HO-1 mitigates acute kidney injury and subsequent kidney-lung cross-talk.

Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). IRI-induced AKI releases proinflammatory cytokines (e.g. IL-1ß, TNF-α, IL-6) that induce a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage. AKI is associated with poor outcomes, particularly when extrarenal complications or distant organ injuries occur. Acute lung injury (ALI) is a major remote organ dysfunction associated with AKI. Hence, kidney-lung cross-talk remains a clinical challenge, especially in critically ill population. The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against renal IRI and may be preventively induced using hemin prior to renal insult. However, the use of hemin-induced HO-1 to prevent AKI-induced ALI remains poorly investigated. Mice received an intraperitoneal injection of hemin or sterile saline 1 day prior to surgery. Twenty-four hours later, mice underwent bilateral renal IRI for 26 min or sham surgery. After 4 or 24 h of reperfusion, mice were sacrificed. Hemin-induced HO-1 improved renal outcomes after IRI (i.e. fewer renal damage, renal inflammation, and oxidative stress). This protective effect was associated with a dampened systemic inflammation (i.e. IL-6 and KC). Subsequently, mitigated lung inflammation was found in hemin-treated mice (i.e. neutrophils influx and lung KC). The present study demonstrates that hemin-induced HO-1 controls the magnitude of renal IRI and the subsequent AKI-induced ALI. Therefore, targeting HO-1 represents a promising approach to prevent the impact of renal IRI on distant organs, such as lung.

Dual effect of hemin on renal ischemia-reperfusion injury.

Acute kidney injury (AKI) is a major public health concern, which is contributing to serious hospital complications, chronic kidney disease (CKD) and even death. Renal ischemia-reperfusion injury (IRI) remains a leading cause of AKI. The stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against renal IRI and may be preventively induced using hemin prior to renal insult. This HO-1 induction pathway called hemin preconditioning is largely known to be effective. Therefore, HO-1 might be an interesting therapeutic target in case of predictable AKI (e.g. partial nephrectomy or renal transplantation). However, the use of hemin to mitigate established AKI remains poorly characterized. Mice underwent bilateral renal IRI for 26 min or sham surgery. After surgical procedure, animals were injected either with hemin (5 mg/kg) or vehicle. Twenty-four hours later, mice were sacrificed. Despite strong HO-1 induction, hemin-treated mice exhibited significant renal damage and oxidative stress as compared to vehicle-treated mice. Interestingly, higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. To determine whether hemin preconditioning remains efficient to dampen postoperative hemin-amplified IRI-induced AKI, we pretreated mice either with hemin (5 mg/kg) or vehicle 24 h prior to surgical procedure. Then, all mice (hemin- and vehicle-pretreated) received postoperative injection of hemin (5 mg/kg) to amplify IRI-induced AKI. In comparison to vehicle, prior administration of hemin to renal IRI mitigated hemin-amplified IRI-induced AKI as attested by fewer renal damage, inflammation and oxidative stress. In conclusion, hemin may have a dual effect on renal IRI, protective or deleterious, depending on the timing of its administration.

Spinal Cord Injury Following Antegrade Scrotal Sclerotherapy for Varcicocele: A Case Report.

Varicocele is one of the causes of male infertility. Treatment aims to improve the chance of conception despite lasting controversies about benefits of varicocele repair on fertility. Many techniques have been described for varicocele management including the antegrade scrotal sclerotherapy (ASS). Interestingly, ASS is often presented as a safe, easy, and cost-effective procedure with low recurrence and complication rates. However, we report the first case of spinal cord paralysis following ASS probably due to embolization of venous anastomoses between left spermatic and ascending lumbar veins, which were undetected at preoperative phlebography. Based on this case and recent literature, we raise questions about the safety of ASS and try to figure out what would be the best way to improve the detectability of potential harmful anastomoses at preoperative phlebography.

Relationship between oxidative stress and erectile function.

