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Background : Searching for genetic and environmental factors predisposing to prostate cancer, common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the number of CAG repeats from AR were investigated in Italian heredo-familial prostate cancer (HFPC) patients controlled for dietary intake and life style habits. Methods : We evaluated differences between HFPC and sporadic cancers, in the pattern of common single-nucleotide polymorphisms in CYP17A1 , CYP19A1 , VDR genes, and the CAG repeat from AR , controlling for dietary intake and lifestyle habits in a regionwide population. Ninety-five patients with HFPC were identified and 378 sporadic prostate cancers were randomly selected as controls. Dietary intake and lifestyle habits were determined through self-administered questionnaires in all patients. Genotyping of polymorphisms for CYP17A1 , CYP19A1 , VDR , and the CAG repeat from AR was carried out using pyrosequencing. Results : HFPC cases were significantly younger than controls, whereas similar proportions of localized tumours, favourable histology, and abnormal prostate serum antigen levels (4–19ng/ml) were detected in the two groups. A statistically evident gene–gene interaction was found: a 5-fold higher probability [odds ratio (OR)=4.83; 95% confidence interval (CI): 1.37–17.02] of HFPC was observed in the subgroup profiling VDR1 T/T genotypes coupled with VDR2 T/T genotype. Among nutrients, an increase in HFPC risk (OR=3.14; 95% CI: 1.12–8.81) was found only for zinc, when associated with the VDR2 T/T genotype. Conclusions : Significant evidence for positive interactions between VDR1 and VDR2 genotypes was demonstrated, suggesting that high-risk multigenic polymorphism profiles could variously sustain HFPC tumorigenesis.

Advancements in imaging and laparoscopy have led to the expansion of minimally invasive techniques in the ablation of small renal masses (SRMs). We report the results of a study aimed at assessing the efficacy of thermoablative microwave (MW) effects on SRMs and the haemostatic as well as necrotic MW effects on the parenchyma surrounding the neoplasm. From November 2008 to October 2010, 10 patients with SRMs underwent laparoscopy-guided Tru-Cut biopsy, MW tumour ablation, and enucleation. Mean age was 66 yr (range: 46–84 yr). Mean renal tumour diameter was 2.75cm (range: 1.3–4.2cm). MW antennas were applied one to three times depending on tumour volume, location, and shape. After MW thermoablation, laparoscopic enucleation was performed to evaluate the histopathologic and haemostatic effects of MW. The mean MW antenna application time was 14.1min (range: 4–30min). Enucleation did not require renal pedicle clamping in any of the cases because no significant bleeding took place. Preablation pathology revealed clear cell renal carcinoma of Fuhrman grade I–II in all cases. Postablation pathology showed extensive coagulative necrosis without skipped tumour areas. No intra- or postoperative complications were reported. Histopathologic effects on SRMs provide consistent proof of principle for future studies.

Study Type – Therapy (case series) Level of Evidence What’s known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib-cage limiting energy delivery. For this study, a purpose-built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications. OBJECTIVE • To test and establish clinical proof of concept for a laparoscopic high-intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface. PATIENTS AND METHODS • Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18-mm laparoscopic port. • HIFU treatment was targeted at a pre-defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed. RESULTS • No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients. • The ablated zones were within the targeted area in all patients and no intra-lesional skipping was seen. • Subcapsular skipping was seen at the probe–tumour interface in two patients with viable tumour cells seen at microscopy. • One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells. • There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow-up of 15 (8–24) months with no evidence of metastatic disease or late complications. CONCLUSIONS • Tumour ablation with laparoscopic HIFU is feasible. • Homogenous ablation can be achieved with no vital tissue within the targeted zone. • The technique is associated with low morbidity and may have a role in the definitive management of small tumours.

