Prostate cancer diagnostic pathway in men with lower urinary tract symptoms or performing opportunistic screening: The Italian Society of Urology (SIU) position paper.

BACKGROUND: Voluntary PCa screening frequently results in excessive use of unnecessary diagnostic tests and an increasing risk of detection of indolent PCa and unaffordable costs for the various national health systems. In this scenario, the Italian Society of Urology (Società Italiana di Urologia, SIU) proposes an organized flow chart guiding physicians to improve early diagnosis of significant PCa avoiding unnecessary diagnostic tests and prostate biopsy. METHODS: According to available evidence and international guidelines [i.e., European Association of Urology (EAU), American Association of Urology (AUA) and National Comprehensive Cancer Network (NCCN)] on PCa, a Panel of expert urologists selected by Italian Society of Urology (SIU, Società Italiana di Urologia) proposed some indications to develop a stepwise diagnostic pathway based on the diagnostic tests mainly used in the clinical practice. The final document was submitted to six expert urologists for external revision and approval. Moreover, the final document was shared with patient advocacy groups. RESULTS: In voluntary men and symptomatic patients with elevated PSA value (>3 ng/mL), the Panel strongly discourage the use of antibiotic agents in absence of urinary tract infection confirmed by urine culture. DRE remains a key part of the urologic physical examination helping urologists to correctly interpret PSA elevation and prioritizing the execution of multiparametric Magnetic Resonance Imaging (mpMRI) in presence of suspicious PCa. Men with negative mpMRI and low clinical suspicion of PSA (PSA density < 0.20 ng/mL/cc, negative DRE findings, no family history) can be further monitored. Men with negative mpMRI and a higher risk of PCa (familial history, suspicious DRE, PSAD>0.20 ng/mL/cc or PSA>20 ng/mL) should be considered for systematic prostate biopsy. While PI-RADS 4-5 lesions represent a strong indication for prostate biopsy, PI-RADS 3 lesions should be further stratified according to PSAD values and prostate biopsy performed when PSAD is higher than 0.20. Accreditation, certification, and quality audits of radiologists and centers performing prostatic mpMRI should be strongly considered. The accessibility and/or the waiting list for MRI examinations should be also evaluated in the diagnostic pathway. The panel suggests performing transperineal or transrectal targeted plus systematic biopsies as standard of care. CONCLUSIONS: Scientific societies must support the use of shared diagnostic pathway with the aim to increase the early detection of significant PCa reducing a delayed diagnosis of advanced PCa. Moreover, a shared diagnostic pathway can reduce the incorrect use of antibiotic, the number of unnecessary laboratory and radiologic examinations as well as of prostate biopsies.

Organized prostate cancer screening program: a proposal from the Italian Society of Urology (SIU).

To contrast opportunistic PCa screening, the European Union Council suggested extending screening programs to PCa by recommending the implementation of a stepwise approach in the EU Countries to evaluate the feasibility and effectiveness of an organized program based on PSA testing in combination with additional MRI as a follow-up test. The objective of this expert-based document is to propose an organized PCa screening program according to the EU Council recommendations. The Italian Society of Urology (SIU) developed a team of experts with the aim to report 1) the most recent epidemiologic data about incidence, prevalence, and mortality of PCa; 2) the most important risk factors to identify categories of men with an increased risk to eventually develop the disease; 3) the most relevant studies presenting data on population-based screening; and 4) the current recommendations of the leading International Guidelines. According to previous evidence, the Panel proposed some indications to develop a new organized PCa screening program for asymptomatic men with a life-expectancy of at least fifteen years. The SIU Panel strongly supports the implementation of a pilot, organized PCa screening program inviting asymptomatic men in the age range of 50-55 years. Invited men who are already performing opportunistic screening will be randomized to continue opportunistic screening or to cross into the organized protocol. Men with PSA level ≤3 ng/mL and familiarity for PCa received a DRE as well as all those with PSA levels >3 ng/mL. All other men with PSA levels greater than 3 ng/mL proceed to secondary testing represented by mpMRI. Men with Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3 and PSAD 0.15 ng/mL/cc or higher as well as those with PI-RADS 4-5 lesions proceed to targeted plus systematic prostate biopsy. The primary outcome of the proposed pilot PCa screening program will be the detection rate of clinically significant PCa defined as a tumor with a ISUP Grade Group ≥2. Main secondary outcomes will be the detection rate of aggressive PCa (ISUP Grade Group ≥4); the detection rate of insignificant PCa (ISUP Grade Group 1); the number of unnecessary prostate biopsy avoided, the metastasis-free survival, and the overall survival. Men will be invited over a one-year period. Preliminary analyses will be planned 2 and 5 years after the baseline enrollment. According to the recent EU Council recommendations on cancer screening, pilot studies evaluating the feasibility and effectiveness of PCa screening programs using PSA as the primary and mpMRI as the secondary screening test in selected cohorts of patients must be strongly promoted by scientific societies and supported by national governments.