The aim of this study was to investigate markers of inflammation and oxidative stress in the corpus cavernosum (CC) and to compare levels of inflammatory markers recorded in CC to venous blood from the arm to examine the potential impact of inflammatory parameters on erectile function and endothelial dysfunction in vitro. Ninety-seven patients with no complaint of erectile dysfunction (ED) at inclusion were prospectively included and completed the Erectile Function domain of the IIEF questionnaire. Several parameters, including lipids, MPO-dependent oxidised LDL (Mox-LDL), IL-8, IL-18, were measured. After RNA extraction, the expression of eNOS was analysed. A paired t-test was used for comparisons between arm and CC blood results. A two-way ANOVA was used to estimate the effects of IL-18 and IL-8 on the IIEF score. Mean patient age was 59 ± 14.5 years. IL-18, Mox-LDL, and Mox-LDL/ApoB levels were significantly increased in CC compared to arm blood. The IIEF score was correlated with IL-18 levels in the venous blood (R = -0.31, p = .003) and in the CC (R = -0.37, p = .004) and with IL-8 (R = -0.31, p = .009 and R = -0.28, respectively, p = .02). There was a significant effect with the IL-18 on IIEF potentiated by high serum IL-8 concentrations. IL-18 and Mox-LDL significantly decreased eNOS mRNA expression in human aortic endothelial cell line (HAEC). These preliminary results address the importance of inflammation in the CC and highlight a difference in marker concentrations between venous and CC blood. However, they do not show any difference in terms of clinical erectile score predictivity. Involvement of inflammatory cytokines isolated in CC in the genesis of ED requires further studies.

European Association of Urology guidelines on priapism.

CONTEXT: Priapism is defined as a penile erection that persists beyond or is unrelated to sexual interest or stimulation. It can be classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent or intermittent). OBJECTIVE: To provide guidelines on the diagnosis and treatment of priapism. EVIDENCE ACQUISITION: Systematic literature search on the epidemiology, diagnosis, and treatment of priapism. Articles with highest evidence available were selected to form the basis of these recommendations. EVIDENCE SYNTHESIS: Ischaemic priapism is usually idiopathic and the most common form. Arterial priapism usually occurs after blunt perineal trauma. History is the mainstay of diagnosis and helps determine the pathogenesis. Laboratory testing is used to support clinical findings. Ischaemic priapism is an emergency condition. Intervention should start within 4-6h, including decompression of the corpora cavernosa by aspiration and intracavernous injection of sympathomimetic drugs (e.g. phenylephrine). Surgical treatment is recommended for failed conservative management, although the best procedure is unclear. Immediate implantation of a prosthesis should be considered for long-lasting priapism. Arterial priapism is not an emergency. Selective embolization is the suggested treatment modality and has high success rates. Stuttering priapism is poorly understood and the main therapeutic goal is the prevention of future episodes. This may be achieved pharmacologically, but data on efficacy are limited. CONCLUSIONS: These guidelines summarise current information on priapism. The extended version are available on the European Association of Urology Website (www.uroweb.org/guidelines/). PATIENT SUMMARY: Priapism is a persistent, often painful, penile erection lasting more than 4h unrelated to sexual stimulation. It is more common in patients with sickle cell disease. This article represents the shortened EAU priapism guidelines, based on a systematic literature review. Cases of priapism are classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent). Treatment for ischaemic priapism must be prompt in order to avoid the risk of permanent erectile dysfunction. This is not the case for arterial priapism.

Validation of use of the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) for impairment rating: a transversal retrospective study of 120 patients.

