Robot-Assisted Radical Cystectomy: A Single-Center Experience and a Narrative Review of Recent Evidence.

Radical cystectomy represents one of the most challenging surgical procedures, exhibiting a high morbidity rate. The transition to minimally invasive surgery in the field has been steep, due to either the technical complexity and prior concerns of atypical recurrences and/or peritoneal spread. More recently, a larger series of RCTs has proven the oncological safety of robot-assisted radical cystectomy (RARC). Beyond survival outcomes, the comparison between RARC and open surgery in terms of peri-operative morbidity is still ongoing. We present a single-center experience of RARC with intracorporeal urinary diversion. Overall, 50% of patients had an intracorporeal neobladder reconstruction. The series confirms a low rate of complications (Clavien Dindo ≥ IIIa 7.5%) and wound infections (2.5%) and the absence of thromboembolic events. No atypical recurrences were found. To discuss these outcomes, we reviewed the literature related to RARC including level-1 evidence. PubMed and Web of Science searches were performed using the medical subject terms "robotic radical cystectomy" and "randomized controlled trial (RCT)". Six unique RCTs comparing robot and open surgery were found. Two clinical trials dealt with RARC with an intracorporeal reconstruction of UD. Pertinent clinical outcomes are summarized and discussed. In conclusion, RARC is a complex but feasible procedure. The transition from extracorporeal urinary diversion (UD) to a complete intracorporeal reconstruction could be the key to improving peri-operative outcomes and reducing the whole morbidity of the procedure.

Dabigatran overload in acute kidney injury: haemodialysis or idarucizumab? A case report and proposal for a decisional algorithm.

Dabigatran overload has been reported in acute kidney injury (AKI), leading to occasional major bleeding. Haemodialysis (HD) was the method used for reversing dabigatran anticoagulant effects before the approval of idarucizumab, which is now indicated for dabigatran reversal in major bleeding or surgical emergencies. There have been reports of rebound of dabigatran levels following idarucizumab administration in AKI, requiring HD to achieve effective dabigatran clearance. However, a decisional algorithm to individualize treatments for dabigatran overload seems lacking. We present a case of dabigatran accumulation in obstructive AKI with minor bleeding that was successfully treated with HD and tranexamic acid without using idarucizumab, and propose a decision-making algorithm including different pathways in the management of suspected dabigatran overload in AKI.

Flower Pollen Extract in Association with Vitamins (Deprox 500®) Versus Serenoa repens in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Comparative Analysis of Two Different Treatments.

OBJECTIVE: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is reported in the literature ranging from 1 to 14.2%. The aim of the present study was to assess the impact on patient's quality of life and symptoms of Flower pollen extract in association with vitamins (Deprox 500®) in comparison with Serenoa repens 320 mg (Permixon 320 mg® by Pierre Fabre) in patients with CP/CPPS. METHODOLOGY: All consecutive patients, with a diagnosis of CP/CPPS, referred to our center from January to August 2016, were screened to be enrolled in this single-center, randomized, controlled trial. The main outcome measure was the evaluation of IPSS/NIHCPSI (International Prostatic Symptom Score/NIH-Chronic Prostatitis Symptom Index) score variation and the assessment of the quality of life and symptoms at the end of the therapy. The second outcome measure was the evaluation of the comorbidity role in the CP/CPPS therapy. 63 patients were analyzed; patients were randomized into two groups: 29 patients were treated with Deprox 500® 2 tablets/day for 6 weeks and 34 patients with Serenoa repens 320 mg, 1 tablet/day for 6 weeks. RESULTS: The mean score variation for IPSS was -12.7 ± 4.3 in the Deprox 500® group and -7.8 ± 4.7 in the Serenoa repens group (p=0.0005) while for NIH-CPSI was -17.3±3.1 in the Deprox 500® group and -13.6±4.8 in the Serenoa repens group (p=0.0016). By accounting only the symptoms part of NIH-CPSI questionnaire, the mean score variation reported was -11.5±2.5 in the Deprox 500® group and -9.02±4.0 in the Serenoa repens group (p=0.009321). Furthermore, analyzing the comorbidity subgroups, in patients with hypertension, the mean IPSS score variation was -14.3±3.2 in the Deprox 500® group and - 9.02±4.0 in the Serenoa repens group. CONCLUSION: In conclusion, in patients with CP/CPPS, Deprox 500® improves IPSS and NIH-CPSI scores up to 74.5% and 84.5% respectively. Furthermore, in patients with hypertension, the antioxidant effect of Deprox 500® reduces the mean IPSS score of 82.7%.

