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Pseudomonas aeruginosa is a major human pathogen, able to establish difficult-to-treat infections in immunocompromised and people with cystic fibrosis (CF). The high rate of antibiotic treatment failure is due to its notorious drug resistance, often mediated by the formation of persistent biofilms. Alternative strategies, capable of overcoming P. aeruginosa resistance, include antivirulence compounds which impair bacterial pathogenesis without exerting a strong selective pressure, and the use of antimicrobial adjuvants that can resensitize drug-resistant bacteria to specific antibiotics. In this work, the dispirotripiperazine derivative PDSTP, already studied as antiviral, was characterized for its activity against P. aeruginosa adhesion to epithelial cells, its antibiotic adjuvant ability and its biofilm inhibitory potential. PDSTP was effective in impairing the adhesion of P. aeruginosa to various immortalized cell lines. Moreover, the combination of clinically relevant antibiotics with the compound led to a remarkable enhancement of the antibiotic efficacy towards multidrug-resistant CF clinical strains. PDSTP-ceftazidime combination maintained its efficacy in vivo in a Galleria mellonella infection model. Finally, the compound showed a promising biofilm inhibitory activity at low concentrations when tested both in vitro and using an ex vivo pig lung model. Altogether, these results validate PDSTP as a promising compound, combining the ability to decrease P. aeruginosa virulence by impairing its adhesion and biofilm formation, with the capability to increase antibiotic efficacy against antibiotic resistant strains.

Quorum sensing (QS) is a bacterial intercellular communication process which controls the production of major virulence factors, such as proteases, siderophores, and toxins, as well as biofilm formation. Since the inhibition of this pathway reduces bacterial virulence, QS is considered a valuable candidate drug target, particularly for the treatment of opportunistic infections, such as those caused by Burkholderia cenocepacia in cystic fibrosis patients. Diketopiperazine inhibitors of the acyl homoserine lactone synthase CepI have been recently described. These compounds are able to impair the ability of B. cenocepacia to produce proteases, siderophores, and to form biofilm, being also active in a Caenorhabditis elegans infection model. However, the precise mechanism of action of the compounds, as well as their effect on the cell metabolism, fundamental for candidate drug optimization, are still not completely defined. Here, we performed a proteomic analysis of B. cenocepacia cells treated with one of these inhibitors, and compared it with a cepI deleted strain. Our results demonstrate that the effects of the compound are similar to the deletion of cepI, clearly confirming that these molecules function as inhibitors of the acyl homoserine lactone synthase. Moreover, to deepen our knowledge about the binding mechanisms of the compound to CepI, we exploited previously published in silico structural insights about this enzyme structure and validated different candidate binding pockets on the enzyme surface using site-directed mutagenesis and biochemical analyses. Our experiments identified a region near the predicted S-adenosylmethionine binding site critically involved in interactions with the inhibitor. These results could be useful for future structure-based optimization of these CepI inhibitors.

Burkholderia cenocepacia is an opportunistic pathogen particularly dangerous for cystic fibrosis (CF) patients. It can cause a severe decline in CF lung function possibly developing into a life-threatening systemic infection known as cepacia syndrome. Antibiotic resistance and presence of numerous virulence determinants in the genome make B. cenocepacia extremely difficult to treat. Better understanding of its resistance profiles and mechanisms is crucial to improve management of these infections. Here, we present the clinical distribution of B. cenocepacia described in the last 6 years and methods for identification and classification of epidemic strains. We also detail new antibiotics, clinical trials, and alternative approaches reported in the literature in the last 5 years to tackle B. cenocepacia resistance issue. All together these findings point out the urgent need of new and alternative therapies to improve CF patients’ life expectancy.

Background: Endourologic interventions for urolithiasis in patients with anomalous kidneys can be challenging, and comparisons between these interventions are not well studied. We aim to compare the safety, outcomes and complications of retrograde intrarenal surgery (RIRS) versus percutaneous nephrolithotomy (PCNL) in patients with urolithiasis in anomalous kidneys., Methods: A propensity score-matched pair analysis (PSM) was performed on pooled patient data from 20 centers. 569 patients with anomalous kidneys (horseshoe kidney [HSK], ectopic kidney, malrotated kidney) and urolithiasis who received either PCNL or RIRS as the primary modality of intervention from 2010 to 2020 were analyzed. Patients were matched based on calculated propensity scores by a regression model using age, sex, comorbidities, stone size, and renal anomaly type as co-variates. Multivariate logistic regression of factors (mode of treatment [PCNL or RIRS], comorbidities, stone size) and their effects on outcomes of stone-free rate (SFR), need to abandon surgery due to intraoperative difficulty, postoperative hematuria and sepsis and were analyzed when applicable., Results: After PSM, there were a total of 127 pairs in each group. Overall, PCNL conferred a higher SFR compared to RIRS (OR=3.69, 95% CI 1.91-7.46, P<0.001), particularly in HSK (OR=3.33, 95% CI 1.22-9.99, P=0.023), and ectopic kidneys (OR=18.10, 95% CI 3.62-147.63, P=0.002), with no significant difference in malrotated kidneys. There was no significant difference in postoperative sepsis observed. Surgery was abandoned more often in RIRS than PCNL (6.3% vs. 0%, P=0.014). Although PSM provides a robust analysis due to baseline differences in the unmatched cohorts, this study was limited by an inevitable degree of selection bias., Conclusions: While both modalities are safe and efficacious, PCNL yields better SFR than RIRS in patients with anomalous kidneys, with no difference in postoperative sepsis rates. Patients may benefit from personalized management best carried out in high volume endourology centers.

