Incontinence

Prostate Cancer continued nist, for the treatment of asymptomatic, hormone-refractory prostate adenocarcinoma (HRPCa) in a double-blind, randomized, placebo-controlled clinical trial conducted in the United States and Europe. A total of 288 asymptomatic men with HRPCa and evidence of metastatic disease were recruited into the study. The men were randomly assigned to a once-daily oral dose of one of the following: placebo; atrasentan, 2.5 mg; or atrasentan, 10 mg. The primary end point of the study was time to progression; secondary end points included time to prostate-specific antigen (PSA) The median time to PSA progression for the atrasentan, 10 mg, group was twice that of the placebo group. progression, bone scan changes, and changes in bone and tumor markers. Results demonstrated that, among the 244 evaluable men, the median time to progression was significantly prolonged in the atrasentan, 10 mg, group compared with the placebo group (196 vs 129 days; P < .03). Furthermore, the median time to PSA progression for the atrasentan, 10 mg, group was twice that of the placebo group (155 vs 71 days; P < .003). Men who received placebo continued to have significant increases from baseline in serum lactate dehydrogenase (LDH), a marker of disease burden, whereas elevations in LDH were uniformly attenuated by atrasentan (P < .01). Adverse events occurred in 16% to 34% of the men who received atrasentan, 10 mg. These events were usually mild to moderate in severity and included dyspnea, headache, rhinitis, and peripheral edema. Although this study demonstrated that atrasentan, with favorable tolerability, delays progression of HRPCa, it failed to investigate the agent’s influence on survival. This important issue needs to be addressed in future phase III protocols. In addition, the investigators reported that quality of life was neither adversely affected nor improved by atrasentan. The wide use of atrasentan for the management of advanced prostate cancer awaits further clinical trials and results of survival and quality-of-life studies. References 1. 2. 3. 4. 5. Wu-Wong JR. Endothelin receptor antagonists: past, present and future. Curr Opin Cardiovasc Pulmon Renal Invest Drugs. 1999;1:345-351. Masaki T. The endothelin family: an overview. J Cardiovasc Pharmacol. 2000; 35(4 suppl 2):S3-S5. Langenstroer P, Tang R, Shapiro E, et al. Endothelin-1 in the human prostate: tissue levels, source of production and isometric tension studies. J Urol. 1993; 150(2 pt 1):495-499. Nelson JB, Hedican SP, George DJ, et al. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med. 1995;1:944-949. Usmani BA, Shen R, Janeczko M, et al. Methylation of the neutral endopeptidase gene promoter in human prostate cancers. Clin Cancer Res. 2000;6:1664-1670. 48 VOL. 6 NO. 1 2004 REVIEWS IN UROLOGY 6. 7. 8. 9. Gohji K, Kitazawa S, Tamada H, et al. Expression of endothelin receptor A associated with prostate cancer progression. J Urol. 2001;165:1033-1036. Nelson JB, Chan-Tack K, Hedican SP, et al. Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res. 1996;56:663-668. Takuwa Y, Masaki T, Yamashita K. The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae. Biochem Biophys Res Commun. 1990;170:998-1005. Nelson JB, Nguyen SH, Wu-Wong JR, et al. New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin A receptor blockade. Urology. 1999;53:1063-1069. Incontinence Incontinence After Childbirth Reviewed by Yongtae Kim, MD, Michael B. Chancellor, MD Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA [Rev Urol. 2004;6(1):48-49] © 2004 MedReviews, LLC Urinary Incontinence After Vaginal Delivery or Cesarean Section Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S, for the Norwegian EPINCONT Study. N Engl J Med. 2003;348:900-907. t is widely accepted that traumatic childbirth is a major cause of pelvic floor damage and stress urinary incontinence. Yet, the actual data to support or refute this are not well characterized. In this noteworthy study, Rortveit and colleagues, from Norway, address this important issue. The investigators studied whether women who deliver by cesarean section have an increased risk of urinary incontinence compared with nulliparous women and whether women who deliver vaginally have an even higher risk. A total of 15,307 women in a community-based cohort were evaluated. Women were included if they answered questions related to urinary incontinence; were younger than 65 years; and had no deliveries, cesarean sections only, or vaginal deliveries only. The prevalence of any incontinence was 10.1% in the nulliparous women, 15.9% in those who had cesarean sections only, and 21.0% in those who had vaginal delivery only. Compared with nulliparous