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Jaclyn C Milose, Christopher P Filson, Alon Z Weizer, Khaled S Hafez, Jeffrey S MontgomeryDepartment of Urology, University of Michigan, Ann Arbor, MI, USAAbstract: Testis cancer is one of the few solid organ malignancies for which reliable serum tumor markers are available to help guide disease management. Human chorionic gonadotropin, alpha fetoprotein, and lactate dehydrogenase play crucial roles in diagnosis, staging, prognosis, monitoring treatment response, and surveillance of seminomatous and nonseminomatous germ cell tumors. Herein we discuss the clinical applications of germ cell tumor markers, the limitations of these markers in the management of this disease, and additional serum molecules that have been identified with potential roles as novel germ cell tumor markers.Keywords: testicular cancer, tumor markers, bhCG, AFP, surveillance, diagnosis

Peter K Sand1, Scott A MacDiarmid2, Heather Thomas3, Kim E Caramelli3, Gary Hoel3 1University of Chicago, Pritzker School of Medicine, Chicago, IL; 2Alliance Urology Specialists, Greensboro, NC; 3Watson Laboratories, Inc., Salt Lake City, UT, USA Background: In a recent placebo-controlled Phase III study, oxybutynin chloride topical gel (OTG) significantly improved urinary continence in patients with overactive bladder. In this post hoc analysis, the effect of incontinence severity on OTG-mediated improvement in continence was evaluated. Methods: Change from baseline in the number of incontinence episodes was evaluated in patients with two to three incontinence episodes/day (moderate incontinence) and those with more than three incontinence episodes/day (severe incontinence). Results: In patients with moderate (n = 171) and severe (n = 556) incontinence, reduction in incontinence episodes (mean ± standard deviation) was greater (P < 0.01) with OTG (moderate, -1.7 ± 1.4; severe, -3.6 ± 3.0) than with placebo (moderate, -1.2 ± 1.3; severe, -3.1 ± 3.4). Continence achievement rate with OTG was 48.2% (placebo, 24.4%) among patients with moderate incontinence and 17.8% (placebo, 12.1%) among those with severe incontinence. Conclusion: Absolute placebo-adjusted reduction in incontinence episodes with OTG was not affected by baseline incontinence severity. Continence achievement was more likely if symptoms were less severe. Keywords: incontinence, overactive bladder, oxybutynin chloride topical gel, continence

Louis C Remynse III, Patrick J Sweeney, Kevin A Brewton, Jay M LonswayUrology Associates of Battle Creek, PC, Battle Creek, MI, USAAbstract: Infectious complications related to prostate ultrasound and biopsy have increased in the past decade with the emergence of increasing fluoroquinolone bacterial resistance. We investigated the addition of intravenous (iv) piperacillin/tazobactam immediately prior to prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis to determine if it would decrease the incidence of serious infectious complications after prostate ultrasound and biopsy. Group 1 patients were a historic control of 197 patients who underwent prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis. Group 2 patients, 104 patients, received standard fluoroquinolone prophylaxis and the addition of a single dose of iv piperacillin/tazobactam 30 minutes prior to prostate ultrasound and biopsy. There were ten serious bacterial infectious complications in group 1 patients. No patients in group 2 developed serious bacterial infections after prostate ultrasound and biopsy. There was approximately a 5% incidence of serious bacterial infection in group 1 patients. Subgroup analysis revealed an almost 2.5 times increased risk of infection in diabetes patients undergoing prostate ultrasound and biopsy. There was a 10% risk of serious bacterial infection in diabetics compared with a 3.8% risk group 1 nondiabetes patients. The addition of a single dose of iv piperacillin/tazobactam along with standard fluoroquinolone prophylaxis substantially reduces the risk of serious bacterial infection after prostate ultrasound and biopsy (P< 0.02).Keywords: piperacillin/tazobactam, fluoroquinolone, prostate biopsy, infectious complications

Anne P Cameron, Allen McNeil HarawayDepartment of Urology, Division of Neurourology and Pelvic Floor Reconstruction, University of Michigan Health System, Ann Arbor, MI, USAObjective: To review the literature on the surgical and nonsurgical treatment options for stress urinary incontinence in women, focusing exclusively on randomized clinical trials and high quality meta-analyses.Materials and methods: A computer-aided and manual search for published randomized controlled trials and high quality meta-analyses investigating both conservative and surgical treatment options for stress urinary incontinence. In the case of a treatment that is not studied in these formats large case series have been used.Results: Articles were reviewed and the results summarized on pelvic floor physical therapy, pharmacotherapy, bulking agents, and surgery (open and minimally invasive).Conclusion: There are numerous high quality studies in the literature. It can be difficult to make definitive conclusions on the most appropriate treatment options due to the variability in the outcomes used to define success in these articles. There is also a dire lack of studies evaluating and comparing the surgical options for patients with intrinsic sphincter deficiency.Keywords: stress urinary incontinence, conservative and surgical treatment

Steven A Kaplan1, Claus G Roehrborn2, Lawrence A Hill3, Weining Volinn31Weill College of Medicine Cornell University, New York, NY, USA; 2University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Watson Laboratories Inc., Salt Lake City, UT, USAObjective: The uroselective α-blocker silodosin significantly improved International Prostate Symptom Score (IPSS) in two 12-week, double-blind (DB), placebo-controlled Phase III studies in men aged ≥ 50 years with symptoms of benign prostatic hyperplasia (BPH) and maintained symptom improvement during a 9-month open-label (OL) extension. This post-hoc analysis evaluated the effects of estimated prostate volume (EPV) on silodosin-mediated symptom improvement.Methods: Patients were stratified by EPV (