AIMS: A urinary incontinence impairment rating must be a highly accurate, non-invasive exploration of the condition using International Classification of Functioning (ICF)-based assessment tools. The objective of this study was to identify the best evaluation test and to determine an impairment rating model of urinary incontinence. METHODS: In performing a cross-sectional study comparing successive urodynamic tests using both the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) and the 1-hr pad-weighing test in 120 patients, we performed statistical likelihood ratio analysis and used logistic regression to calculate the probability of urodynamic incontinence using the most significant independent predictors. Subsequently, we created a template that was based on the significant predictors and the probability of urodynamic incontinence. RESULTS: The mean ICIQ-UI-SF score was 13.5 ± 4.6, and the median pad test value was 8 g. The discrimination statistic (receiver operating characteristic) described how well the urodynamic observations matched the ICIQ-UI-SF scores (under curve area (UDA):0.689) and the pad test data (UDA: 0.693). Using logistic regression analysis, we demonstrated that the best independent predictors of urodynamic incontinence were the patient's age and the ICIQ-UI-SF score. The logistic regression model permitted us to construct an equation to determine the probability of urodynamic incontinence. Using these tools, we created a template to generate a probability index of urodynamic urinary incontinence. CONCLUSIONS: Using this probability index, relative to the patient and to the maximum impairment of the whole person (MIWP) relative to urinary incontinence, we were able to calculate a patient's permanent impairment.

EAU guidelines on penile curvature.

CONTEXT: Penile curvature can be congenital or acquired. Acquired curvature is secondary due to La Peyronie (Peyronie's) disease. OBJECTIVE: To provide clinical guidelines on the diagnosis and treatment of penile curvature. EVIDENCE ACQUISITION: A systematic literature search on the epidemiology, diagnosis, and treatment of penile curvature was performed. Articles with the highest evidence available were selected and formed the basis for assigning levels of evidence and grades of recommendations. EVIDENCE SYNTHESIS: The pathogenesis of congenital penile curvature is unknown. Peyronie's disease is a poorly understood connective tissue disorder most commonly attributed to repetitive microvascular injury or trauma during intercourse. Diagnosis is based on medical and sexual histories, which are sufficient to establish the diagnosis. Physical examination includes assessment of palpable nodules and penile length. Curvature is best documented by a self-photograph or pharmacologically induced erection. The only treatment option for congenital penile curvature is surgery based on plication techniques. Conservative treatment for Peyronie's disease is associated with poor outcomes. Pharmacotherapy includes oral potassium para-aminobenzoate, intralesional treatment with verapamil, clostridial collagenase or interferon, topical verapamil gel, and iontophoresis with verapamil and dexamethasone. They can be efficacious in some patients, but none of these options carry a grade A recommendation. Steroids, vitamin E, and tamoxifen cannot be recommended. Extracorporeal shock wave treatment and penile traction devices may only be used to treat penile pain and reduce penile deformity, respectively. Surgery is indicated when Peyronie's disease is stable for at least 3 mo. Tunical shortening procedures, especially plication techniques, are the first treatment options. Tunical lengthening procedures are preferred in more severe curvatures or in complex deformities. Penile prosthesis implantation is recommended in patients with erectile dysfunction not responding to pharmacotherapy. CONCLUSIONS: These European Association of Urology (EAU) guidelines summarise the present information on penile curvature. The extended version of the guidelines is available on the EAU Web site (www.uroweb.org/guidelines/).

Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation.

CONTEXT: Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions. OBJECTIVE: To present the updated version of 2009 European Association of Urology (EAU) guidelines on ED and PE. EVIDENCE ACQUISITION: A systematic review of the recent literature on the epidemiology, diagnosis, and treatment of ED and PE was performed. Levels of evidence and grades of recommendation were assigned. EVIDENCE SYNTHESIS: ED is highly prevalent, and 5-20% of men have moderate to severe ED. ED shares common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to the patient's complaints and risk factors. Treatment is based on phosphodiesterase type 5 inhibitors (PDE5-Is), including sildenafil, tadalafil, and vardenafil. PDE5-Is have high efficacy and safety rates, even in difficult-to-treat populations such as patients with diabetes mellitus. Treatment options for patients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracavernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penile prosthesis. PE has prevalence rates of 20-30%. PE may be classified as lifelong (primary) or acquired (secondary). Diagnosis is based on medical and sexual history assessing intravaginal ejaculatory latency time, perceived control, distress, and interpersonal difficulty related to the ejaculatory dysfunction. Physical examination and laboratory testing may be needed in selected patients only. Pharmacotherapy is the basis of treatment in lifelong PE, including daily dosing of selective serotonin reuptake inhibitors and topical anaesthetics. Dapoxetine is the only drug approved for the on-demand treatment of PE in Europe. Behavioural techniques may be efficacious as a monotherapy or in combination with pharmacotherapy. Recurrence is likely to occur after treatment withdrawal. CONCLUSIONS: These EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site (http://www.uroweb.org/nc/professional-resources/guidelines/online/).

