of the Veterans Affairs cooperative study
Lepor H; Jones K; Williford W
2000 Apr;163(4):1134-1137, Journal of urology
PURPOSE: We determined the mechanism of adverse events associated with alpha1-blockers for treating benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We randomized 1,229 men with clinical BPH at 31 Veterans Affairs medical centers into equal treatment groups, including those who received placebo, terazosin, finasteride, and combined terazosin and finasteride therapy, respectively. Adverse events were captured at all study visits during our 1-year study. Our current review of adverse events is limited to patients randomized to the placebo and terazosin groups. We compared the incidence of orthostatic blood pressure change, postural symptoms and orthostatic hypotension in men who were normotensive and hypertensive at baseline, respectively. We also determined the association of changes in systolic blood pressure with the incidence of treatment related adverse events. RESULTS: The treatment related rates of dizziness, asthenia, postural hypotension and syncope were 19%, 6%, 6% and 1%, respectively. Of these adverse events only postural hypotension was associated with orthostatic blood pressure changes. The incidence of asthenia, dizziness and postural hypotension was not significantly greater in patients with a systolic blood pressure decrease of 5 or greater and less than 5 mm. Hg, respectively. CONCLUSIONS: Dizziness and asthenia are not associated with changes in blood pressure, suggesting that these treatment related adverse events associated with alpha1-blockers are not related to vascular events. Designing a subtype selective alpha1 antagonist that has less effect on blood pressure may not result in marked improvement in tolerability over commercially available alpha1-blockers
— id: 11785, year: 2000, vol: 163, page: 1134, stat: Journal Article,

Prostatic diseases
Lepor, Herbert
Philadelphia : W.B. Saunders Co., c2000,
— id: 709, year: 2000, vol: , page: , stat: ,

The role of preoperative epoetin alfa in men undergoing radical retropubic prostatectomy
Rosenblum N; Levine MA; Handler T; Lepor H
2000 Mar;163(3):829-833, Journal of urology
PURPOSE: The safety and effects on hematocrit of recombinant human erythropoietin (epoetin alfa) were evaluated in men undergoing radical retropubic prostatectomy. MATERIALS AND METHODS: Between February 1, 1997 and November 2, 1998, 305 men with clinically localized adenocarcinoma of the prostate underwent radical retropubic prostatectomy performed by a single surgeon (H. L.). Of these men 283 with a baseline hematocrit of less than 48% received 600 IU/kg. epoetin alfa 14 days (-14) and 7 days (-7) before radical retropubic prostatectomy. Hematocrit was measured at baseline on day -14, on day -7, just before anesthesia induction on day 0, immediately postoperatively and on the day of discharge home. The number of allogeneic units transfused, and all intraoperative and postoperative complications were recorded. RESULTS: Mean hematocrit at baseline on day -14 and at induction on day 0 was 42.9% and 45.8%, respectively (p = 0.0001). The frequency of hematocrit decreasing, showing no change or increasing 0.1 to 1.9, 2.0 to 3.9 or greater than 4.0 hematocrit points was 16.5%, 0.5%, 23%, 22% and 38%, respectively. Of the men 17% had no increase in hematocrit. A weak correlation existed between baseline hematocrit and the erythropoietic response to epoetin alfa (r2 = 0.06). Mean change in hematocrit after treatment with epoetin alfa in the quartile baseline hematocrit groups 34.2 to 41.4, 41.5 to 43.2, 43.3 to 44.9 and 45.0 to 48.0 hematocrit points was 3.71, 2.45, 3.86 and 1.02 hematocrit points, respectively. Of the surgical candidates 22 (9.1%) achieved an induction hematocrit of greater than 51%. Of the 283 men receiving epoetin alfa 21 (7.4%) also received an allogeneic transfusion. The transfusion rate did not correlate with induction hematocrit. The only adverse cardiovascular event was an uncomplicated postoperative pulmonary embolus. CONCLUSIONS: Our prospective study demonstrates that epoetin alfa given preoperatively in 2 doses of 600 IU/kg. is safe for significantly increasing hematocrit in men before radical retropubic prostatectomy. It is intuitive that the significant increase in hematocrit decreases the requirement for allogeneic blood transfusion
— id: 8557, year: 2000, vol: 163, page: 829, stat: Journal Article,

Generation of active TGF-beta by prostatic cell cocultures using novel basal and luminal prostatic epithelial cell lines
Salm SN; Koikawa Y; Ogilvie V; Tsujimura A; Coetzee S; Moscatelli D; Moore E; Lepor H; Shapiro E; Sun TT; Wilson EL
2000 Jul;184(1):70-79, Journal of cellular physiology
Two prostatic epithelial lines, one of basal origin and one of luminal origin, were established from the dorsolateral prostates of p53 null mice. The cell lines are nontumorigenic when inoculated subcutaneously under the renal capsule or intraprostatically in syngeneic mice. The luminal cell line (PE-L-1) expresses cytokeratins 8 and 18 and the basal cell line (PE-B-1) expresses cytokeratins 5 and 14. The basal cells require serum for growth, whereas the luminal cells grow only in serum-free medium. Both cell lines require the presence of growth factors for optimal growth in culture, with EGF and FGF-2 having the greatest effect on the growth rate. Both lines express androgen receptor (AR) mRNA and protein. Androgen stimulates growth of the basal cell line, indicating that the ARs are functional, whereas growth of the luminal cells is unaffected by androgens. The luminal line is significantly inhibited by exogenous TGF-beta and produces low levels of endogenous TGF-beta. In contrast, the basal cell line produces significant amounts of TGF-beta and its growth is not influenced by this cytokine. Coculture of luminal cells with prostatic smooth muscle cells results in the generation of increased levels of biologically active TGF-beta, indicating a paracrine mechanism of TGF-beta activation that may be involved in the maintenance of normal prostatic function. To our knowledge this is the first report describing both basal and luminal prostatic cell lines from a single inbred animal species and the first indication that prostatic epithelial and stromal cells interact to generate the biologically active form of TGF-beta. These lines will provide an important model for determining basal/luminal interactions in both in vitro and in vivo assays.
— id: 11685, year: 2000, vol: 184, page: 70, stat: Journal Article,

Transforming growth factor-beta is an autocrine mitogen for a novel androgen-responsive murine prostatic smooth muscle cell line, PSMC1
Salm SN; Koikawa Y; Ogilvie V; Tsujimura A; Coetzee S; Moscatelli D; Moore E; Lepor H; Shapiro E; Sun TT; Wilson EL
2000 Dec;185(3):416-424, Journal of cellular physiology
A prostatic smooth muscle cell line (PSMC1) was established from the dorsolateral prostate of p53 null mice. The cell line is nontumorigenic when inoculated subcutaneously, under the renal capsule or intraprostatically in syngeneic mice. These cells express alpha-smooth muscle actin (alpha-SMA), indicating their smooth muscle origin, and TGF-beta significantly enhances expression of alpha-SMA. The cells express both androgen receptor (AR) mRNA and protein, and respond mitogenically to physiological concentrations of androgens. PSMC1 cells produce significant amounts of TGF-beta, which stimulates growth by an autocrine mechanism. Dihydrotestosterone (DHT) increases proliferation of PSMC1 cells by promoting TGF-beta secretion. Considering the significant inhibitory effect of TGF-beta on prostatic epithelial cells and its stimulatory effect on the PSMC1 cells, we postulate that TGF-beta produced by prostatic smooth muscle cells may have a paracrine effect on the prostatic epithelium. We also postulate that TGF-beta may be involved in the etiology of benign prostatic hyperplasia (BPH) by stimulating excessive stromal proliferation. Line PSMC1 is the first reported androgen-responsive murine smooth muscle cell line. It will be useful for in vivo and in vitro experiments to study the mechanisms of androgen action on prostatic stroma and for delineating the interactions that occur between prostatic smooth muscle and epithelium that may lead to prostatic diseases such as BPH
— id: 26907, year: 2000, vol: 185, page: 416, stat: Journal Article,

A continence index predicts the early return of urinary continence after radical retropubic prostatectomy
Twiss C; Martin S; Shore R; Lepor H
2000 Oct;164(4):1241-1247, Journal of urology
PURPOSE: We evaluated the ability of a newly developed continence index to predict the return of urinary continence 3 months after radical retropubic prostatectomy. MATERIALS AND METHODS: We developed and used a continence index to determine continence level after removal of the urinary catheter on postoperative day 15 in 145 men. A total of 20 patients were evaluated independently by 2 nurse specialists to assess continence index reliability. We evaluated continence level, pad use and degree of bothersomeness due to incontinence 3 months after catheter removal. The association of continence score with outcome variables was calculated using the Mantel-Haenszel trend test and the predictive ability of the continence score was determined by logistic regression to produce cumulative odds ratios. RESULTS: The intraclass correlation coefficient was 0.995 for the independently assessed continence index ratings and the Cronbach coefficient alpha was 0.65 for the 5 continence index parameters. Complete continence or continence with heavy activity but not always was achieved by 96%, 85% and 68% of the men in tertiles 1 (continence score 18), 2 (continence score 15 to 17) and 3 (continence score 14 or less), respectively. The cumulative odds ratio of 2.9 (95% confidence interval [CI] 1.9 to 4. 6) per tertile indicated a 2.9-fold increased chance of incontinence for each successively lower tertile. In addition, 96%, 82% and 68% of the men in tertiles 1 to 3, respectively, required no or 1 small pad daily. The cumulative odds ratio for pad use was 2.3 (95% CI 1.5 to 3.5) per tertile. Of the patients in tertiles 1 to 3 100%, 97% and 80%, respectively, had no or slight bothersomeness due to urinary incontinence. The cumulative odds ratio for bothersomeness level was 2.7 (95% CI 1.7 to 4.3) per tertile. The Mantel-Haenszel trend test showed a significant association of continence score with all 3 outcome variables (p < or =0.001). CONCLUSIONS: Our continence index is a simple and reliable instrument that provides useful prognostic information on the early return of continence after radical retropubic prostatectomy
— id: 32246, year: 2000, vol: 164, page: 1241, stat: Journal Article,

Effect of finasteride and or terazosin on serum PSA: Results of VA cooperative study #359
Brawer, MK; Lin, DW; Williford, WO; Jones, K; Lepor, H
1999 JUN 1 ;39(4):234-239, Prostate
BACKGROUND. Medical management of benign prostatic hyperplasia (BPH) giving rise to lower urinary tract symptomatology (LUTS) has emerged as the mainstay for first-line therapy. Prostate-specific antigen (PSA) is the most important method of detecting prostate carcinoma. The effect of finasteride on PSA has been widely: reported. Little data exist with respect to alpha-adrenergic blocking therapy in men treated for BPH. In the present investigation we set out to evaluate the effect of these two forms of therapy. METHODS. Patients enrolled in the VA Cooperative Study #359 trial were evaluated. This study evaluated men with moderate LUTS owing to BPH in four treatment groups: placebo (P), finasteride (F), terazosin (T), and combination of finasteride plus terazosin (C). Men were recruited at 31 VA medical centers and had a baseline in 52-week PSA determination at the respective sites. RESULTS. There was no significant difference in baseline PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically significant reduction in PSA levels was observed at 52 weeks in the F and C arms (P < 0.001), whereas significant increases were observed in the T and P arms (P < 0.01). Additionally, there was no significant difference in PSA response between the T and P arms, Thirty percent of men in the C or F arms had more than 40-60% reduction of PSA. In contrast, the majority of men on T or P had less than 40% change in PSA. Only 35% of men on F or C had the expected 40-60% reduction in PSA level. CONCLUSIONS. These data demonstrate no clinically significant effect of T on PSA level. The heterogeneity of PSA response to F may make monitoring patients for the development of prostate cancer problematic. (C) 1999 Wiley-Liss, Inc
— id: 54049, year: 1999, vol: 39, page: 234, stat: Journal Article,

Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy
Fraiman, MC; Lepor, H; McCullough, AR
1999 ;3(2):109-115 SUM, Molecular urology
There have been anecdotal reports of a decrease in penile size in men with erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (NSRRP). Penile circumference and length measurements are obtained by one physician from 100 men, age 47 to 74, who presented at various intervals (1.7-27.6 months) for the treatment of ED after NSRRP from 1994 through 1997, All patients were asked to complete a brief male sexual function inventory at their initial visit. Penile measurements were obtained both in the flaccid and erect states, with erections being induced with intracorporal injections of Trimix, The sexual inventory scores were compared with those of an age-matched control cohort of 130 men presenting for evaluation of ED during the same time period and 132 age-matched men who completed the inventory at the time of a prostate screening. By self-report, men experiencing ED after NSRRP had better libido but more severe ED than men presenting with ED of other causes. There was a decrease in all penile dimensions after NSRRP. The flaccid and erect measurements of length and circumference decreased 8% and 9%, respectively after surgery (p < 0.05). The most substantial change occurred between the first 4 and 8 months postoperatively, The average change in volume between the first 4 and 8 months was 19% to 22% in the flaccid and erect state, respectively. There is a significant decrease in penile size in men with ED after NSRRP. The etiology may be denervation smooth muscle atrophy, apoptosis, or hypoxia-induced damage to the corpora, Further research is needed to elucidate the nature of these postoperative changes
— id: 53993, year: 1999, vol: 3, page: 109, stat: Journal Article,

Time dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP)
Hong EK; Lepor H; McCullough AR
1999 Sep;11 Suppl 1:S15-S22, International journal of impotence research
PURPOSE: The response to sildenafil after radical retropubic prostatectomy (RRP) has been reported to be approximately 40% by the Sildenafil Study Group. We undertook a study in a large cohort of post-RRP erectile dysfunction (ED) patients in order to examine the relationship between satisfaction with sildenafil and time from surgery to start of sildenafil treatment. METHODS: Pre- and post-operative erectile function was assessed by the O'Leary Brief Sexual Function Inventory questionnaire. Patient satisfaction with sildenafil before and after sildenafil treatment was assessed by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Between April and October 1998, EDITS questionnaires were given to 579 patients who had undergone RRP between 1994 and 1998. 316 (55%) patients returned questionnaires. Of these, 198 (63%) had sildenafil treatment and completed post-treatment questionnaires and were included in the study group. RESULTS: In the study group, mean age was 61y. Pre-operatively, 92% had erections sufficient for vaginal penetration, 95% had bilateral nerve-sparing (NS) RRP. There was a significant increase in the treatment satisfaction rate with increasing time from surgery. Between zero and six months after surgery, the treatment satisfaction rate was 26%, which improved with time, peaking at 60% between 18 months and 2y. Self-perceived erectile function as determined by post-RRP pre-sildenafil treatment O'Leary questionnaires was not as predictive of response to sildenafil as time from surgery. CONCLUSIONS: The response to sildenafil appears to be dependent upon the interval between RRP and the start of sildenafil. The treatment satisfaction rate was found to peak at 60% between 18 months and 2y. Early nonresponders to sildenafil should not be disheartened, as they will more likely later respond
— id: 11934, year: 1999, vol: 11 Suppl 1, page: S15, stat: Journal Article,

Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder
Li SM; Zhang ZT; Chan S; McLenan O; Dixon C; Taneja S; Lepor H; Sun TT; Wu XR
1999 Sep;162(3 Pt 1):931-935, Journal of urology
PURPOSE: Although transitional cell carcinoma of the bladder (TCC) metastasizes frequently with devastating consequences, no marker has been available to monitor this process. Uroplakins are a group of specific markers for normal urothelium and are continuously expressed by the majority of TCCs. Detection of uroplakin-positive cells in the circulation would be a strong indication of hematogenous dissemination of tumor cells in patients with TCC. MATERIALS AND METHODS: Total RNAs were extracted from peripheral blood of 60 patients with TCC (50 non-metastatic and 10 metastatic) and 10 healthy controls, reverse-transcribed and subjected to polymerase chain reaction amplification (RT-PCR) using oligonucleotide primers of human uroplakin II gene. A uroplakin-expressing human bladder cancer cell line (RT4) was used as a positive control to establish the sensitivity of the RT-PCR assay. RESULTS: We showed that the PCR-amplification of the mRNA encoding uroplakin II (UPII), a 15-kDa urothelium-specific marker, constitutes a highly sensitive and specific assay for detecting 100% of transitional cell carcinoma tissue, and that this assay can detect a single bladder cancer cell in a 5-ml. blood sample. UPII mRNA was detected in the blood samples of 2 patients with metastatic bladder cancer without chemotherapy and 1 out of 8 such patients with chemotherapy, but not in those of 50 non-metastatic patients or normal controls. CONCLUSIONS: Uroplakin II is a highly specific marker for human TCC and the detection of uroplakin II in the peripheral blood is associated with metastatic spread of bladder cancer cells. The specific and sensitive detection of uroplakin II provides a useful adjunct for detecting bladder cancer metastasis, staging, and monitoring chemotherapeutic response
— id: 6182, year: 1999, vol: 162, page: 931, stat: Journal Article,

Radical retropubic prostatectomy reduces symptom scores and improves quality of life in men with moderate and severe lower urinary tract symptoms
Schwartz EJ; Lepor H
1999 Apr;161(4):1185-1188, Journal of urology
PURPOSE: We determine the impact of radical retropubic prostatectomy on lower urinary tract symptoms and quality of life due to urinary problems in men with clinically localized prostate cancer. MATERIALS AND METHODS: The American Urological Association (AUA) symptom index, a symptom problem index and a quality of life due to urinary problems question were administered to 104 men before and 12 months after radical prostatectomy. Urinary continence and satisfaction with the decision to undergo radical prostatectomy were also examined. RESULTS: In men with moderate or severe baseline urinary symptoms (AUA score 8 or greater) the total AUA symptom, symptom problem and quality of life question scores decreased by 51 (-6.39), 57 (-4.22) and 25% (-0.65), respectively, after radical prostatectomy. Except for nocturia statistically significant improvements were observed for all questions captured by the AUA symptom index. Radical prostatectomy did not significantly change mean AUA symptom score or symptom problem index in men with mild urinary symptoms (AUA score less than 8). In men with moderate or severe urinary symptoms radical prostatectomy significantly improved quality of life due to urinary problems. Although 10% of men exhibited some degree of clinically relevant stress incontinence, 98% were very satisfied or satisfied with the decision to undergo radical prostatectomy. CONCLUSIONS: In men with moderate or severe urinary symptoms radical prostatectomy improves lower urinary tract symptoms and quality of life due to urinary problems. The overall beneficial impact on voiding makes radical prostatectomy an attractive treatment option for clinically localized prostate cancer
— id: 7442, year: 1999, vol: 161, page: 1185, stat: Journal Article,