Background and Aim: The aim of this study is to validate a totally non biologic training model that combines the use of ultrasound and X ray to train Urologists and Residents in Urology in PerCutaneous NephroLithotripsy (PCNL)., Methods: The training pathway was divided into three modules: Module 1, related to the acquisition of basic UltraSound (US) skill on the kidney; Module 2, consisting of correct Nephrostomy placement; and Module 3, in which a complete PCNL was performed on the model. Trainees practiced on the model first on Module 1, than in 2 and in 3. The pathway was repeated at least three times. Afterward, they rated the performance of the model and the improvement gained using a global rating score questionnaire., Results: A total of 150 Urologists took part in this study. Questionnaire outcomes on this training model showed a mean 4.21 (range 1-5) of positive outcome overall. Individual constructive validity showed statistical significance between the first and the last time that trainees practiced on the PCNL model among the three different modules. Statistical significance was also found between residents, fellows and experts scores. Trainees increased their skills during the training modules., Conclusion: This PCNL training model allows for the acquisition of technical knowledge and skills as US basic skill, Nephrostomy placement and entire PCNL procedure. Its structured use could allow a better and safer training pathway to increase the skill in performing a PCNL.

Percutaneous Nephrolithotomy (PCNL) has evolved over the decades from Standard to Mini to Ultramini PCNL to Micro-perc, with miniaturisation being the dominant theme and supine approach gaining momentum world over. Aim: In literature, miniaturised PCNL with microperc needle access system has raised concerns of intrarenal pressure and has some limitations with its success for larger stones. Our tips and tricks explain how to overcome these pitfalls by utilising the full construct of the needle system to its maximum potential. These will in turn help make the procedure versatile, precise, ergonomical, and enhance a surgeon's experience with improved outcomes for patients especially in large renal stones. Materials and Methods: We describe the limitations of microperc needle access as stated in literature and proposals by the co-authors using microperc for miniaturised access on how to overcome the same. Results: A simplified table describing the limitations and tips and tricks on overcoming these is provided for quick reference. Conclusion: As Technological advancements and techniques for miniaturised access in urolithiasis improve, we believe our suggestions will help surgeons overcome the quoted limitations of microperc needle access for miniaturised PCNL, making this a versatile, safe and efficacious technique even in large and complex stones. A multi centre trial will be the best way to validate the suggestions proposed in this article., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Biligere, Heng, Cracco, Mangat, Ong, Thandapani, Inoue, Sarica, Sabnis, Desai, Scoffone and Gauhar.)

Background: Radical nephroureterectomy (RNU) is the gold standard treatment for upper urinary tract urothelial carcinoma (UTUC); however, patients presenting with small low-grade UTUC have been treated by flexible ureteroscopic laser ablation with good outcomes. Different types of laser have been discussed in the literature including Holmium and Neodymium lasers. We aimed to assess the safety and efficacy of Thulium laser (Tm:YAG) in the ureteroscopic ablation of UTUC., Methods: A retrospective observational multicentre study of patients diagnosed with papillary UTUC between January 2015 and December 2016 was carried out. All patients underwent ureteroscopic biopsy of the UTUC followed by Tm:YAG ablation. Based on the histopathological grade of the tumor, patients were counseled to undergo either RNU (high- grade tumors) or conservative management and follow-up (low-grade tumor)., Results: RNU was performed in 31 patients, while the remaining 47 patients (undergone Tm:YAG ablation only) were followed up for a mean of 11.7 months with only 19.2% of patients showing upper tract recurrence and no patients showed postoperative ureteral strictures. Limitations include the short follow-up and retrospective nature of the study., Conclusions: On the short term, thulium Laser ablation of UTUC is safe and feasible especially in low-grade UTUC.

Introduction: Transurethral resection of the prostate (TURP) remains the gold standard for treatment of benign prostatic hyperplasia (BPH). Yet, the introduction of lasers for the treatment of LUTS due to BPO has dramatically changed the surgical landscape of benign prostatic obstruction (BPO) treatment. Recently, "en-bloc" techniques have shown to prove advantageous in terms of better visualization, more prompt identification of the surgical capsule and the correct plane to dissect. Herein we provide a comprehensive overview of available series of en-bloc enucleation of the prostate, focusing on surgical techniques, perioperative and functional outcomes., Evidence Acquisition: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical techniques and perioperative outcomes of minimally invasive en-bloc surgery for prostate adenoma detachment., Evidence Synthesis: Overall, 16 studies with 2750 patients between 2003 and 2019 were included. Specific technical nuances have been described to maximize perioperative outcomes of en-bloc prostatic enucleation, including early apical release, horse-shape incisions, inverted U-shape tractions and low power. Overall, regardless of the energy employed, en-bloc prostatic enucleation achieved favorable outcomes including low risk of major complications and quality of life improvement. However, a great heterogeneity of study design, patients' inclusion criteria, prostate volume and en-bloc surgical strategy was found., Conclusions: En-bloc endoscopic enucleation of the prostate has been shown to be technically feasible and safe, with potential technical advantages over the classic three-lobe technique. Larger comparative studies are needed to evaluate the ultimate impact of the en-bloc approach on postoperative outcomes, in light of the surgeon's learning curve.