Aim: To evaluate the use of cyanoacrylic glue to fix the kidney in laparoscopic nephropexy for symptomatic nephroptosis. Patients and Methods: From 1998 to 2006 w

OBJECTIVES To report our experience of transvaginal diverticulectomy with pubovaginal sling placement in a series of 32 women with recurrent urethral pseudodiverticula. METHODS A total of 32 women underwent surgical repair from January 2000 to June 2007. Of the 32 women, 12 had undergone other concomitant previous urethral surgery, predominantly for stress urinary incontinence. Transvaginal excision of the diverticulum and concomitant pubovaginal sling placement were performed routinely. The women were evaluated postoperatively for symptom relief, anatomic result, and postoperative continence status at 1, 6, and 12 months and annually thereafter. Pelvic magnetic resonance imaging was repeated after 1 year. RESULTS The mean follow-up was 4.3 years. In all cases, the voiding urethrogram after catheter removal showed a good urethral shape with an absence of urinary leaks. At the postoperative urodynamic investigation, 27 patients had an unobstructed and 5 an equivocal Blaivas-Groutz nomogram. Three patients (20%) reported a persistent degree of stress urinary incontinence, including 2 with grade 1 stress urinary incontinence and 1 with mixed incontinence. Two patients presented with clinically evident diverticulum recurrence, and in 1 patient, an intraurethral diverticulum, was found at the 1-year magnetic resonance imaging examination. CONCLUSIONS A pubovaginal sling added routinely to all diverticulectomy procedures offers significant support to the urethral repair and/or prevention of urinary incontinence, including in recurrent cases, and does not increase the risk of erosion into the urethra or fistula formation.

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment for prostate cancer. Data from the literature show promising oncological outcomes with a favourable side-effect profile. The aim of this study was to re-evaluate and bring up to date the follow-up of a previously published, prospective trial on HIFU as the primary treatment for prostate cancer.Between 2004 and 2007, 163 consecutive men with T1-T3N0M0 prostate cancer underwent HIFU with the Sonablate 500. Follow-up included prostate-specific antigen (PSA) tests every 3 months after treatment and a random prostate biopsy at 6 months. Failure was defined according to positive findings at the 6 month biopsy and biochemical failure was defined according to the Phoenix criteria. Biochemical-free survival, metastasis-free survival and cancer-specific survival were calculated by Kaplan-Meier curves.Median follow-up was 72.0 months. Of the 160 evaluable patients, 104 (65%) were biochemically disease free; in low- to intermediate-risk disease, on Kaplan-Meier analysis the 8 year biochemical-non-evidence of disease (bNED), metastasis-free survival and cancer-specific survival rates were 69.6%, 81.3%, 100% and 40.5%, 60.6%, 100%, respectively. A PSA nadir below 0.40 ng/ml and risk stratification have an independent predictive value for bNED and metastasis-free survival.A long-term favourable outcome of HIFU is associated with careful patient selection, with low- to intermediate-risk disease being the ideal case. A low postoperative PSA nadir is a predictor of long-term bNED.

Objectives: To evaluate the adaptability and the possible advantages of the antireflux mechanism of the serous lined extramural tunnel for ureter re-implantation on a gastrointestinal anastomosis (GIA) Stapler detubularised ileal neobladder Methods: From April 1998 to July 2002 43 male patients underwent radical cystectomy and the creation of a Camey II ileal neobladder using this antireflux technique. Follow-up in all cases included excretory urography or T.C. scan and a retrograde cystography at 6 months and a renal scintigraphy with DMSA at 1 year follow-up, besides serum creatinine, blood urea and serum electrolytes every three months and renal-neovesical ultrasound every six months. Results: Early and late complications were low. At follow-up 1 case of neovesico-ureteral reflux and 2 cases of ureteroileal anastomotic strictures were found. DMSA scintigraphy showed no further renal scars. Conclusions: This preliminary experience was favourable due to overall reduced operating time (about 1hour 45minutes to create the orthotopic neobladder and the ureteroileal anastomosis), simplicity of execution and a low complication rate (6.9%) at a median follow-up of 38 months (range 12–52 months).