Does site specific labeling of sextant biopsy cores predict the site of extracapsular extension in radical prostatectomy surgical specimen
Taneja SS; Penson DF; Epelbaum A; Handler T; Lepor H
1999 Oct;162(4):1352-1357, Journal of urology
PURPOSE: We determine whether site specific labeling of sextant prostate biopsy cores predicts the site of extracapsular extension in a radical prostatectomy specimen, thereby justifying increased cost of pathological evaluation. MATERIALS AND METHODS: Between January 1994 and December 1997, 407 radical prostatectomies were performed at our institution by a single surgeon (H. L.). Surgical specimens showing extracapsular extension were examined by a single pathologist (J. M.) to identify the site of extension. Several different methods of submitting transrectal ultrasound guided biopsy cores were used since the majority of cases did not undergo biopsy at our institution. In 243 cases sextant biopsies were labeled right versus left. Of these cases 103 specimen cores were individually labeled. The ability of the positive biopsy core location to predict the location of extracapsular extension in the surgical specimen was determined. Univariate and multivariate logistic regression analyses were performed to assess the ability of biopsy core characteristics, including Gleason score, percentage of cancer in the core, core location and number of positive cores in the specimen, to predict the site of extracapsular extension. A similar analysis was performed for the 243 cases with right versus left core labeling. RESULTS: The positive predictive value was 8.9+/-2.2% for a single positive core to identify the location of extracapsular extension correctly in the individually labeled core cases. The absence of cancer in a sextant biopsy had a negative predictive value of 96.9+/-1.4%. The overall sensitivity was 59.4+/-3.8% for a positive biopsy core. In the right versus left core cases the positive predictive value was 12.9+/-3.0% with a sensitivity of 85.1+/-3.2%. In an individual core Gleason score 8 or greater and/or cancer in more than 50% of tissue enhanced the positive predictive value but not to a clinically useful level. Multivariate logistic regression identified Gleason score, number of positive ipsilateral cores and base position of the positive biopsy as the most predictive variables for the site of extracapsular extension. CONCLUSIONS: When submitting biopsy specimens by individually labeled core or right versus left core, the positive predictive value of an individual positive core for the location of extracapsular extension is not sufficient to guide the surgical decision to spare or excise a neurovascular bundle. Therefore, the clinical information provided by individually labeled or right versus left core labeling does not justify the increased associated costs
— id: 6203, year: 1999, vol: 162, page: 1352, stat: Journal Article,

Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors in hyperplastic and non-hyperplastic human prostate
Walden PD; Gerardi C; Lepor H
1999 Feb;161(2):635-640, Journal of urology
PURPOSE: To determine the expression and localization of the alpha1A-1, alpha1B and alpha1D-adrenoceptor (AR) subtypes in hyperplastic and non-hyperplastic human prostate tissue. MATERIALS AND METHODS: The expression of the alpha1-AR subtypes was examined at the mRNA level by quantitative solution hybridization, and at the protein level by immunohistochemistry using subtype selective antibodies. RESULTS: While the overall level of alpha1-AR mRNA was not significantly different between hyperplastic and non-hyperplastic tissue, there were significant differences in the ratio of the alpha1-AR subtypes expressed in the two tissue types. The most significant finding from these studies was the reduced expression of the alpha1b-AR mRNA in both glandular and stromal hyperplasia. By immunohistochemistry, the alpha1A-1-AR was detected in the stroma and not in the glandular epithelium. The alpha1B-AR was localized predominantly in the epithelium and was weakly present in the stroma. Lower levels of the alpha1B-AR were detected in the hyperplastic prostatic epithelium. The alpha1D-AR was detected in areas of stroma and was abundantly present in blood vessels. CONCLUSIONS: The alpha1A-1-, alpha1B- and alpha1D-AR subtypes are differentially localized in human prostate, and the expression levels of all three subtypes are altered in BPH. Alterations in a1-AR subtype expression (particularly the alpha1B-AR) in BPH cannot be solely attributed to changes in tissue morphometry resulting from hyperplasia and may be of significance in the pathogenesis of BPH
— id: 7463, year: 1999, vol: 161, page: 635, stat: Journal Article,

Mitogenic activation of human prostate-derived fibromuscular stromal cells by bradykinin
Walden PD; Lefkowitz GK; Ittmann M; Lepor H; Monaco ME
1999 May;127(1):220-226, British journal of pharmacology
Biologically active kinin peptides are released from precursor kininogens by kallikreins. Kinins act on kinin receptors to mediate diverse biological functions including smooth muscle contraction, inflammation, pain and mitogenicity. All components of the kallikrein-kinin system exist in human male genital secretions suggesting that these molecules participate in physiological and pathophysiological genitourinary function. The objective of this study was to assess the consequences of kinin action on prostate cells. Primary cultures of prostate secretory epithelial (PE) and prostate fibromuscular stromal (PS) cells were established from human prostate tissue. Transcripts encoding both the human B1 and B2 bradykinin receptor subtypes were detected in human prostate transition-zone tissue and in cultured cells by RT-PCR. In receptor binding assays, the B1 subtype predominated on PE cell membranes and the B2 subtype predominated on PS cell membranes. In PS cells, but not in PE cells, BK induced significant inositol phosphate accumulation and [3H]-thymidine uptake. These responses were mediated through the B2 receptor subtype. The use of signal transduction inhibitors indicated that mitogenic activation by BK occurred through both protein kinase C (PKC) and protein tyrosine kinase dependent mechanisms. PMA (phorbol 12-myristate 13-acetate) produced maximal [3H]-thymidine uptake by PS cells, resulted in cell elongation and caused the alpha-actin fibres present in PS smooth muscle cells to became organized into parallel arrays along the length of the elongated cells. In summary, the prostate contains a functional kallikrein-kinin system, which could be significant in physiological and pathophysiological prostate function
— id: 6137, year: 1999, vol: 127, page: 220, stat: Journal Article,

Long-term evaluation of tamsulosin in benign prostatic hyperplasia: placebo-controlled, double-blind extension of phase III trial. Tamsulosin Investigator Group
Lepor H
1998 Jun;51(6):901-906, Urology
OBJECTIVES: To evaluate the long-term efficacy and safety of once-daily tamsulosin (0.4 and 0.8 mg), a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia (BPH). METHODS: This trial extended a 13-week, Phase III multicenter placebo-controlled, double-blind outpatient trial for an additional 40 weeks. Of 618 patients, 418 (68%) continued into the extension phase on the same double-blind medication and dose. The primary efficacy parameters were total American Urological Association (AUA) symptom score and maximum urinary flow (Qmax). RESULTS: The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups (P <0.001). Significant improvements were observed in Qmax for both tamsulosin groups but not for the placebo group. The statistically significant improvements from baseline in efficacy parameters observed for each tamsulosin group at the end of the 13-week Phase III trial were maintained during the long-term extension phase. Tamsulosin at both dosages was well tolerated as maintenance therapy. Clinically significant orthostatic hypotension was not observed. Vital sign changes in either hypertensive or normotensive patients were not clinically significantly different across the three groups. CONCLUSIONS: Tamsulosin once-daily at 0.4 or 0.8 mg was shown to be effective, safe, and well tolerated in the target BPH population during long-term use
— id: 12121, year: 1998, vol: 51, page: 901, stat: Journal Article,

Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group
Lepor H
1998 Jun;51(6):892-900, Urology
OBJECTIVES: To evaluate the efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha1A-antagonist studied in clinical trials. METHODS: Patients with benign prostatic hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary efficacy parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary efficacy parameters were improvement in measurements at individual double-blind visits corresponding to the primary efficacy parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric parameters; and investigator's global assessment. RESULTS: Statistically significant improvements in all efficacy parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group. CONCLUSIONS: Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists
— id: 12122, year: 1998, vol: 51, page: 892, stat: Journal Article,

The pathophysiology of lower urinary tract symptoms in the ageing male population
Lepor H
1998 Mar;81 Suppl 1:29-33, British journal of urology
— id: 57192, year: 1998, vol: 81 Suppl 1, page: 29, stat: Journal Article,

The role of bladder neck biopsy in men undergoing radical retropubic prostatectomy with preservation of the bladder neck
Lepor H; Chan S; Melamed J
1998 Dec;160(6 Pt 2):2435-2439, Journal of urology
PURPOSE: Radical retropubic prostatectomy is often performed with preservation of the bladder neck. We examine the incidence of benign and malignant prostatic tissue at the bladder neck margin in men undergoing radical retropubic prostatectomy with preservation of the bladder neck for clinically localized prostate cancer. MATERIALS AND METHODS: The study included 100 cases of radical retropubic prostatectomy with preservation of the bladder neck performed by a single surgeon (H. L.). A 2 mm. thick circumferential specimen was excised from the bladder neck, divided into 4 quadrants (anterior, posterior, right and left) and submitted for frozen section examination. The permanent sections from these bladder neck biopsies and the entire surgical specimens were analyzed by a single pathologist (J. M.). RESULTS: The frozen section diagnosis from the bladder neck biopsies were adenocarcinoma, benign prostatic tissue and no prostatic tissue in 3, 38 and 59 cases, respectively. The permanent section diagnosis of the bladder neck biopsies was adenocarcinoma, benign prostatic tissue and no prostatic tissue in 4, 57 and 39 cases, respectively. The sensitivity specificity, and positive and negative predictive values for examination of the surgical specimen to identify benign prostatic tissue was 67, 90, 90 and 65%, respectively. The bladder neck was re-biopsied because of the findings of adenocarcinoma and benign prostatic tissue in 3 and 8 cases, respectively. The initial bladder neck biopsy resulted in pathological down staging to pT2c in only 1 case. Repeat resection of the bladder neck in all cases with 10% or less benign prostatic tissue showed no prostatic tissue, whereas 50% of the cases with more than 10% benign prostatic tissue demonstrated residual benign prostatic tissue. Serum prostate specific antigen was undetectable immediately after radical retropubic prostatectomy in all cases with benign prostatic tissue only. CONCLUSIONS: Preservation of the bladder neck during radical retropubic prostatectomy does not significantly compromise total extirpation of the malignant process. Benign prostatic tissue at the bladder neck margin is relatively common. Examination of the surgical specimen has limited sensitivity, and negative and positive predictive values for the presence of benign prostatic tissue at the bladder neck margin. The impact of benign prostatic tissue as it relates to future malignant transformation is unknown. Submitting frozen section specimens from the bladder neck is reasonable for the younger man who may be at risk from benign prostatic tissue at the bladder neck margin
— id: 12059, year: 1998, vol: 160, page: 2435, stat: Journal Article,

The impact of medical therapy on bother due to symptoms, quality of life and global outcome, and factors predicting response. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group
Lepor H; Williford WO; Barry MJ; Haakenson C; Jones K
1998 Oct;160(4):1358-1367, Journal of urology
PURPOSE: We determine the effect of placebo, finasteride, terazosin and a combination of drugs on bother due to symptoms, quality of life and patient perception of improvement, and identify baseline clinical factors that predict clinical response to medical therapy. MATERIALS AND METHODS: A total of 1,229 subjects with clinical benign prostatic hyperplasia (BPH) were randomized to 1 year of placebo, finasteride, terazosin or drug combination. The primary outcome measures were American Urological Association (AUA) symptom score and peak flow rate. Relevant secondary outcome measures were symptom problem score, BPH impact score and global rating of improvement. RESULTS: Group mean differences in symptom problem and BPH impact scores between the finasteride versus placebo, and terazosin versus combination groups were not statistically or clinically significant. Group mean differences in all outcome measures were highly statistically significant between the terazosin and finasteride, and combination and finasteride groups. The percentage of subjects who rated improvement as marked or moderate with placebo, finasteride, terazosin and combination was 39, 44, 61 and 65%, respectively. In the subsets of men in the placebo, finasteride, terazosin and combination groups with prostates greater than 50 cm.3 group mean decrease from baseline in AUA symptom score was -2.5, -3.6, -6 and -7, group mean increase in peak flow rate was 0.6, 2.7, 3.6 and 3.7 ml. per second, group mean decrease in symptom problem score was -2.2, - 1.9, -3.1 and -4.5, and group mean decrease in BPH impact score was -0.6, -0.3, -1.1 and -1.5, respectively. A correlational analysis failed to show a significant relationship between baseline prostate volume and treatment response to finasteride. There was a significant but weak relationship between change in AUA symptom score and peak flow rate in the finasteride and combination groups. The symptom responses with terazosin were independent of baseline peak flow rate. CONCLUSIONS: In men with clinical BPH finasteride and placebo are equally effective, while terazosin and combination are significantly more effective. In men with clinical BPH and large prostates the advantage of finasteride over placebo in terms of symptom reduction, impact on bother due to symptoms and quality of life is small at best, while the advantage of terazosin and combination over finasteride and placebo is highly significant. Baseline prostate volume was not a predictor of response to finasteride in the overall study population. On the basis of our results alpha1 blockers, such as terazosin, should be first line medical treatment for BPH
— id: 7651, year: 1998, vol: 160, page: 1358, stat: Journal Article,

5-year outcome of surgical resection and watchful waiting for men with moderately symptomatic benign prostatic hyperplasia: A department of Veterans Affairs cooperative study - Editorial comments
Lepor, H
1998 JUL ;160(1):16-16, Journal of urology
— id: 53432, year: 1998, vol: 160, page: 16, stat: Journal Article,

A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia - Comment
Lepor, H
1998 MAY ;159(5):1593-1594, Journal of urology
— id: 53515, year: 1998, vol: 159, page: 1593, stat: Journal Article,

Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer
Levine MA; Ittman M; Melamed J; Lepor H
1998 Feb;159(2):471-475, Journal of urology
PURPOSE: We investigated the role of performing 2 consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate in a single office visit as the protocol for detecting prostate cancer in men presenting for the first time with an abnormal digital rectal examination and/or elevated serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 137 consecutive men presenting for the first time with a clinically localized prostate nodule on digital rectal examination and/or elevated serum PSA based upon age specific reference ranges underwent 2 consecutive sets of sextant prostate biopsies under transrectal ultrasound guidance in a single office visit. The 2 sets of biopsies were processed and analyzed separately by pathologists. RESULTS: Adenocarcinoma of the prostate was diagnosed in 43 of the patients (31%) undergoing biopsy. Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies in 13 cases (10%). High grade prostatic intraepithelial neoplasia without adenocarcinoma of the prostate was observed in 18 of the first set of biopsies (15%). High grade intraepithelial neoplasia without adenocarcinoma of the prostate was the only pathological diagnosis in the second set of biopsies in 3 cases. The second set of biopsies provided important new clinical information related to prostate cancer in 20 cases (28%) and increased the number of cancers detected by 30%. In addition, 14 patients with high grade intraepithelial neoplasia who would have required a second set of biopsies were found not to have adenocarcinoma of the prostate. Prostate cancer was detected in 43, 27 and 24% of men with prostate volumes less than 30, 30 to 50 and greater than 50 cc, respectively. The percentage of prostate cancers detected only in the second set of biopsies was not significantly related to prostate size. CONCLUSIONS: Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate performed in a single office visit represent a cost-effective biopsy strategy for men presenting with an abnormal digital rectal examination and/or elevated serum PSA. The benefits include increasing the detection of adenocarcinoma of the prostate and providing the recommended second set of biopsies for high grade intraepithelial neoplasia without increased morbidity or cost
— id: 7653, year: 1998, vol: 159, page: 471, stat: Journal Article,

Localization of P2Y1 purinoceptor transcripts in the rat penis and urinary bladder
Obara K; Lepor H; Walden PD
1998 Aug;160(2):587-591, Journal of urology
PURPOSE: The aim of this study was to determine the expression and localization of the P2Y1 purinoceptor mRNA in rat penis and urinary bladder using reverse transcription polymerase chain reaction (RT-PCR), northern blotting and in situ hybridization (ISH). MATERIALS AND METHODS: RT-PCR: First strand cDNA was prepared from rat penis and urinary bladder dome total RNA and used for PCR with primers designed to amplify fragments of the P2Y1 purinoceptor cDNA sequence. Northern blotting: PCR products were subcloned into the pGEM-5Zf(+) plasmid vector, sequenced and random primer labeled using 32p. Labeled probe was hybridized. ISH: Digoxigenin labeled cRNA probes were synthesized by in vitro transcription. RESULTS: P2Y1 purinoceptor mRNA was detected by RT-PCR analysis in both rat penis and urinary bladder. RNA blotting using a P2Y1 purinoceptor cDNA probe revealed a single transcript of 4.2kb in both tissues. This band was the same size as that expressed by the heart, which contains high levels of P2Y1 purinoceptor (Burnstock, G.: Physiological and pathological roles of purines: an update. Drug. Dev. Res., 28: 195, 1993). By ISH, P2Y1 purinoceptor mRNA was localized in detrusor smooth muscle cells and blood vessels in urinary bladder. In penis, positive signals were detected in endothelial cells which line the lacunar space and blood vessels. No hybridization was seen in corpus cavernosum smooth muscle cells and urethra. CONCLUSION: These results indicate that mRNAs for P2Y1 purinoceptor are expressed in detrusor smooth muscle cells and blood vessels of rat urinary bladder. However, in penis, this receptor is expressed in endothelial cells which lines the lacunar space and blood vessels, but not expressed in corpus cavernosum smooth muscle cells and urethra
— id: 7970, year: 1998, vol: 160, page: 587, stat: Journal Article,

Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele
Shapiro E; Seller MJ; Lepor H; Kalousek DK; Hutchins GM; Perlman EJ; Meuli M
1998 Sep;160(3 Pt 2):1047-1053, Journal of urology
PURPOSE: We determine whether smooth and skeletal muscle or nerve density is altered in the lower genitourinary or gastrointestinal tract of male human fetuses with myelomeningocele at 20 weeks of gestation. MATERIALS AND METHODS: We serially cross sectioned the lower genitourinary and gastrointestinal tracts in 7 male fetuses (mean age 20 weeks of gestation) with myelomeningocele and 4 age matched controls. Immunohistochemical staining was performed using Masson's trichrome stain and antibodies to smooth and skeletal muscle actin. S-100 protein staining for Schwann cell localization and neurofilament protein was also done. Fluorescein and rhodamine double immunolabeling was used to demonstrate the co-expression of smooth and skeletal muscle. RESULTS: Peripheral neural innervation of the bladder, prostate and rectum was markedly decreased in myelomeningocele. Masson's trichrome and smooth muscle actin staining also demonstrated that smooth muscle was less well differentiated in myelomeningocele specimens. Scant smooth muscle was present in the myelomeningocele bladder and bladder neck with an excess of collagen in an interfascicular and intrafascicular distribution. Double immunofluorescence staining revealed persistent co-expression of smooth and skeletal muscle actin by myocytes in the myelomeningocele detrusor, while in the control bladder there was only smooth muscle expression. The skeletal muscle component of structures in fetuses with myelomeningocele, including the external sphincter, was similar to that in controls. Prostatic size, ductal morphogenesis and smooth muscle were decreased compared to those in controls. CONCLUSIONS: A global defect exists in the development of smooth muscle in myelomeningocele in the lower genitourinary and gastrointestinal tracts by 20 weeks of gestation. Peripheral nerve density is decreased in smooth muscle in myelomeningocele, suggesting that an intact nervous system is important for the development of normal smooth muscle. Fetal surgery with coverage of the spinal cord in select cases may prevent progressive environmental injury to the somatic nervous system during the second half of gestation. However, achieving normal autonomic function is unlikely due to the extent of early global organ maldevelopment
— id: 12079, year: 1998, vol: 160, page: 1047, stat: Journal Article,

Prostate specific antigen density of the transition zone for early detection of prostate cancer - Comment
Taneja, SS; Lepor, H
1998 AUG ;160(2):418-419, Journal of urology
— id: 53406, year: 1998, vol: 160, page: 418, stat: Journal Article,

Endothelin-1 production and agonist activities in cultured prostate-derived cells: implications for regulation of endothelin bioactivity and bioavailability in prostatic hyperplasia
Walden PD; Ittmann M; Monaco ME; Lepor H
1998 Mar 1;34(4):241-250, Prostate
BACKGROUND: Endothelin-1 (ET-1) interacts with specific G-protein-coupled receptors to initiate short-term (contraction) and long-term (mitogenesis) events in target cells. ET-1 is an abundant prostate secretory protein that, in its biologically active form, elicits prostatic smooth muscle contraction. The present study was designed to determine the effects of ET-1 on prostate cell growth and to examine the regulation of endogenous ET-1 activity and bioavailability. METHODS: Primary cultures of prostate secretory epithelial (PE) and prostate fibromuscular stromal (PS) cells were established from benign human prostate tissue. RESULTS: In culture, PE cells secrete immunoreactive ET-1 (38.5 +/- 1.6 pg/ml/10(6) cells/24 hr) into the conditioned medium. Levels of immunoreactive ET-1 produced by PS cells were more than 10-fold lower. Endothelin-converting enzyme-1 (ECE-1) mRNA was detected in PE cells and not in PS cells; however, big ET-1 was the predominant immunoreactive ET-1 secretory product of PE cells. The ET(B) endothelin receptor was the predominant subtype in both PE and PS cells. In PS cells, but not PE cells, ET-1 induced significant inositol phosphate accumulation and [3H]-thymidine uptake. Agonist activity was inhibited by the ET(B) receptor selective antagonist, BQ 788. Intact PE cell monolayers secrete ET-1 through the apical surface, consistent with secretion of ET-1 into the glandular lumen in vivo. CONCLUSIONS: On the basis of these findings, regulation of ET-1 activity and bioavailability appears to be tightly regulated. Such findings have important implications in the pathophysiology of prostate disease
— id: 7838, year: 1998, vol: 34, page: 241, stat: Journal Article,

Identification of genes associated with stromal hyperplasia and glandular atrophy of the prostate by mRNA differential display
Walden PD; Lefkowitz GK; Ficazzola M; Gitlin J; Lepor H
1998 Nov 25;245(1):19-26, Experimental cell research
Despite the well-characterized histology associated with benign prostatic hyperplasia, very little is known about the underlying etiology of the disease on a molecular basis. The objective of this study was to use the technique of mRNA differential display in order to identify genes differentially expressed in human transition zone prostate tissue with high stromal density, with high epithelial density, and with nonhyperplastic histology. The extracellular matrix chondroitin/dermatan sulfate proteoglycan (CDSP) mRNA was more abundantly expressed in tissue with high stromal density, consistent with earlier findings that dermatan and chondroitin 6-sulfate glycosaminoglycans are increased in hyperplastic prostates. Messenger RNA encoding the negative regulator of cell cycle progression, BTG2, was more abundantly expressed in tissue with high epithelial densities. CDSP mRNA was abundantly expressed in primary cultures of stromal cells but was undetectable in epithelial cells. BTG2 mRNA was expressed in primary cultures of both cell types, but more abundantly in epithelial cells. BTG2 mRNA, but not CDSP mRNA, was subject to significant growth cycle regulation in cultured stromal and epithelial cells, with maximum expression occurring in quiescent cells. Generation of specific antibodies to BTG2 revealed that this protein was expressed at low levels in stroma, nonhyperplastic glands, and in hyperplastic glands. Consistent with a role in cell-cycle regulation, BTG2 protein was abundantly expressed in atrophic glands and preatrophic glands.
— id: 7839, year: 1998, vol: 245, page: 19, stat: Journal Article,

Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate
Wong WC; Chiu G; Wetzel JM; Marzabadi MR; Nagarathnam D; Wang D; Fang J; Miao SW; Hong X; Forray C; Vaysse PJ; Branchek TA; Gluchowski C; Tang R; Lepor H
1998 Jul 2;41(14):2643-2650, Journal of medicinal chemistry
A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate
— id: 57285, year: 1998, vol: 41, page: 2643, stat: Journal Article,

Prostatic alpha(1)-adrenoceptors and uroselectivity
Andersson, KE; Lepor, H; Wyllie, MG
1997 FEB 15 ;30(3):202-215, Prostate
BACKGROUND. alpha(1)-adrenoceptor antagonists (blockers) are now commonly used in the treatment of the symptoms of lower urinary tract obstruction. Originally phenoxybenzamine, a non-selective antagonist at both alpha(1)- and alpha(2)-adrenoceptors, was used by Marco Caine. In an attempt to minimize side effects, selective alpha(1)-antagonists, e.g, prazosin, were subsequently developed. More recently, agents such as alfuzosin, doxazosin, terazosin, and tamsulosin have been introduced and claims of ''uroselectivity'' and ''prostate'' selectivity have emerged. METHODS. This review attempts to put these claims into perspective and represents a comprehensive analysis of all pre-clinical and clinical data including several papers from the Japanese literature. An attempt is made to define what is meant by selectivity at various levels including the test tube, in the laboratory animal and, most importantly, in the clinical context of the whole patient. CONCLUSIONS. The conclusions are interpreted within the context of the subdivision of the alpha(1)-adrenoceptor into alpha(1A), alpha(1B), and alpha(1D) subtypes. (C) 1997 Wiley-Liss, Inc
— id: 53203, year: 1997, vol: 30, page: 202, stat: Journal Article,

Preoperative recombinant human erythropoietin injection versus preoperative autologous blood donation in patients undergoing radical retropubic prostatectomy
Chun TY; Martin S; Lepor H
1997 Nov;50(5):727-732, Urology
OBJECTIVES: In an effort to avoid allogeneic transfusions, many patients scheduled for radical retropubic prostatectomy (RRP) participate in preoperative autologous donation (PAD) programs. Yet, PAD programs are costly, time-consuming, and not without risks. Perioperative administration of recombinant human erythropoietin (Epoetin alfa) also has been shown to reduce patients exposure to allogeneic transfusion. This study sought to compare the costs and transfusion rates associated with either PAD or perioperative Epoetin alfa in patients undergoing RRP. METHODS: The study population consisted of 120 men randomized to one of two treatment groups. Patients in group 1 donated up to 3 U of autologous blood preoperatively, provided that their hematocrit (HCT) was 33% or higher. Patients in group 2 received 600 IU/kg of Epoetin alfa on days -14 and -7 preoperatively, provided that their HCT was 46% or lower. RESULTS: Overall, 107 (89%) of 120 patients underwent RRP. In group 1, 5 (9.6%) of 52 patients received a total of 12 U of allogeneic blood (0.23 U/patient). In group 2, 5 (9.6%) of 52 patients received a total of 10 U of allogeneic blood (0.19 U/patient). Three patients in group 1 but no patients in group 2 experienced an adverse event. The average costs related to PAD and pharmacologic administration per patient were $540 in group 1 and $657 in group 2. Participation in PAD required an average of 5 hours more per patient compared with Epoetin alfa administration. CONCLUSIONS: Preoperative Epoetin alfa therapy is safe, well tolerated, and equally effective as PAD in reducing allogeneic blood transfusion requirements. Epoetin alfa therapy also is comparable in cost to PAD and offers patients greater convenience and less of a time commitment
— id: 12195, year: 1997, vol: 50, page: 727, stat: Journal Article,

Smooth muscle development in the obstructed fetal bladder
Freedman, A L; Qureshi, F; Shapiro, E; Lepor, H; Jacques, S M; Evans, M I; Smith, C A; Gonzalez, R; Johnson, M P
1997 Jan;49(1):104-107, Urology
OBJECTIVES: To evaluate changes in the smooth muscle and connective tissue development in the obstructed and normal fetal bladder. METHODS: The smooth muscle and connective tissue composition of 19 fetal urinary bladders, including those of 9 fetuses with anatomic obstruction and 10 controls free of urologic disease, were analyzed by light microscopy and computer-assisted color image analysis. RESULTS: The bladder wall thickness was markedly increased in obstructed fetuses throughout gestation as compared with that in controls. The disparity in bladder wall thickness increased rapidly during gestation. The percent area density of smooth muscle and connective tissue as well as the ratio of smooth muscle to connective tissue remained the same in the obstructed and normal control fetal bladders. CONCLUSIONS: Although bladder outlet obstruction is associated with a marked increase in bladder wall thickness, the percent of smooth muscle and connective tissue comprising the mural histology remains relatively constant as compared with that of normal fetal controls. This study suggests that bladder outlet obstruction in the fetus is not associated with excess collagen deposition but rather with an increased amount of bladder with normal cellular content and a concomitant increase in smooth muscle development
— id: 89518, year: 1997, vol: 49, page: 104, stat: Journal Article,

Evaluation of the effect of endothelin-1 and characterization of the selective endothelin a receptor antagonist PD155080 in the prostate
Imajo C; Walden PD; Shapiro E; Doherty AM; Lepor H
1997 Jul;158(1):253-257, Journal of urology
PURPOSE: To evaluate the contractile effect of endothelin-1 (ET-1) on prostatic urethral pressure and to characterize the effect of the selective ETA receptor antagonist PD155080 on ET-1 mediated prostatic urethral pressure. MATERIALS AND METHODS: The effect of intravenous ET-1 administration on canine urethral pressure was determined in the presence and absence of PD155080. The affinity of PD155080 for endothelin-mediated contraction was determined using antagonist dissociation studies. Saturation and competition binding studies were performed using [125I] ET-1 in both human and canine prostate. RESULTS: ET-1 bolus injection elicited shallow and prolonged increases the prostatic urethral pressure. Pretreatment with PD155080 totally abolished the urethral contractile response to ET-1. Specific [125I] ET-1 binding was saturable and of high affinity. Two ET receptor subtypes (ETA receptor, ETB receptor) have been identified in human prostate. The ratio of ETA to ETB receptors was approximately 1.5:1 in both human and canine prostates. Isometric tension studies revealed that PD155080 shifted the ET-1 dose-response curves to the right and exhibited no effect on the ETB receptor selective agonist sarafotoxin dose-response curves. CONCLUSION: ET-1 mediates prostate smooth muscle tone and may play a role in the pathophysiology and treatment of benign prostatic hyperplasia (BPH)
— id: 7169, year: 1997, vol: 158, page: 253, stat: Journal Article,

Endothelins in canine genitourinary tissues
Langenstroer, P; Tang, R; Divish, B; Opgenorth, T; Shapiro, E; Lepor, H
1997 Mar;157(3):1044-1048, Journal of urology
PURPOSE: To characterize the functional effect of endothelin-1 (ET1) and endothelin-3 (ET3), immunohistochemically localize ET1-like immunoreactivity, and measure the tissue levels of immunoreactive endothelin (irET) in canine genitourinary (GU) tissues. MATERIALS AND METHODS: Canine GU tissues were characterized by measuring ET1 levels using a RIA, immunohistochemical staining of ET1 and isometric tension studies. RESULTS: Immunoreactive endothelin was present, to varying degrees, in the vas deferens, ureter, prostate, bladder and urethra. Functionally, ET1 demonstrated the typical concentration response characteristics in the canine bladder base, bladder body, and prostate. The maximal tension (Emax) measured following ET1 challenge was approximately 20-fold greater in the bladder body (0.67 +/- 0.21 g/mm.2) and bladder base (0.48 +/- 0.18 g/mm.2) as compared to the prostate 0.04 +/- 0.001 g/mm.2 The Emax of ET3 in the bladder body (0.31 +/- 0.12 g/mm.2) and bladder base (0.19 +/- 0.08 g/mm.2) was significantly lower than the corresponding Emax of ET1. No measurable contractile response was elicited by ET3 in the canine prostate. Immunohistochemical staining localized the ET-like immunoreactivity to the glandular epithelium of the prostate and the transitional epithelium of the bladder. CONCLUSIONS: Endothelins are ubiquitous in the canine lower GU tract with predominant localization to the epithelial elements. Endothelins are also functionally active in canine GU tissues, but the specific role of endothelins in the physiology and pathophysiology of GU tissues requires further investigation
— id: 89517, year: 1997, vol: 157, page: 1044, stat: Journal Article,

Effect of terazosin on prostatism in men with normal and abnormal peak urinary flow rates
Lepor H; Nieder A; Feser J; O'Connell C; Dixon C
1997 Mar;49(3):476-480, Urology
OBJECTIVES: To determine if men with normal peak urinary flow rates (PFR) and prostatism respond to terazosin. METHODS: Forty-one men over the age of 50 years with an American Urological Association (AUA) symptom score greater than 8, postvoid residual urine volume (PVR) less than 300 mL, and no clinical or biochemical evidence of prostate cancer were treated with terazosin independent of the baseline PFR. The effect of terazosin on the AUA symptom score and PFR were compared for subjects with a PFR of 15 mL/s or less (group I) and those with a PFR greater than 15 mL/s (group II). RESULTS: The baseline age, AUA symptom score, prostate volume, and PVR were not significantly different between the two groups. The mean changes in AUA symptom score were -45.0% and -49.5% for groups I and II, respectively. The mean changes in PFR were 7.0% and -26.6% for groups I and II, respectively. CONCLUSIONS: The effect of terazosin on AUA symptom score is independent of baseline PFR, indicating that the mechanism of action of terazosin is not exclusively mediated by reduction of bladder outlet obstruction. Randomized controlled studies are required to confirm this provocative observation
— id: 12361, year: 1997, vol: 49, page: 476, stat: Journal Article,

Total prostate and transition zone volumes, and transition zone index are poorly correlated with objective measures of clinical benign prostatic hyperplasia [see comments]
Lepor H; Nieder A; Feser J; O'Connell C; Dixon C
1997 Jul;158(1):85-88, Journal of urology
PURPOSE: We determined if total prostate volume, transition zone volume or transition zone index is correlated with the severity of clinical benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 93 men 52 to 85 years old, who were referred to a urology outpatient facility for treatment of clinical BPH, elevated serum prostate specific antigen or abnormal digital rectal examination, underwent measurement of total prostate and transition zone volume at transrectal ultrasonography. All men were requested to undergo uroflowmetry and complete the American Urological Association (AUA) symptom score. RESULTS: The pairwise correlations between AUA symptom score, versus total prostate and transition zone volumes and transition zone index were not statistically or clinically significant. A weak pairwise relationship was observed between peak flow rate versus total prostate volume (r2 = 0.160), transition zone volume (r2 = 0.156) and transition zone index (r2 = 0.147). The pairwise relationships between AUA symptom scores versus all prostate volumes were not statistically significant for subjects with mild (score 8 or less) or moderate to severe (score more than 8) symptoms. CONCLUSIONS: Total prostate and transition zone volumes, and transition zone index are not directly related to AUA symptom score and only weakly related to peak flow rate. These findings provide further evidence that the total prostate, total BPH and relative BPH volumes are not useful determinants of the severity of clinical BPH
— id: 12311, year: 1997, vol: 158, page: 85, stat: Journal Article,

Terazosin, finasteride, or both in benign prostatic hyperplasia - Reply
Lepor, H
1997 JAN 23 ;336(4):294-294, New England journal of medicine
— id: 53314, year: 1997, vol: 336, page: 294, stat: Journal Article,