Evaluation of Clinical Research on Novel Multiport Robotic Platforms for Urological Surgery According to the IDEAL Framework: A Systematic Review of the Literature.

Background and objective: Several novel multiport robotic systems have been developed and introduced in clinical practice after regulatory approval. The objective of this systematic review was to assess the evolution status of novel robotic platforms approved for clinical use in urological surgery according to the IDEAL framework. Methods: A systematic review was conducted using the Medline and Scopus databases according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42024503227). Comparative or noncomparative studies reporting on any urological procedures performed with novel robotic platforms (Hugo RAS; Versius, KangDuo, Senhance, REVO-I, Avatera, Hinotori, Dexter, or Toumai) were selected and included in the analysis. Key findings and limitations: Seventy-four eligible studies were included, of which 67 (90.5%) were noncomparative surgical series representing developmental or explorative studies according to the IDEAL criteria. Only one randomised controlled trial (comparing KangDuo vs da Vinci robot-assisted partial nephrectomy) was included. The trial showed comparable perioperative outcomes between the two robotic systems. Four studies assessed clinical outcomes for patients undergoing urological procedures using a REVO-I (1 study), Senhance (2 studies), or Hinotori (1 study) system in comparison to the same procedures performed using a da Vinci system. All studies revealed outcomes comparable to those with the da Vinci system. Limitations include the small sample size in all studies, and assessment of first-generation novel platforms versus the fourth-generation multiarm da Vinci system in most of the comparative studies. Conclusions and clinical implications: A few poor-quality studies have compared the use of novel robotic platforms to da Vinci systems in urological surgery and demonstrated comparable results. Most studies can be classified as developmental or explorative, representing the initial steps of clinical research. Large multicentre series are needed to understand whether these novel robots could offer advantages beyond cost reductions over the da Vinci systems. Patient summary: We reviewed research on new robotic systems for surgery in urology. Several studies have shown the feasibility and safety of these new robots during the most common procedures. Very few studies have assessed clinical outcomes with the new robots in comparison to the reference standard, which is a fourth-generation da Vinci robot. Large multicentre studies are needed to understand whether the new robots could offer advantages other than cost savings over the da Vinci robot.

A Novel Liquid Biopsy Method Based on Specific Combinations of Vesicular Markers Allows Us to Discriminate Prostate Cancer from Hyperplasia.

BACKGROUND: Prostate cancer is the second most common cancer in males worldwide, and its incidence is rising. Early detection is crucial for improving the outcomes, but the current screening methods have limitations. While prostate-specific antigen (PSA) testing is the most widely used screening tool, it has poor specificity, leading to a high rate of false positives and unnecessary biopsies. The existing biopsy techniques are invasive and are associated with complications. The liquid biopsy methods that analyze the biomarkers in blood or other bodily fluids offer a non-invasive and more accurate alternative for detecting and characterizing prostate tumors. METHODS: Here, we present a novel liquid biopsy method for prostate cancer based on the identification of specific proteins in the extracellular vesicles isolated from the blood of patients with prostate cancer. RESULTS: We observed that a specific combination of sEV proteins is a sensitive indicator of prostate cancer. Indeed, we found that the number of clusters expressed by specific combinations of either intra-vesicular (STAT3 and CyclinD1) or surface proteins (ERBB3, ALK, and CD81) allowed us to significantly discriminate the patients with prostate cancer from the individuals with hyperplasia. CONCLUSION: This new liquid biopsy method has the potential to improve prostate cancer screening by providing a non-invasive and more accurate diagnostic tool.