Purpose: The efficacy of nerve sparing techniques to save potency in cystoprostatectomy is about 50%. This radical surgery may be proposed to young men with normal sexual function. We report the results of a 13-year experience with our innovative seminal sparing cystectomy and bladder replacement to maintain sexual function in such patients. Materials and Methods: Seminal sparing cystectomy is a modification of standard radical cystectomy in which the posterior bladder dissection is anterior to the seminal vesicle plane to preserve the vasa deferens, seminal vesicles, prostatic capsule and neurovascular bundles. Ablation of the whole bladder and the prostatic urothelium with surrounding hypertrophic tissue is guaranteed, and injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa is avoided. From April 1990 to December 2002 we performed 68 procedures in 63 patients (7 of whom were lost to followup) with superficial bladder cancer resistant to conservative therapies (18 patients with stage T1G2 disease, 13 TaG2, 11 T1G3 and 14 TaG3) and in 5 patients with invasive bladder cancer (T2G3) which was monofocal and away from the bladder neck. All patients had normal sexual function. A complete clinical evaluation (with prostate specific antigen [PSA], digital rectal examination and transrectal ultrasound) to exclude concomitant prostate cancer was performed. Average patient age was 49 years and mean followup was 68 months. Results: Normal erectile function was preserved in 58 patients (95%). Complete daytime continence was reached in 58 patients (95%) and nighttime continence was reached in 19 patients (31%). The early postoperative complication rate was 18% and the delayed complication rate was 26.2%. A total of 55 patients (90.2%) are alive and 6 patients (9.8%) died, 5 of cancer progression. High grade prostatic intraepithelial neoplasia was noticed in prostatic specimens in 3 patients and prostatic cancer was noted in 1 patient. These patients had a normal PSA before operation and a serum PSA less than 0.2 ng/ml at a mean followup of 19 months. No positive margins were identified on permanent histological analysis of the specimens, nor were local pelvic recurrences observed. Conclusions: Our innovative technique is safe, effective and easy to perform. The oncological and functional results obtained with a long followup justify seminal sparing cystectomy as an excellent surgical procedure which can be proposed to some oncological and nononcological cases.

Aims To report feasibility, safety and effectiveness of “zero-ischemia” laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. Methods We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Results Mean patients age was 68 years (range 56–74), mean tumor size was 3.5 cm (range 2.2–6.3 cm). STE was successfully completed in 16 patients 12–15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a “zero-ischemia” approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5–22). Mean operative time was 123 min (range 115–130) and mean intraoperative blood loss was 250 mL (range 20–450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. Conclusions STE is a viable option to perform “zero-ischemia” LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

Introduction: The main objective was to evaluate feasibility, toxicity and biochemical control rates of salvage external beam radiotherapy (EBRT) in recurrent localized prostate cancer after high-intensity focused ultrasound (HIFU) as primary therapy. Patients and Methods: A total of 24 patients who underwent salvage EBRT after 1 or 2 HIFU sessions and with a minimum post-treatment follow-up of 24 months were retrospectively evaluated. Primary endpoints were toxicity and biochemical disease-free survival (bDFS, defined according to the ASTRO Phoenix definition). Results: Median follow-up was 40.3 months. Gastrointestinal toxicity was low. Acute genitourinary (GU) toxicity grade ≤II rate was 45.8%, with only few patients presenting grade III (8.3%) and grade IV (4.2%) toxicity. Late grade ≥III GU toxicity was registered in 16.7% of patients. The 3-year bDFS rate was 77.8%. Patients achieving a nadir prostate-specific antigen (nPSA) of ≤0.35 ng/ml after EBRT had significantly higher bDFS (3-year bDFS: 87.7 vs. 50%, respectively; p = 0.001). Achieving nPSA ≤0.35 ng/ml was the only factor independently associated to long-term bDFS both on univariate (p = 0.01) and multivariate analysis (HR 7.06, p = 0.039). Conclusions: Salvage EBRT after HIFU failure is feasible and allows to obtain satisfactory biochemical control rates, especially in patients attaining a nPSA ≤0.35 ng/ml after EBRT.

