Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Robot-assisted radical cystectomy with totally intracorporeal urinary diversion: surgical and early functional outcomes through the learning curve in a single high-volume center.

The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60-74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30-90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.

A new training model for robot-assisted urethrovesical anastomosis and posterior muscle-fascial reconstruction: the Verona training technique.

A training model is usually needed to teach robotic surgical technique successfully. In this way, an ideal training model should mimic as much as possible the "in vivo" procedure and allow several consecutive surgical simulations. The goal of this study was to create a "wet lab" model suitable for RARP training programs, providing the simulation of the posterior fascial reconstruction. The second aim was to compare the original "Venezuelan" chicken model described by Sotelo to our training model. Our training model consists of performing an anastomosis, reproducing the surgical procedure in "vivo" as in RARP, between proventriculus and the proximal portion of the esophagus. A posterior fascial reconstruction simulating Rocco's stitch is performed between the tissues located under the posterior surface of the esophagus and the tissue represented by the serosa of the proventriculus. From 2014 to 2015, during 6 different full-immersion training courses, thirty-four surgeons performed the urethrovesical anastomosis using our model and the Sotelo's one. After the training period, each surgeon was asked to fill out a non-validated questionnaire to perform an evaluation of the differences between the two training models. Our model was judged the best model, in terms of similarity with urethral tissue and similarity with the anatomic unit urethra-pelvic wall. Our training model as reported by all trainees is easily reproducible and anatomically comparable with the urethrovesical anastomosis as performed during radical prostatectomy in humans. It is suitable for performing posterior fascial reconstruction reported by Rocco. In this context, our surgical training model could be routinely proposed in all robotic training courses to develop specific expertise in urethrovesical anastomosis with the reproducibility of the Rocco stitch.

Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

PURPOSE: The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. MATERIALS AND METHODS: Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. RESULTS: The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). CONCLUSIONS: This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL.

Idiopathic stuttering priapism treated with salbutamol orally: a case report.

Recurrent ischaemic priapism also known as stuttering priapism is an uncommon form of ischaemic priapism, and its treatment is not yet clearly defined. If left untreated, it may evolve into classic form of acute ischaemic priapism and lead to erectile dysfunction due to fibrosis of corpora cavernosa. Several drugs have been proposed with variable results and only supported with level three or four of evidence. Hormonal therapy such as cyproterone acetate, oestrogen, bicalutamide or Lh-Rh agonist are often effective but can cause side effects such as hypogonadal state and infertility. Other medical options are 5-alpha-reductase and phosphodiesterase-5 inhibitors, ketoconazole, baclofen, digoxin, gabapentin and beta-2-agonist terbutaline. We report the first case of stuttering priapism treated with beta-2-agonist salbutamol.

Bladder tissue biomechanical behavior: Experimental tests and constitutive formulation.

A procedure for the constitutive analysis of bladder tissues mechanical behavior is provided, by using a coupled experimental and computational approach. The first step pertains to the design and development of mechanical tests on specimens from porcine bladders. The bladders have been harvested, and the specimens have been subjected to uniaxial cyclic tests at different strain rates along preferential directions, considering the distribution of tissue fibrous components. Experimental results showed the anisotropic, non-linear and time-dependent stress-strain behavior, due to tissue conformation with fibers distributed along preferential directions and their interaction phenomena with ground substance. In detail, experimental data showed a greater tissue stiffness along transversal direction. Viscous behavior was assessed by strain rate dependence of stress-strain curves and hysteretic phenomena. The second step pertains the development of a specific fiber-reinforced visco-hyperelastic constitutive model, in the light of bladder tissues structural conformation and experimental results. Constitutive parameters have been identified by minimizing the discrepancy between model and experimental data. The agreement between experimental and model results represent a term for evaluating the reliability of the constitutive models by means of the proposed operational procedure.

A unique case of late complication of rectum mesh erosion after laparoscopic sacrocolpopexy.

Sacrocolpopexy, a surgical technique with a low morbidity rate, is a valid procedure for repairing vaginal vault prolapse. To our knowledge, only 1 case of rectum erosion after open sacrocolpopexy has been reported in the literature, and there is no record of any such incident after laparoscopic sacrocolpopexy. We report the first case of mesh erosion involving the rectum instead of the vagina assessed 8 years after laparoscopic sacrocolpopexy.

Human papillomavirus infection and vaginal tape exposure after midurethral sling: a case report.