Abhishek A Solanki, Stanley L LiauwDepartment of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL, USAAbstract: Brachytherapy and external beam radiotherapy are effective and commonly used treatment modalities in men with localized prostate cancer. In this review, we explore the role of radiation therapy in the curative management of prostate cancer, including the use of conformal therapeutic techniques to allow for the escalation of radiation doses to tumor, along with the use of combined radiation and hormonal therapy to enhance disease outcomes in men with aggressive disease. We also review the possible anticancer role of HMG-CoA reductase inhibiting agents (statins) in men with prostate cancer. Laboratory evidence suggests that statins may have antineoplastic effects when used alone and may sensitize cells to radiation therapy when given in combination. We explore the biologic basis for an anticancer effect and the clinical evidence suggesting statins may aid in improving outcomes with radiation therapy for localized prostate cancer.Keywords: HMG-CoA reductase inhibitors, statins, radiotherapy, prostate cancer

Mohammad Kazem Moslemi1, Mohammad Ali Sadighi Gilani2, Hossein Shahrokh31Department of Urology, Kamkar Hospital, School of Medicine, Qom, University of Medical Science, Qom, Iran; 2Department of Urology, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Urology, Hasheminejad Kidney Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, IranBackground: The purpose of this study was to compare the risks and benefits of Mathieu repair of hypospadias with or without circumcision in consecutive operated cases.Methods: Eighty-six children with midshaft or distal hypospadias were randomly divided into two groups and underwent circumcision (Group A) or preputial reconstruction (Group B) during hypospadias repair. Postoperative complications, outcomes, and parental satisfaction were assessed for circumcised and uncircumcised patients. All patients with midshaft or distal hypospadias with or without minimal chordee were included.Results: No statistically significant differences in urethral complications were found between the two groups. Meatal stenosis occurred in one case in Group A and one case in Group B. Fistulae occurred in five cases in Group A and six cases in Group B. Urethral dehiscence occurred in no case in either group. No case of phimosis was seen in Group B. After a mean follow-up of 6 months, all parents of Group A cases stated that they were satisfied with the circumcision for religious and/or social reasons, but no parents of Group B cases were satisfied with preputioplasty (P ≤ 0.05). No case of hypospadias repair failure was seen in our operated cases. Finally, no cases in Group B required redo hypospadias surgery.Conclusion: Mathieu repair with synchronous circumcision is feasible in all patients with distal or midshaft hypospadias with or without minimal chordee, and should be considered in accordance with surgeon preference. In the case of prepuce preservation, parents should be informed that there is a benefit of tissue banking for probable redo hypospadias repair but with an increased risk of complications and a need for another procedure, ie, circumcision.Keywords: hypospadias, circumcision, preputioplasty, distal, midshaft, Mathieu repair

Mohammad Kazem Moslemi1, Mehdi Abedinzadeh2, Mohammad Aghaali11Department of Urology, Kamkar Hospital, School of Medicine, Qom University of Medical Sciences, Qom, Iran; 2Department of Urology, Moradi Hospital, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, IranBackground: Circumcision can be performed for a variety of techniques, including conventional dissection surgery or a Plastibell device, and has religious, ritual, or medical roots. In countries like Iran, circumcision is done purely on religious grounds. In this study, we outline 390 cases in our practice and describe the epidemiology, indications, surgical technique used, and the early complications.Materials and methods: In this retrospective study, the charts for 390 circumcision cases were analyzed for the period March 2005 to August 2010. We reviewed all cases, noting age, indication, type of anesthesia used, technique, cosmetic appearance, and any potential early complications. All cases were followed up 1–4 weeks postoperatively and their notes were evaluated.Results: The age of children who underwent circumcision ranged from 3 weeks to 14 years, with a mean age of 4.25 years. The most common age for circumcision was 4–5 years (14.6%), and the least common age was 11–12 years (1.5%). In 372 cases (95%), the parents had opted for the procedure for religious reasons, and in 18 cases (5%), there was a medical indication, including phimosis (11 cases, 3%), urinary tract infection (5 cases, 1.2%), and balanoposthitis (2 cases, 0.8%). No major early complications were found in our series. Cosmetic appearance was satisfactory in all cases by 4 weeks after the operation.Conclusion: Circumcision was performed for religious reasons in our cases, although medical indications sometimes modified the timing of the procedure. Conventional dissection surgery for circumcision was safe, effective, and without any major complications.Keywords: male circumcision, conventional dissection surgery, neonatal, infant, complication, religious, ritual, meatus, phimosis

Fable Zustovich1, Giuseppe Lombardi1, Davide Pastorelli1, Patrizia Farina1, Massimo Dal Bianco2, Luca De Zorzi2, Maurizia Dalla Palma1, Ornella Nicoletto1, Vittorina Zagonel11Oncologia Medica 1, Istituto Oncologico Veneto-IRCCS, Padova, Italy; 2UO Urologia, Ospedale Sant'Antonio, ULSS 16, Padova, ItalyAbstract: Renal cell carcinoma (RCC) is a common malignancy worldwide with approximately 95,000 new cases per year and ranks as the sixth cause of cancer deaths. Until recently, the slightly active and very toxic cytokines were available for patients with advanced RCC. Advances have been made in understanding the molecular biology of renal cancer. The introduction of targeted agents has led to promising possibilities for treating these highly vascularized tumors. Angiogenesis inhibition is likely to represent the main potential therapeutic target. Sorafenib is an oral multikinase inhibitor with activity against tyrosine kinase receptors that are responsible for blood vessel development and has shown to be active in treating advanced RCC. In this review, we summarize the pharmacology, mode of action, pharmacokinetics, and safety of sorafenib use in therapy for advanced RCC.Keywords: sorafenib, pharmacokinetics, angiogenesis&nbsp