Introduction: Percutaneous nephrolithotomy (PNL) is the treatment of choice for larger and complex renal calculi. First step in performing PNL is to obtain access to the renal cavity using either fluoroscopy or ultrasound (US) guidance or a combination of both. Which guiding method to choose is controversial? A systematic review of the literature was performed comparing image guidance modalities for obtaining access in PNL. Evidence acquisition and synthesis: A PubMed, Scopus and Cochrane search for peer-reviewed studies was performed using the keywords "ultrasound" AND "fluoroscopy" AND "Percutaneous nephrolithotomy". Eligible articles were reviewed according to PRISMA criteria. Two hundred and forty records were identified using the keywords. Of these twelve studies were considered relevant., Results: US guidance seems to be associated with a slightly lower complication rate, which may be related to fewer puncture attempts needed for obtaining access and to better peri-renal organ visualization. On the other hand, US-guidance alone needs the adjunct of fluoroscopy in a significant number of cases for achieving access. Stone free rate (SFR) was comparable between groups. Using US for renal access unequivocally reduces radiation exposure., Conclusion: Current evidence indicates that both fluoroscopy and US guidance may be successfully used for obtaining percutaneous renal access. Combining the image-guiding modalities - US and fluoroscopy - seems to increase outcome in PNL both with regard to success in achieving access and reducing complications. Furthermore, including US in the access strategy of PNL reduces radiation exposure to surgeon and staff as well as patients.

Percutaneous nephrolithotomy (PCNL) is considered to be the first line of treatment for large renal stones. Though PCNL comes with higher morbidity, its efficacy is unbeaten by other minimally invasive modalities. However, potential complications, such as bleeding, occur. Improved skills and modifications of the procedure may reduce the probability of adverse outcomes. This article discusses the current trends and standards in PCNL technique with special focus on all important steps as positioning, access, instruments, dilation, disintegration, and exit, including outcomes, complication management, and training modalities.

Background: The aim of this study was to compare the safety and efficacy of RIRS in men ≥65 years to those <65 years., Materials and Methods: Patients who underwent RIRS were prospectively collected from March 2013 to March 2014 in 5 European centers. Perioperative outcomes and complications in elderly men were compared with men <65 years. Univariable and multivariable analyses were performed for factors predicting overall complications. The groups were compared using Mann-Whitney U test. Categorical variables were compared using chi-squared test and the Yates correction or the Fisher's exact test., Results: A total of 399 patients with renal stones were included, 308 (77.19%) were aged <65 years, 91 (22.8%) were aged ≥65 years. Elderly patients were more likely to have higher ASA scores (35.7% vs 92.3%; p < 001), Charlson Comorbidity Index (1.8 vs. 5.2, p < 0.001), hyperlipidemia (10.06% vs. 30.76%; p = 0,0005) and coronary heart disease (5.51% vs. 17.58; p = 0.005) compared to younger cohort. Perioperative outcomes (stone free rate, operative time and re-intervention rate) did not show differences between the two groups (p > 0.05). Surgical and medical complication rates were similar between the cohorts (14.28% vs 9.89%; p = 0.38). Multivariate analysis did not identify any predictive factors of complications among the two groups (p > 0.05)., Conclusions: In this study, elderly RIRS patients had comparable short term efficacy and perioperative complications to younger patients, despite a higher prevalence of comorbidity. Age itself should not be considered as a risk factor for the development of complications in patients undergoing RIRS for renal stone., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: We evaluated a new digital single-use flexible ureteroscope, LithoVue™ with respect to deflection, image quality and maneuverability., Methods: A prospective cohort study was conducted in eight tertiary reference centers in Europe in December 2015 and January 2016. All consecutive patients included underwent flexible ureteroscopy and were 18 years or older. Deflection and image quality pre- and post-use and maneuverability were rated with a Likert scale., Results: A total of 40 procedures were performed (five per institution). The indication for FURS was treatment of renal stones in 92.5 % of the cases. Before LithoVue™ usage, the median measured upward and downward deflections were both 270°. Image quality was rated as "very good" in 65 % of cases and "good" in 30 %. Maneuverability was "very good" in 77.5 % and "good" in 17.5 %. At the final evaluation, median upward and downward deflections were both 270°. Image quality was still "very good" in 65 % of cases and "good" in 30 % with no significant difference compared with preoperative data (p = 1). Maneuverability was "very good" in 72.5 % and "good" in 17.5 %, with no significant difference compared with preoperative data (p = 0.92). Two LithoVue™ broke during surgery (5 %): one occurring in extreme deflection with acute infundibulopelvic angle and spontaneous loss of vision for the second one., Conclusion: The LithoVue™ displayed good image quality, active deflection and maneuverability. Further evaluation of surgical outcomes and cost analysis will help to present the best utility of this single-use FURS in current practice.