International consensus panel for transurethral resection of bladder tumours metrics: assessment of face and content validity.

OBJECTIVE: To develop performance metrics that objectively define a reference approach to a transurethral resection of bladder tumours (TURBT) procedure, seek consensus on the performance metrics from a group of international experts. METHODS: The characterisation of a reference approach to a TURBT procedure was performed by identifying phases and explicitly defined procedure events (i.e., steps, errors, and critical errors). An international panel of experienced urologists (i.e., Delphi panel) was then assembled to scrutinise the metrics using a modified Delphi process. Based on the panel's feedback, the proposed metrics could be edited, supplemented, or deleted. A voting process was conducted to establish the consensus level on the metrics. Consensus was defined as the panel majority (i.e., >80%) agreeing that the metric definitions were accurate and acceptable. The number of metric units before and after the Delphi meeting were presented. RESULTS: A core metrics group (i.e., characterisation group) deconstructed the TURBT procedure. The reference case was identified as an elective TURBT on a male patient, diagnosed after full diagnostic evaluation with three or fewer bladder tumours of ≤3 cm. The characterisation group identified six procedure phases, 60 procedure steps, 43 errors, and 40 critical errors. The metrics were presented to the Delphi panel which included 15 experts from six countries. After the Delphi, six procedure phases, 63 procedure steps, 47 errors, and 41 critical errors were identified. The Delphi panel achieved a 100% consensus. CONCLUSION: Performance metrics to characterise a reference approach to TURBT were developed and an international panel of experts reached 100% consensus on them. This consensus supports their face and content validity. The metrics can now be used for a proficiency-based progression training curriculum for TURBT.

Short-term effects of bowel function on global health quality of life after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) shows an important impact on quality of life (QoL), for various clinical aspects. The aim of our study was to evaluate the short-term bowel function in patients that underwent RC. METHODS: Two hundred and six patients with MIBC underwent RC with ONB or IC urinary diversion. QoL was measured using the EORTC QLQ C30 and the Short-Form SF-36 questionnaires before surgery and at 12 months postoperatively. Baseline characteristics, including demographic profile, BMI, Charlson Comorbidity Index (CCI), modified Frailty Index (m-FI), pathological tumor stage, Clavien-Dindo grade, and neo-adjuvant chemotherapy were recorded and compared. RESULTS: The uni-variate and multivariate analysis (OR) were performed for constipation, diarrhea and m-FI of patients underwent RC for localized MIBC according to global health status score (poor/good vs. very good). Multivariate analysis showed that constipation medium/high was significant associated with global health status poor/good (OR=2.39; 95% CI: 1.22-4.71; P=0.01); Diarrhea medium/high was associated with global health status poor/good (OR=2.85; 95% CI:1.18-6.92; P=0.02), and m-FI ≥2 score (OR=2.13; 95% CI: 0.99-4.57; P=0.05). CONCLUSIONS: Diarrhea and constipation are associated with a lower QoL in cystectomized patients, both with ONB or IC urinary diversion; such association is especially significant in more fragile patients (Frailty Index ≥2).

Minimally invasive transperitoneal partial versus radical nephrectomy in obese patients: perioperative and long-term functional outcomes from a large perspective contemporary series (RECORd2 project).

BACKGROUND: The aim of this study is to evaluate the perioperative and long-term functional outcomes of laparoscopic (LPN) and robot-assisted partial nephrectomy (RAPN) in comparison to laparoscopic radical nephrectomy (LRN) in obese patients diagnosed with renal cell carcinoma. METHODS: Clinical data of 4325 consecutive patients from The Italian REgistry of COnservative and Radical Surgery for cortical renal tumor Disease (RECORD 2 Project) were gathered. Only patients treated with transperitoneal LPN, RAPN, or LRN with Body Mass Index (BMI) ≥30 kg/m2, clinical T1 renal tumor and preoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min, were included. Perioperative, and long-term functional outcomes were examined. RESULTS: Overall, 388 patients were included, of these 123 (31.7%), 120 (30.9%) and 145 (37.4%) patients were treated with LRN, LPN, and RAPN, respectively. No significant difference was observed in preoperative characteristics. Overall, intra and postoperative complication rates were comparable among the groups. The LRN group had a significantly increased occurrence of acute kidney injury (AKI) compared to LPN and RAPN (40.6% vs. 15.3% vs. 7.6%, P=0.001). Laparoscopic RN showed a statistically significant higher renal function decline at 60-month follow-up assessment compared to LPN and RAPN. A significant renal function loss was recorded in 30.1% of patients treated with LRN compared to 16.7% and 10.3% of patients treated with LPN and RAPN (P=0.01). CONCLUSIONS: In obese patients, both LPN and RAPN showcased comparable complication rates and higher renal function preservation than LRN. These findings highlighted the potential benefits of minimally invasive PN over radical surgery in the context of obese individuals.