Brian M Olson, Douglas G McNeelUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USAAbstract: Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a slight survival benefit while being associated with potentially significant side effects. However, the recent approval of sipuleucel-T has given patients with advanced disease an additional treatment option that has demonstrated benefit without the side effects associated with chemotherapy. Sipuleucel-T is an antigen-presenting cell-based active immunotherapy that utilizes a patient's own immune cells, presumably to activate an antigen-specific immune response against tumor cells. This review focuses on the development and implementation of sipuleucel-T as a therapy for prostate cancer. Specifically, we present some of the issues associated with the management of advanced prostate cancer, the research and development that led to the approval of sipuleucel-T, how the approval of sipuleucel-T could change the clinical management of prostate cancer, and current and future areas of investigation that are being pursued with regard to sipuleucel-T and other treatments for advanced prostate cancer.Keywords: sipuleucel-T, prostatic acid phosphatase, granulocyte-macrophage colonystimulating factor

Vincent R Lucente1, David R Staskin2, Elise De31Institute of Female Pelvic Medicine and Reconstructive Surgery, Allentown, PA, USA; 2Division of Urology, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA; 3Urological Institute of Northeastern New York, Albany, NY, USAAbstract: Overactive bladder (OAB) is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG) is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo-controlled Phase III study.Keywords: oxybutynin topical gel, overactive bladder, transdermal formulation

Maxine Sun1, Firas Abdollah2, Jan Schmitges1, Claudio Jeldres1, Shahrokh F Shariat3, Paul Perrotte4, Pierre I Karakiewicz1,4 1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; 2Department of Urology, Vita Salute San Raffaele University, Milan, Italy; 3Department of Urology, Weill Medical College of Cornell University, New York, NY, USA; 4Department of Urology, University of Montreal Health Center, Montreal, CanadaAbstract: The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR), was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001). Placebo crossovers (80%) contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a seque ntially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor f ailure resulted in an even longer progression-free survival time (5.4 months) than in the entire population (4.9 months). These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated.Keywords: everolimus, metastatic renal cell carcinoma, targeted therapy, sequential therapy, mTOR

Athanasios G Papatsoris, Islam Junaid, Alexandra Zachou, Stefanos Kachrilas, Faruquz Zaman, Junaid Masood, Noor BuchholzDepartment of Endourology, Barts and the London NHS Trust, London, UKAbstract: Bladder outflow obstruction is a very common age-related clinical entity due to a variety of benign and malignant diseases of the prostate. Surgical treatment under general or regional anesthesia is not suitable for high-risk elderly patients who seek minimally invasive management. Unfortunately, for patients who are not fit for transurethral and/or laser prostatectomy, few treatment options remain, other than long-term catheterization and insertion (under local anesthesia) of a prostatic stent. In this review, we present developments in the use of prostatic stents.Keywords: prostatic stent, stent migration, urethal lumen, bladder outlet obstruction

Marty Hinz1 Alvin Stein2 Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Laboratories, Duluth, MN, USABackground: The purpose of this paper is to present the results of statistical analysis of spot baseline urinary norepinephrine and epinephrine assays in correlation with spot baseline urinary serotonin and dopamine findings previously published by the authors. Our research indicates a need for physicians and decision-makers to understand the lack of validity of this type of spot baseline monoamine testing when using it in the decision-making process for neurotransmitter deficiency disorders.Methods: Matched-pairs t-tests were performed for a group of subjects for whom spot baseline urinary norepinephrine and epinephrine assays were performed on samples collected on different days then paired by subject.Results: The reported laboratory test results for urinary serotonin, dopamine, norepinephrine, and epinephrine, obtained on different days from the same subjects, differed significantly and were not reproducible.Conclusion: Spot baseline monoamine assays, in subjects not suffering from a monoamine-secreting tumor, such as pheochromocytoma or carcinoid syndrome, are of no value in decision-making due to this day-to-day variability and lack of reproducibility. While there have been attempts to integrate spot baseline urinary monoamine assays into treatment of peripheral or central neurotransmitter-associated disease states, diagnosis of neurotransmitter imbalances, and biomarker applications, significant differences in day-to-day reproducibility make this impossible given the known science as it exists today.Keywords: neurotransmitter testing, epinephrine, norepinephrine, dopamine, serotonin