Purpose: Retrograde intrarenal surgery (RIRS) is considered a safe procedure; however, infective complications are potentially serious postoperative complications. The aim of this multicentre study was to evaluate prospectively the prevalence of infective complications after RIRS and identify risk factors., Methods: Baseline data were collected, and patients were questioned regarding postoperative infective complications following RIRS. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis., Results: A total of 403 patients from five European centers were included. Antibiotic prophylaxis was administered prior to RIRS in 100 %. Infection complications were recorded in 31 patients (7.7 %), consisting of fever in 18 (4.4 %), SIRS in 7 (1.7), and sepsis in 3 (0.7 %). Three required hospitalization for non-obstructive pyelonephritis (0.7 %). Univariate analysis revealed that coronary heart disease, chronic kidney disease, alteration of lipid metabolism, anticoagulant therapy, past surgery for renal stone, presence of residual fragments were predictors of infective complications. Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection. The low rate of complications may have limited the conclusions from our study., Conclusion: Using a standardized method for the definition and classification of infective complication from a multicentre prospective large database, we find a prevalence of 7.7 % of infective complication among patients undergoing RIRS for renal stone. However, to predict which patients will develop infective complications still remains a clinical challenge.

Purpose: We compare bipolar vs monopolar transurethral prostate resection safety/secondary outcomes including efficacy in patients with large prostate volume or severe lower urinary tract symptoms., Materials and Methods: From July 2006 to June 2009 candidates for transurethral prostate resection were recruited at 4 centers, randomized 1:1 into monopolar/bipolar transurethral prostate resection arms and followed up to 36 months. Post hoc data analysis from patients with large prostate volume or severe lower urinary tract symptoms is presented. Patients with large prostate volume or severe lower urinary tract symptoms were defined as those with transrectal ultrasound based prostate volume greater than 80 ml or International Prostate Symptom Score greater than 19. Safety was estimated using sodium/hemoglobin changes immediately after surgery, complications during the early postoperative period (up to 6 weeks), and short-term (up to 12 months) and midterm (up to 36 months) followup. Secondary outcomes included, among others, efficacy quantified by changes in maximum urine flow rate, post-void residual urine volume and International Prostate Symptom Score compared with baseline., Results: A total of 279 patients were randomized. Post hoc analysis of data from patients with a large prostate volume or severe lower urinary tract symptoms was based on analysis A-in 62 of 279 participants (22.3%) (monopolar transurethral prostate resection 32, bipolar transurethral prostate resection 30) or analysis B-in 126 of 279 participants (45.2%) (monopolar transurethral prostate resection 57, bipolar transurethral prostate resection 69). Mean (SD) prostate volume was 108.0 (25.9) ml for monopolar transurethral prostate resection and 108.9 (23.4) ml for bipolar transurethral prostate resection (p=0.756). Mean International Prostate Symptom Score was 25.0 (4.2) for monopolar transurethral prostate resection and 25.3 (3.7) for bipolar transurethral prostate resection (p=0.402). Neither safety nor any secondary outcome differed significantly between the arms throughout followup. The only exception was the decrease in sodium (analysis A), which was significantly greater after monopolar transurethral prostate resection (-4.2 vs -0.7 mmol/l, p=0.023) and did not translate into a significant difference in transurethral resection syndrome rates (monopolar transurethral prostate resection 1 of 32 vs bipolar transurethral prostate resection 0 of 30, p=1.000)., Conclusions: Bipolar and monopolar transurethral prostate resection show similar safety/efficacy in these patient subpopulations., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess efficacy and safety of prone- and supine percutaneous nephrolithotomy (PCNL) for the treatment of lower pole kidney stones., Methods: Data from patients affected by lower pole kidney stones and treated with PCNL between December 2005 and August 2010 were collected retrospectively by seven referral centres. Variables analysed included patient demographics, clinical and surgical characteristics, stone-free rates (SFR) and complications. Statistical analysis was conducted to compare the differences for SFRs and complication rates between prone- and supine PCNL., Results: One hundred seventeen patients underwent PCNL (mean stone size: 19.5 mm) for stones harboured only in the lower renal pole (single stone: 53.6%; multiple stones: 46.4%). A higher proportion of patients with ASA score ≥ 3 and harbouring multiple lower pole stones were treated with supine PCNL (5.8 vs. 23.1%; p = 0.0001, and 25 vs. 81.5%; p = 0.0001, respectively, for prone- and supine PCNL). One-month SFR was 88.9%; an auxiliary procedure was needed in 6 patients; the 3-month SFR was 90.2%. There were 9 post-operative major complications (7.7%). No differences were observed in terms of 1- and 3-month SFRs (90.4 vs. 87.7%; p = 0.64; 92.3 vs. 89.2%; p = 0.4) and complication rates (7.6 vs. 7.7%; p = 0.83) when comparing prone- versus supine PCNL, respectively., Conclusions: The results confirm the high success rate and relatively low morbidity of modern PCNL for lower pole stones, regardless the position used. Supine PCNL was more frequently offered in case of patients at higher ASA score and in case of multiple lower pole stones.