Anatomy, physiology, and pathophysiology of erectile dysfunction.

INTRODUCTION: Significant scientific advances during the past 3 decades have deepened our understanding of the physiology and pathophysiology of penile erection. A critical evaluation of the current state of knowledge is essential to provide perspective for future research and development of new therapies. AIM: To develop an evidence-based, state-of-the-art consensus report on the anatomy, physiology, and pathophysiology of erectile dysfunction (ED). METHODS: Consensus process over a period of 16 months, representing the opinions of 12 experts from seven countries. MAIN OUTCOME MEASURE: Expert opinion was based on the grading of scientific and evidence-based medical literature, internal committee discussion, public presentation, and debate. RESULTS: ED occurs from multifaceted, complex mechanisms that can involve disruptions in neural, vascular, and hormonal signaling. Research on central neural regulation of penile erection is progressing rapidly with the identification of key neurotransmitters and the association of neural structures with both spinal and supraspinal pathways that regulate sexual function. In parallel to advances in cardiovascular physiology, the most extensive efforts in the physiology of penile erection have focused on elucidating mechanisms that regulate the functions of the endothelium and vascular smooth muscle of the corpus cavernosum. Major health concerns such as atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic syndrome (MetS) have become well integrated into the investigation of ED. CONCLUSIONS: Despite the efficacy of current therapies, they remain insufficient to address growing patient populations, such as those with diabetes and MetS. In addition, increasing awareness of the adverse side effects of commonly prescribed medications on sexual function provides a rationale for developing new treatment strategies that minimize the likelihood of causing sexual dysfunction. Many basic questions with regard to erectile function remain unanswered and further laboratory and clinical studies are necessary.

Effects of phosphodiesterase inhibitors on the inflammatory response of endothelial cells stimulated by myeloperoxidase-modified low-density lipoprotein or tumor necrosis factor alpha.

BACKGROUND: Sildenafil, vardenafil, and tadalafil are phosphodiesterase type 5 inhibitors (PDE5-Is) usually used in the treatment of erectile dysfunction (ED). Previously, we have shown the presence of myeloperoxidase-modified low-density lipoprotein (Mox-LDL) in the penises of patients with ED, and we have shown the impact of Mox-LDL on cyclic monophosphate (cGMP) level. In vitro, Mox-LDL triggered the inflammatory response by increasing the release of both interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) by endothelial cells (ECs) and monocytes respectively. OBJECTIVE: To determine whether or not the three therapeutically PDE5-Is protect against the proinflammatory effects of Mox-LDL or TNF-alpha on ECs. DESIGN, SETTING, AND PARTICIPANTS: ECs (EA.hy926) were incubated in the presence of either TNF-alpha (100 pg/ml) or Mox-LDL (200 microg/ml) with each of the three PDE5-Is (1 microM, 5 microM, and 10 microM) respectively. IL-8 production was measured in the supernatant after 48 h of incubation. MEASUREMENTS: All experiments were repeated at least three times. Statistical analysis was performed with an ANOVA. RESULTS AND LIMITATIONS: Two-way ANOVA analysis showed that TNF-alpha alone (p<0.001) or Mox-LDL alone (p<0.001) increased IL-8 production. Sildenafil, vardenafil, or tadalafil alone did not generate an increase of IL-8 production. Tadalafil in combination with Mox-LDL and TNF-alpha showed a decrease of IL-8 (p<0.05) compared with sildenafil and vardenafil. CONCLUSIONS: Among the three available PDE5-Is, tadalafil showed an additional potentially anti-inflammatory effect on relaxation. Those data could be considered for the chronic use of PDE5-Is, but extrapolations of experimental evidence to the clinical setting should be made cautiously.