Marc C Gittelman1, Leonard S Marks2, Lawrence A Hill3, Weining Volinn3, Gary Hoel31South Florida Medical Research, Aventura, Florida, USA; 2University of California at Los Angeles and Urological Sciences Research Foundation, Los Angeles, California, USA; 3Watson Laboratories, Salt Lake City, Utah, USAPurpose: Pooled results from 2 randomized, placebo-controlled, US phase III studies (NCT00224107, NCT00224120) showed that silodosin, a uroselective α-blocker, significantly improved International Prostate Symptom Scores (IPSS) in men with symptomatic benign prostatic hyperplasia (BPH). This analysis evaluated the effect of silodosin on each symptom assessed by IPSS questionnaire.Materials and methods: Study participants (N = 923) were men aged ≥50 years with IPSS ≥13 and Qmax 4–15 mL/s. They received silodosin 8 mg or placebo once daily for 12 weeks. Patient responses to 7 IPSS questions were collected at weeks 0 (baseline), 0.5, 1, 2, 4, and 12 and scored on a 6-point scale. Efficacy of silodosin versus placebo was assessed by analysis of covariance.Results: For each symptom, the 2 treatment groups had similar mean baseline scores. Decrease in score from baseline (mean ± standard deviation) to last observation was significantly greater with silodosin than with placebo for all symptoms (P < 0.005); symptom improvement with silodosin (versus placebo) was greatest for weak stream (silodosin, -1.1 ± 1.4 versus placebo, -0.5 ± 1.2; P < 0.0001) and smallest for nocturia (silodosin, -0.6 ± 1.1 versus placebo, -0.4 ± 1.2; P = 0.0037). Compared with placebo, silodosin significantly improved nocturia within 1 week (silodosin, -0.5 ± 1.07 versus placebo, -0.3 ± 1.05; P = 0.009) and all other symptoms within 3 to 4 days (P < 0.01).Conclusions: Silodosin significantly improved all BPH-associated symptoms assessed by IPSS questionnaire within the first week of treatment. All improvements were maintained over the 12-week study period.Keywords: BPH, symptoms, rapid onset, silodosin, α1A-adrenoceptor antagonist

Tola Omotosho, Chi Chiung Grace ChenWomen’s Center for Pelvic Health, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USAAbstract: Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER) is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder.Keywords: antimuscarinics, efficacy, quality of life, overactive bladder, tolterodine, urgency, urge urinary incontinence

Marty Hinz1, Alvin Stein2, George Trachte3, Thomas Uncini41Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3Department of Physiology and Pharmacology, University of Minnesota Medical School, MN, USA; 4DBS Labs, Duluth, MI, USAAbstract: This paper analyzes the statistical correlation of urinary serotonin and dopamine data in subjects not suffering from monoamine-secreting tumors such as pheochromocytoma or carcinoid syndrome. Peer-reviewed literature and statistical analyses were searched and monoamine (serotonin and dopamine) assays defined in order to facilitate their proper interpretation. Many research findings in the literature are novel. Baseline assays completed with no monoamine precursors differ from baseline assays performed on a different day in the same subject. There is currently no scientific basis, value, or predictability in obtaining baseline monoamine assays. Urinary assays performed while taking precursors can demonstrate a lack of correlation or unexpected correlations such as inverse relationships. The only valid model for interpretation of urinary monoamine assays is the “three-phase model” which leads to predictability between monoamine assays and precursor administration in varied amounts.Purpose: This paper reviews the basic science of urinary monoamine assays. Results of statistical analysis correlating baseline and nonbaseline assays are reported and provide valid methods for interpretation of urinary serotonin and dopamine results.Patients and methods: Key scientific claims promoting the validity of the urinary neurotransmitter testing (UNT) model applications are discussed. Many of these claims were not supported by the scientific literature. Matched-pairs t-tests were performed on several groupings. Results of all statistical tests were compared with peer-reviewed literature.Results: The statistical analysis failed to support the UNT model. Peer-reviewed literature search failed to verify scientific clams made in support of applications of the UNT model in many cases. Keywords: serotonin, dopamine, urinary neurotransmitter testing

Abigail Mawhinney1,*, Ammar Hameed2,*, Ali Thwaini1, Colin Mulholland11Belfast City Hospital, Urology Department, Belfast, Northern Ireland, UK; 2Addenbrookes University Hospital, Urology Department, Cambridge, UK*These authors contributed equally to this paperIntroduction: We report a case of a vesico-vaginal fistula (VVF) post cold cup biopsy; to our knowledge this is the only reported case. We present the clinical history/presentation, investigation and the outcome of the treatment. VVFs are among the most distressing complications of gynecologic and obstetric procedures. The risk of developing a VVF is more than 1% after radical surgery and radiotherapy for malignancies. Management of these fistulas has been better defined and standardized over the last decade.Methods and results: A case of low grade superficial bladder cancer was treated with multiple resections of bladder tumor and a single installation of mitomycin post initial resection which successfully cleared her bladder cancer, but nevertheless led to a small size and scarred bladder. In addition there was a long history of smoking with its effects on tissue integrity and healing. VVFs are very rare and are an unpleasant outcome post a cold cup biopsy, adding to the psychological and social effects of the surgical treatment.Conclusion: Although cold cup biopsy is a normal day procedure performed by both residents and consultants, consensus should exist on how to treat a patient who has a bladder with defective integrity and small capacity. The rate of successful fistula repair reported in the literature varies between 70% and 100% in nonradiated patients, with similar results when a vaginal or abdominal approach is performed, the mean success rates being 91% and 97%, respectively.Keywords: vesico-vaginal fistula, vaginal fistula, surgical repair of vaginal fistula, management of vaginal fistula

Nina Chi1, Jodi K Maranchie2,3, Leonard J Appleman3,4, Walter J Storkus1,3,51Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 3University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States; 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 5Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAAbstract: Renal cell carcinoma (RCC) remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s) of action, further refined (combinational) vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.Keywords: renal cell carcinoma, vaccines, immunotherapy, combinational therapy, cellular immunity