Midurethral tape placement is the gold standard procedure for stress urinary incontinence (SUI). Among reported complications, tape erosion is uncommon. Several risk factors have been postulated as causes of vaginal erosion, but none have been demonstrated. Cases of vaginal erosion caused by tape infections have been described, but none has been associated with human papillomavirus (HPV) infection. We report the first case of vaginal exposure in a woman who underwent a midurethral sling procedure for SUI after HPV colonization.

[Reporting and grading of complications after urologic surgical procedures: an ad hoc EAU guidelines panel assessment and recommendations]. / Notificación y clasificación de complicaciones después de procedimientos quirúrgicos urológicos: una evaluación y recomendaciones del panel de guías clínicas de la EAU.

CONTEXT: The incidence of postoperative complications is still the most frequently used surrogate marker of quality in surgery, but no standard guidelines or criteria exist for reporting surgical complications in the area of urology. OBJECTIVE: To review the available reporting systems used for urologic surgical complications, to establish a possible change in attitude towards reporting of complications using standardised systems, to assess systematically the Clavien-Dindo system when used for the reporting of complications related to urologic surgical procedures, to identify shortcomings in reporting complications, and to propose recommendations for the development and implementation of future reporting systems that are focused on patient-centred outcomes. EVIDENCE ACQUISITION: Standardised systems for reporting and classification of surgical complications were identified through a systematic review of the literature. To establish a possible change in attitude towards reporting of complications related to urologic procedures, we performed a systematic literature search of all papers reporting complications after urologic surgery published in European Urology, Journal of Urology, Urology, BJU International, and World Journal of Urology in 1999-2000 and 2009-2010. Data identification for the systematic assessment of the Clavien-Dindo system currently used for the reporting of complications related to urologic surgical interventions involved a Medline/Embase search and the search engines of individual urologic journals and publishers using Clavien, urology, and complications as keywords. All selected papers were full-text retrieved and assessed; analysis was done based on structured forms. EVIDENCE SYNTHESIS: The systematic review of the literature for standardised systems used for reporting and classification of surgical complications revealed five such systems. As far as the attitude of urologists towards reporting of complications, a shift could be seen in the number of studies using most of the Martin criteria, as well as in the number of studies using either standardised criteria or the Clavien-Dindo system. The latter system was not properly used in 72 papers (35.3%). CONCLUSIONS: Uniformed reporting of complications after urologic procedures will aid all those involved in patient care and scientific publishing (authors, reviewers, and editors). It will also contribute to the improvement of the scientific quality of papers published in the field of urologic surgery. When reporting the outcomes of urologic procedures, the committee proposes a series of quality criteria.

An overview on mixed action drugs for the treatment of overactive bladder and detrusor overactivity.

OBJECTIVES: To provide an overview on the efficacy, tolerability, safety and health-related quality of life (HRQoL) of drugs with a mixed action used in the treatment of overactive bladder (OAB). EVIDENCE ACQUISITION: MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words 'overactive bladder', 'detrusor overactivity', 'oxybutynin', 'propiverine', and 'flavoxate'. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis. EVIDENCE SYNTHESIS: Old and conflicting data do not support the use of flavoxate, while both propiverine and oxybutynin were found to be more effective than placebo in the treatment of OAB. Propiverine was at least as effective as oxybutynin but with a better tolerability profile even in the pediatric setting. Overall, no serious adverse event for any product was statistically significant compared to placebo. Improvements were seen in HRQoL with treatment by the oxybutynin transdermal delivery system and propiverine extended release. CONCLUSIONS: While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices.

Insight into new potential targets for the treatment of overactive bladder and detrusor overactivity.

Although overactive bladder (OAB) and detrusor overactivity (DO) are not synonyms, they share therapeutic options and partially underlying physiopathological mechanisms. The aim of this overview is to give insight into new potential targets for the treatment of OAB and DO. A narrative review was done in order to reach this goal. Ageing, pelvic floor disorders, hypersensitivity disorders, morphologic bladder changes, neurological diseases, local inflammations, infections, tumors and bladder outlet obstruction may alter the normal voluntary control of micturition, leading to OAB and DO. The main aim of pharmacotherapy is to restore normal control of micturition, inhibiting the emerging pathological involuntary reflex mechanism. Therapeutic targets can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord and brain. Increased expression and/or sensitivity of urothelial-sensory molecules that lead to afferent sensitization have been documented as a possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors and ion channels could be effective to suppress OAB.

Specific learning curve for port placement and docking of da Vinci(®) Surgical System: one surgeon's experience in robotic-assisted radical prostatectomy.