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

Narrow-band imaging (NBI) and white light (WLI) transurethral resection of the bladder in the treatment of non-muscle-invasive bladder cancer.

OBJECTIVE: Narrow-band imaging (NBI) is an optical image enhancement technology Summary that narrows the bandwidth of the light output from the endoscopy system to 415 nm and 540 nm. The aim of the present study is to evaluate the feasibility of NBI transurethral resection of the bladder (TURB NBI) compared to in White Light (TURB WLI) (Feasibility study) and the recurrence rate at the 1-year follow-up in patients treated for non-muscle-invasive bladder cancer (NMIBC) (recurrence study). METHODS: A total of 92 patients with a suspicion of primary or recurrent bladder cancer were prospectively enrolled in our study. Forty-five were consecutively enrolled to undergo WLI TURB and 47 consecutively to undergo NBI TURB. All patients underwent routine follow-up with flexible WLI cystoscopy every 3 months during the first year and every 6 months during the second year, supplemented by urine examination, urine culture, and bladder washout cytology. RESULTS: Type I-II complications were reported in 12 patients in the NBI group (25%) and in 10 patients in the WLI group (22%). Patients with High Grade NMIBC who underwent a second look WLI TURB had residual disease in 33% of NBI group and in 43% of WLI group.The recurrence rate at one year follow-up was 35% in NBI group and 50% in WLI group. No statistic significance can be issued for the clinical differences observed. CONCLUSIONS: TURB performed entirely by the NBI technique is feasible and safe. It guarantees a complete and rapid resection of good quality from a pathological point of view. Moreover, the technique is relatively inexpensive with respect to other methods proposed to enhance the detection rate, for which data on operative endoscopy are lacking. In our clinical experience, even if not statistically significant, NBI TURB reduces at one year follow up the recurrence rate of bladder NMI tumours when compared to WLI TURB (35% vs. 50%). Other larger, randomized, prospective trials with longer follow-up periods are required to confirm our outcomes.

Minute focus of prostate cancer on needle biopsy: correlation with radical prostatectomy specimen.

OBJECTIVES: To determine if the presence of a single minute neoplastic lesion defined as a lesion < or = 0.5 mm in length and Gleason score < or = 6 at biopsy is a reliable predictor of the presence of a potentially clinically insignificant carcinoma at radical prostatectomy. PATIENTS AND METHODS: We searched in our series of 151 consecutive patients submitted to radical retropubic prostatectomy from September 2003 to April 2007 for patients with a single minute focus of cancer at prostate biopsy. In all bioptic samples we calculated the total length of cores, length and percentage of neoplastic areas and Gleason grade. Total PSA and PSA density was obtained in all patients. Potentially clinically insignificant cancers at radical prostatectomy were defined as those with a tumor volume < or = 0.5 cc, Gleason score < or = 6 and organ confined disease. The clinical and pathological characteristics of patients with minute prostatic lesion were compared with other prostate cancers by using the 2-sample t-test and chi square test. RESULTS: In 18 (11.9%) patients the prostate biopsy showed a single neoplastic focus of < or = 0.5 mm in length and Gleason score of < or = 6. At definitive histological analysis of the RRP specimen only 5 patients (27.7%) presented a neoplasia potentially clinically insignificant. These patients on the preoperative criteria didn't show any statistically significant difference from the group with clinically significant neoplastic lesion at radical prostatectomy as far as prostate volume, total PSA, PSA density and total length of bioptic core. CONCLUSION: The weak correspondence between the presence of neoplastic lesions of minimal entity at prostate biopsy and potentially clinical insignificant carcinoma at radical prostatectomy has also been confirmed by our data: only 30% of patients with a single minute focus of well differentiated prostate cancer at biopsy showed at definitive pathology a potentially clinically insignificant cancer. Moreover the parameters we considered as possible predictive factors of clinically insignificant carcinoma did not demonstrate to be reliable criteria in order to identify these patients.

A randomized prospective study of intravesical prophylaxis in non-musle invasive bladder cancer at intermediate risk of recurrence: mitomycin chemotherapy vs BCG immunotherapy.