women, those who had cesarean sections had an adjusted odds ratio (OR) for any I Hydronephrosis incontinence of 1.5. Only stress and mixed-type incontinence were significantly associated with cesarean sections. The adjusted OR for any incontinence associated with vaginal deliveries compared with cesarean sections was 1.7. Only stress incontinence (adjusted OR, 2.4) was associated with the mode of delivery. Results of this study demonstrated that women who delivered vaginally had a 2- to 3-times higher risk of stress incontinence compared with nulliparous women, whereas those who delivered by cesarian section had a 50% higher risk. Other interesting findings were that urge incontinence is not associated with childbirth and that even nulliparous women can develop stress urinary incontinence. However, urologists should not interpret the study as indicating cesarean sections if one wants to prevent incontinence. Hydronephrosis Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Evaluation of Hydronephrosis in Children Reviewed by Ellen Shapiro, MD, FACS, FACP Department of Urology, New York University School of Medicine, New York, NY [Rev Urol. 2004;6(1):49-50] © 2004 MedReviews, LLC ydronephrosis is detected on 1 in 800 to 1500 prenatal sonograms. Most mild grades of dilation resolve spontaneously. Because there is no test that absolutely defines obstruction, moderate-to-severe grades of hydronephrosis pose a diagnostic dilemma for both pediatric urologists and pediatric radiologists. To date, most pediatric urologists employ a combination of sonography, radionuclide scintigraphy, and voiding cystourethrography to elucidate the cause and severity of the hydronephrosis. In previous studies, magnetic resonance imaging (MRI) has been used to evaluate acute pyelonephritis, vesicoureteral reflux, and renal function. In the article below, investigators from Emory University utilized dynamic contrast-enhanced MRI to investigate the pediatric urinary tract. The technology of magnetic resonance urography has continued to evolve, incorporating newer imaging sequences and shorter H acquisition times. Together, these studies demonstrate that MRI has the ability to clearly define normal versus abnormal renal anatomy. A Prospective Study Comparing Ultrasound, Nuclear Scintigraphy and Dynamic Contrast Enhanced Magnetic Resonance Imaging in the Evaluation of Hydronephrosis Perez-Brayfield MR, Kirsch AJ, Jones RA, Grattan-Smith JD. J Urol. 2003;170(4 pt 1):1330-1334. This study compared dynamic contrast-enhanced MRI with other imaging modalities used to evaluate pediatric hydronephrosis. A total of 100 dynamic contrast-enhanced MRIs were performed in children, all of whom had also undergone renal/bladder sonography. Additional imaging modalities employed included 99mtechnetium-diethylenetriamine pentaacetic acid (DTPA) in 39 subjects, 99mmercaptoacetyltriglycine (MAG-3) in 29 subjects, 99mtechnetium-dimercaptosuccinic acid (DMSA) in 3 subjects, and voiding cystourethrography (VCUG) in 64 subjects. Older patients with no history of urinary tract infection did not undergo VCUG. The MRI was performed within 6 months of the other examinations. Of 96 children (girls [n = 35], boys [n = 61]; mean age, 4 years [range, 1 month to 17 years]), 4 subjects underwent MRI after 6 months; only 9 studies were performed postoperatively. Sedation was performed with chloral hydrate in patients younger than 1 year and intravenous pentobarbital plus fentanyl in older patients; there were no complications associated with sedation. The MRI technique evolved over the study period. However, the last 80 patients followed the same standard protocol, which was similar to that used with nuclear scintigraphy. This protocol included catheter drainage, hydration, and administration of furosemide. GadoliniumDTPA was injected, and sequential images revealed perfusion, uptake, and excretion phases. The renal volume was calculated to determine the differential renal function. Threedimensional maximal intensity projections, which provide anatomical detail similar to an intravenous pyelography, were obtained from delayed images. The most common presentations of study subjects were prenatal hydronephrosis (n = 43) and urinary tract infection (n = 22). The final MRI diagnoses in the 96 subjects were ureteropelvic junction obstruction (n = 26), ureterovesical junction obstruction (n = 14), dilation without obstruction (n = 35), duplex system (n = 13; nonfunctioning upper pole [n = 3], ectopic ureter [n = 5], normal duplication [n = 1]), multicystic kidney (n = 5), small scarred kidney (n = 1), pyelonephritis (n = 2), renal mass (n = 1), bilateral polycystic VOL. 6 NO. 1 2004 REVIEWS IN UROLOGY 49