Objective To evaluate the functional results of a new cutaneous continent reservoir, the Turin pouch (TP), consisting of an ileocolonic pouch with an innovative efferent channel (EC). Methods Since 2006, we have performed the TP on 14 patients in whom the appendix was absent. The distal ileum (10 cm) and right colon (40 cm) were isolated. The cecum and right colon were folded to obtain a U-shaped pouch through a stapler detubularization. An artificial EC was created by separating with a stapler a 5-cm tubularized flap of colonic wall and anastomosing this to the umbilicus. Results After a mean follow-up of 45 months (range, 12-72 months), 13 patients were alive and 1 died of bladder cancer progression. Early and late complications occurred in 3 and 4 patients, respectively. Daytime continence was 100% and nighttime continence was 93%. No patient has reported stenosis or difficulties in catheterization. Urodynamic studies (12 months postoperatively) showed a mean maximal pouch capacity of 520 mL (range, 360-720 mL), mean end-filling pressure of 23 cm H 2 O (range, 18-30 cm H 2 O), and mean EC closing pressure of 65 cm H 2 O (range, 52-75 cm H 2 O). Conclusion The TP offers good functional results and could be applied in patients undergoing continent, heterotopic, urinary diversion.

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

Study Type--Therapy (case series) Level of Evidence What's known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib-cage limiting energy delivery. For this study, a purpose-built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications.• To test and establish clinical proof of concept for a laparoscopic high-intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface.• Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18-mm laparoscopic port. • HIFU treatment was targeted at a pre-defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed.• No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients. • The ablated zones were within the targeted area in all patients and no intra-lesional skipping was seen. • Subcapsular skipping was seen at the probe-tumour interface in two patients with viable tumour cells seen at microscopy. • One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells. • There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow-up of 15 (8-24) months with no evidence of metastatic disease or late complications.• Tumour ablation with laparoscopic HIFU is feasible. • Homogenous ablation can be achieved with no vital tissue within the targeted zone. • The technique is associated with low morbidity and may have a role in the definitive management of small tumours.

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

Once previously attempted conservative maneuvers have failed, iatrogenic persistent urinary fistulas usually require difficult repeated operations. We describe 3 patients in whom cyanoacrylic glue was used to repair endoscopically persistent urinary fistulas occurring after major pelvic surgery. At a mean follow-up of 21 months, all patients were free of urinary leakage and had no evidence of recurrent urinary fistulas. This approach may represent a safe and effective way to repair postoperative urinary fistulas.

Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology.

The management of Prostate cancer (PC), since PSA testing has been introduced in the clinical practice, has been significantly spoiled by a "leading-time bias" effect. As a consequence, this has brought to a dramatic diagnosis anticipation at the 4th-5th decade of life in sexually active and otherwise asymptomatic men. Standard options as radical prostatectomy or EBRT are hampered by a significant negative impact on patient's QoL. More recently several alternative minimally-invasive ablative treatment modalities have been proposed with promising results. Among these, TR-HIFU (Trans-Rectal High Intensity Focused Ultrasound) is playing a growing role in the treatment of localized low-intermediate risk PC, although long-term oncologic outcome are still awaited. In order to achieve an optimal result, a specific TR-HIFU's requirement is given by an unchanging target throughout the whole procedure. Therefore, the ideal anaesthesia should be either minimally-invasive and allow to get a motionless target up to 3-4 hours. A retrospective evaluation of efficacy and safety of a spinal anaesthesia in this patient's setting was done.107 patients with localized prostate cancer treated in our institution from October 2004 to December 2007 with TR-HIFU procedure received a subarachnoidal anaesthesia with combined administration of 0.5% normobaric racemic bupivacaine (15 to 17.5 mg) and sufentanil 5 microg.This technique allowed covering the whole TR-HIFU procedure (analgesia and motor blockade up to 4-5 hours). It was well tolerated by patients who only rarely required additional sedative or analgesics. A low anaesthesia-related side effects rate, as arterial hypotension, nausea and vomiting, and no severe side effects of intrathecal opioids, as deep sedation, bradycardia, myosis, bradypnea and oxygen desaturation, occurred. Intraoperative employment of sedatives and postoperative need of analgesics was low.Using a low-dose intrathecal sufentanil an effective spinal block either on the sensitive and motor pathways was provided. Patients' tolerance to the procedure was good and the side-effect rate low. No adverse reactions to intrathecal sufentanil 5 microg were observed. In our experience TR-HIFU can be performed with neuraxial block in most of the cases and it's associated to a favorable cost-benefit rate.