Objective: To evaluate the pre- and postoperative aspects of sexual life (SL) in patients with bulbar urethral stricture who underwent ventral oral graft urethroplasty., Methods: Between 2009 and 2010, 52 men (mean age 36 years) were enrolled in our prospective study to ascertain sexual disorders before and after surgery. The validated Male Sexual Health Questionnaire-Long Form (MSHQ-LF) was completed pre- and postoperatively; the unvalidated but adapted Post-Urethroplasty Sexual Questionnaire (PUSQ) was completed postoperatively. Data were compared using the non parametric Wilcoxon test., Results: Before urethroplasty, most of the patients reported sexual disorders, in particular reduced ejaculatory stream (85%); many of them (35%) feared the risk of a postoperative worsening in the quality of SL. After urethroplasty, nobody reported a worsened erection, while most of the patients noticed a significant improvement in erection, ejaculation, relationship with their partner, sexual activity, and desire. Modifications in the scrotoperineal sensitivity were reported by 42% and 15% noticed esthetic changes without impact on SL. All patients reported an improvement in quality of life (QOL) and were satisfied with the outcome of urethroplasty., Conclusion: Urethral stricture disease may be responsible for sexual disorders that have a significant impact upon SL. Patients confessed a marked anxiety tackling urethroplasty and declared that one of their deepest fears regarded a potential further deterioration in the quality of SL. At short-term follow-up, the minimally invasive ventral graft urethroplasty does not cause sexual complications, apart from the post-ejaculation dribbling. On the contrary, this technique showed to restore SL in all its aspects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Since its initial clinical use in urology, there has been an increasing enthusiasm and a growing interest for laparoendoscopic single-site surgery (LESS). Several clinical series have been reported with an estimated cumulative clinical experience of more than four hundred so far. Nowadays, virtually all extirpative and reconstructive urological procedures have been described and shown to be feasible and safe, including advanced reconstructive procedures and major extirpative ones. Among them, adrenalectomy and partial nephrectomy represent highly complex procedures. Initial clinical data have been recently reported to test the safety and efficacy of these interventions in selected patients. Herein, we describe our initial cases of unclamp LESS partial nephrectomy and adrenalectomy. In our opinion, LESS is an established technique within the field of minimally invasive surgery. Even if further studies are needed to demonstrate its actual benefits, early clinical outcomes are encouraging and LESS might represent the way to go in minimally invasive urological surgery.

Introduction: The prone position has been considered the only position for percutaneous access to the kidney for the past 25 years, whereas the supine Valdivia position has recently started to gain acceptance, although it was originally described in the late 1980s. Even more recently, the Galdakao-modified supine Valdivia position was described. However, there is no consensus on which is the best position for percutaneous nephrolithotomy, and the choice is currently based on the surgeon's preference., Materials and Methods: The prone, supine, and modified supine positions are described, pointing out the advantages, disadvantages, and results of each technique., Results: A number of potential advantages have been described for the supine over the prone position: less cardiovascular change; no need for patient repositioning (with less associated risk of central and peripheral nervous system injury); less X-ray exposure to the surgeon; and less risk of colonic injury. The recently described Galdakao-modified supine Valdivia position allows for a simultaneous anterograde and retrograde approach to the renal cavities for the one-stage treatment of complex renal stones or concurrent renal and ureteral calculi. Moreover, the use of a flexible ureteroscope allows for Endovision puncture to achieve perfect access to the kidney., Conclusions: The prone position still represents the standard for percutaneous access to the kidney, and other positions should be compared with this position. However, the supine and the modified supine positions have potentially important advantages for both patients and surgeons that need to be investigated in a large randomised trial to define their superiority over the traditional prone position.

Randomised prospective studies have shown that single-stage management of cholecysto-choledocholithiasis yields results equal or superior to sequential treatment, with a lower incidence of complications primarily associated with choledochotomy. We report the first case of transcystic Holmium:YAG laser lithotripsy using a flexible ureteroscope. The method was found to be a valuable aid in reducing the percentage of choledochotomies when calculi are too large to be retrieved from the common bile duct with normal graspers.

Background and Purpose: Laparoscopic radical cystectomy is confined to centers where advanced laparoscopy is performed, and its role is not yet well clear. Our aim was to evaluate, through a prospective comparative study, the advantages of the laparoscopic compared with an open approach., Patients and Methods: From November 2002 to December 2005, all the patients in our center who were found to have muscle-invasive bladder cancer without clinical evidence of lymph-node involvement and an American Society of Anesthesiologists (ASA) score <4 were included in a prospective nonrandomized study. Group A (N = 22) underwent open radical cystectomy, whereas group B (N = 20) underwent laparoscopy-assisted radical cystectomy. The two groups were demographically comparable. We evaluated the mean age, clinical stage, ASA score, operative time, blood loss, intraoperative complications and transfusions, type of diversion, time of catheterization, analgesic consumption, start of oral nutrition, rate of postoperative complications, length of hospital stay, pathologic diagnosis of the specimen, number of lymph nodes removed, and the oncologic outcome., Results: No significant statistical difference was observed between the two groups in intraoperative and postoperative parameters except for analgesic consumption and the start of oral nutrition (P < 0.05). The mean operative time was 260 minutes (range 210-290 minutes) for group A and 284 minutes (range 260-305 minutes) for group B. The mean blood loss was 770 mL (range 450-870 mL) in group A and 520 mL (range 400-620 mL) in group B. The rate of autologous transfusion was 18% in group A and 10% in group B. Seventeen ileal diversions and five neobladder creations were performed in group A, whereas the Bricker diversion was used in 10 cases in group B, and a neobladder was chosen in the 10 other cases., Conclusion: Laparoscopy-assisted radical cystectomy is a safe procedure, like open surgery, but it offers the advantage of minimal invasiveness, represented by reduced analgesic consumption and early recovery of peristalsis with rapid oral nutrition.