OBJECTIVE: The present study compared the therapeutic activity of intravesical BCG with intravesical mitomycin C chemotherapy in patients with non-muscle invasive bladder cancer at intermediate risk of recurrence in a prospective randomised trial. METHODS: 96 patients with low grade recurrent non-muscle invasive bladder cancer (Ta or T1) were randomly assigned to intravesical treatment with BCG or mitomycin C. RESULTS: The follow up ranged from 12 to 108 months (mean 65.7+/-25.6 months). Half of the patients were free of recurrence respectively after mitomycin C (23/46) and BCG (23/46) treatment. Recurrences after BCG presented in the first 6 month period (> 50%) or in the long term follow up (> 3 years) whereas early (< 6 months) or long term (> 3 years) recurrences after MMC treatment were less frequent. Time to recurrence in the MMC arm was 17.5+/-15.4 and in the BCG arm 21.9+/-24.8 (p = 0.47). None progressed to muscle-invasive tumour or underwent cystectomy during the observation period. MMC caused grade 1-2 toxicity in 11 patients (mild or moderate cystitis in 6 and mild or moderate hypersensitivity reactions in 5) and grade 3 toxicity in 11 patients (severe cystitis in 4, gross haematuria in 2 and severe hypersensitivity in 5 cases). Nineteen of the BCG treated patients had grade 1-2 toxicity (mild to moderate cystitis or prostatitis in 17, mild fever and myalgia in 2) and 3 developed grade 3 toxicity (severe cystitis in 2 patients and epididymitis that led to the necessity of antituberculous therapy in one patient). Intravesical treatment was discontinued in 11 patients under MMC treatment and in 2 patients under BCG treatment (p = 0.008). CONCLUSIONS: Both MMC and BCG demonstrate efficacy in prolonging the time to recurrence with respect to the period of observation before treatment, so reducing the hospitalisation rate for TUR of the recurrent tumours, but no difference in the recurrence rates was observed between MMC and BCG as primary treatment. A significant number of patients treated with MMC suffered cystitis or hypersensitivity reactions so severe to cause discontinuation of the treatment. The vast majority of patients treated with BCG had only mild or moderate side effects under BCG treatment but a serious infection was observed in one case requiring antituberculous treatment.

Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection.

We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was calculated in patients affected by cat. II, IIIa, IIIb and IV prostatitis after stratification with respect to the concomitant presence or absence of benign prostatic hyperplasia (BPH). PSA was reduced by 41% in cat. II CBP patients without BPH, compared to a 12.7% reduction in patients affected by BPH. Cat. IIIa CP/CPPS patients without BPH showed a 58.3% reduction of PSA levels, compared to a 20.7% reduction observed in CPPS/BPH patients. These data show that the presence of BPH may prevent the reduction of PSA induced by combination pharmacological therapy, and suggest that care has to be taken in the adoption of PSA as a marker of therapeutic efficacy in the presence of confounding factors like BPH. PSA should in our opinion be used as a significant component of a strategy integrating multiple diagnostic approaches.

Percutaneous therapy of low stage and grade urothelial neoplasia: long-term follow up.

Nephroureterectomy with the excision of the ipsilateral ureteral orifice and bladder cuff has been considered the standard treatment of the urinary upper transitional cell carcinoma. With the advent of sophisticated techniques for the endo-urologic management of many benign urologic diseases of the upper tract, there has been growing enthusiasm for the application of these same techniques in the management of upper tract TCC, which is also supported by recent advances in the development of small calibre telescopes with improved optics and the development of small calibre adjunctive instruments and laser fibers. A large number of cases published in the literature has confirmed the safety and efficacy of percutaneous treatment in selected patients with upper tract TCC of low grade and stage. Between 1997 and 2005 we treated 62 pts (37 pelvic transitional cell carcinoma and 25 ureteral). 4 pts (5 renal units: 4 T1G2 and 1 TaG1) underwent percutaneous resection for a tumor in a solitary kidney (2 cases), one case for bilateral neoplasm, and in the other case the lesion was unilateral with chronic renal failure. After preoperative evaluation, (excretory urography, computerized tomography and ureteroscopy with biopsy to confirm the low stage and grade of the lesion) the tumor was resected using an Amplatz sheat of 26-30 Fr and a 24 Fr resectoscope to keep a low intra-caliceal pressure. The tumor base was biopsied and fulgurated After 48 h, contrastography to assure integrity of the urinary system was performed and Mitomycin C was infused over 24 h. Second-look nephroscopy with multiple biopsies was performed in all cases 7 days later and 8 Ch nephrostomy was placed. If the biopsies resulted negative the patient was submitted to 6 weekly endocavitary instillation of BCG through the nephrostomy tube. All pts at a mean follow up of 71 months were tumor free. One patient presented a bladder relapse after 83 months. No complication of percutaneous resection was observed. The endocavitary instillations were well tolerated. In our experience the percutaneous approach is safe and useful in neoplastic lesions of low grade and stage and should be considered as first line therapy in selected patients. Adjuvant topical therapy appears efficacious and some complications may be avoided by maintaining low intracavitary pressures during administration.