Port placement and docking of the da Vinci(®) Surgical System is fundamental in robotic-assisted laparoscopic radical prostatectomy (RALP). The aim of our study was to investigate learning curves for port placement and docking of robots (PPDR) in RALP. This manuscript is a retrospective review of prospectively collected data looking at PPDR in 526 patients who underwent RALP in our institute from April 2005 to May 2010. Data included patient-factor features such as body mass index (BMI), and pre-, intra- and post-operative data. Intra-operative information included operation time, subdivided into anesthesia, PPDR and console times. 526 patients underwent RALP, but only those in whom PPDR was performed by the same surgeon without laparoscopic and robotic experience (F.D.M.) were studied, totalling 257 cases. The PPDR phase revealed an evident learning curve, comparable with other robotic phases. Efficiency improved until approximately the 60th case (P < 0.001), due more to effective port placement than to docking of robotic arms. In our experience, conversion to open surgery is so rare that statistical evaluation is not significant. Conversion due to robotic device failure is also very rare. This study on da Vinci procedures in RALP revealed a learning curve during PPDR and throughout the robotic-assisted procedure, reaching a plateau after 60 cases.

[EAU Guidelines on Urinary Incontinence]. / Guías EAU sobre incontinencia urinaria.

CONTEXT: The first European Association of Urology (EAU) guidelines on incontinence were published in 2001. These guidelines were periodically updated in past years. OBJECTIVE: The aim of this paper is to present a summary of the 2009 update of the EAU guidelines on urinary incontinence (UI). EVIDENCE ACQUISITION: The EAU working panel was part of the 4th International Consultation on Incontinence (ICI) and, with permission of the ICI, extracted the relevant data. The methodology of the 4th ICI was a comprehensive literature review by international experts and consensus formation. In addition, level of evidence was rated according to a modified Oxford system and grades of recommendation were given accordingly. EVIDENCE SUMMARY: A full version of the EAU guidelines on urinary incontinence is available as a printed document (extended and short form) and as a CD-ROM from the EAU office or online from the EAU Web site (http://www.uroweb.org/guidelines/online-guidelines/). The extent and invasiveness of assessment of UI depends on severity and/or complexity of symptoms and clinical signs and is different for men, women, frail older persons, children, and patients with neuropathy. At the level of initial management, basic diagnostic tests are applied to exclude an underlying disease or condition such as urinary tract infection. Treatment is mostly conservative (lifestyle interventions, physiotherapy, physical therapy, pharmacotherapy) and is of an empirical nature. At the level of specialised management (when primary therapy failed, diagnosis is unclear, or symptoms and/or signs are complex/severe),more elaborate assessment is generally required, including imaging, endoscopy, and urodynamics. Treatment options include invasive interventions and surgery. CONCLUSIONS: Treatment options for UI are rapidly expanding. These EAU guidelines provide ratings of the evidence (guided by evidence-based medicine) and graded recommendations for the appropriate assessment and according treatment options and put them into clinical perspective.

Evaluating urinary continence and preoperative predictors of urinary continence after robot assisted laparoscopic radical prostatectomy.

PURPOSE: We evaluated urinary continence using a validated questionnaire in a series of consecutive patients who underwent robot assisted laparoscopic radical prostatectomy, and identified the preoperative predictors of the return to urinary continence. MATERIALS AND METHODS: The clinical records of 308 consecutive patients who underwent robot assisted laparoscopic radical prostatectomy for clinically localized prostate cancer at a tertiary academic center were prospectively collected. All patients were continent before surgery. Urinary continence was evaluated using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form instrument. All of the patients reporting no leak in response to the question, "How often do you leak urine?" were defined as continent. RESULTS: A total of 273 patients (90%) were continent 12 months after robot assisted laparoscopic radical prostatectomy. Continent patients were significantly younger (61.4 +/- 6.4 vs 64.1 +/- 6.1 years, p = 0.02) than those who were incontinent. On univariable regression analysis patient age at surgery (OR 1.075, p = 0.024) and Charlson comorbidity index (OR 1.671, p = 0.007) were significantly associated with 12-month continence status. On multivariable analysis age (OR 1.076, p = 0.027) and Charlson comorbidity index (OR 1.635, p = 0.009) were independent predictors of continence rates. CONCLUSIONS: Using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form 90% of patients undergoing robot assisted laparoscopic radical prostatectomy reported no urine leak 12 months after surgery. Patient age at surgery and Charlson comorbidity index were independent predictors of the return to urinary continence, whereas notably no variable related to prostate cancer was significantly correlated with urinary continence.

How accurate are present risk group assignment tools in penile cancer?

