Best of the 2007 AUA Annual Meeting

Meeting Review

RIU0365_08-31.qxd 8/31/07 6:19 PM Page 133 MEETING REVIEW Best of the 2007 AUA Annual Meeting Highlights from the 2007 Annual Meeting of the American Urological Association, May 19-24, 2007, Anaheim, CA [Rev Urol. 2007;9(3):133-154] © 2007 MedReviews, LLC Key words: Prostate cancer • Prostate-specific antigen • Obesity • PSA velocity • Repeat biopsy • Human glandular kallikrein • Expectant management • Biomarkers • PCA3 • EPCA-2 • CRISP-3 • MSP • Testosterone • Microvessel density • Endoglin • Survivin • Telomeres • Male voiding dysfunction • Lower urinary tract symptoms • Interleukin-8 • Botulinum toxin • PDE-5 inhibitors • Antimuscarinic agents • Benign prostatic hyperplasia • Acute urinary retention • 5Alpha-reductase inhibitors • Nocturia • Doxazosin • Finasteride • LHRH antagonists • Laser ablation • Transurethral microwave thermotherapy • TURP • Perioperative blood loss • Urinary tract infections • Microbial biofilms • Circumcision • HIV • Antibiotic prophylaxis • Stress urinary incontinence • Stem cell injection • Endourology • Urolithiasis • Ureteral stents • Medical expulsive therapy • Shock wave lithotripsy • Hyperoxaluria • Pregnancy • Erectile dysfunction • Prostatectomy • Peyronie’s disease • Ejaculatory dysfunction • Vesicoureteral reflux • Laparoscopic orchiopexy • Bladder exstrophy • Sexual function • Infertility record number of submissions led to the acceptance of 1965 abstracts for the 2007 annual meeting of the American Urological Association (AUA), up from 1725 last year. The meeting, held in Anaheim, CA, attracted nearly 8800 urologists A Reviewed by Michael K. Brawer, MD, Threshold Pharmaceuticals; Danil V. Makarov, MD, Alan W. Partin, MD, PhD, The Johns Hopkins Medical Institutions and Hospital; Claus G. Roehrborn, MD, University of Texas Southwestern Medical Center; J. Curtis Nickel, MD, FRCSC, Queen's University; Michael B. Chancellor, MD, University of Pittsburgh School of Medicine; Dean G. Assimos, MD, Wake Forest University School of Medicine; Ellen Shapiro, MD, FACS, FAAP, New York University School of Medicine; Jacob Rajfer, MD, University of California at Los Angeles. and other health care professionals, 54% of them from outside the United States. Press, exhibitors, family, guests, and staff pushed total attendance to just over 15,000. The editors of Reviews in Urology have culled the enormous volume of information from this premier source and present here the findings most relevant to the practicing urologist. Additional highlights will be published in the next issue of Reviews in Urology. Prostate Cancer Once again prostate tumor markers were a major topic at the AUA annual meeting. Studies presented at the prostate cancer biomarkers sessions included important new work in the link between obesity and prostate cancer, the role of prostate-specific antigen (PSA) velocity in the diagnosis of prostate cancer, techniques to determine which prostate cancers may be suitable for expectant management, and improved serum, urine, and tissue biomarkers for the diagnosis of prostate cancer. PSA and Obesity The winner of the resident essay prize in clinical research examined the potential reasons why PSA concentrations might be lower in obese men. Banez and colleagues1 from Duke University analyzed the relationships among PSA, body mass index (BMI), estimated plasma volume (based on age and estimated body surface area), and total PSA mass (PSA multiplied by estimated plasma volume) within the Shared Equal Access Regional Center Hospital (SEARCH) database. The authors identified 1304 men who had undergone radical prostatectomy between 1991 and 2006. After VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 133 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 134 2007 AUA Annual Meeting continued controlling for common clinical and pathological predictors of outcome, they found that higher BMI was associated with higher plasma volume (P
.005) and lower PSA concentrations (P  .001). There was no significant association between BMI and PSA corrected for total plasma volume (PSA mass) (P
.52). They conclude that hemodilution of PSA may explain the lowered PSA often observed among obese men and may explain why cancers are often discovered at a cant association between PSAV and prostate cancer detection is maintained in men of all ages. On receiver operating characteristic (ROC) analysis, PSAV had an area under the curve (AUC) of 0.80, 0.69, 0.69, and 0.67 for prostate cancer detection in men in their 40s, 50s, 60s, and 70s or above, respectively. Significantly, PSAV is higher in men of all ages with prostate cancer, and it predicts best in younger men. They also concluded that, because the median PSAV among men Because so many men presenting with PSA velocity  2 ng/mL/yr had prostatitis in their initial negative biopsy specimens, the authors recommend that this group undergo a course of antibiotics and a repeat PSA measurement prior to making a recommendation for repeat biopsy. later stage among this group. Many important questions remain. Do alterations of sex hormone levels and binding proteins in obesity play a role in PSA levels? Does weight gain or loss affect absolute PSA level? Does loss of body mass and plasma volume (limb amputation, for instance) raise PSA? Irrespective of these questions, this work is very interesting, deserves this award, and merits follow-up. PSA Velocity The biomarker group from Northwestern headed by William Catalona, MD, evaluated data collected in their large prostate cancer screening study and offered several interesting abstracts assessing the utility of prediagnosis PSA velocity (PSAV) for prognosis. Loeb and associates2 examined the performance of PSAV across age groups. They identified 13,619 men with data on age and calculable PSAV. Of this group, 230 men (2%) were aged 40-49, 3448 (25%) were in their 50s, 5778 (42%) were in their 60s, and 4159 (31%) were aged 70 and above. They found that prostate cancer was detected in 1101 (8%) of the entire group of men and that the signifi- 134 VOL. 9 NO. 3 2007 with prostate cancer is less than 0.75 ng/mL/yr, a lower threshold should be employed when using PSAV to decide regarding biopsy. Using the same large cohort, the next abstract from this group, by Roehl and coworkers,3 examined the predictive capability of PSAV to determine the need for repeat biopsy after an initial negative biopsy. Intriguingly, they observed an inverse correlation between the PSAV prior to initial biopsy and detection of cancer on detected on a repeat biopsy in 2 (11%), 6 (11%), 2 (13%), 1 (50%), and 38 (11%), respectively. Men who had moderate PSAV ( 2 ng/mL/yr) prior to an initial negative biopsy were more likely to have prostate cancer detected on subsequent biopsy than those with PSAV  2 ng/mL/yr prior to an initial negative biopsy. Because so many men presenting with PSAV  2 ng/mL/yr had prostatitis in their initial negative biopsy specimens, the authors recommend that this group undergo a course of antibiotics and a repeat PSA measurement prior to making a recommendation for repeat biopsy. PSA Analysis Connolly and colleagues4 addressed the issue of repeating an abnormal PSA test. Using the Northern Ireland cancer registry, they studied 3502 men with PSAs between 4.0 and 9.99 ng/mL who had a second PSA within 6 months. Thirty-nine percent had an increase on the second determination, and 10.7% had malignancy. In contrast, 61% of men had either no change or a decrease in their PSA, and 5.1% of these had cancer. Of note, 42.8% of men with cancer had a decrease on the second PSA determination. The authors concluded that repeat PSA The authors concluded that repeat PSA testing is not warranted and may delay or prevent the diagnosis of cancer. repeat biopsy. The authors identified 1383 men who had calculable PSAV from the period leading up to a negative initial biopsy. In this group, 432 men had PSAV  2 ng/mL/yr. Their initial biopsies demonstrated benign prostatic hyperplasia (BPH) in 18 (4.2%), prostatitis in 47 (10.9%), highgrade prostatic intraepithelial neoplasia (HGPIN) in 12 (2.8%), atypia in 2 (0.5%), and normal findings in the remainder. Stratified by the previous diagnostic groupings, cancer was REVIEWS IN UROLOGY testing is not warranted and may delay or prevent the diagnosis of cancer. The number of different manufacturers offering PSA assays continues to increase. Absent clear and accepted standards, confusion between values obtained by different manufacturers remains. Kwiatkowski and colleagues5 compared the Beckman Access and the Abbott Aksum methods in 2543 men participating in a screening cohort. Using a cutoff of 3.0 ng/mL, they found that 16.4% of men had RIU0365_08-31.qxd 8/31/07 6:19 PM Page 135 2007 AUA Annual Meeting abnormal levels with the Beckman method as opposed to 11.6% by the Abbott method. Clinicians must be aware of the relative difference of the assays they employ compared to literature standards in guiding patients. In monitoring, patients should be tested with the same method. Korets and colleagues6 provided an update on the role of human glandular kallikrein (hK2) and free PSA along analyzed, including serum results (total and free PSA) and image analysis of DNA in Feulgen-stained nuclei. The authors found that a logistic regression model using 12 nuclear morphometric descriptors had an AUC-ROC (area under the receiver operating characteristic curve) of 87%, whereas a model utilizing standard clinicopathologic characteristics resulted in an AUC-ROC of 68%. A Morphometric analysis of nuclei from initial expectant management prostate biopsies improves the predictive accuracy of models based on traditional clinicopathologic variables alone. with total PSA to predict biochemical recurrence. They evaluated 1382 men following radical prostatectomy. On univariate analysis all 3 markers were associated with biochemical recurrence. The addition of hK2 and free PSA increased the AUC of a model using only total PSA from 0.783 to 0.795. It is unlikely that this modest improvement could justify the additional cost of adding 2 additional analytes. Expectant Management Two interesting abstracts were presented by the group from Johns Hopkins. Analyzing a subset of men with available pathologic biopsy tissue from the expectant management cohort assembled by H. Ballentine Carter, MD,7,8 the group used quantitative nuclear morphometry to predict outcome and infer the nature of low-volume, lowstage prostate cancer. Makarov and associates9 attempted to determine, based on initial prostate biopsy, which patients would eventually require treatment for prostate cancer and which would maintain favorable biopsy pathology (Gleason grade  6,  2 cores involved with cancer,  50% of a core involved with cancer, and no palpable nodules). Demographic and clinical data from the time of enrollment in expectant management were model combining the 2 types of information yielded an AUC-ROC of 88%. They concluded that morphometric analysis of nuclei from initial expectant management prostate biopsies improves the predictive accuracy of models based on traditional clinicopathologic variables alone. Another important question in patients followed with expectant management is whether and how prostate biopsy tissue changes with time. Marlow and coworkers,10 from the same group, assessed changes in morphometry and clinicopathologic information in initial and surveillance biopsies of such men. Significant in morphometry through time on analysis of repeat prostate biopsies suggest that men with clinically significant cancer develop progressive and presumably worsening changes through time. Urine Biomarkers In the area of urine biomarkers, there were 2 very interesting papers presented. Schostak and colleagues11 presented a multi-institutional, prospective, double-blind clinical study examining annexin A3 in urine as a new biomarker for the detection of noninvasive, early prostate cancer. Annexin A3 protein was detected on Western-blot from the supernatants of post-digital rectal examination (DRE) urine samples of 507 patients recruited from 4 clinical centers, who later underwent prostate biopsies. Annexin A3 from the urine demonstrated significantly better prediction of prostate cancer than total, free, or complexed PSA in the 2-6 ng/mL, 4-10 ng/mL PSA ranges, but did not predict as well as any of the PSA isoforms when examining the entire range of PSA values. The combination of annexin A3 and serum PSA yielded AUC-ROCs of 0.80 (PSA range 2-6), 0.75 (PSA range 4-10), and 0.77 for all patients. The authors conclude that The authors conclude that the detection and quantification of annexin A3 provides a novel, superior, noninvasive biomarker for early prostate cancer detection, particularly strong in the PSA 2-6 ng/mL range. changes were observed in the ProPSA quantitative immunohistochemical staining (P  .01) between initial and most recent biopsies in the group. Correlation network analysis of quantitative morphometry also mapped marked visual differences between patients who were to develop unfavorable biopsies and those who would not when initial and recent surveillance biopsies were compared. Changes the detection and quantification of annexin A3 provides a novel, superior, noninvasive biomarker for early prostate cancer detection, particularly strong in the PSA 2-6 ng/mL range. Despite the importance of PSA and its derivatives, there is great need for more specific markers, ideally those that can predict malignant potential. PCA3 is a prostate-specific mRNA that is highly expressed in prostate VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 135 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 136 2007 AUA Annual Meeting continued cancer. Post-DRE urine has been demonstrated to be an adjunct to the diagnosis of prostate cancer in a quantitative assay for PCA3 that is now available outside the United States. Partin and associates12 further characterized the performance characteristics of the PCA3 urine mRNA test for the diagnosis of prostate cancer. In order for a test to be widely accepted for screening, it is important to establish its biologic variability within an indi- (n