Morphometric analysis of pediatric and nonhyperplastic prostate glands: evidence that BPH is not a unique stromal process
Shapiro E; Hartanto V; Perlman EJ; Tang R; Wang B; Lepor H
1997 Nov 1;33(3):177-182, Prostate
BACKGROUND: Although quantitative morphometry of benign prostatic hyperplasia (BPH) has been described, there is a paucity of information on the morphometry of the nonhyperplastic prostate. This study determines the histologic composition of prostates obtained from males, ages 2 days to 40 years, in order to provide insights into the morphometry of the 'normal' gland. METHODS: The histologic composition of 45 prostates was obtained from autopsies of males with age groups stratified to reflect the neonatal, childhood, peripubertal, adolescent, and young adult periods. Double immunoenzymatic staining and computer image analysis were used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (E), and lumen (L). RESULTS: A progressive decrease in SM area density throughout childhood, prepuberty, and puberty was seen. The density of SM significantly increased following puberty and throughout adolescence and early adulthood. There was a concomitant increase in CT from the neonatal period throughout childhood, prepuberty, and puberty, and a decrease after puberty and throughout adolescence and early adulthood. Since the changes in SM and CT were inversely related, the percent contribution of the stromal compartment to the total gland remained constant. CONCLUSIONS: The stromal to epithelial ratio remains constant from birth to age 40 in nonhyperplastic glands and is similar to the ratios in asymptomatic and symptomatic BPH tissues
— id: 12226, year: 1997, vol: 33, page: 177, stat: Journal Article,

Localization of mRNA and receptor binding sites for the alpha 1a-adrenoceptor subtype in the rat, monkey and human urinary bladder and prostate
Walden PD; Durkin MM; Lepor H; Wetzel JM; Gluchowski C; Gustafson EL
1997 Mar;157(3):1032-1038, Journal of urology
PURPOSE: To localize the mRNAs and receptor binding sites for the alpha 1a/A, alpha 1b/B and alpha 1d/D- adrenoceptor (AR) subtypes in the rat, monkey and human urinary bladder and prostate. MATERIALS AND METHODS: alpha 1-AR mRNAs were localized on slide mounted tissue sections by in situ hybridization using [35S]-labeled subtype specific oligonucleotide probes. alpha 1-AR receptor binding sites were localized on slide mounted tissue sections by competitive displacement of [3H]-prazosin using subtype selective ligands. RESULTS: Only the alpha 1a-AR subtype mRNA was discernible by in situ hybridization. The alpha 1a-AR mRNA was localized in all smooth muscle areas of the rat, monkey and human urinary bladder and prostate. High levels of alpha 1a mRNA were detected in bladder dome and bladder base urothelium. Competitive displacement studies using the alpha 1A-AR selective ligand SNAP 5272 revealed that the alpha 1A-AR represented over 80% of the total alpha 1-AR in monkey bladder and prostate. In general, localization of the alpha 1A-AR corresponded to the alpha 1a-AR mRNA localization, that is, receptor protein was localized to smooth muscle areas of the bladder dome, trigone and base and prostate. One notable exception was the bladder urothelium, which contained high levels of alpha 1a-AR mRNA, but undetectable levels of alpha 1A-AR protein. The alpha 1a-AR mRNA appeared to be transcribed but not translated in bladder urothelium. CONCLUSIONS: The alpha 1A-AR represents the major subtype in the smooth muscle of rat, monkey and human urinary systems. Selective alpha 1A-AR agents are therefore potentially useful in the treatment of multiple urinary smooth muscle related disorders
— id: 12372, year: 1997, vol: 157, page: 1032, stat: Journal Article,

Highlights of May 1996 - June 1996 television placements
Bystryn, Jean-Claude; Giangola, Gary; Lepor, Herbert; Lockwood, Charles; Siegel, Stephen
1996,
— id: 727, year: 1996, vol: , page: , stat: ,

The alpha-adrenoceptor antagonist properties of the enantiomers of doxazosin in the human prostate
Hatano A; Tang R; Walden PD; Lepor H
1996 Oct 10;313(1-2):135-143, European journal of pharmacology
The alpha-adrenoceptor antagonist properties of doxazosin and its enantiomers were characterized using human prostate tissue and cell membranes isolated from rat-1 fibroblast expressing each of the cloned human alpha 1-adrenoceptor subtypes. In the alpha 1-adrenoceptor-binding studies on the human prostate with [3H]doxazosin and 2-[beta-(3-[125I],4-hydroxyphenyl)ethyl]aminomethyl-l-tetralone ([125I]HEAT), no significant differences were observed between racemic doxazosin, R-doxazosin and S-doxazosin (mean -log Ki (pKi) values were 8.60-8.63, 8.47-8.55 and 8.61-8.65, respectively), whereas the alpha 2-adrenoceptor-binding studies with [3H]rauwolscine and [3H]clonidine revealed that the alpha 2-adrenoceptor-binding affinity of S-doxazosin (pKi = 5.91-5.94) was slightly (3- or 4-fold), but significantly lower than that of R-doxazosin (pKi = 6.47-6.54). Studies in phenylephrine-contracted prostatic tissue showed no significant difference in alpha 1-adrenoceptor antagonist potency between racemic doxazosin, R-doxazosin and S-doxazosin (pA2 values were 8.43 +/- 0.28, 8.64 +/- 0.56 and 8.75 +/- 0.38, respectively). In the binding studies with cloned alpha 1-adrenoceptor subtypes using [3H]prazosin and [125I]HEAT, racemic doxazosin, R-doxazosin and S-doxazosin showed no selectivity for the alpha 1-adrenoceptor subtypes. The present study demonstrated that doxazosin and its enantiomers are highly selective alpha 1-adrenoceptor antagonists and that there is no evidence suggesting differential alpha 1-adrenoceptor antagonist effects of doxazosin and its enantiomers in the human prostate. Doxazosin, therefore, could be described as displaying balanced activity across all three alpha 1-adrenoceptor subtypes
— id: 12516, year: 1996, vol: 313, page: 135, stat: Journal Article,

Comparison of the cellular composition of benign prostatic hyperplasia in Chinese and Caucasian-American men
Lepor H; Shapiro E; Wang B; Liang YC
1996 Jan;47(1):38-42, Urology
OBJECTIVES. To compare the cellular composition of benign prostatic hyperplasia (BPH) in Chinese and Caucasian-American men. METHODS. Surgical specimens of the prostate were obtained from 9 Chinese and 8 Caucasian-American men undergoing cystoprostatectomy for invasive transitional cell carcinoma. The mean ages of the Chinese and Caucasian-American men were 66.8 years and 66.4 years, respectively (P = 0.94). The mean prostate weight of the Chinese and Caucasian-American men was 53.4 g and 32.1 g, respectively (P = 0.01). Double immunoenzymatic staining with antibodies against actin and prostatic acid phosphatase and computer-assisted color image analysis were performed on whole-mount tissue sections. The percent area density of smooth muscle (SM), connective tissue (CT), epithelium (E), and epithelial lumen (L) were obtained by analyzing 30 fields from each specimen. RESULTS. The mean percent area density of SM, CT, E, and L in the prostate of Chinese men was 32%, 9.1%, 10.8%, and 48.5%, respectively. The mean percent area density of SM, CT, E, and L in the prostate of Caucasian-American men was 52.5%, 27.9%, 12.8%, and 7%, respectively. Overall, the prostates of Chinese men contained significantly more glandular lumen and significantly less SM and CT. CONCLUSIONS. The present study demonstrates that the cellular composition of BPH in the prostates of Caucasian-American and Chinese men is different. These cellular differences may account for previously observed differences in the incidence of clinical BPH
— id: 56830, year: 1996, vol: 47, page: 38, stat: Journal Article,

The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group
Lepor H; Williford WO; Barry MJ; Brawer MK; Dixon CM; Gormley G; Haakenson C; Machi M; Narayan P; Padley RJ
1996 Aug 22;335(8):533-539, New England journal of medicine
BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone
— id: 56879, year: 1996, vol: 335, page: 533, stat: Journal Article,

Prostate selectivity of alpha-blockers: From receptor biology to clinical medicine
Lepor, H
1996 MAR ;29(2):12-16, European urology
alpha-Adrenoceptor antagonists increase urinary flow and improve urinary symptoms in patients with benign prostatic hyperplasia (BPH). The rationale for the use of these agents in this indication is based on evidence that the contraction of prostatic smooth muscle is mediated via alpha(1)-adrenoceptors. The alpha(1)-adrenoceptor can be subdivided into at least three distinct subtypes - 1A, 1B, and 1D. Current opinion that the alpha-1A subtype mediates contraction of the prostatic smooth muscle has led to increased speculation that alpha-blockers selective for the alpha-1A subtype may offer the advantage of prostate selectivity in the clinic. This paper outlines the rationale for alpha-blockade in the treatment of BPH, focusing on the evidence for antagonist subtype selectivity and its potential clinical relevance
— id: 52977, year: 1996, vol: 29, page: 12, stat: Journal Article,

Transurethral microwave thermotherapy v sham treatment: Double-blind randomized study - Comment
Lepor, H
1996 DEC ;10(6):573-573, Journal of endourology
— id: 53370, year: 1996, vol: 10, page: 573, stat: Journal Article,

Treatment of benign prostatic hyperplasia - Reply
Lepor, H; Nitti, VW
1996 MAY 4 ;347(9010):1270-1270, Lancet
— id: 52931, year: 1996, vol: 347, page: 1270, stat: Journal Article,

Report of a unique meeting between the alpha-blocker subcommittee and the pharmaceutical industry
McGrath, JC; Lepor, H; Wyllie, MG
1996 NOV ;48(5):665-667, Urology
— id: 52723, year: 1996, vol: 48, page: 665, stat: Journal Article,

BENIGN PROSTATIC HYPERPLASIA SPECIFIC HEALTH-STATUS MEASURES IN CLINICAL RESEARCH - HOW MUCH CHANGE IN THE AMERICAN-UROLOGICAL-ASSOCIATION SYMPTOM INDEX AND THE BENIGN PROSTATIC HYPERPLASIA IMPACT INDEX IS PERCEPTIBLE TO PATIENTS
BARRY, MJ; WILLIFORD, WO; CHANG, YC; MACHI, M; JONES, KM; WALKERCORKERY, E; LEPOR, H
1995 NOV ;154(5):1770-1774, Journal of urology
Purpose: We assessed the relationship between changes in scores for the American Urological Association (AUA) symptom index and benign prostatic hyperplasia (BPH) impact index with patient global ratings of improvement in a large Veterans Affairs trial comparing different pharmacological therapies for BPH. Materials and Methods: The primary analyses compared absolute score changes from baseline with global ratings of improvement-at 13 weeks for 1,218 men. Results: Subjects who rated themselves as being slightly improved had a mean decrease in AUA symptom index and BPH impact index scores of 3.1 and 0.4 points, respectively. However, the baseline scores strongly influenced this relationship. Conclusions: These data provide guidance for investigators using the AUA symptom index and BPH impact index as outcome measures
— id: 86711, year: 1995, vol: 154, page: 1770, stat: Journal Article,

Characterization and localization of nitric oxide synthase in the human prostate
Burnett AL; Maguire MP; Chamness SL; Ricker DD; Takeda M; Lepor H; Chang TS
1995 Mar;45(3):435-439, Urology
OBJECTIVES. To characterize nitric oxide synthase (NOS), which catalyzes nitric oxide (NO) production, in the human prostate using biochemical and immunohistochemical techniques. METHODS. NOS catalytic assay and NOS immunohistochemistry were performed on histologically verified nonmalignant prostate tissue obtained from the peripheral and transition zones of seven radical prostatectomy specimens. RESULTS. Biochemical analysis revealed NOS activity in the human prostate, with a greater amount in the peripheral zone than in the transition zone (P < 0.01). In both prostate zones, NOS was immunohistochemically localized to nerve fibers and ganglia coursing throughout the smooth musculature of the stroma and to subepithelial nerve plexuses. NOS immunoreactivity was also localized to glandular epithelium. CONCLUSIONS. The presence, activity, and distribution of NOS were described in two regions of the human prostate. The present evidence implicates NO in the automatic innervation and physiology of the human prostate. It is proposed that NO may modulate smooth muscle tone and secretory functions in the human prostate, although functional studies are needed to support these hypotheses
— id: 57433, year: 1995, vol: 45, page: 435, stat: Journal Article,

Alpha 1-adrenoceptor selectivity: clinical or theoretical benefit?
Lepor H
1995 Jul;76 Suppl 1:57-61, British journal of urology
— id: 12760, year: 1995, vol: 76 Suppl 1, page: 57, stat: Journal Article,

Alpha blockade for the treatment of benign prostatic hyperplasia
Lepor H
1995 May;22(2):375-386, Urologic clinics of North America
Randomized double-blind placebo controlled studies have consistently demonstrated the safety and effectiveness of selective alpha 1 blockers for the treatment of clinical BPH. Selective alpha 1 blockers relieve the symptoms of prostatism and decrease bladder outlet obstruction. The advantages of this class of drugs for the medical treatment of BPH include the extremely rapid onset of action, statistically and clinically significant effects on relevant outcome measures, adverse experiences that are generally infrequent, mild, and reversible, serum PSA levels are not affected, and hypertension is also effectively treated. The long-term effectiveness of selective alpha 1 blockers has recently been reported. Prostate smooth muscle tension is mediated by the alpha 1a (previously defined as alpha 1c) AR. The pharmaceutical industry is aggressively pursuing development of alpha 1a 'prostate' selective AR antagonists
— id: 6678, year: 1995, vol: 22, page: 375, stat: Journal Article,

Combination medical therapy for benign prostatic hyperplasia
Lepor H
1995 May;22(2):401-405, Urologic clinics of North America
Preliminary clinical observations suggest that the efficacy of combination therapy (alpha 1 blockade + androgen suppression) is superior to the individual monotherapies. Several randomized double-blind multicenter placebo controlled studies are being done to define the efficacy and safety of combination therapy relative to the monotherapies. The ultimate role of combination therapy in clinical practice depends on a critical assessment of relative efficacy, safety, and cost
— id: 12782, year: 1995, vol: 22, page: 401, stat: Journal Article,

Long-term efficacy and safety of terazosin in patients with benign prostatic hyperplasia. Terazosin Research Group
Lepor H
1995 Mar;45(3):406-413, Urology
OBJECTIVES. To evaluate long-term efficacy and safety of terazosin, a selective alpha 1 blocker, in the treatment of benign prostatic hyperplasia (BPH). METHODS. This was a long-term (42 months), open-label, multicenter study with patients evaluated at 1- to 6-month intervals. Twenty-three outpatient clinics throughout the United States and Canada participated in the study. A total of 494 men with symptomatic BPH, lacking absolute indications for surgery, were enrolled in this study; 298 were transferred into the study from randomized, placebo-controlled studies of terazosin and 196 had no prior terazosin therapy. Terazosin was given starting at 1 mg/d and titrated upward until symptoms were relieved or a maximum dose of 20 mg/d was achieved, whichever came first. RESULTS. Peak urinary flow rates at all visits were significantly higher than baseline values, with mean improvements ranging from 1.0 to 4.0 mL/s. At 3 months, 40% of patients exhibited a 30% or greater improvement in peak flow rate; this improvement was maintained through 42 months. Boyarsky symptom scores improved significantly at all visits; mean total score improved by at least 4.0 points (40%) at all visits beyond 3 months. The most common adverse events resulting in premature termination from the study were dizziness (6.7%), asthenia (3.8%), and somnolence (2.0%). CONCLUSIONS. This study suggests that terazosin is well tolerated and effective in longterm treatment of patients with BPH
— id: 12802, year: 1995, vol: 45, page: 406, stat: Journal Article,

The treatment of benign prostatic hyperplasia: a glimpse into the future
Lepor H
1995 May;22(2):455-459, Urologic clinics of North America
The treatment of BPH has changed dramatically over the last decade. Industry has recognized the potential market for BPH therapies. Urologists have accepted and embrace the development of alternative treatment strategies. The combined resources and talents of industry and academic urology will lead to exciting future advances in this field. The optimal treatment of BPH requires not only new technology but a better understanding of the pathophysiology and natural history of this disease. Urologists are presently engaged in studies to better define these fundamental aspects of the disease process. The end result of these investigative efforts will be to the advantage of patients afflicted with BPH
— id: 6679, year: 1995, vol: 22, page: 455, stat: Journal Article,

Localization of the alpha 1A-adrenoceptor in the human prostate
Lepor H; Tang R; Kobayashi S; Shapiro E; Forray C; Wetzel JM; Gluchowski C
1995 Dec;154(6):2096-2099, Journal of urology
PURPOSE: We determined the tissue localization of the alpha 1a-adrenoceptor in the human prostate. MATERIALS AND METHODS: Autoradiographic localization of the alpha 1a-adrenoceptor in the human prostate was determined by performing competitive displacement experiments on slide mounted tissue sections using the ligand 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat), and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl-1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- yl]propyl)]carboxamido-4-(4-nitrophenyl) (SNAP 5272, 3 x 10(-7) M.). Under these experimental conditions, WB-4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a-adrenoceptor antagonists, respectively. The autoradiographs were quantitatively analyzed using a computer image analysis system. RESULTS: Specific 125I-Heat binding associated with the epithelium and stroma were independently analyzed. WB-4101 and SNAP 5272 inhibited 100% of the specific 125I-Heat binding in the stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha 1a subtype. WB-4101 inhibited none of the specific 125I-Heat binding in the epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the alpha 1b subtype. SNAP 5272 displaced only 25% of the specific 125I-Heat binding in the epithelium, suggesting that a relatively small percentage of the epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. CONCLUSIONS: To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor
— id: 12709, year: 1995, vol: 154, page: 2096, stat: Journal Article,