Partial nephrectomy for renal tumors: recommendations of the Italian Society of Urology RCC working group.

INTRODUCTION: Partial nephrectomy (PN) aims to remove renal tumors while preserving renal function without affecting oncological and perioperative surgical outcomes. Aim of this paper is to summarize the current evidence on PN and to provide evidence-based recommendations on indications, surgical technique, perioperative management and postoperative surveillance of PN for renal tumors in the Italian clinical and health care system context. EVIDENCE ACQUISITION: This review is the result of an interactive peer-reviewing process of the recent literature on PN for renal tumors carried out by an expert panel composed of members of the Italian Society of Urology (SIU) Renal Cell Carcinoma Working Group. EVIDENCE SYNTHESIS: PN for localized renal tumors is not inferior to radical nephrectomy in terms of survival outcomes while significantly better preserving renal function. Loss of renal function after PN is influenced by medical comorbidities/preoperative renal function and surgical variables such volume of parenchyma preserved and ischemia time. Urologists should select the clamping strategy during PN based on their experience and patient-specific factors. PN can be performed with any surgical approach based on surgeon's expertise and skills. Robotic PN has the potential to expand the minimally invasive indications without interfering with oncological outcomes. The use of 3D virtual models, real time ultrasound and fluorescence tools to assess the anatomy and vascularization of renal tumors during PN may allow a more accurate preoperative planning and intraoperative guidance. Proper postoperative surveillance protocols are essential to detect tumor recurrences and assess functional outcomes. CONCLUSIONS: PN is the standard of care for treatment of localized T1 renal tumors. Recent data supports PN also for selected T2-T3a tumors in experienced institutions. Careful preoperative planning, adequate surgical skills and volumes and appropriate postoperative management and surveillance are paramount to optimize PN oncological and functional outcomes.

Open questions on lower urinary tract infections: Results of a Delphi consensus study.

BACKGROUND AND OBJECTIVE: This is a Delphi study that aims to explore expert consensus regarding open questions in current literature evidence on lower urinary tract infections (UTIs). This manuscript deals with adults and analyzed the most recent guidelines and meta-analysis on the topic. METHODS: A panel of leading urologists and urogynaecologists participated in a consensus-forming project using a Delphi method to reach consensus on gray zone issues on recurrent lower UTIns (rUTIs), asymptomatic bacteriuria (AB) in pregnant women, and catheter-associated UTIs (CAUTI) in adults. All the panelists were invited to participate the four phases consensus. Consensus was defined as ≥75% agreement. An ordinal scale (0-10) was used. A systematic literature review was analyzed for diagnostic workup and prevention of rUTIs, AB, and CAUTI. RESULTS: In total, 37 experts participated. All panelists participated in the four phases of the consensus process. Consensus was reached if ≥75% of the experts agreed on the proposed topic. Online meetings and a face-to-face consensus meeting was held in Milan in March 2023. Formal consensus was achieved for 12/13 items. CONCLUSIONS: This manuscript is a Delphi survey of experts that showed interest on some debated points on rUTIs, AB in pregnancy, and prevention of CAUTI. There is still little data on nonantibiotic prevention of UTIs and CAUTI; quite old studies have been reported on AB in pregnancy. The emerging problem of antibiotic resistance is relevant and nonantibiotic prophylaxis may play a role in its prevention.

Combined spinal and epidural anaesthesia for open radical cystectomy: A controlled study.