Alfredo Berruti1, Francesca Vignani1, Lucianna Russo1, Valentina Bertaglia1, Mattia Tullio1, Marcello Tucci1, Massimiliano Poggio2, Luigi Dogliotti11Oncologia Medica, 2Urologia, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliero Universitaria San Luigi, Orbassano, ItalyAbstract: Neuroendocrine (NE) differentiation is a common feature in prostate cancer (PC). The clinical significance of this phenomenon is controversial; however preclinical and clinical data are in favor of an association with poor prognosis and early onset of a castrate resistant status. NE PC cells do not proliferate, but they can stimulate the proliferation of the exocrine component through the production of paracrine growth factors. The same paracrine signals may favor the outgrowth of castrate adapted tumors through androgen receptor dependent or independent mechanisms. Noteworthy, NE differentiation in PC is not a stable phenotype, being stimulated by several agents including androgen deprivation therapy, radiation therapy, and chemotherapy. The proportion of NE positive PC, therefore, is destined to increase during the natural history of the disease. This may complicate the assessment of the prognostic significance of this phenomenon. The majority of clinical studies have shown a significant correlation between NE differentiation and disease prognosis, confirming the preclinical rationale. In conclusion the NE phenotype is a prognostic parameter in PC. Whether this phenomenon is a pure prognostic factor or whether it can influence the prognosis by favoring the onset of a castrate resistance status is a matter of future research.Keywords: prostate cancer, prognosis, neuroendocrine differentiation

Armand Morel, Denis Talbot1Department of Medical Oncology, University of Oxford, Oxford, Oxfordshire, UKAbstract: Urothelial carcinoma (UC) accounts for 5% to 10% of malignancies in men in Europe and the United States. For locally advanced or metastatic disease, there are two standard firstline chemotherapy regimens: MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) and gemcitabine/cisplatin. For refractory disease, there is currently no standard treatment. Vinflunine, a second-generation Vinca alkaloid, is the first chemotherapeutic agent to be evaluated in a large UC second-line population. This review discusses the pre-clinical and clinical data published, and compares vinflunine to alternative single agents and combination regimens tested in this setting. Based on the results of the phase II and III clinical trials, there appears to be sufficient evidence to support the use of vinflunine in the second-line setting.Keywords: vinflunine, Vinca alkaloid, urothelial carcinoma, transitional cell carcinoma, bladder cancer

G Willy DavilaDepartment of Gynecology, Cleveland Clinic Florida, Weston, Florida, USAAbstract: Overactive bladder (OAB), often accompanied by urinary incontinence, is most prevalent among the elderly, but also affects many middle-aged men and women in the US. OAB may severely impair quality of life, and its overall economic costs to society are substantial. Although antimuscarinic agents relieve OAB symptoms effectively, treatment persistence generally is low. This has been attributed in part to the occurrence of dry mouth and other anticholinergic adverse events. High plasma concentrations of N-desethyloxybutynin (DEO), an active metabolite of oxybutynin, have been identified as the major cause of anticholinergic adverse effects associated with oral oxybutynin. Transdermal formulations of oxybutynin generate much lower DEO plasma concentrations compared with oral formulations. In a placebo-controlled US Phase III study in patients with OAB, the recently approved oxybutynin topical gel (OTG) was efficacious and well tolerated. Dry mouth occurred in 6.9% of patients treated with OTG and 2.8% of patients on placebo. Incidences of other anticholinergic events were low and similar for OTG and placebo. OTG rarely caused application site skin reactions. OTG provides significant benefits to patients with OAB, particularly those who are sensitive to anticholinergic adverse effects.Keywords: overactive bladder, oxybutynin topical gel, antimuscarinic, urinary urgency, incontinence

Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC). Intravesical bacillus Calmette-Guerin (BCG) is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin) have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel), and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

Mathew C Raynor, Raj S PruthiDivision of Urologic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: The past decade has seen a dramatic shift in the surgical management of certain urologic conditions with the advent of a robotic surgical platform. In fact, the surgical management of prostate cancer has seen the most dramatic shift, with the majority of cases now being performed robotically. Technical refinements over the years have led to improved outcomes regarding oncologic and functional results. Recently, robotic surgery has also been utilized for the surgical management of bladder cancer, renal cancer, and other benign conditions. As further experience is gained and longer-term outcomes are realized, robotic surgery will likely play an increasing role in the surgical management of many urologic conditions.Keywords: robot-assisted surgery, robotic surgery, cystectomy, prostatectomy, partial nephrectomy

Alvaro C Ucero1,*, Sara Gonçalves2,*, Alberto Benito-Martin1, Beatriz Santamaría1, Adrian M Ramos1, Sergio Berzal1, Marta Ruiz-Ortega1, Jesus Egido1, Alberto Ortiz11Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain; 2Nefrologia e Transplantação Renal, Hospital de Santa Maria EPE, Lisbon, Portugal*Both authors contributed equally to the manuscriptAbstract: Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.Keywords: urinary tract obstruction, renal injury, fluid mechanics, molecular cell biology

Boris Chertin1, Dan Prat1, Ofer Z Shenfeld21Division of Pediatric Urology, 2Department of Urology, Shaare Zedek Medical Center, Jerusalem, Faculty of Medical Science, Hebrew University, Jerusalem, IsraelPurpose: To review the evolution of the technique of hypospadias repair.Methods: A search of Pubmed, Medline and the Journal of Pediatric Urology was performed, and papers dealing with surgical techniques for hypospadias repair were critally reviewed. Special emphasis was given to papers on the effects in the long term of hypospadias repair on voiding and sexual dysfunction.Results: The techniques for hypospadias repair have evolved over the years. The most popular technique now is tubularized incised plate urethroplasty. Long-term results with the use of the new techniques of the hypospadias repair in terms of voiding and sexual problems should be addressed.Conclusion: There is a need for valid studies on the outcomes of hypospadias repair in adults that were performed in childhood in terms of cosmetic appearance, voiding and sexual performance.Keywords: hypospadias, hypospadias surgery, adult, later outcome

