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High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.

Study Type--Therapy (prospective cohort) Level of Evidence 3a. What's known on the subject? and What does the study add? Several short-term studies have shown that intraprostatic injection of botulinum toxin (BTX) improves lower urinary tract symptoms and flow parameters in patients with BPH, but information on patient-reported outcomes is lacking. The present study provides useful data on patient-perceived level of improvement and effectiveness of intraprostatic injection of BTX, as well as on patient's satisfaction with this therapy. Short-term results are promising and comparable with those reported with standard pharmacological therapy. OBJECTIVE: • To evaluate patient-reported and objective outcomes after intraprostatic injection of OnabotulinumtoxinA (BTX-A) in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: • A prospective single-armed cohort study was designed. • Patients diagnosed with LUTS due to BPH and unsatisfactory response to medical therapy, were recruited between November 2010 and July 2011. • Patients received transperineal injection of 200 U BTX-A in the transition zone, under transrectal ultrasonographic guidance. • The outcome assessment was performed at 3 months and included a patient-reported outcomes (PROs) questionnaire with questions on patient global impression of improvement (PGI-I, 0-6 point scale), of satisfaction (PGI-S, 0-5 point scale), and of efficacy (PGI-E, 0-5 point scale). RESULTS: • Of 75 screened patients, 64 with a mean (sd) age of 63 (9.3) years were available for the outcome assessment. • Patients reported a mean reduction of 49% in International Prostate Symptom Score (IPSS), which decreased from 19.7 (7.7) to 10 (7.1) (P < 0.001), and a mean reduction of 44% in IPSS-health-related quality of life item score, from 4.17 (1.2) to 2.3 (1.6) (P < 0.001). • There was a 33% increase in maximum urinary flow rate (P < 0.001) and an 80% reduction in postvoid residual uri

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.

Background: Current therapies for lower urinary tract symptoms (LUTS) due to bladder-neck dyssynergia (BND) have many limitations. Objective: To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A) injection therapy in medically-refractory patients with LUTS due to BND. Design, Setting, and Participants: Prospective single-armed cohort study. Therty-five consecutive ambulatory males, younger than 50 yr and diagnosed with BND refractory to medical therapy, with IPSS>15, Qmax<15 ml/s and total prostate volume <30 cm3, were screened from January 2010 and December 2011. Patients were assessed at baseline, two, six, nine and 12 mo postprocedure and until duration of clinical response. Intervention: Transurethral bladder-neck injection of 200 U of BoNT-A (50 U/ml x 4 sites). Outcome Measurements: Kaplan-Meier survival analysis addressed the response rate according to an improvement in IPSS from baseline ≥25%. Secondary outcomes were changes from baseline in total, storage and voiding IPSS, QoL score, Qmax and post-voiding residual volume (PVR), patient-reported outcome measures, complications and adverse effects. Results: Of 30 enrolled patients (mean age 33.8 yr), 29 (96.7%) completed the study. Response rates were as high as 86.7% ±6.2, 76.7% ±7.7, 31.4% ±8.6, 10.5% ±5.7 and 0.0% at two, six, nine, 12 and 16 mo, respectively. Mean time to failure was 8.9 ±0.7 mo. Statistically significant improvements from baseline of total, storage and voiding IPSS, QoL score, Qmax and PVR were observed until nine mo postprocedure. The proportion of patients with overall satisfaction was favourable although decreasing from 80% at two mo, to 46% at 12 mo. No significant complications and adverse effects were noted. The lack of a placebo arm limits the level of evidence. Conclusions: BoNT-A injection therapy is effective and safe in improving LUTS and uroflow parameters in medically-refractory men with BND, although repeated procedures are required for long-term sustained benefit