Objectives: To assess the clinical role of corticosteroids in the medical expulsive therapy of symptomatic distal ureteral stones., Methods: Between January 2004 and September 2005, 114 patients with symptomatic distal ureteral stones with a >/=5mm diameter were enrolled in this prospective study and divided into four groups based on the urologist (of four) who treated them in the emergency unit. Group A (33 patients) received tamsulosin (0.4mg daily), group B (24 patients) received deflazacort (30mg daily), group C (33 patients) received both (0.4mg tamsulosin+30mg deflazacort daily), and control group D (24 patients) received only analgesics. The treatment duration was 10 d to prevent the side-effects of prolonged corticosteroid therapy. The end points were the expulsion rate, analgesic consumption, number of ureteroscopies, and safety., Results: The groups were comparable in terms of age, sex, and stone location. The stone diameter was 5.96+/-0.33mm for group A, 5.83+/-0.4mm for group B, 5.88+/-0.23mm for group C, and 5.71+/-0.5mm (p>0.05) for group D. The rates of expulsion for the four groups were 60%, 37.5%, 84.8%, and 33.3%, respectively. There was a significant difference between group C and the other groups (p<0.001). The mean analgesic consumption was 42.5+/-0.4mg for group A, 50+/-0.3mg for group B, 27.3+/-0.5mg for group C, and 81+/-0.33mg for group D, with a significant difference between group C and the other groups (p<0.001). During the treatment period, only two cases of drug side-effects related to tamsulosin (without any drop-outs) were recorded., Conclusion: When the medical expulsive therapy for symptomatic distal ureteral stones is considered, the use of steroids (deflazacort) proves efficient only when administered together with alpha(1)-blockers (tamsulosin). In addition, tamsulosin used on its own as a medical expulsive therapy can be considered as an alternative treatment for those patients who are not suitable for steroid therapy, as it is generally efficient.

Objectives: To evaluate the technical advantages of early ligature of the renal artery at the level of the Treitz ligament during left laparoscopic radical nephrectomy (LRN)., Material and Methods: Twenty-six patients underwent LRN for organ-confined lesions. We grouped measured parameters (see Results) on the basis of the first 13 and last 13 patients, and compared both subgroups. All parameters were correlated to stage of disease (pT1 vs pT2-3). The Student t test was used for statistical analysis., Results: The mean (range) for measured parameters are as follows: age: 56.5 +/- 11.6 (41-77) years; American Society of Anesthesiologists score: 2.4 +/- 1 (1-3); body mass index: 23.4 +/- 3.4 (21.1-33); lesion size at computed tomography: (6.2 +/- 2.4 (4-12) cm; operative skin to skin time: 130 +/- 20 (125-170) minutes; blood loss: 255 +/- 120 (100-800) ml; hospital stay: 6.5 +/- 2.0 (4-15) days; analgesic consumption (Tramadol 100 mg): 2.5 +/- 1 (2-4) vials; follow-up time: 30.5 +/- 5.6 (3-48) months. No intra-operative complications occurred. Pathologic analysis showed 12 pT1N0, five pT2N0, eight pT3aN0 and one pT3b N2 with mean lesion size of 6.2 +/- 1.6 (4-13) cm. Mean number of removed lymph nodes was 9.8 +/- 1.6 (7-17). No statistical difference was observed between the two subgroups (p > 0.05), and between pT1 and pT2-3 stage (p > 0.05) groups., Conclusions: Early ligature using direct access to the renal artery at the Treitz ligament permits the surgeon to follow the classic steps and principles of radical nephrectomy.

Objective: The most commonly used staging system for renal cell carcinoma (RCC) is the tumor-node-metastasis (TNM) system. In the most recent TNM edition, lymph node (LN) involvement is defined as pN0, pN1, or pN2, depending on the number of metastatic LNs (none, 1, or >1). This study evaluated the prognostic value of this classification and tried to improve its clinical impact by considering an additional parameter, that is, LN density (ratio between number of positive LNs and total number of LNs retrieved)., Methods: All pathologic reports of radical nephrectomies performed for RCC in two urologic centers between November 1983 and December 1999 were reviewed. For each patient, complete clinical and pathologic data, number of LNs removed, location and number of positive LNs, and LN density were recorded. The Kaplan-Meyer method and the log-rank test were used to calculate cause-specific survival rates and to compare survival curves, respectively., Results: A total of 735 patients underwent radical nephrectomy. Lymphadenectomy was performed in 618 cases, and the rate of positive LNs was 14.2%. The 5-yr cause-specific survival rate of pN+ patients was 18%, with no statistically significant difference between pN1 and pN2. The average number of LNs removed was 13 (range, 1-35). The median number of LNs involved was 3 (range, 1-18). LN density ranged between 3.7% and 100% (median, 22.9%). The number of LNs removed had no impact on survival in pN+ patients. The only significant unfavorable prognostic factors were >4 LNs involved (p = 0.02) and LN density >60% (p = 0.01)., Conclusion: The results show that in RCC the current TNM stratification of positive LNs is not significantly correlated with prognosis. From our data it appears that classification as < or =4 or >4 LNs involved, supported by LN density, better reflects the impact of the disease on survival.