Objectives: To evaluate the feasibility of loco-regional anaesthesia and to compare perioperative outcomes between loco-regional and standard general anaesthesia in patients with bladder cancer undergoing open radical cystectomy (ORC). Patients and Methods: A single-surgeon cohort of 60 consecutive patients with bladder cancer undergoing ORC with an enhanced recovery after surgery protocol between May 2020 and December 2021 was analysed. A study group of 15 patients operated on under combined spinal and epidural anaesthesia was compared with a control group of 45 patients receiving standard general anaesthesia. Intraoperative outcomes were haemodynamic stability, estimated blood loss, intraoperative red blood cell transfusion rate, and anaesthesia time. Postoperative outcomes were pain assessment 24 h after surgery, time to mobilisation, return to oral diet, time to bowel function recovery, length of stay and rate of 90-day complications. Results: No patients required conversion from loco-regional to general anaesthesia. All patients in both groups were haemodynamically stable. No significant differences between groups were observed for all other intraoperative outcomes, except for a shorter anaesthesia time in the study versus control group (250 vs. 290 min, p = 0.01). Pain visual score 24 h after surgery was significantly lower in the study versus control group (0 vs. 2, p < 0.001). No significant differences were observed for all other postoperative outcomes, with a comparable time to bowel function recovery (5 days in each group for stool passage), and 90-day complication rate (46.6% vs. 42.2% for the study vs. control group, p = 0.76). Conclusion: Our exploratory, controlled study confirmed the feasibility, safety and effectiveness of a pure loco-regional anaesthesia in patients with bladder cancer undergoing ORC. No significant differences were observed in intra- and postoperative outcomes between loco-regional and general anaesthesia, except for a significantly shorter anaesthesia time and greater pain reduction in the early postoperative period for the former.

Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening

ABSTRACT Objective: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. Material and Methods: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. Results: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3), and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. Conclusions: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.

Impacts on functional and oncological outcomes of Robotic-assisted Radical Prostatectomy 10 years after the US Preventive Service Taskforce recommendations against PSA screening.

OBJECTIVE: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. MATERIAL AND METHODS: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. RESULTS: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. CONCLUSIONS: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Outcomes and treatment failure after open or robotic ureteral reconstruction for iatrogenic injuries.

Objectives: The aim of this study is to assess the aetiology, perioperative outcomes and treatment failure of contemporary patients undergoing open or robot-assisted ureteral reconstruction for iatrogenic injuries. Patients and methods: We retrospectively analysed consecutive patients who underwent ureteral reconstruction for iatrogenic injuries at two academic centres 07/2013 and 06/2022. A variety of open or robot-assisted procedures were performed, including uretero-cystoneostomy, Boari bladder flap, uretero-ureterostomy, ileal replacement and pyelo-ureteroplasty. All procedures were performed by a single surgeon with extensive experience in open and robot-assisted surgery and preference-based management. Outcome measures were aetiology, estimated blood loss, length of stay, postoperative complications and treatment failure, defined as upper tract obstruction requiring permanent urinary drainage. We also planned a subgroup analysis comparing the outcomes between open and robot-assisted procedures. Results: Fifty-nine patients were included. Most injuries were consequent to endourological procedures (44%). The most frequently performed procedures were uretero-cystoneostomy (49.2%) and Boari bladder flap (32.2%). Forty (67.8%) were open, and 19 (32.2%) were robot-assisted procedures. Major postoperative complications were recorded in seven (11.9%) patients. After a median follow-up of 42 months (interquartile range 12-24), treatment failure was observed in seven (11.9%) cases. Robot-assisted versus open procedures were associated with decreased estimated blood loss (p = 0.01), length of stay (p < 0.001) and treatment failure (0/19 vs. 7/36, p = 0.04). Conclusion: In our series of iatrogenic ureteral lesions requiring reconstructive surgery, endourological procedures were the most frequent cause. Major postoperative complications were infrequent, and treatment failure rate was low. The robot-assisted approach was associated with improved perioperative outcomes and lower failure rate compared with open.

Double-Layered Hand-Sewn versus Stapled Intestinal Anastomosis in Patients Who Underwent Ileal Urinary Diversion in Radical Cystectomy: A Comparative and Cost Effective Study.