Harry A DrabkinMedical University of South Carolina and Hollings Cancer Center, Charleston, SC, USAAbstract: Pazopanib (VotrientTM, GlaxoSmithKline), a multi-kinase inhibitor with activity against VEGFR and other receptors, was recently approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). Here, we review the history of its development, together with an overview of VEGF and its receptors and co-receptors. Results from selected clinical trial data in RCC and other malignant diseases are presented. Based on available evidence, pazopanib is an effective VEGFR inhibitor with demonstrable clinical activity in metastatic RCC and promising activity in other diseases. Like most kinase inhibitors, its activity is not restricted to VEGF receptors, which is reflected in its side-effect profile.Keywords: pazopanib, VEGFR, renal cell carcinoma

Emilio Sacco, Daniele Tienforti, Alessandro D’Addessi, Francesco Pinto, Marco Racioppi, Angelo Totaro, Daniele D’Agostino, Francesco Marangi, Pierfrancesco Bassi Urologic Clinic, Department of Surgery, “Agostino Gemelli”, Hospital, Catholic University Medical School, Rome, ItalyAbstract: Overactive bladder (OAB) is a highly prevalent urinary syndrome with a profound impact on quality of life (QoL) of affected patients and their family because of its adverse effects on social, sexual, interpersonal, and professional function. Cost-of-illness analyses showed the huge economic burden related to OAB for patients, public healthcare systems, and society, secondary to both direct and indirect costs; however, intangible costs related to QoL impact are usually omitted from these analyses. Recently many novel treatment modalities have been introduced and the need to apply the modern methodology of health technology assessment to these treatment strategies was immediately clear in order to evaluate objectively their value in terms of both improvement in length/quality of life and costs. Health utilities are instruments that allow a measurement of QoL and its integration in the economic evaluation using the quality-adjusted life-years model and cost-utility analysis. The development of suitable instruments for quantifying utility in the specific group of OAB patients is vitally important to extend the application of cost-utility analysis in OAB and to guide healthcare resources allocation for this disorder. Studies are required to define the cost-effectiveness of available pharmacological and nonpharmacological therapy options for this disorder.Keywords: overactive bladder, burden, health utility, cost-utility

Alexandra Karadimou, Meletios A Dimopoulos, Aristotle Bamias Dept of Clinical Therapeutics, University of Athens Medical School, Athens, Greece Abstract: Testicular cancer is a highly curable neoplasm, even in the case of extragonadal disease. Nevertheless, patients with adverse prognostic features or relapsing after first-line cisplatin-based chemotherapy have a worse prognosis with a death rate greater than 50%. Highdose chemotherapy (HDC) has long been used in this group of patients. The introduction of stem cells, instead of bone marrow, as the source of hemopoietic cells and the use of leukocyte growth factors have substantially reduced the mortality and morbidity of this procedure although the role of HDC is not well defined. This review summarizes the available data, focusing on published randomized studies. The problems associated with the design of these studies and the interpretation of data are discussed. Currently this HDC approach is mainly used in patients who relapse after first-line chemotherapy. Nevertheless, selection of patients likely to benefit from this treatment remains an issue of intense clinical research.Keywords: high-dose chemotherapy, testicular cancer, salvage therapy

Michael L Eisenberg1, Keith L Lee1, BenjaminN Breyer1, Thomas J Walsh2, Badrinath R Konety1, Marshall L Stoller11Department of Urology, University of California San Francisco, San Francisco, CA, USA; 2Department of Urology, University of Washington, Seattle, WA, USAObjectives: Many patients present with bilateral stones. There is a unique group of patients, however, that presents with stones exclusively on one side. We hypothesize that in such situations, 24-hour urine collections may not reveal specific defects on the affected stone-bearing kidney. We therefore evaluated selective 12-hour urine collections after percutaneous nephrolithotomy (PNL) to help determine if there is differential renal excretion.Methods: We collected urine specimens from patients with nephrolithiasis who underwent unilateral PNL. Urine samples were collected and analyzed from nephrostomy tubes, representing the affected kidneys, and from Foley bladder catheters, representing the contralateral mate kidney.Results: Thirty-one patients were studied (14 with unilateral nephrolithiasis and 17 with bilateral). Treated kidneys from patients with unilateral nephrolithiasis displayed lowered urine excretion of uric acid, sodium, chloride, calcium, and total osmoles when compared to patients with bilateral nephrolithiasis. Stone size and length of procedure were not predictive of urine composition after PNL.Conclusions: Treated kidneys from patients with a history of unilateral stone disease revealed marked differences in urine excretion compared to those with bilateral nephrolithiasis after unilateral PNL. These findings could be secondary to the surgical insult, urinary stone disease, or could be a responsible factor for stone pathogenesis.Keywords: percutaneous nephrolithotomy, kidney, stone, nephrolithiasis

Tomonori Yamanishi1, Tomoya Mizuno1, Takao Kamai1, Ken-ichiro Yoshida1, Ryuji Sakakibara2, Tomoyuki Uchiyama31Department of Urology, Dokkyo Medical University, Tochigi, Japan; 2Department of Neurology, Sakura Hospital, Toho University, Toho, Japan; 3Department of Neurology, Chiba University, Chiba, JapanAbstract: It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B- and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia.Keywords: alpha-blocker, silodosin, benign prostatic hyperplasia, lower urinary tract symptoms