30), men with BPH (n
35), men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (n
33), as well as men with prostate cancer and PSAs  2.5 ng/mL (n
18) and those with PSA  2.5 ng/mL (n
40). Use of a cut point of 30 EPCA-2 has a specificity of 94% and sensitivity of 91% in separating the healthy men, men with BPH, and men with CP/CPPS from those with prostate cancer, regardless of PSA levels. They Preliminary data suggest that random, short-term, physiological variation does not significantly affect an individual’s PCA3 score. vidual patient. One-hundred men with previously diagnosed prostate cancer provided urine samples (randomized either to receive a standard or an extended DRE) once a week for 4 weeks. Twenty-nine subjects have completed all 4 visits. Their mean and median variations over the visits were 22% and 20%, respectively; there were no significant differences in the variation of the PCA3 score between the DRE methods (routine or attentive). The authors conclude that their preliminary data suggest that random, shortterm, physiological variation does not significantly affect an individual’s PCA3 score. Serum Biomarkers Leman and colleagues,13 from Dr. Robert Getzenberg’s laboratory at Hopkins, utilized a proteomic approach to detect EPCA-2, a structural element of the nucleus, expressed specifically in prostate cancer. The main objective of their recently published study14 was to further delineate the ability of serum EPCA-2 to detect prostate cancer in patients with normal PSA levels, as well as in those with elevated PSA levels. The authors determined the sensitivity and specificity for EPCA-2 among healthy men with PSA  2.5 ng/mL (n
33), healthy men with PSA  2.5 ng/mL 136 VOL. 9 NO. 3 2007 conclude that a serum enzyme-linked immunosorbent assay (ELISA) for EPCA-2 has a high specificity for the detection of men with prostate cancer (PSA  and  2.5 ng/mL). Bjartell and associates15 from Memorial-Sloan Kettering performed an excellent analysis of cysteine-rich secretory protein 3 (CRISP-3) and microseminoprotein (MSP). MSP is abundantly secreted by the prostate and binds CRISP-3 with high affinity; these have both been reported to have association with prostate cancer outcomes. The authors elegantly demonstrated through the use of a tissue microarray of 947 patients that these 2 proteins are significantly associated with biochemical recurrence after radical prostatectomy on both univariate and multivariable analysis. Despite these both seeming to be amazing biomarkers, however, the authors actually demonstrated that they are limited in their predictive power. Adding CRISP-3 to a base model that included PSA, pathologic stage, and grade did not enhance discrimination of recurrence from nonrecurrence, and adding MSP improved the model only marginally. Although this strategy has been well known for a number of years,16 it is striking to see how infrequently this kind of thorough analysis is performed. The authors conclude REVIEWS IN UROLOGY that before further studies of these markers can be conducted, further research needs to elucidate their functional role in prostate cancer. Testosterone There has been great interest in the adverse effects of prostate cancer emerging in the setting of low testosterone (T) levels. Lane and coworkers17 measured T level in 380 men undergoing radical prostatectomy. Low T was defined a priori as  220 ng/dL. Low T correlated with Gleason pattern 4-5 and risk of biochemical recurrence (P
.049 and .044, respectively). The significance was not borne out in multivariate analysis. The authors concluded that if there is a prognostic effect of T level, it is marginal. Similarly, dihydrotestosterone (DHT) levels were investigated by Kjellman and colleagues,18 who studied a population-based screening cohort consisting of 1782 men, following 65 men with prostate cancer for 15 years. At the end of follow-up, 41 of these had died, and 17 of the deaths were attributed to prostate cancer. Patients with DHT levels above the median had significantly better survival than those with lower levels (P
.0075). This association was not seen among those succumbing to other disease. These findings suggest that DHT level is a tumor-progressive factor. The authors commented that these data support the findings of the Prostate Cancer Prevention trial, in which men on finasteride, which lowers DHT, had higher-grade malignancy. Sex hormone binding globulin (SHBG) has been shown to be increased in prostate cancer. Salonia and associates19 studied SHBG in 205 men undergoing radical prostatectomy. They demonstrated that the level of SHBG was significantly higher in the 29 men with extra-capsular extension (P
.003). This was highly significant in univariate (P
.005) and multivariate analysis (P
.006). RIU0365_08-31.qxd 8/31/07 6:19 PM Page 137 2007 AUA Annual Meeting These authors extended their investigation to look at SHBG’s ability to predict pelvic lymph node metastases. Among 168 men who underwent radical prostatectomy and extended pelvic lymph node dissection, 7.7% had N disease. SHBG was significantly higher in these (P  .001), and this significance persisted in univariate and multivariate analysis. A nomogram for predicting nodal status showed accuracy of 74.9% without addition of SHBG versus 83.9% with SHBG. These encouraging results deserve confirmatory studies. Novel Markers Neovascularity as measured by microvessel density (MVD) continues to garner interest by investigators. Haese and coworkers20 evaluated this as identified by CD31 immunohistochemistry in specimens from 1987 patients who were followed for up to 14 years. MVD was associated significantly with advancing Gleason grade and pathologic stage but not with baseline PSA. MVD was a significant predictor of biochemical progression. Karam and associates21 studied endoglin, a glycoprotein highly expressed by human vascular endothelial cells. They compared preoperative plasma endoglin levels with the findings at radical prostatectomy in 425 men. Median follow-up was 36.8 months. Endoglin levels were higher in men with higher PSA, positive surgical margins, higher grade cancer, and N disease. In multivariate analysis, endoglin and Gleason sum correlated with N disease, and endoglin correlated with biochemical progression. This analyte deserves further investigation and may provide an easy marker of angiogenesis. Survivin is involved in both promotion of mitosis and inhibition of apoptosis and is expressed in the cytoplasm and nuclei. Zeng22 investigated nuclear survivin in 77 archived prostate cancer specimens and 34 BPH samples. Survivin was expressed in 83.1% of cancers, but only 1 in 34 BPH specimens demonstrated this. Nuclear survivin was much more pronounced in specimens of advanced prostate cancer compared with localized (mean index 6.31% vs 3.71%). Nuclear survivin expression was an independent predictor of progression. Telomeres are nucleoprotein complexes that protect the ends of chromosomes from degradation. If the telomere length is significantly shortened, genetic instability progressing to the malignant phenotype may ing clinical research and a plethora of new insights into the surgical treatment of BPH, particularly comparisons of laser technologies. Basic Research Basic research was presented in a podium session, which may not be as appealing to the presenter or typical audience as a moderated poster session. A group from Chengdu, China,24 examined interleukin-8 (IL-8) levels in expressed prostatic secretions (EPS) in patients with BPH about to undergo transurethral resection of the Among the 46% of men who had PSA progression, those with the low telomere content had a significantly higher risk of PSA failure. result. Treat and colleagues23 investigated telomere DNA content (a surrogate for telomere length) in prostate biopsy specimens and correlated it with biochemical recurrence in 103 men undergoing radical prostatectomy. Among the 46% of men who had PSA progression, those with the low telomere content had a significantly higher risk of PSA failure (hazard ratio of 2.31, P
.013). Certainly these findings are encouraging and deserve further investigation. [Michael K. Brawer, MD, Danil V. Makarov, MD, Alan W. Partin, MD, PhD] Male Voiding Dysfunction, LUTS, and BPH At the AUA annual meeting, 74 abstracts dealt with male voiding dysfunction, male lower urinary tract symptoms (LUTS), and BPH. They were organized into 5 sessions (basic research: 12; epidemiology and natural history and marker: 12; medical and hormonal therapy: 20; surgical therapy and new technologies sessions I and II: 30). Although no major trials of medical and hormonal therapy were completed this year, the presentations included interesting ongo- prostate (TURP). This research follows recent interest in the role of chronic inflammatory infiltrates in the prostate. The mean level of IL-8 in EPS was 8175 ng/mL in men with chronic inflammatory infiltrates, whereas in men without chronic inflammatory infiltrates, the level was only 2806 ng/mL (P
.000). The IL-8 is a direct mediator of leukocyte accumulation and activation of inflammation and could, therefore, easily be responsible for the chronic inflammatory infiltrates seen in approximately 40% to 60% of all resected prostates. The goal of the research was to identify an easily obtainable marker that could predict with adequate certainty the presence of inflammatory infiltrates that prior research has associated with a more aggressive form of BPH with an accelerated natural history and subsequent acute urinary retention and surgery episodes. To obtain such diagnostic information from EPS fluid is certainly a good step in this direction. Lin and associates25 examined the effect of botulinum toxin A on contractile function in dog prostates. To this end, 100 or 200 units of botulinum toxin A were injected in dog prostates, while a sham-control group VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 137 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 138 2007 AUA Annual Meeting continued received normal saline injections. There was virtually no effect with the 100-unit dose, but 200 units reduced contractile function while maintaining the relaxation response of the prostate. The authors concluded that the result verifies the usefulness of this treatment modality in men with male LUTS and clinical BPH. The interesting point is that the authors found no effect with 100 units of botulinum toxin, as both 100 and 200 units per injection have However, contractile forces in response to electrical field stimulation, carbachol, and potassium chloride in the obstructed group were only 30% to 50% of those observed in the sham group. Vardenafil in ascending doses and dosed dependently offset the reduction in contractile response induced by bladder outlet obstruction when compared with the obstructed group without vardenafil. For example, the contractile force in the highest varde- One has to wonder whether—in the absence of an appropriately conducted dose ranging study—investigators embarking on clinical protocols utilizing botulinum toxin A are choosing the correct dose for their patients. been used with nearly equal success in clinical practice. Considering the smaller size of dog prostates compared with human prostates, one has to wonder whether—in the absence of an appropriately conducted dose ranging study—investigators embarking on clinical protocols utilizing botulinum toxin A are choosing the correct dose for their patients. Treatment of male LUTS with phosphodiesterase-5 (PDE-5) inhibitors has recently gained tremendous interest. A group of investigators from Japan26 examined the commonly utilized PDE-5 inhibitor, vardenafil, in an experimental model of obstructed female rats. Vardenafil was given in ascending doses from 0.5 to 8 mg/kg BW/day in the drinking water, and following a period of 4 weeks the bladder was excised and strips of detrusor muscle were examined in isometric organ-assay. Bladder outlet obstruction induced a 4.4-fold increase in bladder weight compared with the sham group. The bladder weights of the vardenafil-treated animals were not significantly different from those in the obstructed group, indicating that vardenafil in ascending dosages does not influence the development of detrusor hypertrophy. 