Objectives: The prognostic role of the invasion of the urinary collecting system (UCS) by renal cell carcinoma (RCC) has not attracted a notable amount of attention. The aim of this study was to investigate incidence and prognostic value of UCS involvement in RCC., Material and Methods: All pathological reports of radical nephrectomies performed in two centres of urology from November 1983 to December 1999 were reviewed in order to evaluate the invasion of the UCS (calices, renal pelvis, ureter). Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of UCS invasion. The stage was determined according to the TNM 6th edition. Overall and cause-specific survival rates were evaluated. Univariate and multivariate analyses were performed., Results: The evaluable specimens were 671 from the 735 examined; in 64 cases it was not possible to ascertain or to exclude UCS involvement. Invasion of the UCS was found in 59 cases (8.8%). Median follow-up was 59.0 months (range 0-216). Tumours invading the UCS were usually symptomatic, with high nuclear grade and predominantly high stage. At univariate analysis the 5 year overall and cause-specific survival rates of tumours invading the UCS were significantly lower when compared to those without UCS invasion (42.8% versus 60.8% and 45.5% versus 64.7%, respectively). When groups were stratified, according to the pT category, the 5-year cause-specific survival rate was only significantly different for the pT2 category (33.3% versus 76.9%). At the multivariate analysis TNM staging, symptoms at diagnosis and tumour grade were the only independent prognostic factors., Conclusion: The invasion of the UCS by RCC is unusual, particularly in small tumours. UCS involvement does not represent an independent prognostic factor. However, in organ-confined tumours (i.e. pT2) UCS involvement has an influence on the prognosis and should be taken into account when planning adjuvant treatments and follow-up.

Objective: To determine the number of lymph nodes that need to be examined to accurately stage the pN variable in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC)., Patients and Methods: We reviewed the operative and pathology reports of 725 patients with RCC submitted for RN. All tumours were classified using the fifth edition of the Tumour-Nodes-Metastasis classification. For each patient the number of lymph nodes removed was recorded. The patients were divided into five different groups according to the number of nodes removed, i.e. group 1, 1-4; group 2, 5-8; group 3, 9-12; group 4, 13-16; and group 5, >or= 17. We evaluated the factors that affected the number of lymph nodes removed with nodal dissection and the variables that influenced the incidence of nodal involvement., Results: Lymphadenectomy was performed in 608 patients (83.8%); in these patients the rate of lymph node metastases was 13.6%. The median (range) number of nodes removed was 9 (1-43); there was a statistically significant correlation between the number of nodes removed and the percentage of nodal involvement (r = 0.6; P < 0.01). The rate of pN+ was significantly higher in the patients with >or= 13 than in those with < 13 nodes examined (20.8% vs 10.2%; P < 0.001). For organ-confined and locally advanced tumours there was a statistically significant difference in the pN+ rate between patients with < 13 or >or= 13 nodes examined (3.4% vs 10.5%, and 19.7% vs. 32.2%, respectively)., Conclusions: The proportion of tumours classified as pN+ increased with the number of lymph nodes examined. In RCC,> 12 lymph nodes need to be assessed for optimal staging.

Purpose: Previous in vitro investigations recorded an inhibition of cell proliferation by BCG when added to different cell cultures. The induction of apoptosis by BCG is controversial. Our study aimed to evaluate the influence of BCG on the expression of tumor suppressing proteins p53 and p21Waf1-Cip1 and apoptosis of the urothelial cells in vivo., Materials and Methods: Twenty-one cases of superficial bladder cancer, treated with TUR and subsequent intravesical BCG, were studied retrospectively. The assays evaluated the expression of p53 and p21Waf1-Cip1 by immunochemistry (IHC), and the presence of apoptosis by TUNEL assay. The estimates were performed, in each case, on the following specimens: one tumor sample and one non-neoplastic sample collected during the TUR which preceded the administration of BCG; one non-neoplastic sample collected 3 months after the diagnosis; and one non-neoplastic sample collected in the first 2 weeks after the completion of the treatment. Samples of 6 cancer recurrences detected during BCG were examined too., Results: As usual for non-neoplastic urothelium, the pre-BCG samples displayed poor p53 and p21Waf1-Cip1 immunoreactivity. By contrast, the samples collected during and in the aftermath of BCG showed an overall increase of the expression of both proteins. The rare occurrence of apoptosis proved to be chronologically unrelated to the BCG treatment., Discussion: The relationship between changes of the IHC features and BCG suggests that BCG, at least under some circumstances, can induce the activation of wild type p53 and p21Waf1-Cip1 in the urothelium. The mechanism of the BCG-p53 status interaction and its role in the antitumor activity of BCG remain to be clarified.