The 80 kDa soluble form of E-cad (sE-cad) and the cytokine IL-6 are being discussed as supplemental serum markers for prostate cancer (PCa). To address this issue we determined serum levels of sE-cad and IL-6 in sixty-one patients with localized or locally advanced PCa, who did not receive any previous treatment. Serum samples were collected with standard procedure, before and after prostatectomy. The samples were kept at -80°C till the time of assays, performed by using commercially available ELISA kits. At the same time, serum PSA levels were measured. sE-cad levels were 6.0 ± 2.7 (mean ± SD) μg/ml and 4.6 ± 2.3 μg/ml, before and after prostatectomy, respectively. A highly statistically significant decrease in sE-cad concentrations after prostatectomy was observed (p<0.0001, paired Student’s t-test), in 50/61 patients (82%). sE-cad levels before and after surgery were correlated (Pearson’s correlation coefficient, r=0.6993, p<0.0001). sE-cad values detected after surgery were higher in patients with PSA levels >10 ng/ml (p<0.05, Student’s t-test). sE-cad levels before prostatectomy were significantly higher in patients with G3 tumours with respect to those with G2 tumours (p<0.02, Student’s t-test). sE-cad concentrations both before and after surgery were higher in tumours with Gleason score 7 with respect to those with Gleason score <7 (p<0.002 and p<0.05, respectively, Student’s t-test). Preliminary data from 20 patients indicated a statistically significant increase in IL-6 levels after prostatectomy (11.2 vs 7.2 pg/ml, p<0.001, paired Student’s t-test). No correlation was found between sE-cad or IL-6 and PSA or other pathological parameters. Our results clearly show that prostatectomy determines a reduction in the levels of sE-cad in patients affected by localized or locally advanced PCa. One more relevant finding is that concentrations of sE-cad are higher in preoperative samples of less differentiated PCa. This suggests that sE-cad might be used as a marker

BACKGROUND AND AIM: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. METHODS: Literature search of peer-reviewed papers published by October 2010. RESULTS: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. CONCLUSIONS: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools.

The aim of this article is to describe the circumcision procedure during history, its therapeutic and preventive goals, with focus on bioethical, economic and law issues. The origins of this practice are lost in antiquity. It was performed since 3000 BC by the Egyptians for hygienic and religious reasons. Moreover, male circumcision is a religious commandment in Judaism and Islam, and it is customary in some Oriental Orthodox and other Christian churches of Africa. Nowadays, circumcision is performed as a routine procedure by the Jews and the Muslims for religious reasons. The world prevalence of men with circumcision is 12.5-33%, especially in USA, Canada, Islamic people and Africa; in Europe the prevalence rate is low (in Great Britain it is 1.5%). Currently, male circumcision is being highly debated because of ethical, law and scientific issues and the different roles of this procedure: therapeutic, prophylactic (but there is no universal consensus) and ritualistic role. Nowadays, in Italy there is a strong debate about the consensus for this practice and its indications. The Italian law does not allow performing ritualistic circumcision, as a free of charge procedure in public hospitals, at the government's expenses, because the Italian law must protect different religious cultures, in name of the laity of the State. Thus, national bioethical committee (CNB) has established that ritualistic circumcision may only be performed on a paying basis in public hospitals. As a protective practice, circumcision has decreased in the entire world because of the improvement of hygienical conditions and, above all, the lack of unanimous consent on the real usefulness of protective circumcision, even if several studies have recently demonstrated the protecting role of male circumcision against HIV infection

Prostate cancer (PCa) remains a major health concern for the male population. Detection and primary diagnosis of PCa are based on digital rectal examination, serum prostate-specific antigen levels, and transrectal ultrasound (TRUS)-guided random biopsy. Moreover, the gold standard for detecting PCa, systematic biopsy, lacks sensitivity as well as grading accuracy. This review summarizes recent developments of ultrasonography modalities and functional magnetic resonance imaging (MRI) in the diagnosis of PCa. A comparison between the different methods is presented, including their clinical value and usefulness. It is concluded that innovative ultrasound techniques (including ultrasound contrast agents, 3-D and 4-D sonography, elastography and harmonic sonography) promise benefits in comparison to standard TRUS to accurately diagnose PCa. Promising advances have been made in the detection of PCa with multiparametric MRI. The combination of conventional and functional MRI techniques (including diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy) can provide information for differentiating PCa from noncancerous tissue and can be used for MRI-guided biopsies, especially in patients with persistent elevation of serum prostate-specific antigen and previous negative TRUS-guided biopsies. However, functional MRI technique and MRI-guided biopsy remain expensive and complex tools presenting inherent challenges.

Overactive bladder syndrome (OAB) is a highly prevalent condition associated with a significant impairment of patients' Quality of Life (QoL) because of its adverse effects on social, sexual, interpersonal, and professional functions. 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. These types of cost analyses, however, exclude intangible costs related to QoL impairment. Recently, many novel therapies have been introduced, arising the need to apply the modern methodology of Health Technology Assessment (HTA) to new therapies in order to evaluate objectively their value in terms of both improvement in length/Quality of Life and costs. By producing information on the clinical, economic, organizational, social and ethical impact of health technologies, HTA has been used worldwide to inform decision makers at different levels in health systems. The HTA approach demonstrated, worldwide, to be a useful approach to increase the level of appropriateness in the use of medical technology and, as a consequence of that, of resources. Health utilities are instruments that allow a measurement of QoL and its integration in the economic evaluation using the Quality-of-life-Adjusted-Life-Years (QALYs) 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 non-pharmacological therapy options.

Urinary lithiasis is one of the most common benign urological diseases. There is growing evidence that a delicate equilibrium regulated by the function of proteins, soluble peptides, membrane proteins and intracellular mechanisms actually exists. We have studied the urinary protein composition of patients affected by calcium oxalate nephrolithiasis in order to discover a biomarker or any predisposing factors.

OBJECTIVE: The aim of the present paper is to review findings from the most relevant studies and evaluate the potential of new drugs in treatment of metastatic urothelial cancer. METHODS: Studies were identified by searching MEDLINE and Pubmed databases up to 2009 using both medical subject heading (Mesh) and a free text strategy with the name of known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'urothelial/transitional carcinoma', 'chemotherapeutics drugs and agents'. At the end of our research in literature we selected 63 articles and we have considered only studies in which almost 30 patients were enrolled. RESULTS: Radical cystectomy with pelvic lymph node dissection is the gold standard of treatment for clinically localized muscle-invasive bladder cancer. While more extensive lymph node dissection may have both prognostic and therapeutic significance, effective systemic therapies that eliminate micrometastases may improve outcome. Perioperative chemotherapy can be administered before (neoadjuvant) or after (adjuvant) cystectomy to eradicate subclinical disease and to improve survival. CONCLUSION: The challenge remains as to how to integrate all of the relevant knowledge and data in a systematic manner so that researchers can gain the knowledge needed to devise the best therapeutic and diagnostic strategies. Future improvements in the treatment of advanced bladder cancer will rely not only on the optimization of currently available cytotoxic agents but also on the biologic profile of individual patient tumors and the appropriate therapies that target molecular aberrations unique to this malignancy.

The role of statistics in medical research starts at the planning stage of a clinical trial or laboratory experiment to establish the design and size of an experiment that will ensure a good prospect of detecting effects of clinical or scientific interest. Statistics is again used during data analysis (sample data) to make inferences valid in a wider population. In simple situations, computation of simple quantities such as P-values, confidence intervals, standard deviations, standard errors or application of some standard parametric or nonparametric tests may suffice. Moreover, despite the wide use of statistics in medical research, simple notions are sometimes misunderstood or misinterpreted by medical research workers, who have only a limited knowledge of statistics. This article, written for non-statisticians, is to explain what are the most common statistical tests used today in the field of medical research, tracing the evolution of statistical tests over time, in particular the introduction of nonparametric methods and, more recently, the NonParametric Combination (NPC) methodology. At the same time, this work seeks to identify some of the errors associated with their use, that often lead to an incorrect assessment and interpretation of results of medical research.

The current techniques used as the gold standard of care for the diagnosis and surveillance of urological malignancies such as cystoscopy, urine cytology and prostate-specific antigen (PSA) present many limitations such as invasiveness, insufficient accuracy and unsatisfactory cost-effectiveness. This is the reason for the explosion of interest in research into novel biomarkers that could either complement current gold standard diagnostic methods or, ideally, replace them. The list of established and experimental biomarkers for urological malignancies is huge, especially in the field of bladder and prostate cancers. Although many novel biomarkers have come and gone or are far from having the ideal characteristics of a tumour biomarker, some of them have proved to be of additional value in everyday practice. Multiple biomarker approaches and high-throughput genomic and proteomic technologies appear to be very promising, although the exciting expectations raised from the progress in these fields still need to be realised. © Touch Briefings 2010.