High intensity focused ultrasound is a minimally invasive treatment option for prostate cancer. Data from the literature show promising early oncological outcomes and a favorable side effect profile. This study is a preliminary report of the Italian experience (Perugia and Turin) of patients treated with the Sonablate(R)500 high intensity focused ultrasound device.Between 2004 and 2007, 163 consecutive men with T1-T3 N0M0 prostate cancer underwent high intensity focused ultrasound with the Sonablate 500. Followup included prostate specific antigen tests at 1 month and then every 3 months after treatment, and a random prostate biopsy at 6 months. Failure was defined according to prostate specific antigen nadir, positive findings on followup biopsy and biochemical failure according to Phoenix criteria.Median patient age was 72 years old, median baseline prostate specific antigen was 7.3 ng/ml, and disease stage was T1 in 44.1%, T2 in 42.5% and T3a in 13.4% of patients. Median followup was 23.8 months. After high intensity focused ultrasound treatment prostate specific antigen decreased to a median nadir of 0.15 ng/ml. Median prostate specific antigen at 3 and 6 months was 0.30 and 0.54 ng/ml, respectively. At 6 months the negative biopsy rate was 66.1%. There was no biochemical evidence of disease in 71.9% overall. On multivariate analysis prostate specific antigen nadir became the only independent predictor of no biochemical evidence of disease and positive biopsy at a cutoff of 0.40 ng/ml.A favorable outcome of high intensity focused ultrasound is associated with lower baseline prostate specific antigen, lower prostate specific antigen nadir, lower Gleason score and lower tumor stage. As with any novel technology long-term data will be required before this technique gains widespread clinical acceptance.

The study's aim is to evaluate the role of Perineal Ultrasound (PU) in the outcome assessment for the TVT procedures and correlate PU findings to clinical outcomes in a subgroup of patients with postoperative voiding obstructive complaints.From 2001 to 2005, 100 patients were evaluated by PU in our institution who had previously undergone TVT procedure for SUI. Eight had postoperative Bladder Outlet Obstruction (BOO). Mean age was 61,8 years.Main PU findings are synthesized as follows: 1. The TVT sling was positioned at an higher level, mainly towards the proximal urethra/bladder neck and above the posterior edge of pubic bone. 2. The reduction of tape distance from the pubic symphysis associated with urethral kinking at tape's crossing point.PU might represent a useful, inexpensive and non invasive tool for the diagnosis of BOO in TVT failures with LUTS. It can easily assess the relationship between bladder neck/urethra and the TVT tape providing the surgeon an important diagnostic and prognostic clue.

MicroRNAs (miRNAs) are noncoding small RNAs that repress protein translation by targeting specific messenger RNAs. miR-15a and miR-16-1 act as putative tumor suppressors by targeting the oncogene BCL2. These miRNAs form a cluster at the chromosomal region 13q14, which is frequently deleted in cancer. Here, we report that the miR-15a and miR-16-1 cluster targets CCND1 (encoding cyclin D1) and WNT3A, which promotes several tumorigenic features such as survival, proliferation and invasion. In cancer cells of advanced prostate tumors, the miR-15a and miR-16 level is significantly decreased, whereas the expression of BCL2, CCND1 and WNT3A is inversely upregulated. Delivery of antagomirs specific for miR-15a and miR-16 to normal mouse prostate results in marked hyperplasia, and knockdown of miR-15a and miR-16 promotes survival, proliferation and invasiveness of untransformed prostate cells, which become tumorigenic in immunodeficient NOD-SCID mice. Conversely, reconstitution of miR-15a and miR-16-1 expression results in growth arrest, apoptosis and marked regression of prostate tumor xenografts. Altogether, we propose that miR-15a and miR-16 act as tumor suppressor genes in prostate cancer through the control of cell survival, proliferation and invasion. These findings have therapeutic implications and may be exploited for future treatment of prostate cancer.