Randomized double-blind study comparing the efficacy of terazosin versus placebo in women with prostatism-like symptoms [see comments]
Lepor H; Theune C
1995 Jul;154(1):116-118, Journal of urology
PURPOSE: We attempt to determine whether terazosin is effective therapy for the treatment of prostatism-like symptoms in women. MATERIALS AND METHODS: A total of 29 women 47 to 79 years old with prostatism-like symptoms entered a randomized double-blind study comparing terazosin (14) versus placebo (15). The salient inclusion and exclusion criteria consisted of an American Urological Association (AUA) symptom score of 8 or more, post-void residual volume less than 300 ml. and absence of stress urinary incontinence. RESULTS: The baseline and final visit AUA symptom scores were 12.7 and 10.7 respectively, in the placebo group, and 16.4 and 13.6, respectively, in the terazosin group. The differences between the change in AUA symptom score in the placebo and terazosin groups were not clinically or statistically significant. CONCLUSIONS: Our study demonstrates that terazosin is not effective for the treatment of prostatism-like symptoms in aging women
— id: 12752, year: 1995, vol: 154, page: 116, stat: Journal Article,

ALPHA-BLOCKADE FOR BENIGN PROSTATIC HYPERPLASIA (BPH)
LEPOR, H
1995 MAR ;80(3):750-753, Journal of clinical endocrinology & metabolism
— id: 87397, year: 1995, vol: 80, page: 750, stat: Journal Article,

BENIGN PROSTATIC HYPERPLASIA
LEPOR, H
1995 MAY ;153(5):1540-1542, Journal of urology
— id: 87375, year: 1995, vol: 153, page: 1540, stat: Journal Article,

DOXAZOSIN IN TREATMENT OF BENIGN PROSTATIC HYPERPLASIA IN NORMOTENSIVE PATIENTS - MULTICENTER STUDY - COMMENT
LEPOR, H
1995 JUL ;154(1):109-109, Journal of urology
— id: 87281, year: 1995, vol: 154, page: 109, stat: Journal Article,

Advances in benign prostatic hyperplasia
Lepor, Herbert
Philadelphia : W.B. Saunders, 1995,
— id: 693, year: 1995, vol: , page: , stat: ,

Urology. Controversies old and new
Nitti VW; Lepor H
1995 Dec 23-30;346 Suppl:s26-s26, Lancet
— id: 12168, year: 1995, vol: 346 Suppl, page: s26, stat: Journal Article,

Matrix changes in the bladder associated with normal aging
Shapiro E; Lepor H
1995 ;385:187-190, Advances in experimental medicine & biology
— id: 56848, year: 1995, vol: 385, page: 187, stat: Journal Article,

Pathophysiology of clinical benign prostatic hyperplasia
Shapiro E; Lepor H
1995 May;22(2):285-290, Urologic clinics of North America
The pathophysiology of clinical BPH has been attributed to bladder outlet obstruction resulting from the enlarged prostate. A direct relationship does not exist between prostate size, symptom severity, or bladder outlet obstruction. The pathophysiology of prostatism is most likely multifactorial. Elucidating the factors contributing to symptoms will likely provide the foundation for the development of new pharmacological alternatives for the medical treatment of BPH
— id: 6749, year: 1995, vol: 22, page: 285, stat: Journal Article,

Effects of nitric oxide on human and canine prostates
Takeda M; Tang R; Shapiro E; Burnett AL; Lepor H
1995 Mar;45(3):440-446, Urology
OBJECTIVES. To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS. EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS. These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates
— id: 56793, year: 1995, vol: 45, page: 440, stat: Journal Article,

NITRIC-OXIDE SYNTHASE IN DOG URETHRA - A HISTOCHEMICAL AND PHARMACOLOGICAL ANALYSIS
TAKEDA, M; LEPOR, H
1995 NOV ;116(5):2517-2523, British journal of pharmacology
I To examine the presence of nitric oxide synthase (NOS) activity in female dog urethra, pharmacological experiments were performed using electrical held stimulation (EFS), guanethidine, atropine, N-G-nitro-L-arginine methyl ester and L-arginine, NOS immunohistochemistry using specific anti-NOS antibody, and reduced nicotinamide adenine dinucleotide phosphate (NADPF) diaphorase staining were also performed. 2 EFS caused frequency-dependent contractions in all urethral preparations, but in the presence of guanethidine and atropine, EFS caused significant relaxation in the proximal urethra and was without effect on the distal urethra. 3 In the presence of guanethidine, atropine, and N-G-nitro-L-arginine methyl ester, small contractions to EFS were re-established in the proximal urethra, but not in the distal urethra. N-G-nitro-D-arginine methyl ester had no such effect. 4 In the presence of guanethidine, atropine, and N-G-nitro-L-arginine methyl ester, the addition of L-arginine, restored the EFS-elicited relaxant responses previously seen with guanethidine and atropine alone in the proximal urethra (at 30 Hz; 12.89 +/- 5.27% to -2.44 +/- 4.43%, mean +/- s.e., P < 0.05). D-Arginine had no such effect. 5 In the distal urethra, the addition of N-G-nitro-L-arginine methyl ester and then L-arginine had no effect on responses to EFS in preparations treated with guanethidine and atropine. 6 Sodium nitroprusside caused relaxation in both the proximal and distal urethra. The relaxant responses per cm(2) cross sectional area in the proximal and distal urethra were 1.23 +/- 0.29, and 2.02 +/- 0.54 g cm(-2) cross sectional area (mean +/- s.e.), respectively: there was no significant difference between them. 7 Both NOS and NADPH diaphorase-positive neurones were present in dog urethra, the densities of both being higher in the proximal urethra than in the distal urethra. 8 These results show that female dog urethra possesses NOS nerves and that endogenous NO may play a role in relaxation in the proximal but not the distal urethra
— id: 86678, year: 1995, vol: 116, page: 2517, stat: Journal Article,

The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype
Forray, C; Bard, J A; Wetzel, J M; Chiu, G; Shapiro, E; Tang, R; Lepor, H; Hartig, P R; Weinshank, R L; Branchek, T A
1994 Apr;45(4):703-708, Molecular pharmacology
Molecular cloning studies have revealed the existence of three subtypes of alpha 1-adrenergic receptors. However, the link between any individual subtype and its functional role in the body has remained elusive. In an effort to bridge the gap between molecular biology and pathophysiology, we have chosen a model smooth muscle system, the human prostate, and investigated the role of alpha 1 subtypes in this tissue. To determine which alpha 1-adrenergic receptor subtype mediates the contractile response of the human prostate, we first studied the pharmacological properties of three cloned human alpha 1 subtypes (alpha 1a/d, alpha 1b, and alpha 1c). Prazosin, terazosin, doxazosin, alfuzosin, and abanoquil showed no selectivity for the human alpha 1 subtypes. WB-4101 and 5-methylurapidil showed a rank order of potency of alpha 1c > alpha 1a/d >> alpha 1b. Indoramin and (+)-niguldipine were selective for the alpha 1c-adrenergic receptor, with at least 10-fold lower affinity at either alpha 1a/d or alpha 1b subtypes. SK&F104856 was found to be 6-fold more potent at the alpha 1a/d receptor subtype than at alpha 1b- or alpha 1c-adrenergic receptors. We next determined the potency of these antagonists to inhibit the phenylephrine-induced contraction of human prostatic tissue in vitro. The potencies of indoramin, 5-methylurapidil, and SK&F104856 to inhibit the contractile response and to displace [3H]prazosin from the cloned human alpha 1c subtype were similar. Our data suggest that the alpha 1 receptor that mediates the contraction of human prostate smooth muscle has the pharmacological properties of the cloned human alpha 1c-adrenergic receptor. The findings of the present study suggest that selective alpha 1c-adrenergic receptor antagonists may be clinically more efficacious and better tolerated agents for the treatment of symptomatic benign prostatic hyperplasia
— id: 89520, year: 1994, vol: 45, page: 703, stat: Journal Article,

Binding and functional properties of endothelin receptor subtypes in the human prostate
Kobayashi, S; Tang, R; Wang, B; Opgenorth, T; Langenstroer, P; Shapiro, E; Lepor, H
1994 Feb;45(2):306-311, Molecular pharmacology
The objective of the present study was to characterize the binding and functional properties of endothelin (ET) receptor subtypes in the human prostate. Human prostatic tissue was obtained from male subjects undergoing radical prostatectomy for low-volume prostate cancer. The optimal assay conditions for characterizing human prostatic ET-1 binding sites on slide-mounted tissue sections were defined. Maximal specific 125I-ET-1 binding was achieved after a 10-min preincubation, a 120-min incubation, and a washing procedure that consisted of a brief rinse and a 1-min wash. The mean equilibrium dissociation constant (Kd) and density (Bmax) of ET-1 binding sites determined from six saturation studies were 0.72 +/- 0.13 nM and 40.4 +/- 6.9 fmol/mg of wet weight, respectively. The mean Hill coefficient was 0.99 +/- 0.01, indicating that 125I-ET-1 identifies a single population of binding sites. The pharmacology of 125I-ET-1 binding sites was characterized using competitive binding experiments. The competition plots for ET-1 were best fit by a one-binding site model, whereas the plots for sarafotoxin 6C (S6C) and BQ123 were consistently best fit by a two-site model. The mean Ki value of ET-1 was 0.34 +/- 0.12 nM. The mean Ki values for the high and low affinity S6C binding sites were 0.50 +/- 0.09 nM and 0.84 +/- 0.28 microM, respectively. The mean Ki values for the high and low affinity BQ123 binding sites were 5.51 +/- 1.05 nM and 24.9 +/- 6.5 microM, respectively. The ratio of ETA to ETB binding sites was approximately 2:1. The ET receptor subtype mediating prostatic smooth muscle tension was investigated using agonist-antagonist competition studies. ET-1, a nonselective ET agonist, elicited a potent contraction of prostate smooth muscle. The pA2 of BQ123 for inhibiting ET-1-mediated contraction was 6.84. S6C, a selective ETB agonist, also elicited a potent contraction of prostate smooth muscle. BQ123 at concentractions between 0.1 and 10 microM did not shift the S6C dose-response curve. These functional studies suggest that both ETA and ETB receptors mediate the tension of prostate smooth muscle. Endogenous ETS may be involved in the pathophysiology of bladder outlet obstruction in men with benign prostatic hyperplasia. If this is the case, then ET antagonists may represent effective treatment for benign prostatic hyperplasia
— id: 89522, year: 1994, vol: 45, page: 306, stat: Journal Article,

Localization of endothelin receptors in the human prostate
Kobayashi, S; Tang, R; Wang, B; Opgenorth, T; Stein, E; Shapiro, E; Lepor, H
1994 Mar;151(3):763-766, Journal of urology
The objective of the present study was to localize endothelin receptors in the human prostate using quantitative autoradiography. Slide-mounted tissue sections 20 microns. in thickness were obtained from the transition zones of seven patients undergoing radical prostatectomies for low volume prostate cancer. Sarafotoxin (S6C) and BQ123 have been used to distinguish endothelin receptor subtypes (ETA and ETB). The prostatic tissue sections were incubated in four different stock solutions containing the following: 0.1 nM. 125I-endothelin-1 (125I-ET-1) (total ET-1 binding); 0.1 nM. 125I-ET-1 and 100 nM. S6C (total ETA binding); 0.1 nM. 125I-ET-1 and 1 microM. BQ123 (total ETB binding); and 0.1 nM. 125I-ET-1 and 1 microM. ET-1 (nonspecific ET-1 binding). Nonspecific binding accounted for only 12 and 15% of total 125I-ET-1 binding in the stroma and glandular epithelium. Autoradiograms were quantitatively analyzed using a computerized image analysis system. Specific radioactive densities (nCi/mg.) were determined for the stromal and glandular epithelial elements of the prostate. The specific radioactive densities of ETA and ETB binding sites in the stroma were 7.57 +/- 0.65 and 2.98 +/- 0.81. The specific radioactive densities of ETA and ETB binding sites in the glandular epithelium were 1.59 +/- 0.15 and 7.87 +/- 1.35. The present study demonstrates that the predominant endothelin receptors in the stroma and glandular epithelium are the ETA and ETB subtypes, respectively
— id: 89521, year: 1994, vol: 151, page: 763, stat: Journal Article,

Perianastomotic injection of autologous fat at the time of radical retropubic prostatectomy
Lepor H; Guerena M; Dixon CM
1994 Nov;44(5):783-788, Urology
OBJECTIVES. The present study represents the first attempt to improve urinary continence following radical prostatectomy (RP) by perianastomotic injection of autologous fat at the time of the surgical procedure. METHODS. A total of 15 consecutive men with clinically localized carcinoma of the prostate underwent nerve-sparing radical retropubic prostatectomy (RRP) with perianastomotic injection of autologous fat. The autologous fat was obtained using a liposuction cannula connected to a power aspirator. The fat was harvested from the adipose tissue immediately adjacent to the lower midline incision. After the pelvic floor musculature was perforated, a total of 30 mL of autologous fat was injected through a 12 gauge angiocatheter under cystoscopic guidance. RESULTS. There were no complications resulting from the harvesting or injection of the autologous fat. All of the patients were evaluated for 6 months. Of the 15 patients, 12 (80%) achieved total urinary control within 6 months. The average time required to achieve total urinary continence was 89 days. None of the patients experienced total or nocturnal incontinence. Of the 3 patients with stress urinary incontinence (S
— id: 12867, year: 1994, vol: 44, page: 783, stat: Journal Article,

Detection of prostate cancer in males with prostatism
Lepor H; Owens RS; Rogenes V; Kuhn E
1994 Sep;25(3):132-140, Prostate
The present study was designed to compare the prostate cancer detection rate, sensitivity, specificity, and positive predictive value of digital rectal examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive cohort of males presenting to a single institution with clinically significant prostatism. The study population was comprised of 224 consecutive males with clinically significant prostatism referred to the Prostate Center at the Medical College of Wisconsin between June 1990 and December 1991. Subjects were considered to have clinically significant prostatism if they elected to pursue medical or surgical therapy following exclusion of carcinoma of the prostate. The initial examination consisted of a Boyarsky symptom score assessment, DRE, uroflowmetry, postvoid residual determination, serum PSA level, and transrectal prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4 ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects, 40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4 ng/dl. The overall detection rate of prostate cancer in the study population was 6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8% and 5.3%, respectively. The sensitivity, specificity, and positive predictive values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%, and 30.0%, respectively. Receiver operator characteristic (ROC) curves were constructed for the entire study population in order to compare the screening measures serum PSA and PSA density. The area under the curves was 0.88 for both tests, indicating that these screening tests for prostate cancer were not significantly different. The present study demonstrated that males with clinically significant prostatism represent a high risk cohort for detecting prostate cancer. DRE and PSA are equally effective measures for detecting prostate cancer. PSA density does not offer any advantage over serum PSA in screening for prostate cancer, except in the subset of patients with a normal DRE and serum PSA levels between 4.0 and 9.9 ng/dl
— id: 12913, year: 1994, vol: 25, page: 132, stat: Journal Article,

Prostatic alpha adrenoceptors
Lepor H; Shapiro E
1994 ;386:271-277, Progress in clinical & biological research
— id: 13045, year: 1994, vol: 386, page: 271, stat: Journal Article,

A comparison of the binding and functional properties of alpha-1 adrenoceptors and area density of smooth muscle in the human, canine and rat prostates
Lepor H; Zhang W; Kobayashi S; Tang R; Wang B; Shapiro E
1994 Aug;270(2):722-727, Journal of pharmacology & experimental therapeutics
The present study was designed to compare the binding and functional properties of alpha-1 adrenoceptors and the area density of smooth muscle in the human, canine and rat prostates. Chloroethylclonidine (CEC)-sensitive and -insensitive alpha-1 adrenoceptors were characterized on slide-mounted prostatic tissue sections using the ligand [3H]prazosin. The mean equilibrium dissociation constants (Kd) for [3H]prazosin binding sites were not significantly different among the three different species. The densities (Bmax) of CEC insensitive [3H]prazosin binding sites in the human, canine and rat prostates were 1.71 +/- 0.32, 0.35 +/- 0.04 and 0.84 +/- 0.11 fmol/mg of wet weight, respectively. The Bmax of CEC-sensitive [3H]prazosin binding sites in the human, canine and rat prostates were 1.32 +/- 0.83, 0.44 +/- 0.11 and 0.25 +/- 0.10 fmol/mg of wet weight, respectively. The contractile response elicited by the rat prostate in the presence of phenylephrine was consistently negligible. The mean maximal force after phenylephrine challenge (phenylephrine Emax) in the human and canine prostates were 0.125 +/- 0.025 g of force/mm2 cross-sectional area and 0.096 +/- 0.014 g of force/mm2 cross-sectional area, respectively. CEC inactivated 80 and 53% of the phenylephrine contractile response in man and dog, respectively. The mean percentage of area densities of smooth muscle in the human, canine and rat prostates were 38.8, 12.9 and < 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 6438, year: 1994, vol: 270, page: 722, stat: Journal Article,

Relationship between prostatic epithelial volume and serum prostate-specific antigen levels
Lepor, H; Wang, B; Shapiro, E
1994 Aug;44(2):199-205, Urology
OBJECTIVES. The present study was designed to determine the relationship between serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes. METHODS. Forty-two men between the ages of 50 and 79 years of age with either an abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL underwent transrectal ultrasonography (TRUS) and ultrasound-guided random systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and transition zone (TZ) were calculated, assuming that the total prostate and TZ are ellipsoidal structures. Six random systematic biopsies were directed into the PZ and four random systematic biopsies were directed into the TZ under ultrasound guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy specimens of the subjects without histologic evidence of prostate cancer were stained with Mallory trichrome stain, and the percentage area density of epithelium in the biopsy cores was determined using computer-assisted color image analysis. The relationships between serum PSA and total, PZ, and TZ epithelial volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined using regression analysis. RESULTS. The difference between the mean percentage epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2 values for the relationship between serum PSA and total prostatic volume were 0.016 and 0.260, respectively. Statistically significant correlations were also observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 = 0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically significant correlations were not observed between serum PSA levels and the following parameters: PZ volume, PZ epithelial volume, and total prostatic epithelial volume. CONCLUSIONS. Although the PZ contains a significantly greater area density and absolute volume of epithelium than the TZ, the serum PSA level is most strongly correlated only with the volume of epithelium in the TZ
— id: 89519, year: 1994, vol: 44, page: 199, stat: Journal Article,