INTRODUCTION: Intestinal anastomosis can be performed by hand suturing (single layer or double layer) or by a mechanical suturing machine. The aim of the study was to compare complications, operative time, and costs of the intestinal anastomosis techniques. METHODS: A retrospective comparative study was conducted including patients who underwent radical cystectomy and uretero-ileo-cutaneostomy or vescica ileale Padovana orthotopic neobladder. Double-layered hand-sewn intestinal anastomosis (HS-IA) were performed using Vicryl stitches. Mechanical-stapled intestinal anastomosis (MS-IA) were performed with a mechanical stapler. RESULTS: Data of 195 patients who underwent were collected. 100 (51.3%) patients underwent HS-IA and 95 (48.7%) patients underwent MS-IA. Considering the complications classified according to Clavien-Dindo, a statistical difference with higher incidence for grade one in the HS-IA both in the ileal conduit group and in the neobladder one than the MS-IA (15.8% and 8.7%, respectively, in HS-IA vs. 1.7% and none in MS-IA). There is not a significant difference in time to flatus and time to defecation. Difference is recorded in the ileal conduit groups for the length of stay (10 days, range 9-12 with HS-IA vs. 13 days range 12-16 days with MS-IA (p < 0.001). The cost of the suture thread used for a single operation was 0.40 euros, whereas the overall cost of a disposable mechanical stapler and one refill was 350.00 €. CONCLUSION: Both HS-IA and MS-IA are safe and effective for patients. The cost for the stapling device is 350 €, in contrast, the cost for Vicryl sutures is negligible.

Nature of the Interaction of Alpha-D-Mannose and Escherichia coli Bacteria, and Implications for its Regulatory Classification. A Delphi Panel European Consensus Based on Chemistry and Legal Evidence.

The nature of alpha-D-mannose-natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections-in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. PRISMA systematic review approach was applied; Delphi Panel method was used to target consensus on statements retrieved from evidence. Based on regulatory definitions and research evidence, the mechanism of D-mannose does not involve a metabolic or immunological action while there is uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. On the basis of current regulation, the uncertainty as regard a pharmacological action of alpha-D-mannose makes possible its medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

Incidence of Rectal Injury After Radical Prostatectomy: A Systematic Review and Meta-analysis.

Context: Rectal injury (RI) is a dreaded complication after radical prostatectomy (RP), increasing the risk of early postoperative complications, such as bleeding and severe infection/sepsis, and late sequelae, such as a rectourethral fistula (RUF). Considering its traditionally low incidence, uncertainty remains as to predisposing risk factors and management. Objective: To examine the incidence of RI after RP in contemporary series and to propose a pragmatic algorithm for its management. Evidence acquisition: A systematic literature search was performed using the Medline and Scopus databases. Studies reporting data on RI incidence were selected. Subgroup analyses were conducted to assess the differential incidence by age, surgical approach, salvage RP after radiation therapy, and previous benign prostatic hyperplasia (BPH)-related surgery. Evidence synthesis: Eighty-eight, mostly retrospective noncomparative, studies were selected. The meta-analysis obtained a pooled RI incidence of 0.58% (95% confidence interval [CI] 0.46-0.73) in contemporary series with significant across-study heterogeneity (I2 = 100%, p < 0.00001). The highest RI incidence was found in patients undergoing open RP (1.25%; 95% CI 0.66-2.38) and laparoscopic RP (1.25%; 95% CI 0.75-2.08) followed by perineal RP (0.19%; 95% CI 0-276.95) and robotic RP (0.08%; 95% CI 0.02-0.31). Age ≥60 yr (0.56%; 95% CI 0.37-06) and salvage RP after radiation therapy (6.01%; 95% CI 3.99-9.05), but not previous BPH-related surgery (4.08%, 95% CI 0.92-18.20), were also associated with an increased RI incidence. Intraoperative versus postoperative RI detection was associated with a significantly decreased risk of severe postoperative complications (such as sepsis and bleeding) and subsequent formation of a RUF. Conclusions: RI is a rare, but potentially devastating, complication following RP. RI incidence was higher in patients ≥60 yr of age, and in those who underwent open/laparoscopic approach or salvage RP after radiation therapy. Intraoperative RI detection and repair apparently constitute the single most critical step to significantly decrease the risk of major postoperative complications and subsequent RUF formation. Conversely, intraoperatively undetected RI can lead more often to severe infective complications and RUF, the management of which remains poorly standardised and requires complex procedures. Patient summary: Accidental rectum tear is a rare, but potentially devastating, complication in men undergoing prostate removal for cancer. It occurs more often in patients aged 60 yr or older as well as in those who underwent prostate removal via an open/laparoscopic approach and/or prostate removal after radiation therapy for recurrent disease. Prompt identification and repair of this condition during the initial operation are the key to reduce further complications such as the formation of an abnormal opening between the rectum and the urinary tract.