OBJECTIVE To investigate metabolic disturbances, possibly leading to stone disease, in the Camey II technique for creating a urinary reservoir from an intestinal segment. PATIENTS, SUBJECTS AND METHODS Thirty patients with a Camey II ileal neobladder and 26 controls had metabolic investigations of blood samples, and 24-h and fasting urine samples, to assess renal function, the risk of stone formation, and bone turnover. The state of saturation with calcium oxalate, uric acid and brushite were calculated using a computer program. RESULTS The patients had lower renal clearances than the controls (P

The treatment of choice for superficial bladder TCC is endoscopic resection, followed or not by intravesical immuno/chemotherapy. Some patients are not responders to common intravesical therapy and are more exposed to disease progression. In this case the suitable treatment is radical cystectomy. Because gemcitabine is effective against advanced bladder cancer, we have initiated a study to evaluate the efficacy of its intravesical use to prevent relapse and disease progression, and tolerance and safety of this drug in patients with multi-treated bladders. In this preliminary study, we cite only data on tolerance.64 patients were selected, and 61 were evaluable (age range 39-84 years), with multiple-recurrent bladder TCC. All patients were previously treated with intravesical chemotherapy and/or immunotherapy. The protocol provided for intravesical instillation of gemcitabine (2000 mg) once per week for 8 weeks. We collected data regarding problems noted by the patients (both local and systemic).53 patients out of 61 (86.9%) completed the cycle. Side effects appeared in 14 patients, 8 of these had to suspend the treatment. Severe side effects were systemic in 4 patients (1 systemic edema, 1 malaise and dysgeusia, 1 hyperthermia and severe strangury, 1 elevated transaminases and asthenia), and local in 4 patients (1 severe urinary urgency, 1 hematuria, 1 urinary incontinence, and 1 case of pelvic pain). In 6 patients we observed pelvic pain, hematuria, strangury and UTI of medium magnitude that did not require treatment interruption.We believe that the severe side effects requiring treatment interruption are attributable primarily to increased sensitivity in patients with multi-treated bladders. In our experience, the side effects responsible for suspension occurred at the start of treatment in 7 cases out of 8. Our study demonstrates the safety of intravesical gemcitabine in patients with recurrent and multi-treated superficial TCC of the bladder.

Purpose: We evaluated the adaptability and the efficacy of a cyanoacrylic glue for the conservative treatment of urinary fistulas of different etiologies using an endoscopic, percutaneous or endovaginal approach.Materials and Methods: From May 1998 to July 2004, 13 patients with long lasting iatrogenic and/or inflammatory urinary fistulas were treated conservatively with endoscopic, percutaneous or endovaginal application of 1 to 3 cc of cyanoacrylic glue.Results: The complication rate in this cohort of 13 patients was low. Occlusion therapy failed in 2 genitourinary fistulas which were wider (diameter greater than 1 cm) and short. In the remaining 11 cases urinary fistulas were successfully sealed and at a median followup of 35 months no relapses were observed.Conclusions: Cyanoacrylic glue is suitable for endoscopic, percutaneous and endovaginal use. This occlusion therapy represents a safe and minimally invasive approach that might be offered as a first line option for the treatment of urinary ...

A singular case of female accessory urethra associated to a mobile bladder stone with an unusual clinical presentation is reported. The role of perineal ultrasound is emphasized as a useful diagnostic tool to study female urethra in a static and dynamic setting, including cases of partial or complete urethral duplication.

Pelvic collections are not an uncommon complication of pelvic surgery. Usually, such a complications are managed by TC-guided percutaneous drainage or even by more invasive surgical operations. Here, we describe a transperineal TRUS-guided drainage technique of pelvic urinomas occurring after a radical cystectomy (RC) for invasive Bladder Cancer (BC) in two patients, respectively 55 and 77 YOM. Respectively, 10 and 20 days after catheter had been taken out patients began complaining a severe pelvic pain associated to fever (over 40 degrees C). Physical examination and an ultrasound, followed by a CT-scan, showed a huge retroanastomotic pelvic urinoma (width over 10 cm). CT-guided percutaneous drainage was considered at increased risk of iatrogenic injury of mesenterial neobladder because of its location. A TRUS-guided percutaneous perineal drainage of urinomas with a pig-tail 8 ch was carried out. Urinomas were successfully drained and no significant complications were encountered. At a median follow-up of 11 months no late complications were found. Our preliminary experience with this procedure is favourable regarding mininvasivity, lack of complications and its feasibility by urologists themselves. Its impact on cost/benefit rate is favorable too. We believe that this technique might be considered as an alternative to CT-guided percutaneous drainage.