In the bladder cancer the most important prognostic factors are the stage, the grade, the presence or absence of lymph nodal metastasis, the response to therapy with B. C. G. etc.... In any case, even in the context of the same clinical stage, it is not possible to correctly evaluate the evolution of the disease. The Author did a literature revision and got a personal contribution about the effective utility of same biological prognostic factors. In a study about superficial bladder tumor using monoclonal antibody MIB-1 (Ki-67) a correlation between proliferation index (P.I.) and grade was noted. In particular the presence of a P.I. above 40% correlated with greater precocity and frequency of recurrences. A similar study showed that the expression of protein p21 correlated with a greater precociousness and with recurrence frequency. In conclusion, we have also carried out an evaluative study on the expression of oncosuppressor gene p53. In superficial bladder cancer this study showed up a correlation between the expression of protein p53 and a greater precociousness and frequency of recurrences.

Objectives: The aim of our study is the evaluation of the prognostic importance of p21 protein in superficial bladder cancer., Methods: One hundred and fourteen patients with an initial diagnosis of monofocal bladder cancer (stage Ta-T1) following TUR were investigated. On the tissue removed by TUR, besides the usual pathological evaluation, an immuno-histochemical investigation was carried out in order to ascertain the presence of c-ras oncogene product (protein p21). The actuarial curves concerning the time free from the first recurrence were computed, comparing different subgroups in regard to protein p21 presence, grade and stage of the tumour., Results: The analysis of the results shows the importance of tumour stage as a predictor of recurrence, as well as that of the presence of c-ras products. This last factor increases the risk of recurrence almost 2-fold, in the same time lag, for c-ras-positive patients (p < 0.001). The prognostic significance of c-ras is independent of stage., Conclusion: Our data underline the possibility of acquiring important information on the prognosis of superficial bladder cancer patients, pointing out the significance of c-ras oncogene product.

We studied the proliferative activity of bladder carcinoma using monoclonal antibody Ki-67, which is able to stain a nuclear antigen exclusively present in cells in the cell cycle, that is with activated deoxyribonucleic acid (DNA). We used this immunohistochemical technique on neoplastic tissue removed by transurethral resection from 101 patients. A significant correlation was observed (p less than 0.003) between cells with activated DNA and histological grading, even though within the context of each grade we observed tumors with a different proliferation index. Furthermore, we studied the location of the activated cells in the context of the tumor. In invasive tumors (stages T1 to T4) cells with activated DNA were always present at the base of implant of the tumor and in the neoplastic tissue that infiltrates the bladder wall. In regard to noninvasive tumors (stage Ta), in 57% of the cases most cells with activated DNA were present in the vegetative portion of the tumor and there were no recurrences at followup, while in 43% of the cases such cells were present also or especially at the base of implant of the tumor, near the lamina propria. In the latter patients we observed a 94% recurrence rate. These results suggest that the immunohistochemical assessment of the proliferative activity of transitional tumors of the bladder, using monoclonal antibody Ki-67, and the evaluation of the location of stained neoplastic cells provide a more reliable estimate of biological aggressiveness than that obtained with histopathological patterns alone.

Priapism, that is a long lasting erection in absence of sexual desire and is sometimes painful, has represented a rare occurrence until few years ago; such occurrence has become much frequent since pharmaco-erection have been used. There are still many doubts about the etiopathogenesis of priapism, that anyway happens because of a long lasting pathological discrepancy between arterious flux to penis corpora cavernosa and venous down flowing. For to establish how and when we must treat priapism, it is very important to know the causes of it, so that we can use the more properly therapy for each case. It's possible to classify the therapies in the following ways: a) extracavernosa, b) located in the corpus cavernosum. These last ones are most used and include the punction and the drainage of the blood of the cavernous body and sometime the "shunt" spongio-cavernosum. The treatment must be effected without loss of time in those rare cases of spontaneous priapism. Indeed, according to our experience, it's not necessary to be extremely supporting for intervention for priapism post pharmaco-erection. In fact the wait of 8-10 hours reduces the number of invasive treatments, without danger for the integrity of cavernous tissue.

The Authors observed a group of 20 patients, each of them suffering from prostatic carcinoma clinically localized in only one lobe. All patients were investigated by trans-rectal US tomography, performed with a 5 MHz linear sound, and by prostatic biopsy in both lobes. The Authors evaluate US tomography results in comparison with biopsy executed on the apparently normal lobe and appreciable sensibility, specificity and predictive capability of this method. The Authors believe that trans-rectal US tomography, after having considered sensitivity and specificity values is not to propose as a screening method for early diagnosis of prostatic carcinoma.

The paper reports the case of a particularly large retroperitoneal liposarcoma (diameter 60 x 28 x 32 cm, weight 11.200 kg) and focuses on the diagnostic and therapeutic aspects of this tumour. The need for radical surgery to remove the entire mass is stressed, even if it is particularly large; likewise, the patient must be carefully monitored since retroperitoneal recurrence is frequent and must be treated, wherever possible, surgically.