Is EMA warning on quinolones and fluoroquinolones really assessed? An EudraVigilance database analysis.

BACKGROUND: On March 11th 2019, European Medicines Agency (EMA) issues a warning after a review of serious, disabling and potentially permanent adverse events (AEs), particularly on musculoskeletal and nervous system, with quinolone (QN) and fluoroquinolone (FQ) antibiotics. Aim of this study was to evaluate the effect of the EMA warning on the rate of AEs after QN and FQ treatments, reported in the EudraVigilance (EV) database. METHODS: EV database is the system for managing and analyzing information on suspected AEs to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We retrospectively explored the effect of FQs and QNs on musculoskeletal and nervous system from the EMA warning up to now (21 months) and compared these results with the 21 months before the EMA warning. RESULTS: Main part of AEs in EV database were reported for ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin. Ciprofloxacin total AEs before 21 months till 12 months of EMA warning were 2763. 12 months before EMA Warning they were 2935. Twelve months after EMA Warning they were 3419. Between 12 months till 21 months they were 3174. Musculoskeletal disorders were respectively 574 (21% of the total) 21 months before, 558 (19%) 12 months before, 1048 (31%) after 12 months, 540 (17%) after 21 months of EMA Warning. Nervous system disorders were respectively 606 (22% of the total) 21 months before, 517 (18%) 12 months before, 680 (20%) after 12 months, 560 (18%) after 21 months of EMA Warning (respectively OR 1,16 95%CI 1,10 -1,22, P 0,12 ; OR 0,76 95%CI 0,69-0,83, P 0,27 ; OR 1,01 95%CI 0,96-1,06 P 0,05). CONCLUSIONS: Our analysis clearly showed no significant differences before and after EMA warning, opening new insights in the role of the EMA warning in clinical practice.

Impact of anabolic androgenic steroids on male sexual and reproductive function: a systematic review.

INTRODUCTION: Anabolic-androgenic steroids (AASs) are a complex cluster of synthetic derivatives of testosterone. AAS abuse is considered a major public health issue since it has increased among young/adolescent males. The use of steroids has a prevalence rate of 14% in young athletes and 30-75% in professional athletes or bodybuilders. AASs simulate the testosterone mechanism, binding the intracellular androgen receptor, and dysregulating the normal hypothalamic-pituitary-gonadal axis in the same way as exogenous testosterone. Abuse can produce several side effects on organs, such as the genital system. The physio-pathological mechanisms that cause AAS abuse-related, genital system disorders in humans are still not completely known. EVIDENCE ACQUISITION: This study focuses on the effect of AASs on the male reproductive organs in humans and animals. EVIDENCE SYNTHESIS: A systematic review was performed using SCOPUS, PubMed, Google Scholar, and Web of Sciences database up to 31 December 2021 using the keywords: "anabolic-androgenic steroids," "erectile dysfunction," "spermatogenesis" and "infertility;" (anabolic agents) "erectile dysfunction," "spermatogenesis" and "infertility." The review of the literature identified 66 articles published until 2021. Sixty-two articles were included. The use of AASs induces testicular atrophy and azoospermia known as "anabolic steroid-induced hypogonadism." Anabolic steroid induced infertility is characterized by oligo or azoospermia and abnormalities in sperm motility and morphology. Although sperm quality recovers in most cases within 4 months of stopping anabolic steroid abuse, the negative consequences on spermatogenesis can take up to 3 years to disappear. Human studies reported a positive correlation between AAS abuse in athletes and an increase in morphologically abnormal spermatozoa. Animal studies showed the destruction of Leydig cells and testicular atrophy in animals treated with cycles of AASs. CONCLUSIONS: The present review of the literature highlights how little is known about the action of AASs on the male genital system. However, although their use is prohibited in many countries, the black market for these substances is still very frequent. The scientific landscape still has a lot to invest in the research of AAS on the male genital system to make young people even more aware of the negative aspects of these substances, contributing to the reduction of these products in an inappropriate way.