e16099 Background: The management of rising PSA in metastatic CRPC remains controversial. In Italy, abiraterone and enzalutamide are not at all approved in this setting of patients (pts). Ketoconazole is an inhibitor of adrenal androgen synthesis that has shown anti-tumor activity by interfering with C-17,20-lyase and could be used as secondary hormonal manipulation. In this retrospective study we report our experience with low doses of ketoconazole and prednisone in the treatment for CRPC. Methods: From March 2007 to March 2012, 73 pts with progressive CRPC who were previously treated with maximal androgen blockade received 200 mg ketoconazole orally 2 times daily, orally replacement prednisone (5 mg bid) and maintained LHRH-agonists. Overall, 40/73 (55%) pts had only bone metastases, 13/73 (18%) had nodal metastases, 20/73 (27%) both. Pts were monitored clinically and with serial PSA measurements every month. Partial biochemical response (PR) was defined as a >50% fall in PSA from baseline. Progressive disease (PD) was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. The endpoints of the study were biochemical response (BR), progression free survival (PFS), overall survival (OS) and adverse events assessment. Results: Median age was 74 (70-78) years; median baseline PSA was 33.09 (1.18-1348.8) ng/ml; median duration of the treatment was 5.05 (0-56.8) months. Twenty out 73 pts (27%) showed a decrease in PSA >50%, with a median duration of PSA response of 3.56 (1.17-33.58) months and 3 pts (4%) a PD. Fifty out 73 pts (68%) achieved a SD with an overall disease control (PR+SD) of 85%. PFS was 10 months for pts who achieved PR and 4 months for those with SD. Differences in PFS stratified according to site of metastases showed better prognosis in patients with only lymph nodes disease (p

BACKGROUND: Routine laboratory blood tests for biomarkers could dramatically simplify and improve cancer diagnosis, prognosis and tailored therapy. The tumor and its microenvironment, produce cascades of information that enrich the blood proteome with potential cancer biomarkers that could be highly informative about the establishment, progression and metastatic dissemination of cancer. Nevertheless, the identification of low abundance and labile cancer specific biomarkers in blood remains extremely challenging. Low abundance markers are masked by high abundance proteins such as albumin, and by non-specific markers whose changes accompany many diseases. In this study, we analyzed a large cohort of human serum samples from a wide-range of cancer conditions and benign states, and utilized a rapid and powerful nanoparticle-based biomarker capture technology. METHODS- We utilized isopropylacrylamide (NIPAm) core shell hydrogel particles, functionalized with two chemical baits, Cibacron blue F3GA and vinylsulfonic acid, for biomarker capture from 450 serum/plasma samples. Twenty age and stage-matched cancer and 20 to 40 benign/inflammatory controls were processed for each of the 7 cancer types, and proteins eluted from the particles were analyzed by high resolution LC-MS/MS analysis using an LTQ-Orbitrap (Thermo Fisher). All specimens were analyzed in a randomized, batch fashion, followed by an accurate comparison of the results in order to 1) identify a panel of biomarkers for each cancer type and distinguish protein which are involved in commons cancer mechanism and proteins which could uniquely indicate a particular cancer type and 2) avoid the technological bias that could be associated with the comparison of separated studies. RESULTS: For each cancer type we obtained a panel of hundreds of candidates biomarkers, a large number of them not previous identified by MS and/or never measured in plasma. Within the proteins identified are kinases, cytokines, growth factors, structural and nuclear proteins. Each panel of candidate biomarkers includes a) proteins unique for a cancer type, such as the tyrosine kinase Tec, specific for prostate cancer; b) proteins common to many cancer types such as, PRKAG2, CD9, Lipocalin 2, Annexin I, and SDFR-1 and c) numerous proteins whose role in cancer is novel or not well-described. CONCLUSIONS: Cancer-specific low abundance marker candidates have been identified using NanoTrap ™ nanoparticles, a novel rapid upfront sample processing biomarker capture technique. We are developing a protocol for the validation of the biomarkers based on MRM-MS. Further investigation will be required to understand the biological meaning and clinical value of the proteins identified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4787. doi:1538-7445.AM2012-4787