Karan Wadhwa, Raj Singh, Lemke Z SolomonDepartment of Urology, Queen Alexandra Hospital, Portsmouth, UKAbstract: A 69-year-old man presented with sudden onset of macroscopic hematuria. While an ultrasound of the bladder revealed a posterior bladder mass, subsequent flexible cystoscopy demonstrated only an area of irregular urothelium. Initial general anesthetic cytoscopy and biopsy revealed conventional G2/3 T1 TCC. Histology of a further formal resection of this irregular area revealed carcinoma-in-situ and population of atypical cells with enlarged nuclei, prominent nucleoli, and varying quantities of cytoplasm showing plasma cell features. The immunohistochemistry was consistent with a plasmacytoma. There must be a high index of suspicion when ultrasound demonstrates a mass not detected by flexible cystoscopy, and biopsies/resection are advised to exclude extramedullary plasmacytoma (EMP) as the cause. EMP of the urinary bladder is a rare entity with only 21 cases reported in the literature. In this report we describe a further case of EMP of the bladder associated with synchronous transitional cell carcinoma (TCC) of the urothelium. We also highlight the important histopathological findings and review the current literature to report the outcomes of existing approaches to management of this rare form of bladder cancer. We believe this to be the first case reported in which a patient presented concurrently with bladder EMP and urothelial TCC. EMPs are highly radiosensitive tumors and in the case of head/neck disease, survival at 10 years is in the order of 65% following radical radiotherapy. Given the paucity of reported cases of primary bladder EMP, the optimal treatment regime remains unclear. In keeping with other anatomical sites current treatment is based to the assumed benefit of radical radiotherapy and prognosis appears to be better in those with no evidence of systemic disease.Keywords: bladder cancer, extramedullary plasmacytoma, urothelial transitional cell carcinoma

Tanweer Karim, Margaret Topno, Vinod Sharma, Raymond Picardo, Ankur HastirSurgery, MGM Medical College, Kamothe, Navi Mumbai, IndiaAbstract: Bladder injuries are very common in patients who have had road traffic accidents. The method of diagnosis and management of such injuries is well established and accepted. However, trauma to the bladder can be associated with other life-threatening injuries which are frequently missed, and often diagnosed during laparotomy for other reasons. The aim of this study was to diagnose bladder injury in polytrauma patients as early as possible, taking into consideration the fact that these patients are hemodynamically unstable and require rapid evaluation and management. In order to achieve our objective, we used bedside sonography with retrograde instillation of normal saline to diagnose bladder injury in addition to use of the conventional retrograde cystogram.Keywords: bladder injury, bladder rupture, retrograde cystogram

Kylie J MansfieldGraduate School of Medicine, University of Wollongong, NSW, AustraliaAbstract: Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Improvements in health related quality of life following treatment with fesoterodine is indicated by improvements in 7 of the 9 variables measured by the King’s Health Questionnaire. Also like other antimuscarinic agents, fesoterodine use is associated with adverse events including dry mouth. However the incidence of dry mouth is reduced with fesoterodine, compared to oxybutynin, due to the improved bladder selectivity of 5-HMT.Keywords: fesoterodine, 5-hydroxymethyl-tolterodine, muscarinic, overactive bladder, urgency, incontinence

Alex Gomelsky1, Roger R Dmochowski21Department of Urology, Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA, USA; 2Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USAAbstract: Overactive bladder (OAB) is a common condition that causes a profound impact on an individual’s overall health and quality of life. Muscarinic receptor antagonists are the mainstay of oral pharmacotherapy for OAB. Although all of the medications in this class are significantly more effective than placebo, they are also associated with more adverse events that may limit their overall use. Although newer preparations of these medications have sought to improve tolerability and efficacy through alternative routes of delivery and once-daily dosing, improved adherence to treatment and treatment persistence continue to be an ongoing challenge. An improved understanding of the factors involved in persistence of medical OAB therapy is imperative in efforts to optimize therapeutic benefits in this chronic and potentially morbid condition.Keywords: adherence, overactive bladder, antimuscarinic receptor antagonists

Janet ColliDepartment of Urology, Tulane University School of Medicine, New Orleans, LA, USAThis is the third year of publication of Open Access Journal of Urology, and I am enthusiastic about the future prospects of this journal. As science and technology becomes increasingly complex, researchers require methods to improve efficiencies.