Several substances such as growth hormone (GH), erythropoietin (Epo), and anabolic steroids (AS) are improperly utilized to increase the performance of athletes. Evaluating the potential cancer risk associated with doping agents is difficult since these drugs are often used at very high doses and in combination with other licit or illicit drugs. The GH, via its mediator, the insulin-like growth factor 1 (IGF-1), is involved in the development and progression of cancer. Animal studies suggested that high levels of GH/IGF-1 increase progression of androgen-independent prostate cancer. Clinical data regarding prostate cancer are mostly based on epidemiological studies or indirect data such as IGF-1 high levels in patients with prostate cancer. Even if experimental studies showed a correlation between Epo and cancer, no clinical data are currently available on cancer development related to Epo as a doping agent. Androgens are involved in prostate carcinogenesis modulating genes that regulate cell proliferation, apoptosis and angiogenesis. Most information on AS is anecdotal (case reports on prostate, kidney and testicular cancers). Prospective epidemiologic studies failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk. Currently, clinical and epidemiological studies supporting association between doping and urological neoplasias are not available. Nowadays, exposure to doping agents starts more prematurely with a consequent longer exposition period; drugs are often used at very high doses and in combination with other licit or illicit drugs. Due to all these elements it is impossible to predict all the side effects, including cancer; more detailed studies are therefore necessary.

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

Advances in imaging have an increasingly significant role in the diagnosis, staging and restaging of patients with bladder cancer. This paper reviews the current use of imaging in bladder neoplasms, comparing the different radiologic investigations, and discusses the potential applications of novel imaging techniques in the management of patients with bladder cancer. Copyright © 2010 S. Karger AG, Basel.

A retroperitoneal metastasis from malignant melanoma is an uncommon event and mostly secondary to a primary lesion of the posterior trunk. We report on a 38-year-old patient with malignant melanoma of the anterior trunk who presented a symptomatic metastatic mass of the left renal hilum not originating from the retroperitoneal lymph nodes of the renal hilum, surrounding and infiltrating the renal pelvis, treated with left nephrectomy, complete mass excision and regional lymph node dissection. The patient later developed also brain metastases and is now undergoing immunotherapy.

Bladder cancer is among the top eight most frequent cancers. Its natural history is related to a combination of factors that impact on its aggressiveness. Cystoscopy and urine cytology are the currently used techniques for the diagnosis and surveillance of non-invasive bladder tumors. The sensitivity of urine cytology for diagnosis is not high, particularly in low-grade tumors. The combination of voided urine cytology and new diagnostic urine tests would be ideal for the diagnosis and follow-up of bladder cancer. However, in order to have some clinical utility, new diagnostic and/or prognostic markers should achieve better predictive capacity that the currently used diagnostic tools. None of the markers evaluated over the last years showed remarkable sensitivity or specificity for the identification of any of the diverse types of bladder cancer in clinical practice. The limitations of the known prognostic markers have led to the research of new molecular markers for early detection of bladder cancer. This research focused in particular on the discovery of biomarkers capable of reducing the need for periodic cystoscopies or, ideally, offering a non-invasive examination instead. In this review, we will examine various new markers of bladder cancer and their value in the diagnosis and follow-up of non-muscle-invasive bladder cancer. When compared with urine cytology, which showed the highest specificity, most of these markers demonstrated an increased sensitivity. © 2008 Wichtig Editore.

Introduction: Normal and abnormal bladder contractions are principally mediated by acetylcholine released from postganglionic parasympathetic nerves. Since amikacin was reported to affect neurotransmission by a prejunctional mechanism, we investigated the effect of amikacin on isolated detrusor smooth muscle contraction to further evaluate its potential relaxant properties. Materials and Methods: Detrusor smooth muscle obtained from 15 rats and 8 patients undergoing surgery were studied through measurement of isometric muscular contraction induced with electrical field stimulation (EFS) (10-60 Hz), carbachol (10-7 to 10-3M) and nicotine (10-7 to 10-3M) in the presence or absence of 1 mM amikacin in a low-Ca medium. Results: Amikacin (1 mM) significantly reduced EFS-induced contraction of isolated rat and human detrusor muscle by 33 ± 6.57% (p < 0.005) and 40 ± 1.14% (p < 0.001), respectively. Contraction was restored after addition of calcium chloride (1 mM). The effect of amikacin was comparable to that of magnesium ions. Rat and human detrusor contractile response to nicotine was inhibited by 70 ± 8.27% (p < 0.001) and 64 ± 14.09% (p < 0.01) after the addition of amikacin (1 mM), while no significant effect was observed on carbachol-induced stimulation. Conclusion: Amikacin significantly inhibited detrusor contraction evoked by prejunctional stimulation in vitro, suggesting a depressant effect on autonomic neurotransmission in urinary bladder. Copyright © 2008 S. Karger AG.