138 VOL. 9 NO. 3 2007 nafil group was 40% to 80% of that observed in group I (sham). The authors deduced that vardenafil in some way protects the detrusor muscle of the bladder in this obstructed rat model and suggest this as a mechanism of why PDE-5 inhibitors are useful in the treatment of male LUTS. Other investigators27 utilized a long acting PDE-5 inhibitor, udenafil, and demonstrated a significant relaxation of bladder smooth muscle strips stimulated with carbachol via the nitric oxide pathway. This effect was enhanced by the utilization of tamsulosin, and the authors speculate a synergistic mechanism between the alpha-adrenergic receptor blockers and the PDE-5 inhibitors. The use of antimuscarinic agents in the treatment of male LUTS is increasing, but the pathophysiology and exact mechanism of action are not completely understood. A group of investigators from the United Kingdom28 addressed the question by examining muscle strips from prostate chips in 32 patients undergoing prostate surgery. They found reproducible contractures not stimulated with the alpha-adrenergic agonist phenylephrine, and these contractions were enhanced by carbachol. The antimuscarinic agent selective to REVIEWS IN UROLOGY the M3 receptor was most effective in blocking this carbachol enhancement of the PE contractility. Therefore, they speculate, this effect is most likely related to the M3 receptor, which they found localized in the stromal compartment next to the prostate smooth muscle. This type of research certainly would help elucidate the effectiveness of antimuscarinic agents addressing the M3 receptor in male LUTS with or without bladder outlet obstruction. Epidemiology and Natural History and Marker Obesity is certainly a most urgent health problem in the United States and also affects a significant number of urological disorders. Regarding prostate diseases, it has been shown that the relative risk of death due to a variety of cancers is increased in men in the highest BMI category compared with those in a lower BMI category. A study by Calle and colleagues29 found that the relative risk for prostate cancer death was 1.34, whereas the relative risk for kidney cancer death was 1.70. At last year’s AUA, Parsons and coworkers30 presented data from the Baltimore Longitudinal Study of Aging demonstrating that the odds ratio for an enlarged prostate—defined as a prostate volume of over 40 mL—increased in a group of men with the highest BMI category greater than 35. The odds ratio was, in fact, 3.5 compared with those men with a BMI of less than 25. Similar observations were made regarding other parameters of the metabolic syndrome such as fasting glucose and waist circumference, each increasing the odds ratio of an enlarged prostate. An analysis of baseline data from the Dutasteride BPH and Prostate Cancer Chemoprevention Study encompassing almost 19,000 subjects, also presented at last year’s AUA,31 demonstrated a continuing increase of measures of sexual dysfunction RIU0365_08-31.qxd 8/31/07 6:19 PM Page 139 2007 AUA Annual Meeting with increasing BMI. Several abstracts extended a similar line of research this year. Kaplan and associates32 correlated waist circumference, which presumably is a better indicator than BMI for obesity as well as a good indicator for the metabolic syndrome, to a variety of urological measures. In a relatively small cohort, approximating only 30 patients in each group, they demonstrated that from the group of men with waist circumference of 30 to 36 inches to the group with waist circumference greater than 40 inches, prostate volume increased from 28 to 37 mL, PSA from 2.3 to 3.5, and International Prostate Symptom Score (IPSS) from 11.6 to 15.8. The percent of patients with diabetes, hypertension, and ejaculate dysfunction increased in an equally significant manner (Table 1). In an analysis of a far greater number of men, also from the Dutasteride BPH and REDUCE Study baseline data population, Kaplan and Wilson33 searched for an association between prostate volume and metabolic syndrome parameters similar to last year’s presentation by Parsons and associates.30 Stratifying the men by prostate volume—less than 30, 30 to 50, and 50 to 80 mL—they noted an increase in PSA, IPSS, body mass index, incidence of obesity and diabetes, and hypertension, as well as a significant increase in insulin, HDL, LDL, and glucose levels. Epidemiological evidence of this sort certainly supports a strong link among obesity, Epidemiological evidence of this sort certainly supports a strong link among obesity, metabolic syndrome, and diseases of the lower genitourinary tract or male pelvic disorders. metabolic syndrome, and diseases of the lower genitourinary tract or male pelvic disorders. Two groups of investigators studied the behavior of serum PSA following prostatectomy for BPH and the subsequent development of prostate cancer. In the first study,34 average preoperative PSA dropped from 7.4 to 1.37 immediately following surgery, and the average postoperative PSA velocity was calculated at 0.48. Among the Table 1 Association Between Waist Circumference and Parameters Associated With Voiding and Sexual Health Waist Circumference (inches) 30-36 (n
27) 36-40 (n
36)  40 (n
25) P Value Age, years 61.39 62.36 63.89  .08 PV, cc 28.53 31.67 36.78  .001 2.32 2.92 3.54  .003 IPSS at Screening 11.57 13.67 15.78  .001 Diabetic, % 11.2 22.3 34.5 .001 Hypertension, % 12.6 24.7 37.8 .001 PSA, ng/mL 5 patients with subsequent cancer development, however, PSA velocity was significantly different at 1.18 compared with 0.20 for the noncancer patients. The second group of investigators35 performed a similar calculation, stratified by type of intervention. Preoperative PSA ranged from 2.72 in the Holmium laser prostatectomy group to 13.4 in the simple prostatectomy group, and Qmax, mL/sec 10.6 ED, % 34.6 49.5 9.45 78.6 8.65 .002 .03 EjD, % 27.8 47.2 74.5 .002 PV, prostate volume; PSA, prostate-specific antigen; IPSS, International Prostate Symptom Score; Qmax, maximum flow rate; ED, erectile dysfunction; EjD, ejaculatory dysfunction. Reprinted from Kaplan et al32 with permission from the American Urological Association. average postoperative PSA differed significantly between those men who developed prostate cancer during their follow-up and those who did not. For example, in the open prostatectomy group, the median postoperative velocity was 0.046 in BPH patients versus 0.512 in the prostate cancer patients. In the TURP group, it was 0.39 versus 0.560. Although these data differ slightly from those of the first group of investigators, it appears clear that physicians performing tissue ablative procedures for men with BPH only should follow those patients’ immediate postoperative PSA and assure an appropriate drop. Subsequent annual PSA measurements should be interpreted on the background of these data. A velocity greater than 0.5 appears to indicate the subsequent development of prostate cancer and should trigger biopsies of the remaining peripheral zone of the prostate. Armitage and colleagues36 presented data from a very large database from the United Kingdom reporting on increased risks of mortality within 90 days and 1 year of acute urinary retention (AUR)-related hospital admission. The standardized mortality ratio (SMR) was 10.36 compared with controls in men 45 to 54 years of age. VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 139 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 140 2007 AUA Annual Meeting continued Table 2 Age Specific Mortality Rates and Standardized Mortality Ratios (SMR) After AUR Mortality Rate % (95% CI) SMR (95% CI) Age Group 30 Days 90 Days 365 Days 365 Days 45-54 1.05 (0.82-1.34) 2.23 (1.88-2.64) 4.23 (3.74-4.79) 10.36 (9.14-11.75) 55-64 1.06 (0.91-1.24) 2.36 (2.13-2.61) 5.61 (5.25-6.00) 5.28 (4.93-5.65) 65-74 1.84 (1.71-1.99) 4.21 (4.01-4.43) 10.16 (9.84-10.49) 3.43 (3.32-3.55) 75-84 2.98 (2.82-3.14) 7.39 (7.15-7.64) 18.32 (17.95-18.69) 2.33 (2.28-2.39) 85-100 6.01 (5.66-6.38) 14.47 (13.95-15.01) 32.10 (31.38-32.83) 1.64 (1.59-1.68) AUR, acute urinary retention. Reprinted from Armitage et al36 with permission from the American Urological Association. This excess mortality decreased to SMR of 1.64 in men 85 to 100 years of age. In all age groups, however, a hospital admission for AUR was associated with a mortality rate above and beyond that expected in a normal population (Table 2). The authors control for comorbid conditions using the Charlson Comorbidity Index. Although there is no clear understanding of the comorbidities underlying this excess mortality, the observation alone warrants closer consideration of treatments aimed to prevent episodes of acute urinary retention and subsequent BPH-related surgery from a public health policy point of view. Nickel and coworkers had used the baseline biopsy material from the Dutasteride Prostate Cancer Prevention Chemoprevention Trial (REDUCE trial) in the past to demonstrate that there is virtually no relationship between the presence of inflammatory infiltrate and the baseline biopsy in the presence of clinical symptoms of what is normally called chronic prostatitis or chronic pelvic pain syndrome. This year, the same group presented data regarding the relationship between the presence of chronic inflammatory infiltrate and LUTS symptomatology. They found a weak but statistically significant correlation 140 VOL. 9 NO. 3 2007 between the presence of chronic inflammation and total as well as irritative and obstructive IPSS score and nocturia subscore. Although the relationships were relatively weak, with the correlation coefficient ranging from 0.041 to 0.057, it remains to be seen whether the presence of chronic inflammation in the REDUCE population predicts a differential behavior in terms of symptoms, prostate growth, and retention and surgery episodes in this patient population similar to that observed in the MTOPS population during the 4-year follow-up of this trial. It is well understood that in medical therapy trials for LUTS and BPH, a placebo lead-in phase tends to reduce the screening IPSS score to a significant degree. Roehrborn and associates38 demonstrated in the combined populations from the COMBAT and REDUCE trials that in fact the decrease in the IPSS from screening to baseline during the 4-week placebo run-in period can be predicted with mathematical precision and is strictly dependent on the baseline score (Figure 1). In the statistical model, no improvement was predicted in subjects with a screening score of 8 (which is below the normal inclusion criteria for BPH trials), whereas an improvement of 3 points is predicted in subjects with a screening score of 20, and in those with a screening score of 35 a decrease of 6.8 and 6.9 points or nearly 7 points may be expected. This type of data may be of importance when planning clinical trials, because it predicts how a screening IPSS score may translate into a baseline score after a placebo run-in period. Figure 1. Predicted decrease in IPSS during placebo run-in. IPSS, International Prostate Symptom Score. Reprinted from Roehrborn et al 38 with permission from the American Urological Association. REVIEWS IN UROLOGY Predicted Improvement in Symptoms (Decrease in IPSS) 10 8 6 4 2 0 2 0 5 10 15 20 IPSS at Screening 25 30 35 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 141 2007 AUA Annual Meeting Medical and Hormonal Therapy Combination medical therapy using both alpha blocking agents as well as 5alpha-reductase inhibitors has been popularized by the results of the MTOPS study. The SMART-1 study demonstrated in a placebo-controlled withdrawal design that after 24 weeks of combination therapy for men with moderate baseline symptom severity, the alpha blocker could be withdrawn with only a minority of patients noting the difference when asked 8 weeks later.39 In patients with severe symptoms at baseline, however, 30% distinctly felt a difference after the placebo control withdrawal of the alpha blocker and presumably wished to resume combination therapy. At this year’s AUA, Barkin and coworkers40 presented an equivalency design study in which patients were given finasteride together with an alpha blocker for 9 months, and thereafter participants in an extension arm had the alpha blocker withdrawn. At the end of the combination therapy, the IPSS score had dropped from 19.4 points to 11.3 points. At the end of the monotherapy extension phase the IPSS score was 11.8, which was not statistically significantly different (ie, equivalent to the combination phase of the trial). The authors concluded that in patients with moderate to severe LUTS symptoms, finasteride therapy alone for 9 months maintains similar urinary symptom control and quality of life as compared to the initial 9 months of combination therapy. Presumably, as 5alpha-reductase inhibitors are disease-modifying drugs, this improvement would be ongoing with no further need for alpha blockers even after the 9-month period of the study. One of the most difficult symptoms to treat effectively in men with LUTS and clinical BPH is nocturia. Neither behavioral therapy, nor medications, nor surgical procedures reliably reduce the nocturia episodes or eliminate the need for nighttime urination. Johnson and colleagues41 examined the effect of placebo versus doxazosin versus finasteride versus combination therapy in the MTOPS study on nocturia episodes at year 1 and year 4. They found that, in general, doxazosin and combination therapy improved nocturia statistically significantly against placebo whether considering men (including those  70 years of age, who were analyzed separately) with  1 nocturia episodes at baseline or those with  2 nocturia episodes at baseline, whereas finasteride did not seem to significantly improve nocturia episodes either at year 1 or year 4 (Table 3). PDE-5 inhibitors are firmly established as the mainstay of treatment for men with erectile dysfunction. Data presented at last year’s AUA suggested that several PDE-5 inhibitors currently in clinical use are quite effective in treating male voiding dysfunction. Roehrborn and associates42 found tadalafil at a dose of 5 and 20 mg improved the IPSS score by 6.2 and 7.1 points, respectively, and McVary and coworkers43 reported on a similarly designed study showing that sildenafil citrate improved the IPSS score by 6.3 points. Lastly, Kaplan and colleagues44 showed data combining sildenafil citrate 25 mg with alfuzosin 10 mg once daily and demonstrated a reduction in the IPSS score in the combination group by 3.8 points from baseline, whereas each drug alone had a lesser improvement suggesting a beneficial combined effect. This year, Stief and coworkers45 presented a randomized, double-blind, placebo-controlled study in men 45 to 64 years of age with an IPSS score  12 points who Table 3 Effect of Placebo vs Doxazosin vs Finasteride vs Combination Therapy on Nocturia Episodes at Year 1 and Year 4 Placebo # Mean Change Doxazosin # Finasteride Mean Change Mean Change # Combination # Mean Change Participants completing at least 1 year of trial with  1 episode nocturia at baseline Year 1 628 0.35 649 0.54*† 653 0.40 653 0.58*† Year 4 488 0.38 533 0.53* 516 0.42 528 0.55* Subgroup analyses Participants  70 years of age‡ Year 1 501 0.41 521 0.56*† 527 0.43 539 0.61*† Year 4 389 0.46 428 0.52 417 0.45 442 0.58† 0.29* 114 0.42* 0.29 89 0.40* Participants  70 years of age Year 1 127 0.11 128 0.46* 126 Year 4 99 0.08 105 0.59* 99 Participants, all ages, with 2 or more nocturia episodes at baseline Year 1 459 0.61 484 0.77*† 496 0.60 487 0.80*† Year 4 354 0.66 393 0.77 385 0.68 393 0.79 *P  .05 versus placebo. † P  .05 versus finasteride. ‡ There is a treatment versus time interaction for men  70 who were allocated to doxazosin when compared with those allocated to finasteride. Data from Johnson et al.41 VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 141 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 142 2007 AUA Annual Meeting continued were given 8 weeks treatment with vardenafil 10 mg twice a day versus placebo. The IPSS score decreased from 16.8 baseline to 11.0 in the vardenafil group and 13.2 in the placebo group (P
.0013) for a net decrease of 5.8 points, quite comparable with sildenafil and tadalafil data. Of interest, in none of these studies was there a significant effect of the PDE-5 inhibitors on urinary flow rate or PVR recordings suggesting a mechanism of action different from that which might have been expected, namely a relaxation of the smooth muscle with improved outflow conditions and increase in urinary flow rates. Ongoing research in this area includes an invasive urodynamic study being conducted with tadalafil as well as a phase III pivotal trial using tadalafil in men with LUTS and clinical BPH. There are 3 compounds in the class of luteinizing hormone releasing hormones (LHRH) antagonists, namely ozarelix, cetrorelix, and teverelix. LHRH antagonists differ from the more commonly employed LHRH agonists used for prostate cancer by avoiding the initial flare phenomenon induced by the agonists, which stimulate the LHRH receptor and increase testosterone temporarily, followed by a desensitization and receptor downregulation. The fast onset of action with no flare theoretically leads to a better tolerability and diminished risk of side effects and would offer on the one hand the opportunity for intermittent therapy in prostate cancer, but on the other might be used for the treatment of men with LUTS and clinical BPH. These agents have been shown to suppress serum testosterone in a dose-dependent manner, but apparently also have a direct effect on growth factors in the prostate such as insulin-like growth factor (IGF) and epidermal growth factor (EGF) involved in cell proliferation and apoptosis. Debruyne46 randomized 144 patients 142 VOL. 9 NO. 3 2007 to either placebo, 1 of 3 dosing groups receiving ozarelix 5 mg, 10 mg, or 15 mg IM on days 1 and 15, or a final group receiving ozarelix 20 mg IM on day 1 and a placebo injection on day 15. In a dose-dependent manner, ozarelix reduced serum testosterone for a period not exceeding 5 weeks during the initial treatment phase. Of note, the lowest recorded serum testosterone did not reach the castrate level and was achieved with the highest doses of ozarelix. Compared with placebo, ozarelix in a dose-dependent manner improved the IPSS score and peak flow rate without affecting the IIEF sexual function inventory. The figure below demonstrates the effect on the symptom score. The response to the 15  15 dosing scheme is particularly pronounced, reaching an overall improvement from baseline by 9 points maintained out to over 6 months following the initial 2 injections (Figure 2). Phase III trials of ozarelix and cetrorelix are either planned or underway in the United States and worldwide. The chemically similar compound teverelix has been tested in a placebo-controlled phase II trial in central Europe and was presented at this year’s European Association of Urology meeting in Berlin, Germany. Further research in this area, including extension of the drugs’ indication to intermittent hormone treatment for prostate cancer, might be expected. Two abstracts47,48 reported the results of the Tolterodine and Tamsulosin in Men with LUTS including OAB (TIMES) study. This is the first large-scale, randomized, placebocontrolled, multicenter trial over 12 weeks evaluating the safety and efficacy of tolterodine extended release or tamsulosin alone and in combination versus placebo in a population of men characterized by typical symptoms of both BPH and OAB, namely micturition frequency of  8 over 24 hours, a mean of  3 urgency episodes with or without incontinence, and judging their bladder problems as moderate to severe. Eight-hundred and seventy-nine men were randomized into the 4 arms of the trial. At baseline, these men had rather severe symptomatology with a mean IPSS score of around 20 points, a mean quality of life (QOL) score of about 4.6 points (scale from 0 to 6), and on average, 6.7 to 7.6 urgency episodes and 11.8 to 12.1 micturition episodes per 24-hour period. Figure 2. Dose-dependent improvement in IPSS with ozarelix. IPSS, International Prostate Symptom Score. Data from Debruyne.46 REVIEWS IN UROLOGY 0 5⫹5 Placebo ⫺1 10 ⫹ 10 20 ⫹ 0 15 ⫹ 15 ⫺2 ⫺3 ⫺4 ⫺5 ⫺6 ⫺7 ⫺8 ⫺9 ⫺10 0 4 8 12 16 Weeks 20 24 28 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 143 2007 AUA Annual Meeting The primary outcome, namely subjective global assessment of benefit over placebo, was reached only in the combination therapy group. In terms of all other outcomes, combination therapy achieved statistical significance in 12 of 13 outcome parameters. Tamsulosin was only effective regarding the total and voiding portion of the IPSS, and tolterodine was only effective regarding urgency incontinence episodes per 24-hour period. The drugs were remarkably well tolerated, with the exception of a seemingly additive effect on dry mouth observed in 7% each in the tolterodine and tamsulosin monotherapy arms versus 21% in the combination group. Urinary retention episodes requiring catheterization were uncommon and only observed once each in the tolterodine and combination therapy groups. Future efforts toward understanding the relative efficacy of tolterodine monotherapy or combination therapy in men with male voiding dysfunction focus on stratified analyses of men with smaller versus larger prostates and those with PSAs below and above the median value in the TIMES study. In addition, other pharmaceutical companies are researching the use of antimuscarinic agents, either alone or combined with alpha blockers, in similar populations of men suffering from OAB and LUTS suggestive of clinical BPH. Minimally Invasive Treatment Interventions and New Technology Laser ablation with the 820 nanometer Indigo® Laser (Ethicon Endo-Surgery, Inc., Cincinnati, OH) (ILC) has received limited attention over the years, and it was interesting to see long-term follow-up of a randomized control study in which 100 patients were treated with the ILC laser and compared with 50 patients treated by TURP.49 A significant improvement in the IPSS score comparable with the TURP control group was maintained out to 6 years (Table 4). Even the peak urinary flow rate improvement to 14.6 mL/sec from 8.4 mL/sec is quite remarkable, although not as high as the 20.8 mL/sec achieved in the TURP group. Treatment of men with BPH with botulinum toxin A (botox) has been commented upon at this and other meetings and received significant attention in the peer-reviewed literature, but we still lack a basic understanding as to the mechanism of action. In fact, appropriate dose finding or ranging studies have not yet been conducted. The poster presented by Kuo50 serves to emphasize this point. Thirty patients were treated with combination medical therapy and, if they failed, were offered botox injection therapy. The administered dose of botox varied greatly from 200 to 600 units, and it is difficult to determine precisely what the effective dosage might be. The authors report an improvement in the IPSS from 19.3 to 10.3 and a shrinkage of the prostate from 91 to roughly 71 mL with a concomitant improvement in peak urinary flow rate from 7.6 to 10.5 mL/sec. Chuang and colleagues51 treated 37 patients with either 100 or 200 units of botox and focused their attention on the relationship between symptomatic improvement and prostate volume changes. Although 11 of 37 patients had no change in prostate volume, 6 of these 11 patients still experienced a more than 30% improvement in peak flow rate, IPSS, or QOL. The authors concluded that there is no relationship between the volume changes and changes in symptoms or flow rate and suggested the mechanism of action of botox in the prostate must be independent of volume changes (Figure 3). Taking into consideration the basic research presentation discussed earlier,25 where a smooth muscle relaxation effect was shown in dog prostates with a 200 unit dosage of botox but a dose of 100 units was found to be completely ineffective, this might certainly give an alternative explanation as to the mechanism of action. Still, it begs the question of the appropriate dosage in human prostates, which are on average larger than dog prostates. Two abstracts examined long-term outcomes of cooled transurethral microwave thermotherapy (TUMT), 1 from the United States and the other Table 4 Long-Term Outcome of Laser Ablation vs Transurethral Resection of Prostate ILC (n
100) IPSS QOL TURP (n
50) Qmax IPSS QOL Qmax Pre-op 20.5 5* 4.2 1* 8.4 2* 20.1 5* 3.8 1* 8.4 1 year 6.7 6* 1.6 1* 17.2 6* 5.1 4* 1.0 1* 21 2* 2 years 7.0 6* 1.7 2* 17.3 7* 5.8 5* 1.1 1* 19 10* 3 years 7.0 5* 1.5 1* 16.2 7* 4.9 4* 1.0 1* 21.7 11* 4 years 7.3 6* 1.7 1* 17.6 8* 5.6 5* 1.0 1* 18.9 11* 5 years 6.7 5* 1.5 1* 16.1 6* 5.8 6* 1.0 1* 20.3 11* 6 years 8.0 6* 1.6 1* 14.6 6* 5.5 4* 1.0 1* 20.8 11* 11* *P value  .001. ILC, Indigo laser; TURP, transurethral resection of prostate; IPSS, International Prostate Symptom Score; QOL, quality of life; Qmax, maximum flow rate. Reprinted from Chandrasekar et al49 with permission from the American Urological Association. VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 143 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 144 2007 AUA Annual Meeting continued % Change of Prostate Volume 30 IPSS Qmax QOL 25 20 15 10 5 0 0 20 40 60 % Change of IPSS, Qmax, QOL 80 100 Figure 3. Relationship between symptomatic improvement and prostate volume change with botulinum toxin treatment. IPSS, International Prostate Symptom Score; Qmax, maximum flow rate; QOL, quality of life. Reprinted from Chuang et al51 with permission from the American Urological Association. from Europe. The US multicenter trial52 utilized the cooled ThermoCath (TARGIS®; Urologix, Inc., Minneapolis, MN) and reported 4-year outcomes data. In a matched pair analysis, the AUA Symptom Score was improved from 20.7 to 10.5 points and the peak urinary flow rate from 8.6 to 14.6 mL/sec. These authors report freedom from retreatment of any kind of 75% at approximately 4 years, implying that 1 out of 4 patients had to be retreated either with medication or by surgery. Waldert and associates53 reported on 614 patients who underwent highenergy TUMT with the TARGIS device between 1996 and 2004 in several centers in Europe and were followed up to 8 years. They reported that 50% or greater improvement in symptom score was achieved in 78.4% of patients at 2 years, 51.2% of patients at 6 years, and 43.4% of patients at 9 years. The actuarial rate of retreatment was reported at 20.5% at 3 years and 35.4% at 9 years, but it is unclear whether medical therapy was considered as retreatment. The authors found that PSA, large transition zone volume, and mostly obstructive voiding symptoms correlated with a significantly higher probability of symptom improvement. 144 VOL. 9 NO. 3 2007 As the datasets mature, it does appear that between 3 and 5 years after treatment with this particular microwave device approximately 1 out of every 4 patients requires retreatment either medically, by repeat TUMT, or surgically. Providers can utilize this number when counseling patients regarding this treatment alternative. Surgical Interventions De Beradinis and coworkers54 reported a randomized trial in which 200 patients were given either 5 mg of finasteride twice daily for a total of 60 days or no treatment and then underwent a TURP. The tissue staining demonstrated a lowered microvascular density and a lower vascular endothelial growth (VEGF) index, observations that have been made before and that are related to the antiangiogenic effect of finasteride. The authors reported a decrease of 1.5 gm/dL hemoglobin in the non-treated patients versus the finasteride pretreated patients, suggesting a beneficial effect of finasteride pretreatment on blood loss during TURP. In this context, a recent paper by Hahn and colleagues55 should be considered. In that trial 213 patients were given placebo, dutasteride 0.5 mg, REVIEWS IN UROLOGY or dutasteride 1 mg daily. The observation in this carefully conducted study was that the blood loss during the TURP was not statistically different among the 3 drug groups. The incidence of blood transfusion, clot retention, or other outcomes of the surgery were not significantly different and neither was the incidence or severity of bleeding after the TURP. The treatment resulted in a significant reduction of intraprostatic DHT, which was 3155 pg/g in the placebo group, 365 in the 0.5-mg group, and 290 in the 1.0-mg group. However, the authors concluded that dutasteride, even in a twice normal dose, had no impact upon bleeding during, immediately after, or delayed after TURP. Other randomized controlled trials have resulted in controversial findings. Donahue and associates56 reported a blood loss of 2.7 versus 4.7 g hg/gr of resected tissue after only 2 weeks of pretreatment using finasteride, whereas Sandfeldt and coworkers57 reported no difference after 3 months of treatment with finasteride, similar to Boccon-Gibod and colleagues,58 who used 4 weeks of treatment with dutasteride and found no difference in the amount of blood loss per gram of resected tissue. It is my opinion that the utility of 5alphareductase inhibitors for any length of time prior to a TURP in an attempt to reduce perioperative blood loss, thereby facilitating the surgery and reducing morbidity, is probably not warranted. Three abstracts focused on laparoscopic simple prostatectomy. Sotelo and associates59 from Venezuela treated 71 patients and reported an estimated blood loss (EBL) of 275 mL with a length of stay (LOS) of 1.2 days and a catheterization of 7 days and excellent improvement in symptoms. The group from Italy60 reported on 30 patients with an EBL of 351 mL (ranging from 50 to 2000 mL), an LOS of 7.4 days, and a catheterization of 6.3 days. Lastly, a group from Belgium61 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 145 2007 AUA Annual Meeting reported on 75 patients with an EBL of only 150 mL and LOS of 4 days with 3-day catheterization. Three patients had excessive LOS and catheterization duration due to capsular leak. It appears that laparoscopic simple prostatectomy utilizing either a Millin approach or an approach modified and made suitable for the laparoscopic approach is technically feasible. There is likely to be a considerable learning curve, however, and given the alternatives available, in particular the HolEP procedure, I do wonder whether or not this operation will find mainstream acceptance. The Holmium laser enucleation of the prostate (HolEP) procedure has come of age, and several of the pioneering groups reported on their outcomes. The Indianapolis group led by Lingeman62 reported on the outcomes of the HolEP procedure in over 550 patients stratified by prostate size at less than 75, 75 to 125, and over 125 grams, and found excellent tissue ablation with PSA dropping from 4.3 to 1.3 in the lowest and from 10.7 to 1.1 in the highest volume category, suggesting a near total ablation of the transition zone independent of baseline volume. Postoperative symptom scores were 7.2, 5.5, and 5.9 in the 3 groups, and peak urinary flow rates were 19.9, 21.1, and 19.2 mL/sec, respectively. Two groups reported on long-term outcomes of HolEP. Elzayat and Elhilali63 treated 118 patients and reported a 6year follow-up IPSS score of 5.6 and a peak flow rate of 16.2 mL/sec. Retreatment rate was 4.2%. Gilling and coworkers64 from New Zealand reported on 70 patients treated between 1997 and 2002 of which 38 were available for follow-up with an IPSS score of 8.5, a Qmax of 18.6 mL/sec, and a retreatment rate of 3%. It is quite clear that the HolEP procedure has come of age and in the hands of experienced surgeons is a procedure very suitable to even extremely large prostates. Other lasers have also reached maturity, and yet others have just now entered into the mainstream of urology. One such laser is the Thulium: YAG laser (Revolix™; HealthTronics, Austin, TX), which operates at a wavelength of 2090 nanometers and is, therefore, invisible. It has a high absorption coefficient in water, less in oxyhemoglobin, with a coagulation depth of 0.5 mm and optimum penetration of 0.4 mm. Data were presented65 on 54 patients who were treated with the 70 watt laser and a bare end fiber with an average resection time/vaporization time of 52 minutes. The IPSS score dropped from 19.8 to 6.1 and the flow rate increased from 4.2 to 20.1 mL/sec. It will be of interest to further follow clinical experience with the Thulium: YAG 70 watt laser in clinical applications. Considering the fact that the KTP PVP laser prostatectomy uses a wavelength that is highly absorbed in oxyhemoglobin, there has been a question as to whether or not patients pretreated with a 5alpha-reductase inhibitor such as finasteride or dutasteride would respond equally well to treatment compared with men not pretreated. Araki et al66 treated patients with or without prior treatment with a 5alpha-reductase inhibitor and compared the outcomes after 1 year regarding the IPSS score and the peak urinary flow rate. As Table 5 demonstrates, there are virtually no differences between the 2 groups, suggesting that KTP laser is as effective in patients pretreated with 5alpha-reductase inhibitors compared with those who have not been treated. Table 5 Effect of 5Alpha-Reductase Inhibition Therapy on Efficiency of KTP Laser PVP IPSS Baseline Follow-up Period (weeks) Without 5 -Reductase Inhibition (n) 26.9 6.9 (117) 1 14.7 4 10.7 12 With 5 -Reductase Inhibition (n) P Value 27.0 7.8 (43) .46 8.0 (104) 14.8 7.5 (40) .46 7.2 (97) 10.4 6.1 (40) .40 9.6 7.3 (81) 8.4 5.2 (32) .21 24 8.5 6.0 (46) 6.4 4.5 (21) .10 52 5.6 4.4 (21) 7.0 7.1 (8) .36 Qmax (mL/sec) Baseline Follow-up Period (weeks) Without 5 -Reductase Inhibition (n) 10.7 5.8 (117) 1 17.1 4 20.5 12 With 5 -Reductase Inhibition (n) P Value 11.4 6.1 (43) .25 8.2 (104) 18.0 7.0 (40) .29 9.0 (97) 21.7 8.7 (40) .24 21.9 9.3 (81) 23.1 8.0 (32) .28 24 20.6 8.2 (46) 23.9 76 (21) .08 52 18.2 6.3 (21) 16.9 1.1 (8) .39 KTP, potassium-titanyl-phosphate; PVP, photoselective vaporization prostatectomy; Qmax, maximum flow rate. Reprinted from Araki et al 66 with permission from the American Urological Association. VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 145 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 146 2007 AUA Annual Meeting continued Hamann and associates67 subjected 40 patients treated with the KTP PVP 80 watt laser to invasive urodynamic studies and demonstrated an improvement in peak flow rate from 9.7 to 17.6 mL/sec with a concomitant decrease in detrusor pressure (Pdet) at Qmax from 76.7 to 33.8 and a reduction in the Schaefer Index from 3.57 to 0.91. It is of interest as well that the tissue ablative capacities of the PVP laser vaporization utilizing the 80 watt GreenLight laser (AMS, Minnetonka, MN) resulted in significant unobstruction of patients. Two abstracts focused on utilization of the KTP 80 watt laser for large prostates. Araki and coworkers68 focused on 51 patients with a mean prostate volume of 131 mL. Their mean laser time was 59 minutes and the energy usage on average 172 120 kilojoules. Even in this group of patients with very large prostates, the symptom score dropped from 23 to 6 points at 24 weeks with an increase in maximum flow rate from 9 to 16. Jung and Ok69 treated 108 patients with a mean prostate volume of 121 grams. Their mean OR time was 93 minutes and 12 patients underwent a staged procedure. Twenty-four months of data are available suggesting a decrease in IPSS from 24.7 to 14.2 and an improvement in Qmax from 5.1 to 13.6 mL/sec. Based on these data, it seems that the KTP laser can be used in patients with very large prostates effectively, although the actual amount of tissue ablation measured directly or indirectly by PSA reduction was not reported by the authors. Final Comments The 2007 AUA provided again an interesting spectrum of observations regarding translational research, epidemiology, medical and hormonal therapy, and surgical and minimally invasive treatments for male LUTS and BPH. Overall, basic research effort presentations this year were somewhat 146 VOL. 9 NO. 3 2007 disappointing both in quality and number, and the majority of the abstracts presented in the podium sessions were translational research efforts trying to explain how and why certain interventions might work. The section on epidemiology, natural history, and markers again provided interesting insights and some clinically relevant questions, but it was in the area of medical and hormonal therapy that the greatest interest occurred. New targets and new classes of drugs are available with the PDE-5 inhibitors, LHRH antagonists, and the growing use of antimuscarinics. Whether recognition of the linkage among BMI, obesity, metabolic syndrome, and lower urinary tract disorders will result in any clinical utility remains to be seen, but in the meantime, clinicians should be aware of these connections and advise and counsel their patients accordingly. In the area of minimally invasive treatments, there are now mature data on some of the transurethral microwave devices with established retreatment rates of approximately 25% at 3 to 5 years. The field of botox injections is still lacking scientific foundation, and a properly done dose finding study spon- Urinary Tract Infection Plenary sessions of the 2007 AUA meeting provided the most excitement in the field of urinary tract infections (UTIs). Topics included relevance of bacterial biofilms to urology, UTI guidelines, catheter-associated infections, HIV prevention with circumcision, and antibiotic prophylaxis. Microbial Biofilms Costerton70 provided an explanation of how bacteria interact with each other in nature and disease. He convinced the urology audience that bacteria in the urinary tract, much like a mountain stream or an oil pipe, consists of 2 related populations; a planktonic “floating” population that is susceptible to antibiotics and host defenses and a sessile or “biofilm” population that attaches to mucosal and biomaterials in aggregates that are relatively immune to antimicrobials, macrophages, and antibodies. These biofilm bacterial colonies have evolved into a highly sophisticated community with nutrient/water channels and bioelectric The problem with medical microbiology is that we make clinical decisions based on the planktonic populations of bacteria as assessed by microbiological techniques that are almost a century old. sored by the NIH/NIDDK and the MIST Study Group is ongoing. Lastly, regarding laser procedures for the prostate, data are mature for the Holmium laser ablation as evidenced by the very long term follow-up presented at this year’s AUA. Although there is also mature data on the KPT PVP 80-watt laser, it should be noted that this laser currently is being replaced in many centers by the more powerful Greenlight HPS 120-watt laser for which no data have been presented to date. [Claus G. Roehrborn, MD] REVIEWS IN UROLOGY communications. The problem with medical microbiology is that we make clinical decisions based on the planktonic populations of bacteria as assessed by microbiological techniques that are almost a century old. Our results may not reflect the many organisms possibly growing in the biofilm, because these bacteria do not grow quickly on standard agar plates. New methods to prevent bacterial biofilm development and to disrupt established bacterial biofilm are being developed and may soon be RIU0365_08-31.qxd 8/31/07 6:19 PM Page 147 2007 AUA Annual Meeting available for use in urology for chronic and biomaterial-related UTIs. UTI Management Hooton71 summarized the previously published Infectious Diseases Society of America (IDSA) Guidelines for the treatment of urinary tract infections. These guidelines were published 8 years ago and still appear to be relevant today, but the IDSA is working on updating them. The guidelines place the greatest emphasis on trials with a randomized, double-blind design of sufficient size that meet a priori inclusion and exclusion criteria. The IDSA systematic review revealed that single-dose therapy was signifi- lines for management of these infections. The suggestions included the use of a closed catheter system and instituting a catheter reminder system. Most importantly, he outlined many non-evidence-based clinical routines that we employ in urology, believing that they might reduce catheter-associated infections. These unhelpful routines included daily meatal cleansing, bladder irrigation with antibiotics or anti-encrustation agents, antibiotic prophylaxis for long-term catheter use or at time of catheter change, antibiotic-impregnated or low-friction catheters, and frequent catheter changes. He looks forward to the day when Costerton These unhelpful routines included daily meatal cleansing, bladder irrigation with antibiotics or anti-encrustation agents, antibiotic prophylaxis for longterm catheter use or at time of catheter change, antibiotic-impregnated or low-friction catheters, and frequent catheter changes. cantly less effective in eradicating initial bacteriuria than were longer durations of treatment with trimethoprim-sulfamethoxazole (TMPSMX), TMP, norfloxacin, ciprofloxacin, fleroxacin, and, as a group, betalactam antimicrobials. Unlike singledose therapy, 3 days of therapy is equivalent in efficacy to longer durations in studies of sufficient power for TMP-SMX and the fluoroquinolones. Beta-lactams were less effective than TMP-SMX, TMP, or fluoroquinolones. The evidence for nitrofurantoin suggested that a 7-day course was the most effective. For empirical treatment of uncomplicated UTI, TMPSMX or TMP was recommended unless the prevalence of resistance to these drugs was  10%-20%. In that case, the fluoroquinolones were recommended. Hooton also provided updates on prevention of catheter-associated UTI based on best clinical evidence. The IDSA is presently developing guide- and his colleagues develop techniques to prevent and disrupt bacterial biofilms on the catheter surface. Circumcision and HIV Prevention Krieger72 reported for the first time to a major urological meeting the latebreaking news from 2 large, randomized, placebo-controlled trials that showed circumcision reduces the risk increase in sexually risky behavior. These studies have profound implications for urology. It is imperative that all urologists be aware of them and their implication for areas such as Africa where HIV is pandemic. Less clear are the ramifications for the role of circumcision in North American men, where prevalence is much less than in Africa. Antibiotic Prophylaxis Bennett76 presented the draft recommendations from the committee tasked with developing the Practice Guidelines for Antibiotic Prophylaxis in Urology. She explained that antimicrobial prophylaxis is the periprocedural systemic administration of an antimicrobial agent intended to reduce the risk of post-procedural local and systemic infections. She further explained that it is recommended only when the potential benefit outweighs the risks and anticipated costs (expense, adverse effects, and risk of development of bacterial resistance). For urological procedures, prophylaxis should begin 60 to 120 minutes before the surgical incision and generally should be discontinued within 24 hours. One major change will be the recommendations made for prophylaxis of subacute endocarditis for urological procedures. The Best Practice Policy Statement, rather than Circumcision appeared to reduce the risk of HIV by 50%-60% over 2 years and, in the short term at least, did not result in an increase in sexually risky behavior. of developing HIV infection in young men. The results from the 2 fasttracked articles, published earlier this year in Lancet,73,74 were reported in the previous edition of Reviews in Urology.75 To summarize the presentation (and previous report in RIU), circumcision appeared to reduce the risk of HIV by 50%-60% over 2 years and, in the short term at least, did not result in an practice guidelines, is presently undergoing peer review and should be published in the near future. [J. Curtis Nickel, MD, FRCSC] Tissue Engineering and Regenerative Medicine Stem Cell Injection for SUI Women with stress urinary incontinence (SUI) treated using muscle- VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 147 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 148 2007 AUA Annual Meeting continued derived stem cell injections to strengthen their sphincter muscles experience long-term improvements in their condition, according to a study from Carr and researchers at the Sunnybrook Health Science Centre of the University of Toronto School of Medicine and also the University of Pittsburgh School of Medicine.77 The study, which followed patients for more than 1 year, suggests that the approach is safe, improves patients’ quality of life, and may be an effective treatment for SUI. The finding was presented at the Tissue Engineering and Regenerative Medicine in Urology press briefing at the AUA annual meeting. “This clinical trial is extremely encouraging, given that 13 million people in the United States, most of them women, cope with stress urinary incontinence,” said Michael B. Chancellor, MD, the study’s senior author and professor of urology and gynecology restoration of the deficient muscles. The results of these studies formed the basis for the clinical trial. In the study, Carr and colleagues took biopsies of skeletal muscle tissue from 8 female patients and isolated and expanded the stem cells from the tissue in culture. In an outpatient setting, the patients then received injections of the muscle-derived stem cells into the area surrounding the urethra. Each patient received an equal dose of stem cell injections using 3 different injection techniques—a transurethral injection with either an 8-mm or 10-mm needle or a periurethral injection. Five of the 8 women who participated reported improvement in bladder control and quality of life with no serious short- or long-term adverse effects 1 year after the initial treatment. These improvements were associated with both the 10-mm needle “We now have preliminary evidence that stem cells are safe to use and appear to improve female stress urinary incontinence.” at the University of Pittsburgh School of Medicine. “We’re demonstrating for the first time that we may be able to offer people with SUI a long-term and minimally invasive treatment option.” “The technique to achieve optimal efficacy is evolving, but we are pleased with what this study has shown,” added principal investigator Lesley Carr, MD, urologist at Sunnybrook Health Sciences Centre and assistant professor at the University of Toronto. “We now have preliminary evidence that stem cells are safe to use and appear to improve female stress urinary incontinence.” Previous studies in animal models of SUI78 completed at the University of Pittsburgh School of Medicine demonstrated that injecting stem cells into the urethral muscles increases leak point pressure, leading to the 148 VOL. 9 NO. 3 2007 injections and the periurethral injections, which allowed the investigators to deliver the stem cells close to the damaged sphincter muscle. The 8-mm Endourology and Urolithiasis There were a number of informative and innovative papers presented in the endourology and urolithiasis forums that focused on methods of improving patient care and provided insights into the pathophysiology of nephrolithiasis. I will review what I think were the most pertinent papers. Indwelling Ureteral Stents Patients with indwelling ureteral stents frequently have bothersome voiding symptoms, flank pain, and abdominal pain that can impact quality of life. Two presentations indicated that the administration of -1 blockers can attenuate such symptoms. Mo and associates79 randomized patients who had indwelling ureteral stents placed at the time of ureteroscopic stone removal to receive one of 3 regimens—placebo, alfuzosin, phloroglucinol—for 1 week after the procedure. The patients treated with alfuzosin had less pain as assessed by a visual analog scale and fewer LUTS as indexed by IPSS score. Chrisofos and colleagues80 randomized patients with indwelling ureteral stents placed for management of ureteral stones to one of the following 3 regimens for 1 month after stenting: placebo, alfuzosin, tamsulosin. The The patients [with indwelling ureteral stents] treated with alfuzosin had less pain as assessed by a visual analog scale and fewer LUTS as indexed by IPSS score. needle was not able to deliver the muscle stem cells deep enough into the tissue to reach the sphincter. A multicenter study in Canada including Drs. Carr and Sender Herschorn and several urogynecologists, is underway. A study in the United States is getting underway and will allow researchers to determine the optimal dose of muscle stem cells needed to effectively treat SUI. [Michael B. Chancellor, MD] REVIEWS IN UROLOGY subjects treated with -1 blockers had less pain, fewer narcotic requirements, and an improved general health index compared with those administered placebo. Confirmatory studies are warranted, and similar investigations should be undertaken in those requiring chronic stenting. Medical Expulsive Therapy Insights into ureteral transport mechanisms and pharmacologic agents RIU0365_08-31.qxd 8/31/07 6:19 PM Page 149 2007 AUA Annual Meeting influencing this process provide direction for improving medical expulsive therapy (MET, the administration of drugs to facilitate stone passage). Owusu-Ofori and associates81 demonstrated that stretch-induced COX-2 over-expression in cultured primary urothelial cells is mediated by a PK-13 kinase dependent APKC signaling pathway. The pharmacologic modulation of the latter pathway may prove to be useful for MET. Phosphodiesterase is present in ureteral tissue, pared with 51% for the faster group, even though the mean number of shock waves administered was significantly higher for the latter group. It has been previously shown that air trapping at the interface of the shock wave head and patient’s skin attenuates shock wave energy in non-water bath SWL.85 Thus, improvements in coupling should improve treatment efficiency. Neucks and colleagues86 assessed various methods of applying coupling gel to the patient. They The [ureteral] stone free rate was 68% for the slower rate as compared with 51% for the faster group, even though the mean number of shock waves administered was significantly higher for the latter group. and its inhibition could induce ureteral smooth muscle relaxation, which is thought to promote stone passage. Coyle and colleagues82 demonstrated in an in-vitro model that the exposure of porcine ureteral strips to T0156, a PDE-5 inhibitor, promoted a reduction in contractility that was further augmented with the addition of doxazocin. This suggests PDE-5 inhibitors may be potential MET agents, and there may be a role for dual therapy with alpha-1 blockers. Shock Wave Lithotripsy Shock wave lithotripsy (SWL) is commonly used to treat patients requiring stone removal. Practical methods for improving treatment results are still being discovered. It has been previously demonstrated that slower shock wave delivery rates improve fragmentation and stone-free status in patients with renal stones.83 Until now, this has not been shown for ureteral stone cases. Pace and associates84 randomized patients with proximal ureteral stones  5 mm undergoing SWL to be treated at rates of either 60 or 120 shocks per minute. The stone free rate was 68% for the slower rate as com- demonstrated that delivering the gel as a bolus to the skin and subsequent inflation of the shockwave head to the skin interface was the best method of limiting air bubble interference. Use of a spray bottle or direct hand application were both significantly inferior. Hyperoxaluria Hyperoxaluria is a risk factor for kidney stone formation. Hyperoxaluria is typically classified as idiopathic, enteric, or primary. Patients subjected to contemporary bariatric surgery may be at risk for developing hyperoxaluria, which is thought to be enteric. Pedro and colleagues87 evaluated patients just before and 3 months after laparoscopic Roux en Y gastric bypass with 24-hour urine studies. The percentage of patients with hyperoxaluria increased to 23.1% from 7.6% at 3 months after surgery. The optimal treatment strategy for managing patients who have stones and hyperoxaluria due to bariatric surgery has not been established. These patients would most likely benefit from calcium supplementation and dietary fat and oxalate restriction. Probiotic therapy with oxalate degrading organism has also been described.88 The administration of oxalate degrading enzymes could theoretically benefit this group of patients. Grujic and associates89 reported that the oral administration of a crystalline, cross-linked oxalate degrading enzyme, ALTU-237, in 2 different animal models of hyperoxaluria resulted in a significant reduction of oxalate excretion. A 25%-40% decrease was demonstrated in rats with ethylene glycol-induced hyeroxaluria, and a 30%-50% decrease was reported in a knockout mouse model for type 1 primary hyperoxaluria. A phase I study will need to be undertaken in humans to establish that this agent has an appropriate safety profile. If so, further clinical trials should be considered in patients with enteric and primary hyperoxaluria, both therapeutic challenges. Nephrolithiasis in Pregnancy Pregnant patients may have acute stone events and require analgesic therapy and in some cases a surgical intervention. The impact of such events on the fetus has not been well characterized. Swartz and associates90 performed a retrospective case study of 2239 pregnant patients admitted for treatment of nephrolithiasis in the state of Washington from 1987 to 2003. They found that these subjects were at almost twice the risk for preterm delivery. A total of 471 (24.9%) underwent one or more procedures for stone management, and this did not influence the risk of preterm delivery. These studies provide insight on why stones develop; describe possible measures to prevent or attenuate stone activity, potential strategies to facilitate spontaneous stone passage, and techniques to optimize SWL; and suggest that stone events during pregnancy may cause fetal morbidity. They provide a bright forecast for the VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 149 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 150 2007 AUA Annual Meeting continued future management of patients afflicted with nephrolithiasis. [Dean G. Assimos, MD] Pediatric Urology Vesicoureteral Reflux Birusingh and the investigators from Iowa City presented their experience using distal ureteral diameter versus reflux grade to determine rate of reflux resolution.91 Reflux grading has always been based on calyceal appearance. At times, the dilation of the calyces is discordant with the degree of ureteral dilation. This study evaluates reflux based on the diameter of the distal ureter. Children (N
189) ranging from 1 month to 7.5 years underwent a voiding cystourethrogram (VCUG). The largest ureteral diameter within the pelvis was measured and normalized by dividing the value by the distance from the L1–L3 vertebral body to determine the distal ureteral diameter : L1–L3 ratio (UDR). Outcomes were defined as either spontaneous resolution or surgical correction. A significant association between grade of reflux and UDR was found. The mean UDR was significantly greater in those undergoing surgery than in those who had spontaneous were all significantly associated with time to VUR resolution. In general, younger age, male sex, lower grades, and unilateral reflux were significantly associated with earlier resolution. These data will be very useful in clinical decision making and counseling parents. Alam and colleagues from Cincinnati Children’s Hospital presented a retrospective cohort study of 46 consecutive children with primary VUR undergoing injection therapy with dextranomer/hyaluronic acid copolymer.93 Sixty-seven renal units were treated. The average age of the patients was 7.1 years. All but 3 of the 46 patients were female. The reflux grades ranged from grade I to IV. A Fowler Stephens procedure is indicated when the testes were greater than 2.5 cm from the internal ring, despite the inherent increased risk for atrophy. Cystograms were performed at 3 and 12 months. Patients with dysfunctional voiding were not included in this analysis. Twenty-nine of 46 patients (43 renal units) underwent both a 3- and 12-month VCUG. The success rate at 3 months following treat- Ureteral diameter ratio may be more predictive of outcome than grade alone. resolution of their reflux (0.34 .02 vs 0.18 0.02). The investigators concluded that UDR is an objective measurement of reflux severity and is significantly associated with reflux grade. The UDR may be more predictive of outcome than grade alone. Estrada and colleagues from Children’s Hospital of Philadelphia presented a study formulating nomograms for predicting yearly resolution rates of primary vesicoureteral reflux (VUR).92 The nomograms were formulated using age, sex, grade, and laterality. Age at diagnosis, sex, grade, and laterality 150 VOL. 9 NO. 3 2007 orchidopexy for intra-abdominal testes.94 Seventy-six boys age 5.3 months to 13 years underwent laparoscopic orchidopexy. Thirteen patients with less than 6 months follow-up were excluded from the outcomes assessment. A single-stage orchidopexy with spermatic vessels left intact was performed on 46 testes. A singlestage Fowler Stephens (FS) procedure was performed on 3 testes, and a 2stage FS procedure was performed on 23. Follow-up of 31.7 months (range 6 months to 11 years) revealed a 7.9% atrophy rate in 5 of 63 testes. Testicular loss was found in 2 of the singlestage FS procedures, 1 of the 2-stage FS orchidopexies, and 2 primary orchidopexies with a testicular distance ment was 79.3% (69.8% of renal units). Five patients (7 renal units) with negative cystograms at 3 months had recurrent VUR at 1 year, representing 17.3% of patients and 16.3% of renal units. The average grade of recurrent reflux was grade 2. These investigators recommend that a VCUG should be performed at 1 year to confirm resolution of reflux. Laparoscopic Orchidopexy Passerotti and associates from Boston Children’s Hospital presented their long-term follow-up of laparoscopic REVIEWS IN UROLOGY above the inguinal ring greater than 2.5 cm. The authors proposed that an FS procedure is indicated when the testes were greater than 2.5 cm from the internal ring, despite the inherent increased risk for atrophy. Bladder Exstrophy Nelson and the Johns Hopkins Hospital investigators presented patient-reported data regarding adult outcomes in bladder exstrophy.95 They evaluated voiding status, urinary incontinence, and impact of urinary function on quality of life. Twenty-four of 201 patients treated since 1975 agreed to participate in the study. Seventeen males and 7 females were identified with mean age of 29.9 10.3 years (range 19 to 68 years). Spontaneous voiding was reported in 50%. Urethral catheterization was required in 8%, and catheterization of an augmentation or reservoir was performed in 33%. Only 8% had a urinary diversion. Most of the patients reported some RIU0365_08-31.qxd 8/31/07 6:19 PM Page 151 2007 AUA Annual Meeting degree of urinary incontinence, including about 75% of those who void or catheterize through the urethra. Approximately 75% reported stress urinary incontinence only rarely, 52% experienced urge incontinence, and almost 40% have nocturnal leakage at least once a week. Three fourths of these patients did not report incontinence to be a problem, and most noted that it was uncommon to change their daily activities due to their incontinence. The authors conclude that urinary incontinence remains a significant problem for patients in the modern era of exstrophy management despite surgical advances. These patients tolerate their condition well, most likely because of the congenital nature of their incontinence. [Ellen Shapiro, MD, FACS, FAAP] Sexual Function and Infertility One of the main themes of the Sexual Function/Infertility programs at the AUA was the emphasis on impotence post prostatectomy or post cavernosal injury and the use of various agents to ameliorate this condition. This began with a debate at the Sexual Medicine Society (SMS) meeting regarding the use of daily PDE-5 inhibitors post prostatectomy for the treatment and/or prevention of erectile dysfunction. It became evident from the debate that the clinical outcomes data to support the concept of using these drugs daily in this setting is lacking. Nevertheless, the consensus was that robust basic science evidence was emerging to show that the continuous use of PDE-5 inhibitors following cavernosal nerve damage has a salutatory effect on the erectile mechanism by 1) preserving the cells of the corporal smooth muscle, and 2) preventing the deposition of collagen within the cavernosa. Furthermore, it seems if these PDE-5 inhibitors are going to be used on a daily basis post-prostatectomy, they need to be started immediately after the prostatec- tomy because the pro-apoptotic and pro-fibrotic molecular events that lead to the changes in the cavernosa post prostatectomy, at least in the animal models, begin within 24 hours of the cavernosal nerve damage. Indeed, in the Basic Research Posters on Sexual Function/Dysfunction/Andrology (MP20 and MP23), 10 different research groups reported on some of the molecular and biochemical characteristics of the cavernosal tissue following various forms of cavernosal nerve injury and provided insight into why the PDE-5 inhibitors may be effective in such a setting. With respect to the use of neuromodulators to reduce the neuropathic effects of radical prostatectomy, the long awaited multi-institutional study looking at the use of an immunophilin ligand in these patients was reported at this meeting.96 The preliminary data from this placebo-controlled study suggest that the drug used did not demonstrate the clinical efficacy the authors expected. One of the most interesting talks was that from Cornell, where the authors perused the web pages of 75 institutions or practices promoting robotic radical prostatectomy.97 They found that 1) only 61% of these 75 had information related to what happens to erectile function post robotic prostatectomy while 39% did not, 2) of the 61% that had information about erectile function, 78% of these or 36 of the original 75 institutions stated that robotic prostatectomy is either better at preventing or preserving erectile function when compared with standard open radical prostatectomy. The authors conclude that this misinformation—because there are no data to support such a statement—gives patients unrealistic expectations. In keeping with the theme of side effects that may occur to the radical prostatectomy patient, the group from Houston reported on the safety and efficacy of treating these men post prostatectomy who subsequently were or developed hypogonadism with exogenous testosterone.98 Although not every one of their patients so treated had an improvement in erectile function, what must be most reassuring to the urologist from this study is that none of the 21 patients had an increase in PSA level, although the postoperative and pre-treatment PSAs were essentially zero, suggesting that these patients were cured of their prostate cancer, at least biochemically. In the realm of Peyronie’s disease, the following became evident from not only a State of the Art lecture at the SMS meeting but also from various posters and podium presentations. First of all, it is apparent that there are no large, randomized, controlled trials that prove that any medical therapy including the use of injectable verapamil into the plaque of patients with Peyronie’s disease is efficacious. Despite this, a number of investigators reported on the beneficial effects of injectable verapamil in patients with Peyronie’s disease.99 The regimen that most investigators use is 10 mg verapamil in 10 mL of volume injected with a 25-G needle into the plaque every 2 weeks for a minimum of 6 weeks. The group from Baylor100 reported on their series of using a dose escalation of 20 mg of verapamil instead of 10 mg every 2 weeks for 6 weeks and found that there was the suggestion of an increased efficacy with the greater dose. Again, it should be emphasized that there were no randomized, controlled trials to unequivocally recommend one dose of verapamil over the other. The only other novel therapy that was reported for Peyronie’s disease came from investigators101 in Norfolk, VA, who presented their preliminary data in 25 men injected with mixed collagenase subtypes into their plaque and found this product to be very VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 151 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 152 2007 AUA Annual Meeting continued promising. Finally, another group from Europe102 reported on the lack of efficacy of shock wave lithotripsy (SWL) to treat Peyronie’s disease, hopefully putting to rest the use of this modality to treat Peyronie’s disease. Another very interesting report dealt with premature ejaculation.103 This study involved the use of 25 mg of tramadol, an anti-inflammatory agent, given on demand 1-2 hours prior to sexual activity. The multi-institutional authors reported in this single-blinded, placebo-controlled study a high efficacy with the use of such a regimen with an increase in intravaginal latency time of about 7.4 minutes compared with 1.7 minutes on placebo. In summary, the radical prostatectomy patient took center stage in the Sexual Function programs. Many studies attempted to decipher the changes such as impotence, Peyronie’s disease, and penile shortening that occur in the penis following this operative procedure and propose potential therapeutic targets to ameliorate these QOL issues that afflict these men. It appears that much progress has been made in this arena and that, with the double pronged approach of both basic science research and clinical trials, solutions to these issues are on the horizon. [Jacob Rajfer, MD] References 1. 2. 3. 4. 5. 152 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Banez LL, Hamilton RJ, Vollmer RT, et al. Can hemodilution explain the lower PSA concentrations among obese men? [abstract 1418]. J Urol. 2007;177(4 suppl):468. Loeb S, Roehl KA, Catalona WJ, Nadler RB. Is the utility of PSA velocity for prostate cancer detection affected by age? [abstract 1420]. J Urol. 2007;177(4 suppl):468-469. Roehl KA, Loeb S, Graif TM, Catalona WJ. Followup on patients with high PSAV and negative intial biopsy [abstract 1421]. J Urol. 2007;177(4 suppl):469. Connolly D, Black A, Murray LJ, et al. The value of repeating an abnormal PSA test [abstract 1608]. J Urol. 2007;177(4 suppl):533. Kwiatkowski M, Seiler D, Huber A, Recker F. Clinical implications for use of various PSA assays VOL. 9 NO. 3 2007 6. 17. 18. 19. REVIEWS IN UROLOGY in prostate cancer early detection [abstract 1609]. J Urol. 2007;177(4 suppl):533. Korets R, Serio AM, Wenske S, et al. Longitudinal evaluation of molecular psa isoforms and human glandular kallikrein 2 in predicting biochemical failure following radical prostatectomy [abstract 1607]. J Urol. 2007;177(4 suppl):532. Carter HB, Walsh PC, Landis P, Epstein JI. Expectant management of nonpalpable prostate cancer with curative intent: preliminary results. J Urol. 2002;167:1231-1234. Warlick C, Trock BJ, Landis P, et al. Delayed versus immediate surgical intervention and prostate cancer outcome. J Natl Cancer Inst. 2006;98:355357. Makarov DV, Marlow C, Epstein JI, et al. Predicting the need for treatment among men with low grade, low stage prostate cancer enrolled in a program of expectant management with curative intent [abstract 1434]. J Urol. 2007;177 (4 suppl):473. Marlow C, Makarov DV, Zhang Z, et al. Surveillance of men with low grade and stage prostate cancer enrolled in an expectant management program: changes in clinical, pathological and nuclear morphometry patterns observed over time [abstract 1626]. J Urol. 2007;177(4 suppl):539. Schostak M, Schwall G, Slobodan P, et al. Annexin A3 quantification from supernatants of urine after DRE provides a novel and clinically easy available biomarker for the non-invasive diagnosis of prostate cancer [abstract 1425]. J Urol. 2007;177(4 suppl):470. Partin AW, Mangold LA, Gurganus RT, et al. Biological variation of PCA3 score in men previously diagnosed with prostate cancer [abstract 1623]. J Urol. 2007;177(4 suppl):538. Leman ES, Cannon GW, Trock BJ, et al. Further analysis of serum based EPCA-2 as a specific prostate cancer associated biomarker [abstract 1431]. J Urol. 2007;177(4 suppl):472. Leman ES, Cannon GW, Trock BJ, et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology. 2007;69:714-720. Bjartell AS, Al-Ahmadie H, Serio AM, et al. Association of cystein-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy: evaluation with a tissue microarray of 947 primary prostate cancers [abstract 1430]. J Urol. 2007;177(4 suppl):472. Kattan MW. Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst. 2003;95:634-635. Lane BR, Stephenson AJ, Reuther AM, et al. Low pretreatment total testosterone levels are associated with a predominance of pattern 4 prostate cancer at prostatectomy and risk of biochemical recurrence [abstract 1617]. J Urol. 2007;177(4 suppl):536. Kjellman A, Akre O, Norming U, et al. Dihydrotestosterone as a prognostic factor in men with screening-detected prostate cancer [abstract 227]. J Urol. 2007;177(4 suppl):76. Salonia A, Gallina A, Briganti A, et al. Sex hormone binding globulin is a significant predictor of extra capsular extension in patients undergoing radical retropubic prostatectomy [abstract 1615]. J Urol. 2007;177(4 suppl):535. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. Haese A, Dix K, Erbersdobler A, et al. Microvessel density is signifiantly associated with pathologic stage, Gleason score and biochemical recurrence in patients with clinically localized prostate cancer undergoing radical retropubic prostatectomy [abstract 1621]. J Urol. 2007;177 (4 suppl):537. Karam JA, Svatek RS, Adam JA, et al. Pre-operative plasma endoglin levels predict metastasis to lymph nodes and disease progression in patients treated with radical prostatectomy [abstract 1426]. J Urol. 2007;177(4 suppl):470471. Zeng H. Nuclear expression of survivin is an independent predictor for progression of prostate adenocarcinoma [abstract 1429]. J Urol. 2007; 177(4 suppl):471-472. Treat EG, Heaphy CM, Bisoffi M, et al. Telomere DNA content predicts biochemical recurrence in a retrospective analysis of prostate cancer biopsies [abstract 1432]. J Urol. 2007;177(4 suppl): 472-473. Wei Q, Li Q, Han P, et al. Il-8 levels in expressed prostatic secretion of BPH with chronic prostatitis [abstract 1349]. J Urol. 2007;177(4 suppl):445. Lin AT, Yang AH, Chen KK. Effects of botulinum toxin A on the contractile function of dog prostate [abstract 1356]. J Urol. 2007;177 (4 suppl):447. Matsumoto S, Watanabe E, Nakata Y, et al. Bladder protective effects of PDE5 inhibitor-efficacy of vardenafil on rat bladder with outlet obstruction [abstract 1354]. J Urol. 2007;177(4 suppl):446. Bae JH, Moon DG, Shim KS, et al. Relaxation effects of udenafil, a long-acting phosphodiesterase-5 inhibitor, on carbachol-induced bladder smooth muscle contraction [abstract 1564]. J Urol. 2007;177(4 suppl):516-517. Blake-James B, Li CY, Emberton M, Fry CH. Muscarinic receptor sub-types in the human prostate: effects upon smooth muscle contractility and localization using immunohistochemistry [abstract 1358]. J Urol. 2007;177(4 suppl):448. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-1638. Parsons JK, Carter HB, Partin AW, et al. Metabolic factors associated with benign prostatic hyperplasia: the Baltimore Longitudinal Study of Aging [abstract 1344]. J Urol. 2006;175(4 suppl):432. Roehrborn CG, Marberger M, Wolford ET, Wilson TH. Explanatory variables for measures of sexual dysfunction in LUTS/BPH and prostate cancer risk reduction studies: baseline data from dutasteride studies involving a total of 18,914 subjects [abstract 1348]. J Urol. 2006;175(4 suppl):434. Kaplan S, Fisch H, Berriman SJ, et al. Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms, sexual dysfunction, and components of the metabolic syndrome [abstract 1508]. J Urol. 2007;177(4 suppl):497-498. Kaplan S, Wilson TW. Association between BPH and the metabolic syndrome in the REDUCE population [abstract 1548]. J Urol. 2007;177 (4 suppl):511. RIU0365_08-31.qxd 8/31/07 6:19 PM Page 153 2007 AUA Annual Meeting 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. Espy PG, Wind A, Wade B, et al. Long-term trends following subcapsular prostatectomy for benign prostatic hyperplasia [abstract 1498]. J Urol. 2007;177(4 suppl):494. Helfand BT, Vyas A, Fine M, et al. Post-operative PSA values and PSA velocity predict the presence of prostate cancer following various surgical interventions for benign prostatic hyperplasia (BPH) [abstract 1503]. J Urol. 2007;177(4 suppl):496. Armitage J, Sibanda N, Cathcart P, et al. Acute urinary retention is associated with an increased risk of mortality [abstract 1507]. J Urol. 2007; 177(4 suppl):497. Nickel JC, Roehrborn CG, O’Leary MP, et al. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial [abstract 98]. J Urol. 2007;177(4 suppl):34-35. Roehrborn CG, Marberger M, Tubaro A, et al. Relationship between screening IPSS and the placebo run-in response in the pooled REDUCE and COMBAT population [abstract 1557]. J Urol. 2007;177(4 suppl):514-515. Barkin J, Guimarães M, Jacobi G, et al. Alphablocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol. 2003;44(4):461-466. Barkin J, Koch C, Dupont C, et al. Finasteride monotherapy maintains stable urinary symptoms (IPSS) in men with benign prostatic hyperplasia for 9 months after 9 months of combination therapy using both an alpha-blocker and finasteride [abstract 1561]. J Urol. 2007;177(4 suppl):516. Johnson TM, Burros PK, Kusek JW, et al. The effect of doxazosin, finasteride, and combination therapy on nocturia in men with benign prostatic hyperplasia [abstract 1549]. J Urol. 2007; 177(4 suppl):511. Roehrborn CG, McVary KT, Kaminetsky JC, et al. The efficacy and safety of tadalafil administered once a day for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) [abstract 1636]. J Urol. 2006;175(4 suppl): 527. McVary KT, Swierzewski MJ, Monnig WB, et al. Sildenafil improves erectile function and concomitant lower urinary tract symptoms in men [abstract 920]. J Urol. 2006;175(4 suppl):298. Kaplan SA, Gonzalez RR, Ogiste J, et al. Combination of an alpha blocker, alfuzosin SR and a PDE-5 inhibitor, sildenafil citrate is superior to monotherapy in treating lower urinary tract symptoms (LUTS) and sexual dysfunction [abstract 1638]. J Urol. 2006;175(4 suppl):528. Stief CG, Porst H, Evers T, Ulbrich E. Varedenafil in the treatment of symptomatic benign prostatic hyperplasia [abstract 1565]. J Urol. 2007;177 (4 suppl):517. Debruyne FMJ. The efficacy and safety of ozarelix, a novel GNRH antagonist, in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) [abstract 1552]. J Urol. 2007;177(4 suppl):512. Kaplan SA, Rovner ES, Sussman DO, et al. Effects of tolterodine extended release and/or tamsu- 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. losin on bladder diary variables in men with lower urinary tract symptoms including overactive bladder [abstract 1553]. J Urol. 2007;177(4 suppl):512-513. Roehrborn CG, Kaplan SA, Steers WD, et al. Effects of tolterodine extended release and/or tamsulosin on international prostate symptom scores in men with lower urinary tract symptoms including overactive bladder [abstract 1554]. J Urol. 2007;177(4 suppl):513. Chandrasekar P, Kapasi F, Virdi JS. Interstitial laser ablation (Indigo™) of the prostate; a prospective, randomised study, six year results [abstract 1741]. J Urol. 2007;177(4 suppl):579. Kuo HC. Therapeutic effect of botulinum toxin A on large benign prostatic hyperplasia with persistent lower urinary tract symptoms and suboptimal treatment outcome of combination medical therapy—clinical and histological investigation of effects [abstract 1836]. J Urol. 2007; 177(4 suppl):609-610. Chuang YC, Chiang PH, Yoshimura N, et al. Efficacy and length of symptom improvement after botulinum toxin type A injection in BPH patients not correlated with change in prostate volume [abstract 1837]. J Urol. 2007;177(4 suppl):610. Mynderse LA. Continuing results of a multicenter trial of a new generation cooled TUMT for BPH [abstract 1835]. J Urol. 2007;177(4 suppl): 609. Waldert M, Seitz C, Harik M. Evaluation of the long-term efficacy, safety, and retreatment rates of targeted high energy transurethral microwave thermotherapy [abstract 1834]. J Urol. 2007;177(4 suppl):609. De Beradinis E, Antonini G, Busetto GM, et al. Risk decrease of intra-operative bleeding during TURP with the uptake of finasteride: evaluation of VEGF and CD 34 [abstract 1726]. J Urol. 2007;177(4 suppl):575. Hahn RG, Fagerström T, Tammela TL, et al. Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. BJUI. 2007;999 (3):587-594. Donohue JF, Hayne D, Karnik U, et al. Randomized, placebo-controlled trial showing that finasteride reduces prostatic vascularity rapidly within 2 weeks. BJU Int. 2005;96(9): 1319-1322. Sandfeldt L, Bailey DM, Hahn RG. Blood loss during transurethral resection of the prostate after 3 months of treatment with finasteride. Urology. 2001;58(6):972-976. Boccon-Gibod L, Valton M, Ibrahim H, et al. Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate. Prog Urol. 2005 Dec;15(6):10851089. Sotelo RJ, Garcia AJ, Carmona O, Banda E. Laparoscopic simple prostatectomy. Experience in 71 cases [abstract 1738]. J Urol. 2007;177(4 suppl):578. Porpiglia F, Renard J, Volpe A, et al. Laparoscopic transcapsular simple prostatectomy (Millin): An evolving procedure [abstract 1739]. J Urol. 2007;177(4 suppl):578. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. Ngninkeu BN, de Fourmestreaux N, Lufuma E. Digitally-assisted laparoscopic prostatic adenomectomy: a preliminary report of 75 cases [abstract 1740]. J Urol. 2007;177(4 suppl):578-579. Humphreys MR, Miller NL, Handa SE, et al. Holmium laser enucleation of the prostate: outcomes are independent of prostate size [abstract 1735]. J Urol. 2007;177(4 suppl):577. Elzayat E, Elhilali M. Long-term results of holmium laser enucleation of the prostate (HOLEP): the reoperation rate including the learning curve [abstract 1734]. J Urol. 2007;177(4 suppl):577. Gilling PJ, King C, Williams A, et al. The longterm durability of Holmium laser enucleation of the prostate (HOLEP) [abstract 1736]. J Urol. 2007;177(4 suppl):577. Bach T, Herrmann TRW, Ganzer R, Gross AJ. Revolix 70 watt 2 micron continuous wave laser vaporesection of the prostate. Preliminary results after a 1 year follow-up [abstract 1848]. J Urol. 2007;177(4 suppl):614. Araki M, Po PN, Culkin DJ, et al. Decreased efficiency of potassium-titanyl-phosphate (KTP) laser photoselective vaporization prostatectomy (PVP) with long-term 5A-Reductase inhibition therapy: is it true? [abstract 1839]. J Urol. 2007; 177(4 suppl):611. Hamann MF, Seif C, Naumann M, et al. Urodynamics and functional outcome after photoselective vaporisation of the prostate [abstract 1845]. J Urol. 2007;177(4 suppl):613. Araki M, Po PN, Culkin DJ, et al. High power (80 W) potassium-titanyl-phosphate (KTP) laser photoselective vaporization prostatectomy (PVP) for large volume benign prostatic hyperplasia (BPH) [abstract 1846]. J Urol. 2007;177(4 suppl):613. Jung G, Ok Y. Photoselective vaporization of the prostate (PVP) for treatment of huge benign prostatic hyperplasia (BPH) [abstract 1847]. J Urol. 2007;177(4 suppl):613. Costerton JW. State of the art: microbial biofilms—implications for the urologist. Presented at: Annual Meeting of the American Urological Association, Plenary Session II; May 21, 2007; Anaheim, CA. Hooton T. New concepts in UTI management: guidelines of the IDSA. Presented at: Annual Meeting of the American Urological Association, Plenary Session II; May 21, 2007; Anaheim, CA. Krieger J. Late breaking news: circumcision reduces HIV infection risk. Presented at: Annual Meeting of the American Urological Association, Plenary Session II; May 21, 2007; Anaheim, CA. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomized controlled trial. Lancet, 2007;369:643-656. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet, 2007;369: 657-666. Nickel, JC. Circumcision and HIV: the jury is in! Rev Urol. 2007;9(2):89-90. Bennett CJ. AUA update: Practice guidelines— antibiotic prophylaxis in urology. Presented at: Annual Meeting of the American Urological VOL. 9 NO. 3 2007 REVIEWS IN UROLOGY 153 RIU0365_08-31.qxd 8/31/07 6:19 PM Page 154 2007 AUA Annual Meeting continued 77. 78. 79. 80. 81. 82. 83. 84. 85. 154 Association, Plenary Session IV; May 23, 2007; Anaheim, CA. Carr LK, Steele D, Steele S, et al. University of Toronto clinical trial of muscle-derived cell injection in women with stress urinary incontinence [abstract 1331]. J Urol. 2007;177(4 suppl):439. Lee JY, Cannon TW, Pruchnic R, et al. The effects of periurethral muscle-derived stem cell injection on leak point pressure in a rat model of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(1):31-37. Mo K, Lee KS, Seo YJ, et al. Effects of alphablocker on lower urinary tract symptoms due to ureteral stent: prospective study [abstract 1273]. J Urol. 2007;177(4 suppl):419. Chrisofos M, Gkougkousis E, Skolarikos A, et al. Alfuzosin vs tamsulosin in treating double-J stent related morbidity; a prospective comparative study [abstract 1641]. J Urol. 2007;177(4 suppl):544. Owusu-Ofori K, Coyle TLC, Jerde TJ, et al. Stretch-induced COX-2 over-expression is mediated through a pi3-kinase-dependent APKC signaling pathway in human urothelial cells [abstract 1642]. J Urol. 2007;177(4 suppl):544. Coyle TLC, Jerde TJ, Nakada SY. The phosphodiesterase-5 inhibitor T0156 alone and in combination with doxazosin relaxes porcine ureter: implications in medical expulsive therapy for urolithiasis [abstract 1640]. J Urol. 2007;177(4 suppl):544. Kato Y, Yamaguchi S, Hori J, et al. Improvement of stone comminution by slow delivery rate of shock waves in extracorporeal lithotripsy. Int J Urol. 2006 Dec;13(12):1461-1465. Pace KT, Ghiculete D, Razvi H, et al. Shock wave lithotripsy for upper ureteral stones: a randomized trial of 60 vs. 120 shocks/min [abstract 1312]. J Urol. 2007;177(4 suppl):431-432. Pishchalnikov YA, Neucks JS, VonDerHaar RJ, et al. Air pockets trapped during routine coupling VOL. 9 NO. 3 2007 86. 87. 88. 89. 90. 91. 92. 93. 94. REVIEWS IN UROLOGY in dry head lithotripsy can significantly decrease the delivery of shock wave energy. J Urol. 2006 Dec;176(6 Pt 1):2706-2710. Neucks JS, Pishchalnikov YA, Zancanaro AJ, et al. Coupling is a significant source of variability in dry-head lithotripsy: strategies to improve outcomes [abstract 1257]. J Urol. 2007;177(4 suppl):414-415. Pedro RN, Duffey B, Weiland D, et al. Impact of bariatric surgery on urinary stone risk factors in the morbidly obese [abstract 1367]. J Urol. 2007; 177(4 suppl):451. Hoppe B, von Unruh G, Laube N, et al. Oxalate degrading bacteria: new treatment option for patients with primary and secondary hyperoxaluria? Urol Res. 2005 Nov;33(5):372-375. Grujic D, Salido EC, Cachero TG, et al. Oral therapy with crystalline formulation of oxalate degrading enzyme in rodent models with hyperoxaluria [abstract 1639]. J Urol. 2007;177(4 suppl):543-544. Swartz MA, Lydon-Rochelle MT, Simon D, et al. Admission for nephrolithiasis in pregnancy and risk of adverse birth outcomes [abstract 1365]. J Urol. 2007;177(4 suppl):450. Birusingh KK, Knudson MJ, Austin JC, Cooper CS. Distal ureteral diameter compared to reflux grade and resolution [abstract 510]. J Urol. 2007;177(4 suppl):170. Estrada CR, Passerotti CC, Graham D, et al. Nomograms for predicting yearly resolution rates of primary vesicoureteral reflux [abstract 513]. J Urol. 2007;177(4 suppl):171. Alam S, Minevich E, Sheldon CA. Recurrent vesicoureteral reflux after dextranomer/hyaluronic acid copolymer injection: is a 1 year follow-up cystogram necessary? [abstract 517]. J Urol. 2007;177(4 suppl):172. Passerotti CC, Nguyen HT, Retik AB, et al. Longterm follow-up of the intra-abdominal testis 95. 96. 97. 98. 99. 100. 101. 102. 103. treated laparoscopically [abstract 365]. J Urol. 2007;177(4 suppl):121. Nelson CP, North A, Gearhart JP, Lakshmanan Y. Patient-reported urinary function and incontinence among adults born with classic bladder exstrophy [abstract 372]. J Urol. 2007;177(4 suppl):123. Burnett AL, McCullough AR, Smith JA, et al. Neuromodulation to preserve erectile function after radical prostatectomy: results from the gpi1485 neuroimmunophilin ligand clinical trial [abstract 1162]. J Urol. 2007;177(4 suppl):383-384. Rojas-Cruz C, Mulhall JP. Sexual health misinformation on robotic prostatectomy websites [abstract 1034]. J Urol. 2007;177(4 suppl):342. Khera, M, Colen J, Grober ED, et al. The safety and efficacy of testosterone replacement therapy following radical prostatectomy [abstract 1164]. J Urol. 2007;177(4 suppl):384. Gwynn ES, Phillips JJ, Carbone DJ. Variable timing of response for improvement in pain, curvature, and sexual function following intraplaque injection of verapamil for Peyronie's disease [abstract 753]. J Urol. 2007;177(4 suppl):253. Grober ED, Khera, M, Gahan JC, et al. Efficacy and safety of dose escalation (10 to 20 mg) intralesional verapamil therapy for Peyronie's disease [abstract 751]. J Urol. 2007;177(4 suppl):252. Jordan GH. Injectable mixed collagenase subtypes for the treatment of Peyronie's disease [abstract 746]. J Urol. 2007;177(4 suppl):250. Hatzichristodoulou G, Meisner C, Stenzl A, Lahme S. Efficacy of extracorporeal shock wave therapy on plaque size and sexual function in patients with Peyronie's disease—results of a prospective, randomized, placebo-controlled study [abstract 747]. J Urol. 2007;177(4 suppl):251. Salem EA, Delk JR, Wilson SK, et al. Tramadol hcl has promise in on demand use to treat premature ejaculation [abstract 1043]. J Urol. 2007;177(4 suppl):345.