OFN Ozoemena1, JO Ezugworie2, AU Mbah3, EA Esom4, BO Ayogu5, FE Ejezie61Department of Anatomy and Surgery, 2Department of Obstetrics and Gynecology, 3Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria Teaching Hospital, 4Department of Anatomy, College of Medicine, University of Nigeria Enugu Campus; 5Urology Unit, Department of Surgery, University of Nigeria Teaching Hospital, Ituku/Ozalla; 6Department of Medical Biochemistry, College of Medicine, University of Nigeria, Enugu Campus, Enugu, NigeriaBackground: Hormonal derangements potentially contribute to the diagnosis of infertility in over 60%–70% of couples investigated. Use of hormonal and antihormonal agents has achieved great success in the treatment of male infertility. Our aim was to investigate the prevalence of hormonal abnormalities in males diagnosed with infertility.Methods: Males diagnosed clinically with infertility and referred from the gynecologic clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu State University Teaching Hospital, and some private hospitals in and around Enugu metropolis were recruited for the study. They were grouped according to whether they had primary or secondary infertility on the basis of the World Health Organization definition. Routine fertility test profiles for the subjects were evaluated, and detailed hormonal assays were analyzed.Results: Of 216 men, 173 (80.1%) were found to have a hormonal imbalance. The mean age was 47.7 ± 3.5 (range 30–55) years for primary infertility and 47.2 ± 6.8 (range 33–61) years for secondary infertility. Patterns of hormonal abnormalities diagnosed amongst the 62 (35.80%) primary infertility subjects included hypergonadotrophic hypogonadism in 39 (62.90%), hypogonadotrophic hypogonadism in 18 (29.03%), and hyperprolactinemia in five (8.07%). Among the 111 (64.2%) cases of secondary infertility, there were 55 (49.55%) cases of hypergonadotrophic hypogonadism, 52 (46.85%) of hypogonadotrophic hypogonadism, and four (3.60%) of hyperprolactinemia. There was no statistically significant difference in the mean values between the two groups (χ2 < 1.414; P > 0.05) for hormonal indices.Conclusion: The hormonal profile should be considered as the gold standard for diagnosis and management of male infertility.Keywords: infertility, hormonal indices, males

Prostate cancer is among the most common types of cancer and causes of cancer-related deaths in men worldwide.1 Capsular transgression of prostatic tumors or relapse following radical prostatectomy results in a worse prognosis.2 Treatment consists of hormonal manipulation to deprive the cancer cells of androgenic growth stimulation either by orchidectomy or use of luteinizing hormone-releasing hormone (LHRH) analogs and steroidal or nonsteroidal antiandrogens, respectively.3 Androgen suppression (AS) is conventionally performed as a continuous treatment and leads to apoptotic regression of the tumor cells in the majority of cases. However, surgical or medical castration results in median progression-free survival of only two to three years with treatment options of limited efficacy remaining.4 Responses to cytotoxic therapy are low, and only recently has a possible benefit of incorporating chemotherapeutic agents in treatment regimen for prostate cancer been highlighted.5 Continuous androgen suppression therapy (CAS) may be counterproductive in the long term due to accelerated selection of androgen-independent tumor cell populations.6 In contrast, hormone dependence is maintained in intermittent androgen suppression therapy (IAS) owing to the availability of low levels of testosterone. Therefore, IAS was proposed as a new clinical concept, assuming that during limited regrowth in treatment cessation periods tumorigenic stem cells are residing in an androgen-responsive state.7 Since then, regrowing tumors in IAS patients were consistently shown to be sensitive to several cycles of androgen withdrawal and IAS to result in improved quality of life.7,8 A total of 140 patients were recruited since we initiated an IAS study at our institution in 1993, with the first patients reaching their seventh IAS cycle.9 Meanwhile, IAS has been established as a therapy seeming equivalent to CAS, leading to IAS being proposed as a standard therapy for progressing prostate cancer.10,11 The amelioration of side effects of CAS achieved by regular treatment cessations in IAS, as reported in quality of life assessments so far, however, needs further clinical evaluation. CAS leads to increased incidence of osteoporosis and concomitant bone fractures.12 Therefore, it was expected that the off-treatment periods during IAS would allow for recovery of testosterone levels and cessation of bone material degradation. Higano et al13 observed loss of bone mass density (BMD) after nine months of AS at a significantly greater rate than the expected 0.5%–1% annual loss, although interruption of AS attenuated the rate of bone loss without full recovery. In the present study levels of CrossLaps, a degradation product of collagen I, were analyzed retrospectively in serum samples to characterize bone metabolism during IAS.14

Jacob Grinfeld, Akimichi Inaba, Alastair J HutchisonManchester Institute of Nephrology and Transplantation, The Royal Infirmary, Manchester, UK Abstract: Sevelamer (Renagel and Renvela), is an orally administered weakly basic anion exchange resin that binds dietary phosphate in the gastrointestinal tract, and is approved for use in the US, Europe and many other countries for the treatment of hyperphosphatemia in adult patients on hemodialysis or peritoneal dialysis. Clinical evidence shows that sevelamer is at least as effective as calcium-based oral phosphate binders in controlling serum phosphate, but with a lower incidence of hypercalcemia. Whilst sevelamer hydrochloride is associated with mild acidosis, sevelamer carbonate does not have this drawback. Use of sevelamer and avoidance of calcium-based binders may slow the progression of vascular calcification in hemodialysis patients, and it also reduces serum low-density lipoprotein-cholesterol levels. There was no between-group difference in all-cause mortality between sevelamer and calcium-based phosphate binder therapy in the primary efficacy analysis of the large (n >2100), 3-year DCOR trial. In the smaller (n = 109) nonblind RIND trial in patients new to hemodialysis, data suggest there may be an overall survival benefit with sevelamer versus calcium-based phosphate binder treatment but the evidence on the efficacy of sevelamer in reducing mortality and hospitalization is not strong. The balance of evidence, however, does not strongly support the use of sevelamer over the much less costly calcium-based binders except in patients at risk of hypercalcemic episodes. Further research into cardiovascular and all-cause mortality over a longer time period would be needed to settle this issue, and the relative survival benefits and cost effectiveness of all phosphate binder therapies remains to be fully determined. Despite the relative paucity of data available, sevelamer has established itself as the most widely used binder in the United States and the most widely used noncalcium-based binder worldwide. However, affordability is a major issue for most health economies and in the light of recent economic events is likely to become more prominent.Keywords: sevelamer, phosphate, phosphorus, binder, dialysis, vascular calcification