Is there a rationale for the chronic use of phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia?

OBJECTIVES: To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations. METHODS: We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported. RESULTS: Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported. CONCLUSIONS: There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.

Expression of MUC1 and sialyl-Tn in benign prostatic glands, high-grade prostate intraepithelial neoplasia and malignant prostatic glands: a preliminary study.

OBJECTIVE: To postulate a possible role of MUC1 and sialylated mucins (sTn) in prostate malignancy. STUDY DESIGN: One sample histologic paraffin block of 24 radical prostatectomies was selected for presence of both benign and malignant glands; 17 samples also included PIN. Serial cuts were stained with MUC1 and sTn mouse monoclonal antibodies. Description and percentage of cell expression for MUC1 and sTn antibodies were obtained by light microscopy. RESULTS: MUC1 immunostaining was more often positive for neoplastic cells, progressively from benign (4.7+/-5.3%) to PIN (27.1+/-19.7%) and malignant glands (34.5+/-28.4%). The same observation was made for sTn, respectively, from 3.9+/-4.9% to 54.8+/-26.1% and 62.8+/-25.6%. Both antibodies showed a statistical difference between benign glands and PIN or malignant glands but not between PIN and malignant. CONCLUSION: MUC1 and sTn were expressed more intensely in PIN and malignant prostate glands than in benign glands. sTn seemed more specific in favor of cell malignancy.

Laparoscopic partial nephrectomy with "on-demand" clamping reduces warm ischemia time.

OBJECTIVES: To investigate the impact of "on-demand" clamping during laparoscopic partial nephrectomy on warm ischemia time. METHODS: We retrospectively reviewed 39 consecutive patients with renal tumors who had undergone transperitoneal laparoscopic partial nephrectomy from April 2002 to May 2006. Median tumor size was 2.3 cm. In all cases, the hilum was dissected early and extracorporeal clamping performed. The pedicle was clamped only in case of excessive bleeding, and it was released immediately after the closure of the renal defect with knot-tying sutures over Surgicel bolsters. RESULTS: Median operative time was 120 min. Renal clamping was required in 31 of 39 patients and in this subgroup the median warm ischemia time was 9 min. Median operative blood loss was 150 ml. Eight patients required blood transfusion and among these two were converted to open surgery. Positive surgical margin was observed in one case. Renal cell carcinoma was present in 22 (54.4%) specimens. No recurrence was observed after a median follow-up of 15 mo. CONCLUSIONS: This novel technique using extracorporeal clamping significantly decreases warm ischemia time, avoiding clamping of the pedicle in selected cases. Our study underlines the feasibility of performing laparoscopic partial nephrectomy with extracorporeal hilar clamping, allowing the shortest ischemia time ever published.

[Laparoscopic radical nephrectomy for a tumor in a horseshoe kidney]. / Néphrectomie elargie par voie laparoscopique pour une tumeur d'un rein en fer a cheval.

A minimally invasive approach to the treatment of these lesions offers several advantages. We want to describe a laparoscopic nephrectomy involving a tumor in a horseshoe kidney.

The influence of age on treatment outcomes in men with erectile dysfunction treated with two regimens of tadalafil: results of the SURE study.