The pathophysiology of clinical BPH
Shapiro E; Lepor H
1994 ;386:253-261, Progress in clinical & biological research
— id: 13046, year: 1994, vol: 386, page: 253, stat: Journal Article,

FUNCTIONAL-ACTIVITY OF NITRIC-OXIDE SYNTHASE (NOS) IN HUMAN AND CANINE PROSTATE
TAKEDA, M; TANG, R; SHAPIRO, E; LEPOR, H; BURNETT, AL
1994 MAR ;8(4):A362-A362, FASEB journal
— id: 52534, year: 1994, vol: 8, page: A362, stat: Journal Article,

LOCALIZATION OF ALPHA1C ADRENOCEPTORS (ALPHA-1C AR) IN THE HUMAN PROSTATIC TISSUE
TANG, R; LEPOR, H; SHAPIRO, E; FORRAY, C; WETZEL, J; GLUCHOWSKI, C
1994 MAR 18 ;8(5):A875-A875, FASEB journal
— id: 52520, year: 1994, vol: 8, page: A875, stat: Journal Article,

Characterization and localization of prostatic alpha 1 adrenoceptors using radioligand receptor binding on slide-mounted tissue section
Kobayashi, S; Tang, R; Shapiro, E; Lepor, H
1993 Dec;150(6):2002-2006, Journal of urology
Alpha 1 adrenoceptor binding sites have been characterized in prostatic tissue homogenates using radioligand receptor binding studies. The objective of the present study was to characterize and localize prostatic alpha 1 adrenoceptor binding sites using slide-mounted tissue sections and the ligand 3H-prazosin. The present study demonstrated that preincubation is not required; the optimal incubation interval is 40 minutes; and a 1-minute wash (once or twice) maximizes the proportion of specific 3H-prazosin binding. Saturation studies were performed at 8 different concentrations of 3H-prazosin ranging between 0.0625 nM. to 8.0 nM. The binding of 3H-prazosin was consistently saturable and of high affinity. The mean Kd and Bmax determined from 6 saturation studies was 4.16 x 10(-10) M. and 1.30 fmol./mg. wet weight, respectively. The pharmacology of these 3H-prazosin binding sites was characterized using competitive displacement experiments. The mean IC50 corrected for prazosin, phentolamine and yohimbine was 7.8 x 10(-10) M., 6.0 x 10(-9) M. and 2.1 x 10(-6) M. The rank order of the IC50 corrected values indicates that alpha 1 binding sites were measured under the assay conditions. In the present study, the mean values for Kd, Bmax and IC50 corrected are similar to values previously reported using prostatic tissue homogenates. Prostatic tissue sections were apposed to x-ray film after being incubated with 3 nM. 3H-prazosin (total prazosin binding) and 3 nM. 3H-prazosin + 8 microM. prazosin (nonspecific prazosin binding). The autoradiograms were analyzed using a computerized analyzing system. The specific radioactive densities of 3H-prazosin in the stroma and glandular epithelium were 1099 +/- 48 pCi/mg. and 163 +/- 42 pCi/mg. The present study validates the technique of assaying alpha 1 adrenoceptor binding sites on slide-mounted prostatic tissue sections and provides further evidence that alpha 1 adrenoceptor binding sites are localized primarily to the stromal elements of the prostate
— id: 89523, year: 1993, vol: 150, page: 2002, stat: Journal Article,

Endothelin-1 in the human prostate: tissue levels, source of production and isometric tension studies
Langenstroer, P; Tang, R; Shapiro, E; Divish, B; Opgenorth, T; Lepor, H
1993 Aug;150(2 Pt 1):495-499, Journal of urology
Endothelins mediate contractile responses in many types of vascular and nonvascular smooth muscle. The present study represents the first detailed characterization of endothelins in the human prostate. The objectives of this study were to determine the tissue levels and source of endogenous endothelin-1 (ET1) in the human prostate. The contractile effects of ET1 were also investigated using in vitro isometric tension studies. The mean tissue level of ET1 was 0.58 +/- 0.08 pg./mg. tissue wet weight. Endothelin-like activity was markedly prominent in the glandular epithelium of the human prostate, whereas minimal endothelin-like activity was observed in the prostatic stroma. Strips of human prostatic tissue were suspended in isolated tissue chambers and challenged to a concentration response of ET1. The mean EC50 and Emax for ET1 was 3.2 x 10(-8) M. and 0.12 +/- 0.02 gm. force per mm.2 cross-sectional area (CSA), respectively. Preincubation with indomethacin, terazosin, or nifedipine did not alter the concentration-dependent response to ET1. A calcium-free buffer abolished the contractile response to ET1. Thus, ET1 mediates a potent contraction of human prostatic smooth muscle that is not mediated via alpha 1 adrenergic or dihydropyridine sensitive calcium channels or prostaglandin synthesis. The presence of marked endothelin-like immunoreactivity strongly suggests a biological significance for endogenous endothelins in the human prostate
— id: 89524, year: 1993, vol: 150, page: 495, stat: Journal Article,

Medical therapy for benign prostatic hyperplasia [see comments]
Lepor H
1993 Nov;42(5):483-501, Urology
— id: 13059, year: 1993, vol: 42, page: 483, stat: Journal Article,

Alpha 1 adrenoceptor subtypes in the human prostate
Lepor, H; Tang, R; Meretyk, S; Shapiro, E
1993 Mar;149(3):640-642, Journal of urology
High affinity alpha 1 adrenoceptors have been characterized in the human prostate. The tension of prostatic smooth muscle is mediated by the alpha 1 adrenoceptor. The present study represents the first characterization of human alpha 1 adrenoceptor subtypes using radioligand receptor binding techniques. Binding studies were performed on tissue homogenates obtained from the human prostate. Competitive inhibition studies were performed in the presence of an 80 pM. 125I-Heat and 16 concentrations of unlabelled 5-methylurapidil (5 MU) or WB-4101 (10(-10) M. to 10(-5) M.). Saturation experiments were also performed with and without chloroethylclonidine (CEC, 10(-5) M.), a compound that selectively inactivates the alpha 1B subtype. The individual displacement plots for WB-4101 and 5-MU in the human prostate were consistently best fit by a 2 binding site model. WB-4101 and 5-MU exhibited a 594- and 186-fold higher affinity for the prostatic alpha 1A binding site relative to the alpha 1B binding site. The ratios of prostatic alpha 1A/alpha 1B binding sites discriminated by WB-4101 and 5-MU were 1.8 and 1.6, respectively. CEC inactivated 44% of the prostatic alpha 1 binding sites. The binding studies suggest that the dominant alpha 1 subtype in the human prostate is the alpha 1A. We are characterizing the functional properties of the alpha 1 subtypes in the human prostate
— id: 89526, year: 1993, vol: 149, page: 640, stat: Journal Article,

Binding and functional properties of alpha1 adrenoceptors in different regions of the human prostate
Lepor, H; Tang, R; Meretyk, S; Shapiro, E
1993 Jul;150(1):253-256, Journal of urology
The objective of the present study was to determine the density and functional properties of alpha 1 adrenoceptors in different regions of the human prostate. Binding and functional studies were performed on eight different topographical regions of the prostate. The contractile response (gm. force/mm.2 cross-sectional area [CSA]) was determined at varying concentrations of phenylephrine, and saturation experiments were performed at seven different concentrations of 125I-Heat. The maximal response to phenylephrine (Emax) ranged from 0.067 to 0.272 gm. force/mm.2 The CSA and the EC50 ranged from 25 to 41 microM. The differences between EC50 and Emax were not significantly different among the eight prostatic regions. A 1.8-fold difference between the Emax for peripheral and central regions of the prostate was statistically significant (p = 0.04). The equilibrium dissociation constant (Kd) of 125I-Heat and the receptor density Bmax were determined from the Scatchard plots. The mean Kd and Bmax ranged from 0.15 to 0.26 nM. and 0.30 to 0.72 fmol. per mg. wet weight, respectively. There were no statistically significant differences between mean Kd and mean Bmax for the eight prostatic regions. The 1.7-fold difference between central and peripheral mean Bmax was not statistically significant (p = 0.07). A direct relationship was not observed between phenylephrine mean Emax and mean Bmax. The present study demonstrates regional differences of the binding and functional properties of prostatic alpha 1 adrenoceptors in the human prostate. These regional differences must be taken into account when investigating the pharmacologic and physiologic properties of the prostate
— id: 89525, year: 1993, vol: 150, page: 253, stat: Journal Article,

The alpha-adrenoceptor subtype mediating the tension of human prostatic smooth muscle
Lepor, H; Tang, R; Shapiro, E
1993 ;22(4):301-307, Prostate
We have characterized the alpha 1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the alpha 1 subtype mediating the tension of prostatic smooth muscle. Fresh human tissue was obtained from 9 males between 50 and 80 years of age undergoing prostatectomy for BPH. The incubation of prostatic tissue with the irreversible antagonist chlorethyclonidine (CEC) resulted in an 80% reduction of the maximal contractile response produced by phenylephrine. However, the alpha 1A-selective antagonists WB-4101 and 5-methylurapidil (5-MU) competitively inhibited the contractile response induced by phenylephrine, with KB = 2.64 and 4.46 nM, respectively, consistent with their affinity at the alpha 1A receptor subtype. The pharmacological profile of the alpha 1-receptor-mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an alpha 1A or alpha 1B subtype. Alternatively, when compared with the properties of the cloned alpha 1 receptors, our results suggest that the alpha 1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine alpha 1C receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the alpha 1-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective alpha 1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH)
— id: 89527, year: 1993, vol: 22, page: 301, stat: Journal Article,

Quantitative morphometry of the adult human bladder
Lepor H; Sunaryadi I; Hartanto V; Shapiro E
1992 Aug;148(2 Pt 1):414-417, Journal of urology
The primary objective of the present retrospective study was to characterize the effects of aging and BPH on bladder morphometry. Eighty-six bladder specimens were obtained from the autopsy archives of the Milwaukee County Medical Complex. The bladder specimens were divided into 4 groups based upon age and gender: Group I: males between the ages of 35-45 years; Group II: males between the ages of 65-75 years; Group III: females between the ages of 35-45 years; and Group IV: females between the ages of 65-75 years. The age groups were selected in order to identify a group of males with and without BPH. The area density of smooth muscle:connective tissue was determined in bladder specimens using color assisted computer image analysis. Masson-trichrome and double immunoenzymatic staining techniques were used to discriminate the smooth muscle and connective tissue elements of the bladder. The area density of smooth muscle:connective tissue in the Masson-trichrome stained sections was significantly greater in Group I vs. Group II (2.90 +/- 0.22 vs. 2.33 +/- 0.16) and in Group III vs. Group IV (2.85 +/- 0.13 vs. 2.03 +/- 0.20). Aging was associated with a decrease in the area density of smooth muscle:connective tissue ratio in both males and females. The area density of smooth muscle:connective tissue was not significantly different in younger males and females (Group I vs. Group III) and older males and females (Group II vs. Group IV). The present morphometric study suggests that aging and not BPH, is associated with a relative increase in detrusor fibrosis. Infravesical obstruction in BPH may effect bladder function via mechanisms unrelated to the histologic composition of the bladder
— id: 18503, year: 1992, vol: 148, page: 414, stat: Journal Article,

Binding and functional properties of alpha 1 adrenoceptors and area density of smooth muscle in the canine prostate
Lepor H; Tang R; Meretyk S; Hartanto V; Shapiro E
1992 Oct;148(4):1310-1313, Journal of urology
The present study was designed to compare the area density of smooth muscle, and the binding and functional properties of alpha 1 adrenoceptors in 8 different regions of the canine prostate. The area density of smooth muscle, alpha 1 adrenoceptor density, and contractile response to phenylephrine were investigated using immunoenzymatic staining with color assisted computer image analysis, radioligand receptor binding, and isometric tension studies, respectively. The equilibrium dissociation constants (Kd) for 125I-Heat binding and the alpha 1 adrenoceptor densities (Bmax) in the prostatic regions ranged between 138-230 pM and 0.32-0.52 fmol/wet wt., respectively. The maximal tension generated in the presence of phenylephrine (phenylephrine Emax) and phenylephrine EC50s ranged between 0.043-0.129 gm. force/mm.2 CSA and 4.0-11.0 microM, respectively. The differences between Kd, Bmax, Emax, and EC50 were not significantly different between the different regions of the prostate. The percent area density of smooth muscle ranged between 10.6-24.4%. A direct relationship was not observed between alpha 1 adrenoceptor density and phenylephrine Emax, or alpha 1 adrenoceptor density and percent area density of smooth muscle. A direct relationship was observed between the phenylephrine Emax and percent area density of smooth muscle (p = 0.003; r = 0.90). The phenylephrine Emax and percent area density of smooth muscle was threefold and 1.6-fold greater in the peripheral prostate relative to the central prostate, respectively. The morphometrical and isometric tension studies provides evidence that the canine prostate is a heterogeneous gland
— id: 18502, year: 1992, vol: 148, page: 1310, stat: Journal Article,

Alpha 1-adrenoceptor properties of terazosin HCl and its enantiomers in the human prostate and canine brain
Meretyk, S; Tang, R; Shapiro, E; Kyncl, J J; Lepor, H
1992 ;20(2):159-165, Prostate
The objective of the present study was to characterize the alpha 1-adrenoceptor binding properties of terazosin and its enantiomers in human prostate and canine brain. Human prostate adenomas were obtained from 7 males undergoing prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from 6 male beagles. Competitive displacement experiments were carried out on these tissue homogenates in the presence of a constant concentration ([180 pM]) of 125I-Heat and varying concentrations of unlabelled terazosin and its enantiomers. The Ki of terazosin and its enantiomers were determined from these binding studies. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in human prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between these mean Ki values were not statistically significant. The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in canine brain were 6.7 nM, 8.4 nM, and 5.6 nM, respectively. The differences between these mean Ki values were not significantly different. The mean Ki of terazosin and its enantiomers were consistently lower in the human prostate compared to canine brain (P less than 0.05). The present study does not provide any evidence suggesting differential effects of terazosin enantiomers on the human prostate. The twofold difference between the Ki values in the prostate and brain suggests that different subtypes of the alpha 1-receptor might be present in these tissues
— id: 89529, year: 1992, vol: 20, page: 159, stat: Journal Article,

The effect of obstruction on the developing bladder
Peters, C A; Vasavada, S; Dator, D; Carr, M; Shapiro, E; Lepor, H; McConnell, J; Retik, A B; Mandell, J
1992 Aug;148(2 Pt 2):491-496, Journal of urology
Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to-deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation
— id: 89528, year: 1992, vol: 148, page: 491, stat: Journal Article,

The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia
Shapiro E; Becich MJ; Hartanto V; Lepor H
1992 May;147(5):1293-1297, Journal of urology
The specific features of the prostate adenoma predisposing to the development of symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to determine whether the histological composition of the prostate adenoma is related to the development of symptomatic BPH. Prostate adenomas were obtained from men with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy, transurethral resection of the prostate and pharmacotherapy. The severity of bladder outlet obstruction was evaluated with the Boyarsky symptom score and uroflowmetry. The percentages of stroma, epithelium and glandular lumen were determined in the prostate adenomas via quantitative image analysis on a computer-assisted morphometry system. The prostate adenomas from the 33 men with symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium and glandular lumen, respectively. The prostate adenomas from 6 men with asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma, epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the prostate adenomas from men with symptomatic and asymptomatic BPH were statistically significant. Our study suggests that the histological composition of the prostate adenoma is related to the development of symptomatic BPH
— id: 8412, year: 1992, vol: 147, page: 1293, stat: Journal Article,

Anti-desmin vs. anti-actin for quantifying the area density of prostate smooth muscle
Shapiro E; Hartanto V; Lepor H
1992 ;20(4):259-267, Prostate
Anti-desmin and anti-actin are commercially available antibodies that bind to smooth muscle. The present study was designed to compare the staining properties of anti-desmin and anti-actin in the human prostate in order to determine the optimal antibody for quantifying the smooth muscle content of the human prostate. Nineteen male subjects with symptomatic BPH underwent needle biopsy of the prostate. Double-immunoenzymatic staining was performed with peroxidase-anti-peroxidase (PAP) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) techniques. Rabbit anti-desmin:mouse anti-human prostatic acid phosphatase and mouse anti-actin:rabbit anti-human prostatic acid phosphatase were utilized. Computer assisted color image analysis was performed using the Bioquant image analysis system. The percent area density of stroma and epithelium was independent of the antibodies used. The percent area density of smooth muscle in the anti-actin stained tissue sections was twofold greater than the anti-desmin stained tissue sections. A direct relationship was observed for the area density of smooth muscle (r = 0.71; P = 0.0006) and the area density of connective tissue (r = 0.82; P less than 0.001) determined from anti-desmin and anti-actin stained tissue sections. Anti-actin represents the optimal antibody for quantifying the area density of prostate smooth muscle. The reproducibility of the immunoenzymatic staining technique is inferred from the direct relationship observed for area density of epithelium between the different staining techniques
— id: 8230, year: 1992, vol: 20, page: 259, stat: Journal Article,

Quantifying the smooth muscle content of the prostate using double-immunoenzymatic staining and color assisted image analysis
Shapiro E; Hartanto V; Lepor H
1992 Apr;147(4):1167-1170, Journal of urology
The primary objective of the present study was to develop a method for quantifying the smooth muscle content of the prostate adenoma. A double immunoenzymatic staining technique was coupled with color assisted image analysis to determine the area density of the smooth muscle within the prostate adenoma. Eight males with symptomatic BPH underwent transrectal biopsy of the prostate. Four micron thick tissue sections were used for the double immunoenzymatic staining process. Rabbit anti-desmin and mouse anti-human prostatic acid phosphatase antibodies were used to selectively bind smooth muscle and prostatic epithelium, respectively. The two different tissue antigens were identified with peroxidase-antiperoxidase (PAP) and alkaline phosphatase-antialkaline phosphatase techniques. The alkaline phosphatase activity and peroxidase activity were developed with fast red and DAB chromogens. The BQ MEG IV Vista color system image analysis was used to discriminate color differences from the stained tissue sections. The thresholds were set to identify smooth muscle (dark brown), epithelium (red), fibrous tissue (pale brown), and glandular lumina (colorless). The mean area density of smooth muscle, fibrous tissue, glandular epithelium, and glandular lumina was 22%, 54%, 16%, and 9%, respectively. The present study suggests that a significant component of the prostate adenoma is smooth muscle. The application of this technique will be utilized to provide further insights into the role of smooth muscle in the pathogenesis and therapy of BPH
— id: 8231, year: 1992, vol: 147, page: 1167, stat: Journal Article,

The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle
Shapiro E; Hartanto V; Lepor H
1992 ;21(4):297-307, Prostate
The objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long-acting selective alpha 1 blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer-assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonresponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle
— id: 18504, year: 1992, vol: 21, page: 297, stat: Journal Article,

Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia
Lepor, H; Gup, D I; Baumann, M; Shapiro, E
1991 May;67(5):493-498, British journal of urology
The objective of this study was to compare the binding and functional properties of alpha 1 adrenoceptors in prostate capsules obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH) undergoing simple retropubic prostatectomy and cystoprostatectomy respectively. Saturation experiments using 125I-Heat demonstrated that the density and binding affinity of alpha 1 adrenoceptors in the prostate capsules obtained from men with symptomatic and asymptomatic BPH were similar. Non-cumulative dose response experiments using phenylephrine demonstrated that the magnitude of the contractile response to phenylephrine was 4-fold greater in the prostate capsules from men with symptomatic BPH than from those with asymptomatic BPH. The EC50 of phenylephrine in the prostate capsules of men with symptomatic and asymptomatic BPH was similar. A correlation between alpha 1 adrenoceptor density and phenylephrine Emax was not observed, implying that either alpha 1 adrenoceptors are not localised exclusively to the prostate smooth muscle or that spare alpha 1 adrenoceptors exist. This study suggests that the neuropharmacological properties of the prostate capsule may play a significant role in the development of infravesical obstruction in the ageing male population
— id: 89532, year: 1991, vol: 67, page: 493, stat: Journal Article,

Bladder wall abnormalities in myelodysplastic bladders: a computer assisted morphometric analysis
Shapiro, E; Becich, M J; Perlman, E; Lepor, H
1991 May;145(5):1024-1029, Journal of urology
Myelodysplasia represents the most common cause of neurogenic bladder dysfunction in children. The specific histological features associated with myelodysplastic bladders have not been previously characterized. Our objective was to study the relationship between smooth muscle and connective tissue in control and myelodysplastic bladders using classical morphometric analysis with the assistance of an automated image analysis system. Gross histological analysis of the bladder specimens of normal stillborn fetuses showed organized muscle bundles embedded in a small amount of connective tissue. The bladder specimens of myelomeningocele stillborn fetuses showed a marked paucity of muscle bundles as well as a significantly diminished size of the muscle bundles. The myelomeningocele bladder specimens obtained from patients undergoing autopsy and those undergoing augmentation cystoplasty revealed significant interfascicular and pericellular infiltration of the smooth muscle by dense connective tissue. Quantitative morphometric analysis showed that the myelomeningocele stillborn fetuses have a significant increase in the volumetric content of connective tissue compared to control stillborn fetuses. The bladders of myelomeningocele patients who underwent autopsy or augmentation cystoplasty had a 3-fold increase in connective tissue when compared to normal controls. These findings reveal that structural changes in the histological components of the myelodysplastic bladder can be demonstrated not only in patients of varying ages undergoing autopsy or augmentation cystoplasty but also in the developing fetus. These findings enhance our understanding of the relationship of connective tissue proliferation to smooth muscle in the myelodysplastic bladder. We discuss the relationship of these findings to pathological detrusor morphology and detrusor dysfunction
— id: 89531, year: 1991, vol: 145, page: 1024, stat: Journal Article,

The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders
Shapiro, E; Tang, R; Rosenthal, E; Lepor, H
1991 Aug;146(2 ( Pt 2)):520-523, Journal of urology
The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function
— id: 89530, year: 1991, vol: 146, page: 520, stat: Journal Article,

Autonomic receptors in human prostate adenomas
Gup, D I; Shapiro, E; Baumann, M; Lepor, H
1990 Jan;143(1):179-185, Journal of urology
Radioligand receptor binding techniques were used to characterize alpha 1 adrenergic, alpha 2 adrenergic and muscarinic cholinergic (MCh) binding sites in human prostate adenomas obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH). Prostate adenoma specimens were obtained from nine men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). A quantitative symptoms score analysis and urinary flow rate determinations documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The mean equilibrium dissociation constants (Kd) and the mean densities of 125I-Heat (alpha 1 adrenergic) and 3H-NMS (MCh) binding sites were similar in tissue homogenates obtained from men with asymptomatic and symptomatic BPH. The mean Kd of 3H-Rauwolscine (3H-Ra) was significantly greater in the prostatectomy specimens obtained from men with symptomatic BPH compared to the specimens obtained from men with asymptomatic BPH (p less than 0.05). The density of 3H-Ra (alpha 2 adrenergic) binding sites was significantly greater in the prostate adenomas obtained from men with symptomatic BPH compared to the prostate adenomas obtained from men with asymptomatic BPH (p less than 0.05). The difference in alpha 2 adrenoceptor density was accounted for by an increased receptor density in the open prostatectomy specimens. There was no significant correlation between alpha 2 adrenergic, alpha 1 adrenergic, and MCh receptor densities and prostate weight or patient age. This study indicates that the development of infravesical obstruction in men with BPH is not related to upregulation or altered binding affinity of alpha 1 adrenergic or MCh receptor binding sites. The significance of the observed upregulation of alpha 2 adrenoreceptors in the prostate adenomas obtained from men undergoing open prostatectomy is unknown, and requires further investigation
— id: 89538, year: 1990, vol: 143, page: 179, stat: Journal Article,

Binding and functional properties of doxazosin in the human prostate adenoma and canine brain
Lepor, H; Baumann, M; Shapiro, E
1990 ;16(1):29-38, Prostate
The binding and functional properties of doxazosin were characterized in the canine brain and human prostate. 3H-Doxazosin binding sites were characterized in canine brain and human prostate homogenates using saturation experiments. The binding of 3H-doxazosin in the canine brain was consistently saturable and of high affinity. The mean equilibrium dissociation constant (Kd) and density (Bmax) of 3H-doxazosin binding sites in the canine brain were 0.19 nM and 2.17 fmol/mg wet wt, respectively. The binding of 3H-doxazosin in human prostate homogenates was not consistently linear owing to a relatively high proportion of nonspecific doxazosin binding sites. The mean Kd and Bmax of 3H-doxazosin binding sites in the prostate determined from the saturation experiments yielding linear Scatchard plots were 0.2 nM and 0.51 fmol/mg wet wt. The pharmacology of doxazosin binding sites was further characterized in the canine brain using competitive binding experiments. The rank order of IC50corr values for norepinephrine, clonidine, yohimbine, terazosin, and prazosin indicated that doxazosin binds selectively to alpha 1 and alpha 2 adrenergic binding sites. The relative affinity of unlabeled doxazosin for alpha 1 and alpha 2 binding sites in the human prostate was determined by displacing 125I-Heat or 3H-rauwolscine with varying concentrations of unlabeled doxazosin. The affinity of doxazosin for alpha 1 binding sites in the prostate adenoma was approximately 100-fold greater than its affinity for alpha 2 binding sites. The potency of doxazosin for inhibiting phenylephrine-induced contractions in the prostate indicated that prostate smooth muscle contraction is mediated by alpha 1 adrenoceptors
— id: 89537, year: 1990, vol: 16, page: 29, stat: Journal Article,

Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum
Lepor, H; Rigaud, G; Shapiro, E; Baumann, M; Kodner, I J; Fleshman, J W
1990 Apr;107(4):461-467, Surgery
The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments
— id: 89535, year: 1990, vol: 107, page: 461, stat: Journal Article,

This month in investigative urology: alpha adrenergic innervation of the prostate: insights into pharmacotherapy of BPH
Lepor, H; Shapiro, E
1990 Mar;143(3):590-591, Journal of urology
— id: 89536, year: 1990, vol: 143, page: 590, stat: Journal Article,

Determination of norepinephrine levels in the adult human prostate
Lepor, H; Shapiro, E; Bowsher, R R; Henry, D P
1990 Nov;144(5):1263-1266, Journal of urology
Tissue levels of norepinephrine were measured in prostate tissue from 24 men ranging in age between 41 and 83 years. Prostatic tissue was obtained from men with subtle palpable prostate nodules undergoing transperineal needle biopsy. None of the patients were shown to have histologic evidence of adenocarcinoma. The severity of the symptoms of prostatism was evaluated prospectively using a standardized micturition symptom score questionnaire. Norepinephrine levels were quantified using a sensitive radioenzymatic assay (REA). Overall, the prostates contained relatively high levels of norepinephrine (1666 +/- 124 ng./gm.). Inverse correlations were observed between tissue norepinephrine levels and severity of symptoms of prostatism (r = -0.58; p = 0.003); age (r = -0.53; p = .008); and prostate size (r = -0.48; p = .02). Norepinephrine levels were also measured in tissue specimens obtained from men undergoing enucleation prostatectomy and transurethral resection of the prostate (TURP). The level of norepinephrine in these prostatectomy specimens (115 ng./gm.) was only 14% the level of the prostate biopsy specimens. The relatively low level of norepinephrine in the specimens obtained from patients with symptoms necessitating prostatectomy provides further evidence that norepinephrine levels are inversely related to the degree of symptomatic bladder outlet obstruction
— id: 89534, year: 1990, vol: 144, page: 1263, stat: Journal Article,

Characterization of 1,4, dihydropyridine calcium channel binding sites in the human prostate
Rosenthal, E; Shapiro, E; Lepor, H
1990 Dec;144(6):1539-1542, Journal of urology
The binding and functional properties of calcium channel receptors have not been previously characterized in the normal or hyperplastic prostate. Dihydropyridine (DHP) binding sites have been characterized in other tissues using the ligands 3H-nitrendipene and (+)3H-PN200-110. Saturation experiments were performed on homogenates obtained from five human prostate adenomas using these ligands. The binding of 3H-nitrendipine and (+)3H-PN200-110 in the prostate was saturable and of high affinity. The mean Kd of 3H-nitrendipine and (+)3H-PN200-110 was 0.92 +/- 0.11 nM and 0.14 +/- 0.02 nM, respectively. The mean Bmax of 3H-nitrendipine and (+)3H-PN200-110 was 0.57 +/- 0.06 and 0.19 +/- 0.02 fmol/mg. wet wt., respectively. The percent specific binding of 3H-nitrendipene and (+)3H-PN200-110 was 18 +/- 1% and 38 +/- 4%, respectively. The pharmacology of (+)3H-PN200-110 binding sites was further characterized using competition displacement experiments. The IC50 corrected values for Bay K 8644, nifedipine, verapamil, and diltiazem in the human prostate and other tissues are of the same order of magnitude. The prostate contains an abundance of high affinity DHP binding sites. The physiologic significance of the DHP binding sites in the prostate requires further investigation
— id: 89533, year: 1990, vol: 144, page: 1539, stat: Journal Article,

Muscarinic cholinergic receptors in normal pediatric and myelodysplastic bladders
Gup, D I; Baumann, M; Lepor, H; Shapiro, E
1989 Aug;142(2 Pt 2):595-599, Journal of urology
Radioligand receptor binding experiments and in vitro muscle contractile studies were performed to determine the binding and functional properties of detrusor muscarinic cholinergic receptors in control and myelodysplastic bladders. Control bladder tissue was obtained from 8 children with primary vesicoureteral reflux undergoing ureteral reimplantation and 1 child at the time of organ transplant harvesting. Bladder specimens also were obtained from 10 children with myelomeningocele undergoing augmentation cystoplasty. Preoperative cystograms revealed that all children with vesicoureteral reflux had a smooth-walled bladder with normal capacity, whereas those with myelomeningocele undergoing augmentation cystoplasty had a small capacity bladder with trabeculations. Experiments were performed on detrusor tissue obtained from the bladder body in all cases. Radioligand receptor binding experiments with the 3H-N-methylscopolamine revealed that the equilibrium dissociation constant in control and myelodysplastic bladders was 0.44 +/- 0.09 and 0.40 +/- 0.10 nM., respectively. The equilibrium dissociation constant was similar in control and myelodysplastic bladders. The muscarinic cholinergic receptor density (Bmax) in control and myelodysplastic bladders was 0.66 +/- 0.12 and 0.24 +/- 0.03 fmol. per micrograms, protein, respectively. The significantly lower density of muscarinic cholinergic receptors in the myelodysplastic bladders may be explained by either a down regulations or by the histologically observed development of fibrosis. Concentration response experiments were performed on 7 control and 6 myelodysplastic bladders using carbachol and potassium chloride. The carbachol and potassium chloride concentrations producing half of the maximal response were similar in the control and myelodysplastic bladders, suggesting that detrusor dysfunction in myelodysplasia is not associated with detrusor supersensitivity. The maximal response (Emax) for potassium chloride was less in the myelodysplastic bladders than in the control bladders but the carbachol Emax was not significantly different. Concentration inhibitory experiments with oxybutynin and imipramine demonstrated that the myelodysplastic and control bladders were identically inhibited by these antagonists. Radioligand receptor binding studies and in vitro contractile experiments indicate that the detrusor dysfunction associated with myelomeningocele is not mediated by changes in the binding or functional properties of detrusor muscarinic cholinergic receptors
— id: 89540, year: 1989, vol: 142, page: 595, stat: Journal Article,

Contractile properties of human prostate adenomas and the development of infravesical obstruction
Gup, D I; Shapiro, E; Baumann, M; Lepor, H
1989 ;15(2):105-114, Prostate
The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma
— id: 89542, year: 1989, vol: 15, page: 105, stat: Journal Article,

Muscarinic cholinergic receptors in the normal and neurogenic human bladder
Lepor, H; Gup, D; Shapiro, E; Baumann, M
1989 Sep;142(3):869-874, Journal of urology
Bladder dysfunction secondary to neurologic conditions occurs in all age groups and is associated with significant morbidity. The role of neuroreceptors in the development of detrusor dysfunction has not been studied previously. Control bladder tissue specimens were obtained from eight children with ureterovesical reflux undergoing ureteral reimplantation and 14 adults with bladder carcinoma undergoing cystectomy. Neurogenic bladder specimens were obtained from 10 children with myelomeningocele and five adults with neurogenic bladder dysfunction undergoing augmentation cystoplasty. Saturation experiments using 3H-N-methylscopolamine (3H-NMS) were performed in these control and neurogenic bladder homogenates. The mean equilibrium dissociation constants in the neurogenic and control bladders were 0.41 nM and 0.55 nM, respectively. The mean density of muscarinic cholinergic (MCh) receptor binding sites in the neurogenic and control bladders was 0.34 fmol/mg wet wt. and 0.65 fmol/mg. wet wt., respectively. Competitive binding experiments with 3H-NMS and various unlabelled MCh antagonists indicated that the pharmacology of MCh binding sites was similar in neurogenic and control bladders. Age was not significantly correlated with MCh receptor density in the control and neurogenic bladders. Muscarinic cholinergic binding sites are homogeneous in neurogenic and control bladders. The lower density of MCh receptors in the neurogenic bladders may represent down regulation of MCh receptors or a replacement of smooth muscle by fibrosis
— id: 89539, year: 1989, vol: 142, page: 869, stat: Journal Article,

Comparison of muscarinic cholinergic and alpha adrenergic receptors in canine ileum, colon, intestinal urinary reservoirs and bladder
Lepor, H; Mohler, J; Baumann, M; Shapiro, E
1989 Jul;142(1):204-208, Journal of urology
The muscarinic cholinergic (MCh) and alpha 2 adrenergic receptor densities in canine ileum, colon, ileal and colonic urinary reservoirs and bladder were determined using radioligand receptor binding methods in order to provide a rational basis for pharmacologic management of urinary incontinence following bladder replacement with intestinal segments. Muscarinic cholinergic and alpha 2 adrenergic receptor binding sites were studied in these tissues using saturation experiments with 3H-NMS and 3H-rauwolscine, respectively. The mean equilibrium dissociation constants for 3H-NMS binding (0.13 to 0.17 nM) in these tissues were similar (p greater than 0.05) indicating homogeneity of muscarinic cholinergic binding sites. The mean equilibrium dissociation constants for 3H-rauwolscine binding (1.27 to 1.98 nM) in these tissues were also similar (p greater than 0.05). A substantial density of MCh (1.06 to 1.22 fmol/mg. wet wt.) and alpha 2 adrenergic (0.47 to 1.11 fmol/mg. wet wt.) binding sites was identified in the intestinal tissues assayed. The density of ileal and colonic MCh and alpha 2 adrenergic binding sites was not altered following construction of urinary intestinal reservoirs. The presence of a substantial density of MCh and alpha 2 adrenergic binding sites in the intestinal tissues suggests that MCh and alpha 2 adrenergic analogs may be utilized for the management of urinary incontinence following bladder replacement with intestinal urinary reservoirs
— id: 89541, year: 1989, vol: 142, page: 204, stat: Journal Article,

The alpha adrenergic binding properties of terazosin in the human prostate adenoma and canine brain
Lepor, H; Baumann, M; Shapiro, E
1988 Sep;140(3):664-667, Journal of urology
Clinical trials are currently underway to evaluate the efficacy of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). Terazosin is a potent and selective alpha 1 adrenergic blocking agent structurally similar to prazosin. The alpha adrenergic binding properties of terazosin were studied in human prostate adenomas and canine brains using radioligand receptor binding methods. Saturation analyses were performed at varying concentrations of [125I]-Heat and [3H]rauwolscine [( 3H]Ra) in human prostate adenomas and canine brains. The binding of [125I]-Heat and [3H]Ra in the human prostates and canine brains was consistently saturable and of high affinity. The equilibrium dissociation constant (Kd) for [125I]-Heat binding in the canine brains and human prostate adenomas was 84.4 +/- 4.3 pM and 65.4 +/- 19.2 pM, respectively (p greater than 0.05). The (Kd) for [3H]Ra binding in the human prostate adenomas and canine brains was 1.21 +/- 0.23 nM and 1.52 +/- 0.28 nM, respectively (p greater than 0.05). The density of alpha 1 (0.37 +/- 0.15 fmol/mg. wet wt.) and alpha 2 (0.29 +/- 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p greater than 0.05). The IC50 corrected (IC50 corr) of terazosin for [125I]-Heat and [3H]Ra binding sites in the human prostate was 2.5 nM and 1.0 micron., respectively. The IC50 corr of terazosin for [125I]-Heat and [3H]Ra binding sites in the canine brain was 2.0 nM and 0.8 microM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha 1 adrenergic binding sites in the human prostate and canine brain
— id: 89546, year: 1988, vol: 140, page: 664, stat: Journal Article,

The stereospecificity of LY253352 for alpha 1-adrenoceptor binding sites in the brain and prostate
Lepor, H; Baumann, M; Shapiro, E
1988 Sep;95(1):139-144, British journal of pharmacology
1. The stereospecificity of the enantiomers of LY253352, a potent and selective alpha 1-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding methods. 2. The mean equilibrium dissociation constant (KD) in the canine brain and human prostatic adenoma was 84.4 pM and 65.4 pM, respectively. 3. The alpha 1-adrenoceptor density in the canine brain was approximately eight fold greater than in the human prostatic adenoma. 4. The mean Ki values of (-)-LY253352 and (+)-LY253352 in the prostate were 0.19 nM and 5.79 nM, respectively. 5. The mean Ki values of (-)-LY253352 and (+)-LY253352 in the brain were 0.29 nM and 34.7 nM, respectively. 6. This study indicates that the stereochemical specificity of the optical isomers of LY253352 is a manifestation of differential affinities of the enantiomers for alpha 1-adrenoceptor binding sites. 7. The differential affinities of (+)-LY253352 in the brain and prostate are suggestive of subtle unique properties of adrenoceptor binding sites in these tissues
— id: 89544, year: 1988, vol: 95, page: 139, stat: Journal Article,

Laboratory assessment of terazosin and alpha-1 blockade in prostatic hyperplasia
Lepor, H; Gup, D I; Baumann, M; Shapiro, E
1988 Dec;32(6 Suppl):21-26, Urology
The alpha-1 adrenergic innervation of the human prostate has been studied using radioligand receptor binding methods and in vitro contractile experiments. The density of alpha-1 adrenergic binding sites is of the same order of magnitude as alpha-2 adrenergic and muscarinic-cholinergic (MCh) receptors in the human prostate adenoma. The contractile response of human prostate adenomas to selective alpha-1, alpha-2, and MCh agonists indicated that smooth muscle contraction of the human prostate is mediated by alpha-1 adrenoceptors. The selective affinities of terazosin for alpha-1 and alpha-2 binding sites were determined using competitive displacement assays. Terazosin was shown to have a four hundred-fold greater affinity for alpha-1 binding sites. The concentration of terazosin-inhibiting phenylephrine-induced contractions suggested that terazosin inhibits prostate smooth muscle contraction via alpha-1 adrenoceptors
— id: 89543, year: 1988, vol: 32, page: 21, stat: Journal Article,

The effect of electrocautery on neurotransmitter receptor binding assays in the canine prostate
Lepor, H; Shapiro, E; Gup, D; Baumann, M
1988 Sep;140(3):668-671, Journal of urology
The purpose of this study was to determine whether resection of the prostate with electrocautery alters the binding properties of various neurotransmitter ligands. Prostate glands were removed from four adult male dogs. The prostates were divided in the midsaggital plane and one half of the prostate was resected using a resectoscope. Saturation experiments were performed on the resected and control prostatic tissue using 3H-NMS, 125I-Heat, and 3H-rauwolscine. The mean equilibrium dissociation constants (Kd) and the mean densities of 3H-NMS, 125I-Heat, and 3H-Rauwolscine binding sites were similar in tissue homogenates obtained from control and resected portions of the prostate (p greater than 0.05). Resection of the prostate using electrocautery did not alter the binding properties of various neurotransmitter ligands for characterizing and quantifying muscarinic cholinergic, alpha 1 adrenergic, and alpha 2 adrenergic binding sites in the canine prostate. Approximately 90% of prostatectomies for symptomatic BPH (benign prostatic hyperplasia) are performed transurethrally. The ability to accurately measure neurotransmitter receptor densities in prostate tissues obtained following transurethral resection is imperative for our future studies designed to elucidate the role of alpha adrenergic receptors in the development of bladder outlet obstruction in men with BPH
— id: 89545, year: 1988, vol: 140, page: 668, stat: Journal Article,

Identification and characterization of alpha 1 adrenergic receptors in the canine prostate using [125I]-Heat
Lepor, H; Baumann, M; Shapiro, E
1987 Nov;138(5):1336-1339, Journal of urology
We have recently utilized radioligand receptor binding methods to characterize muscarinic cholinergic and alpha adrenergic receptors in human prostate adenomas. The primary advantages of radioligand receptor binding methods are that neurotransmitter receptor density is quantitated, the affinity of unlabelled drugs for receptor sites is determined, and receptors can be localized using autoradiography on slide-mounted tissue sections. Recently, [125I]-Heat, a selective and high affinity ligand with high specific activity (2200 Ci/mmole) has been used to characterize alpha 1 adrenergic receptors in the brain. In this study alpha 1 adrenergic receptors in the dog prostate were characterized using [125I]-Heat. The Scatchard plots were linear indicating homogeneity of [125I]-Heat binding sites. The mean alpha 1 adrenergic receptor density determined from these Scatchard plots was 0.61 +/- 0.07 fmol/mg. wet wt. +/- S.E.M. The binding of [125I]-Heat to canine prostate alpha 1 adrenergic binding sites was of high affinity (Kd = 86 +/- 19 pM). Steady state conditions were reached following an incubation interval of 30 minutes and specific binding and tissue concentration were linear within the range of tissue concentrations assayed. The specificity of [125I]-Heat for alpha 1 adrenergic binding sites was confirmed by competitive displacement assays using unlabelled clonidine and prazosin. Retrospective analysis of the saturation experiments demonstrated that Bmax can be accurately calculated by determining specific [125I]-Heat binding at a single ligand concentration. [125I]-Heat is an ideal ligand for studying alpha 1 adrenergic receptors in the prostate and its favorable properties should facilitate the autoradiographic localization of alpha 1 adrenergic receptors in the prostate
— id: 89547, year: 1987, vol: 138, page: 1336, stat: Journal Article,

Alpha 1 adrenergic receptors in canine lower genitourinary tissues: insight into development and function
Shapiro, E; Lepor, H
1987 Oct;138(4 Pt 2):979-983, Journal of urology
Radioligand receptor binding methods were used to characterize the alpha 1-adrenergic receptor in the bladder body, bladder base, prostate and urethra of the male dog. Saturation experiments were performed in tissue homogenates using [125iodine]-Heat, an alpha 1-adrenergic antagonist of high specific activity (2,200 Ci. per mmol.). The equilibrium dissociation constant Kd for [125iodine]-Heat binding in the bladder body (0.56 pM.), bladder base (0.81 +/- 0.11 pM.), prostate (0.86 +/- 0.19 pM.) and urethra (0.55 pM.) was similar, suggesting homogeneity of alpha 1-adrenergic binding sites in lower genitourinary tissues. The receptor density in the bladder body, bladder base, prostate and urethra, expressed as fmol. per mg. wet weight, was 0.22 +/- 0.02, 0.82 +/- 0.09, 0.55 +/- 0.06 and 0.27 +/- 0.06, respectively (mean +/- standard error of mean). Competitive binding experiments with [125iodine]-Heat and unlabeled prazosin and clonidine confirmed the selectivity of Heat for alpha 1-adrenergic binding sites. Anatomical dissections have revealed that a major component of the smooth muscle of the bladder base and prostate originates from the ureter, whereas a major component of the smooth muscle of the urethra originates from the bladder. The measured alpha 1-adrenergic receptor densities support these developmental theories
— id: 89548, year: 1987, vol: 138, page: 979, stat: Journal Article,

Alpha 2 adrenergic receptors in canine prostate: biochemical and functional correlations
Shapiro, E; Tsitlik, J E; Lepor, H
1987 Mar;137(3):565-570, Journal of urology
The sympathetic innervation of human prostate adenomas has been previously demonstrated using fluorescence microscopy and in vitro isometric studies. A clinical implication of these observations is that bladder outlet obstruction in men with benign prostatic hypertrophy may be subject to pharmacologic manipulation using adrenergic drugs. Randomized clinical trials have demonstrated the efficacy of alpha adrenergic antagonists for symptomatic BPH. We have previously characterized the alpha1 and alpha2 adrenergic receptors in the human prostate using [3H]prazosin and [3H]rauwolscine, respectively. The mean alpha1 and alpha2 receptor densities in the adenomas studied were equivalent. The effect of alpha2 adrenergic drugs on prostatic urethral pressure has not been examined in the human or in an animal model. In this study a canine model was used to define the effect of alpha2 drugs on prostatic urethral pressure. Intravenous administration of clonidine, a selective alpha2 agonist, resulted in a dose dependent increase in prostatic urethral pressure. The maximal increase in urethral pressure ranged between 18 to 30 cm. H2O. The maximal response to clonidine was approximately 50% less than the response to epinephrine, indicating that clonidine acts as a partial agonist. Pretreatment with yohimbine, a selective alpha2 adrenergic antagonist, abolished the effects of clonidine and epinephrine. The alpha2 adrenergic receptors were then studied in the canine prostates using [3H]rauwolscine. The equilibrium dissociation constant, Kd, ranged between 0.68 to 1.80 nM and the receptor density ranged between 14.8 to 69.3 fmol./mg. protein. The receptor density was homogeneous in specimens obtained from the proximal, midportion, and distal canine prostate suggesting that the effect of alpha2 drugs is not sphincter mediated. These in vitro and in vivo studies provide the basis for investigating the effects of alpha2 antagonists in men with symptomatic BPH
— id: 89549, year: 1987, vol: 137, page: 565, stat: Journal Article,

Alpha 2 adrenergic receptors in hyperplastic human prostate: identification and characterization using [3H] rauwolscine
Shapiro, E; Lepor, H
1986 May;135(5):1038-1042, Journal of urology
[3H]Rauwolscine ([3H]Ra), a selective ligand for the alpha 2 adrenergic receptor, was used to identify and characterize alpha 2 adrenergic receptors in prostate glands of men with benign prostatic hyperplasia. Specific binding of [3H]Ra to prostatic tissue homogenates was rapid and readily reversible by addition of excess unlabelled phentolamine. Scatchard analysis of saturation experiments demonstrates a single, saturable class of high affinity binding sites (Bmax = 0.31 +/- 0.04 fmol./microgram. DNA, Kd = 0.9 +/- 0.11 nM.). The relative potency of alpha adrenergic drugs (clonidine, alpha-methylnorepinephrine and prazosin) in competing for [3H]Ra binding sites was consistent with the order predicted for an alpha 2 subtype. The role of alpha 2 adrenergic receptors in normal prostatic function and in men with bladder outlet obstruction secondary to BPH requires further investigation
— id: 89550, year: 1986, vol: 135, page: 1038, stat: Journal Article,

Muscarinic cholinergic receptors in bladder exstrophy: insights into surgical management
Shapiro, E; Jeffs, R D; Gearhart, J P; Lepor, H
1985 Aug;134(2):308-310, Journal of urology
The surgical management of classical bladder exstrophy (functional bladder closure or urinary diversion) should be influenced by the inherent detrusor function of the exstrophied bladder. Cystometrograms performed previously on individuals with successful exstrophy closures demonstrate normal bladder function. The biochemical and neurophysiological properties of the exstrophied bladder have otherwise not been investigated. In this study radioligand receptor binding techniques were used to compare the density and equilibrium dissociation constant of muscarinic cholinergic receptors in control and exstrophy bladders. The density of muscarinic cholinergic receptors in the control and exstrophy groups was 1.97 plus or minus 0.29 and 1.44 plus or minus 0.21 fmol. per microgram deoxyribonucleic acid (mean plus or minus standard error of mean), respectively. The dissociation constant of the control and exstrophy groups was 0.15 plus or minus 0.02 and 0.14 plus or minus 0.02 nM. (mean plus or minus standard error of mean), respectively. These data show that the muscarinic receptor density and binding affinity in control and exstrophy bladders are similar. Therefore, the neurophysiological composition of the exstrophied bladder is not grossly altered during the anomalous development
— id: 89551, year: 1985, vol: 134, page: 308, stat: Journal Article,

Down regulation of the muscarinic cholinergic receptor of the rat prostate following castration
Shapiro, E; Miller, A R; Lepor, H
1985 Jul;134(1):179-182, Journal of urology
Prostatic secretion is dependent upon the integrity of the endocrine and autonomic nervous systems and is dramatically influenced by muscarinic cholinergic analogs. In this study, we have used radioligand receptor binding methods on whole tissue homogenates and slide mounted tissue sections of rat prostate to determine whether androgens regulate the density of muscarinic cholinergic receptors in the prostate. The muscarinic cholinergic receptor binding affinities (Kd) of [3H] N-methylscopolamine in prostatic homogenates obtained from intact, castrate, and castrate rats receiving testosterone replacement (castrate + T) were similar (0.07 to 0.10 nM). The muscarinic cholinergic receptor binding capacity decreased 73 per cent following castration. Testosterone administration restored the density of muscarinic cholinergic receptors in castrate rats to intact levels. In order to ensure that the loss of receptor density was not due to a decrease in the epithelial: stromal cell ratio, the number of muscarinic cholinergic receptors per unit area of epithelium was determined in the 3 treatment groups using autoradiography on slide mounted tissue sections. The density of muscarinic cholinergic receptors in a unit area of epithelium was decreased 91 per cent following castration. Testosterone administration restored the density of muscarinic cholinergic receptors in the castrate rats to intact levels. The modulation of neurotransmitter receptors by steroid hormones may be a mechanism by which sex steroids regulate biological responsiveness of target tissues
— id: 89552, year: 1985, vol: 134, page: 179, stat: Journal Article,

Characterization of alpha1 adrenergic receptors in human benign prostatic hyperplasia
Lepor, H; Shapiro, E
1984 Dec;132(6):1226-1229, Journal of urology
Bladder outlet obstruction in men with benign prostatic hyperplasia is decreased following administration of prazosin, a selective alpha1 adrenergic antagonist. Prazosin presumably binds and antagonizes alpha1 adrenergic receptors on the smooth muscle cells of the prostatic adenoma. This study represents the first identification and characterization of alpha1 adrenergic receptors in the prostate using radioligand receptor binding methods. The binding of [3H] prazosin in homogenates obtained from human prostatic adenomas was saturable and a single high affinity prazosin binding site was identified (Kd = 0.29 +/- 0.09 nM). The alpha1 adrenergic receptor concentration in these homogenates ranged between 0.28 to 2.05 fmol./ mg. wet wt. prostate. The equilibrium dissociation constant and density of prazosin binding sites were similar in different regions of an enucleated prostate suggesting homogeneity of receptor density and receptor binding sites within an adenoma. The receptor density was not directly proportional to the weight of the surgically removed adenoma. The pharmacology of the prazosin binding sites was characterized by competitive binding experiments using [3H] prazosin and several unlabelled adrenergic analogs. The IC50's determined from competitive binding experiments using [3H] prazosin and alpha-methylnorepinephrine, rauwolscine and corynanthine were characteristic of alpha1 adrenergic receptor binding
— id: 89553, year: 1984, vol: 132, page: 1226, stat: Journal Article,

Urethral reconstruction in boys with classical bladder exstrophy
Lepor, H; Shapiro, E; Jeffs, R D
1984 Mar;131(3):512-515, Journal of urology
A total of 24 boys with classical bladder exstrophy underwent initial urethral reconstruction at our hospital between 1975 and 1982. Penile reconstruction in male patients with classical bladder exstrophy includes penile lengthening, release of the dorsal chordee and reconstruction of the urethra. The former 2 procedures are performed during the primary bladder closure and urethroplasty usually follows bladder neck reconstruction. A modified Young urethroplasty was done in 22 of the 24 patients. Preputial pedicle grafts of free full thickness skin grafts were used for urethroplasty in 2 boys with insufficient penile skin. Fistulas requiring surgical revision developed after urethroplasty in 21 per cent of the patients. A prior osteotomy was associated with a decreased fistula rate. The cosmetic and preliminary functional results of the penile reconstruction were assessed by parental interviews. The definitive assessment of the penile reconstruction will be determined when these boys reach sexual maturity
— id: 89555, year: 1984, vol: 131, page: 512, stat: Journal Article,

The inheritance of the exstrophy-epispadias complex
Shapiro, E; Lepor, H; Jeffs, R D
1984 Aug;132(2):308-310, Journal of urology
The inheritance pattern of the exstrophy-epispadias complex was investigated by a combined literature review and a survey of the personal experience of pediatric urologists in North and South America, and Europe. Bladder exstrophy recurred in only 9 of approximately 2,500 families (1 in 275) with bladder exstrophy or complete epispadias. The recurrence of the exstrophy-epispadias complex in offspring of parents with bladder exstrophy or complete epispadias has never been described previously. We identified 215 offspring produced by parents with bladder exstrophy or epispadias, and bladder exstrophy was inherited in 3 of the offspring (1 in 70 live births). The recurrence of bladder exstrophy in offspring of parents with the exstrophy-epispadias complex is greater than previously assumed
— id: 89554, year: 1984, vol: 132, page: 308, stat: Journal Article,