OBJECTIVES: To evaluate the accuracy of the predictive models available to estimate the risk of lymph node metastases and cancer-specific survival in patients with squamous cell carcinoma of the penis. METHODS: A nonsystematic review of the literature was performed searching MEDLINE in January 2008. RESULTS: Most of the authors select patients for early inguinal lymphadenectomy according to the pathologic extension of the primary tumor and its histologic grade, as recommended by the EAU Guidelines and the Solsona risk groups. Although the Solsona risk groups performed slightly better, both risk groups had low predictive accuracy. A nomogram including eight clinical and pathologic variables (tumor thickness, microscopic growth pattern, Broder's grade, presence of vascular or lymphatic embolization, infiltrations of the corpora cavernosa, corpus spongiosum or urethra, and the clinical stage of groin lymph nodes) was developed to estimate the risk of lymph node involvement at follow-up. Two nomograms are currently available able to estimate the 5-year cancer-specific survival probabilities of the patients. The first nomogram included the clinical lymph node stage and the same pathological variables of the primary tumor at penectomy, while the pathological stage of the lymph nodes replaced the clinical one in the second model. All the 3 nomograms had good prognostic accuracy. CONCLUSIONS: Both the Solsona and EAU risk group assessment had low prognostic accuracy, although the Solsona risk groups performed slightly better. The nomograms designed to predict the risk of lymph node metastases showed and cancer-specific survival had good prognostic accuracy but their external validation is still lacking.

[Transperineal TRUS-guided prostate biopsy]. / La biopsia prostatica transperineale TRUS guidata

Prostate biopsy can be performed through different approaches, with several differences in patient preparation, procedural technique and post-biopsy patient management. On the basis of our personal experience, and comparing it with literature data, this paper presents our data reviews regarding enema and antibiotic prophylaxis administration, biopsy technique, prostate sampling, core pathological management and post-operative management. We also provide a possible standardization of these procedures in patients undergoing transperineal TRUS-guided prostate biopsy. We accordingly classify antibiotic prophylaxis and bowel preparation as optional/advisable, ultrasound prostate examination before biopsy and local anaesthesia as recommended. Prostate sampling should be performed with at least 8 cores, to be increased proportionally to prostate volume. Each sample should be sent to the pathologist in single containers, according to the pre-embedding sandwich method. Finally, the patient should be evaluated for early complications before discharging, and for delayed complications within one month after the procedure.

Overactive bladder: The importance of new guidance.

Overactive bladder (OAB) affects an estimated 49 million people in Europe, but only a minority receive appropriate treatment. Others are bothered by unacceptable levels of symptoms that severely impair their quality of life and represent a significant financial burden to themselves and to their healthcare providers. Recently updated guidelines from the International Consultation on Incontinence (ICI) and the European Association of Urology (EAU) take account of important new developments in the management of bladder problems in both primary and secondary care. However, local implementation of previous guidance has been variable, with many patients with OAB and other bladder problems failing to gain full benefit from current clinical and scientific understanding of these conditions. The recent expansion of the range of treatments available for OAB and stress urinary incontinence makes it especially important that physicians become aware of the differential diagnosis of these conditions - the questions they need to ask, and the investigations which will help determine the most appropriate course of action.

Obstructive primary bladder neck disease: evaluation of the efficacy and safety of alpha1-blockers.

OBJECTIVE: The efficacy and safety of using alpha(1)-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men was assessed as the first therapeutic step, before surgery, in a symptomatic non-neurogenic selected group of patients. MATERIALS AND METHODS: From January 1995 to December 2001, primary bladder neck obstruction was diagnosed in 41 men whose average age was 43 years. All of them were evaluated by a complete clinical history, American Urological Association (AUA) symptom score index, physical examination, uroflowmetry, transabdominal ultrasound prostatic volume determination, ultrasound post-void residual determination, videourodynamics including pressure-flow analysis and upper urinary tract screening with renal ultrasound or an excretory urogram. A full daily dose of alpha(1)-adrenergic blockers (alfuzosin or tamsulosin) was administered for at least 6 months. Successful treatment was defined as improved symptoms, voiding diary, maximum flow rate and pressure-flow parameters. Patients who did not gain improvement of symptoms with pharmacological treatment were offered surgery. RESULTS: Overall, pharmacological treatment was successful in 29/41 patients (70.7%) whereas bladder neck endoscopic incision was mandatory in 12/41 (29.3%). CONCLUSIONS: alpha(1)-Blockers were effective and safe for treating young and middle-aged men with symptomatic bladder neck obstruction.