OBJECTIVE: To evaluate whether patterns of sexual activity and efficacy over time to two dosing regimens of tadalafil differ with ageing in men with erectile dysfunction (ED). PATIENTS AND METHODS: The SURE study was a multicentre, crossover, open-label study. In all, 4262 men with ED were randomly assigned to treatment with tadalafil 20 mg on-demand before sexual activity, or three times per week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternative regimen for 5-6 weeks. This post hoc analysis evaluated the pattern of sexual attempts, efficacy and safety of these two regimens of tadalafil across several age groups. RESULTS: The mean number of sexual attempts per week decreased from a range of 2.6-2.8 at age < or = 40 years to 1.9 at age >70 years. Age did not significantly influence the time of sexual activity after dosing. A high percentage of attempts occurred >4 h after dosing for all age groups ( approximately 70% for men taking tadalafil three times per week and approximately 50% for men taking tadalafil on-demand). For all age groups, most attempts took place in the late evening. The mean per-patient rate of successful attempts was similar for each interval up to 36 h after dosing and decreased with increasing age (> or =75% at age < or = 60 years, > or = 68% at age >60 to < or = 70 years, and > or = 60% at age >70 years). Tadalafil was well tolerated at all ages. CONCLUSIONS: Patterns of sexual activity with tadalafil 20 mg, taken on-demand or three times per week, were similar in the different age groups. Tadalafil was effective up to 36 h after dosing for all age groups.

Presence of LDL modified by myeloperoxidase in the penis in patients with vascular erectile dysfunction: a preliminary study.

OBJECTIVE: Erectile dysfunction (ED) is a major vascular disorder. Atherosclerosis is closely related to lipoprotein metabolism and especially, oxidative modifications of low-density lipoproteins (LDLs), which are involved in early development of the atherosclerotic lesions. Current major questions include how LDLs are oxidised (OxLDL) in vivo. Myeloperoxidase (MPO) is an enzyme present in the azurophile granules of neutrophils and monocytes that can contribute to LDL oxidation in the presence of H(2)O(2). We have developed a new monoclonal antibody against LDL modified by MPO (Mox-LDL) and have used it on penile biopsies from patients operated on for penile implant. METHODS: Seven patients with vascular ED and one impotent patient after radical prostatectomy (RP) underwent biopsy of the cavernous body during penile implant procedures. An immunohistochemical study with a monoclonal antibody against Mox-LDL and an antibody against apoprotein B (ApoB), the protein moiety of LDL, to confirm the presence of LDL was performed. RESULTS: The staining was positive for Mox-LDL and ApoB and was present between the endothelial cells of the sinusoid spaces and the smooth muscle cells in the seven patients with vascular ED. The patient with RP was negative for Mox-LDL. DISCUSSION: Because it is known that modified LDL could decrease nitric oxide production, Mox-LDL could be one of the agents responsible for ED. Further studies are needed to confirm this hypothesis.

Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation.

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.

EAU Guidelines on erectile dysfunction: an update.

The introduction of new oral therapies has completely changed the diagnostic and therapeutic approach to erectile dysfunction. A panel of experts in this field has developed guidelines for the clinical evaluation and treatment based on the review of available scientific information.

An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries.

OBJECTIVE: To examine the preference for 2 dosing regimens (on demand or 3 times/week) for tadalafil, a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction (ED). DESIGN AND METHODS: SURE is a 14 European country, multicenter, crossover, and open-label study. Men with ED (N=4262) were randomized to tadalafil 20mg treatment on demand (maximum one dose per day and before sexual activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for 5-6 weeks. The patient's response to a treatment preference question (TPQ) was used to determine the preferred treatment regimen. RESULTS: The mean age of the randomized patients was 55 years and 85.2% reported a history of ED for one year or greater. Overall, the responses of 3861 men to the TPQ assessment showed that 57.8% preferred the on-demand regimen and 42.2% preferred the 3 times/week dosing. Both regimens were efficacious and well tolerated. CONCLUSIONS: In this study, while 57.8% of men preferred the on-demand regimen of tadalafil 20mg, a substantial number (42.2%) preferred the 3 times/week treatment. The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil.