Background: Intravesical alternatives to bacillus Calmette-Guérin (BCG) are needed to treat patients with non-muscle-invasive bladder cancer (NMIBC) not responding to BCG or high-risk NMIBC. Electromotive drug administration (EMDA) enhances the penetration of mitomycin C into the bladder wall and could be used also with other drugs. We aimed to investigate whether EMDA accelerates intravesical delivery of gemcitabine and docetaxel as compared to passive diffusion (PD). Methods: We instilled fifteen porcine bladders with gemcitabine and docetaxel using EMDA or PD. Drug concentrations in the mucosa, muscle, and adventitious layers of the bladder were quantified using reversed-phase high-performance liquid chromatography. Results: Docetaxel mean total tissue penetration increased from 2.9% with PD to 6.4% with EMDA after pretreatment with gemcitabine. When no gemcitabine pretreatment was done, docetaxel absorption was statistically significantly higher with EMDA than with PD. Hyaluronic acid did not improve or worsen penetration and no statistically significant difference was observed between the treatment arm with saline (95% confidence intervals of the mean [95% CI] vs PD: 5.92-19.91) and hyaluronic acid/chondroitin sulphate solution (95% CI vs PD: 7.67-23.32). For gemcitabine, no statistically significant difference was observed among treatment arms. Total gemcitabine tissue penetration was similar in both treatment arms, but EMDA shortened the time needed to achieve similar tissue concentrations compared to passive diffusion, reducing the gemcitabine uptake time by 70 minutes and the docetaxel uptake time by 40 minutes. Conclusions: EMDA accelerates gemcitabine and docetaxel uptake and enhances intravesical delivery of docetaxel.
Introduction and objectives: A PI-RADS 3 lesion on multiparametric magnetic resonance imaging (mpMRI) carries an intermediate risk of prostate cancer that existing parameters characterize poorly, and the biopsy decision remains unsettled. This study evaluated whether the pre-biopsy systemic immune-inflammation index (SII) and neutrophil- to-lymphocyte ratio (NLR) provide diagnostic information beyond two prostate-specific parameters, PSA density (PSAD) and the free-to-total PSA ratio (%fPSA), in biopsy-naïve men. Methods: Eighty-two biopsy-naïve men with an index PI-RADS 3 lesion, evaluated between January 2022 and December 2024, were retrospectively reviewed. All patients underwent transrectal ultrasonography (TRUS)-guided 12-core systematic biopsy with additional cognitively targeted cores from the index lesion. SII, NLR and the platelet-to-lymphocyte ratio (PLR) were calculated from pre-biopsy complete blood counts. Cut-off values were determined by receiver operating characteristic (ROC) analysis at the maximum Youden index, except for PSAD, for which a predefined cut-off of 0.15 ng/mL/mL was used. Independent predictors were identified by multivariable logistic regression. Results: Prostate cancer was detected in 20 men (24.4%) and clinically significant cancer (ISUP grade group ≥ 2) in 13 (15.9%). Age, total PSA and prostate volume did not differ between men with and without cancer. Men with cancer had a higher PSAD (0.16 ± 0.08 vs. 0.12 ± 0.06 ng/mL/mL, p = 0.024) and a lower %fPSA (14.2 ± 5.8% vs. 19.6 ± 7.4%, p = 0.004). SII and NLR were also significantly higher in the cancer group (p = 0.042 and p = 0.016), whereas PLR did not differ. The area under the ROC curve (AUC) was highest for %fPSA (0.743) and PSAD (0.712), and lower for NLR (0.651) and SII (0.634). In multivariable analysis, only PSAD ≥ 0.15 ng/mL/mL (OR 2.86, 95% CI 1.12-7.32, p = 0.028) and %fPSA (OR 0.94, 95% CI 0.89-0.98, p = 0.012) remained independent predictors; SII and NLR did not. Conclusions: In biopsy-naïve men with a PI-RADS 3 lesion, SII and NLR were higher in those with cancer on biopsy, but they were not independent predictors after adjustment for PSAD and %fPSA. The statistical power of the model to detect a modest effect was limited. In this setting, the biopsy decision should still be based on prostate-specific parameters. SII and NLR may complement these parameters, and their additional value should be tested within multivariable models rather than in isolation.
Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a challenging disease for all urologists. Several therapeutic approaches haven been purposed for symptoms relief and quality of life improvement. Here, we aim to evaluate the efficacy of a new nutraceutical compound in patients affected by CP/CPPS and perform a detailed evaluation of pro-inflammatory mediators [interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10)] in order to establish the treatment mechanism of action and evaluate its clinical efficacy. Methods: All patients with a diagnosis of CP/CPPS attending the same urologic centre between January and December 2024 were enrolled in this randomised controlled phase III study. Participants were randomised to receive oral capsules of a dietary supplement containing solanum lycopersicum (100 mg), brassica oleracea (333 mg), silybum marianum (50 mg), glutathione (50 mg), aesculus hippocastanum (2 mg), tryptophane (25 mg), camellia sinensis (25 mg) (one capsule every 24 h) or placebo (one capsule every 24 h) for three months. At the enrolment time, all patients underwent baseline questionnaires (NIHCPSI, SF-36), urological examination and microbiological evaluation by using the Meares-Stamey test. Moreover, level of IL-6, IL-8 and IL-10 have been evaluated in seminal plasma collected at the enrolment time and at the follow-up time (3 months after the enrolment with a urological and microbiological examination and questionnaire collection). The main outcome measures were: the improvement of quality of life and the decrease of proinflammatory mediators, at the end of the whole study period. Results: In the per-protocol analysis, 77 males (mean age of 31.9 ± 2.5 years) were randomly allocated to the dietary supplement (n = 38) or placebo (n = 39) groups. At the follow-up examination, in the dietary supplement group, 21/38 patients (55.3%) showed a significant reduction of the NIH-CPSI total score (more than 25% from baseline), compared with 12/39 (30.7%) in the control group (p < .0001). In addition, at the 3 months follow-up visit, the mean level of IL-8 was significantly lower in the dietary supplement group compared with control group [IL-8 316 pg/ml vs IL-8 986 pg/ml] (p < .0001). In the dietary supplement group, we found a statistically significant reduction of IL-8 level between the enrolment and follow-up visit [IL-8 856 pg/ml vs IL-8 298 pg/ml] (p < .0001). No statistically significant difference in terms of IL-6 or IL-10 evaluation have been reported. Conclusions: This new antioxidant dietary supplement treatment is able to improve quality of life in patients affected by CP/CPPS through the reduction pro-inflammatory cytokine levels (IL-8).
Background: Postoperative hydrocele is a clinically relevant complication of varicocelectomy and is largely attributed to disruption of testicular lymphatic drainage. Several vital dyes and fluorescence-based tracers have been used to improve intraoperative identification and preservation of lymphatic vessels, but their comparative effectiveness remains uncertain. Methods: We conducted a systematic review and network metaanalysis in accordance with PRISMA 2020 and the PRISMA extension for network meta-analyses. Comparative randomized controlled trials (RCTs) and non-randomized studies evaluating isosulfan blue, methylene blue, Patent Blue V, indocyanine green, or no dye during varicocelectomy were eligible. RCTs and non-RCTs were synthesized in separate frequentist randomeffects networks using CINeMA version 2.0.0. Ranking analyses were performed in R version 4.4.3 using meta version 8.3-0 and netmeta version 3.4-0. Odds ratios (ORs) were used for dichotomous outcomes and mean differences (MDs) for operative time. No dye was selected as the common reference. Treatment ranking was summarized using the surface under the cumulative ranking curve (SUCRA). Results: The evidence set comprised 12 eligible reports: four RCTs and eight observational reports. Eleven reports contributed arm-level data to at least one outcome-specific quantitative synthesis. Because some Italian cohorts may overlap across reports, a single unduplicated participant total was not calculated. In the RCT network, isosulfan blue reduced postoperative hydrocele compared with no dye (OR 0.083, 95% CI 0.010- 0.673), whereas estimates for methylene blue (OR 0.100, 95% CI 0.005-1.924) and Patent Blue V (OR 0.094, 95% CI 0.005- 1.849) were imprecise. In the non-RCT postoperative-hydrocele network, isosulfan blue was associated with lower odds of hydrocele (OR 0.028, 95% CI 0.004-0.201); indocyanine green (OR 0.084, 95% CI 0.004-1.683) and methylene blue (OR 0.573, 95% CI 0.242-1.355) numerically favoured hydrocele prevention but remained inconclusive. In the non-RCT hydrocele-requiringintervention network, all active estimates were highly imprecise. In the non-RCT recurrence network, no tracer showed a statistically clear difference from no dye. Conclusions: Randomized evidence suggests that isosulfan blue provides the most consistent signal toward reducing postoperative hydrocele after varicocelectomy. Observational evidence also favoured isosulfan blue for postoperative hydrocele, although possible cohort overlap, confounding, sparse events, and star-shaped networks limit certainty. Recurrence and hydrocele-requiring-intervention estimates did not establish reliable benefit or harm for any tracer.
Background: Persistent stress urinary incontinence (SUI) remains one of the most troublesome functional complications after robot-assisted radical prostatectomy (RARP). Although pelvic floor muscle training (PFMT) represents the standard conservative treatment, a proportion of patients continue to experience bothersome symptoms. Aquatic rehabilitation may facilitate pelvic floor activation through reduced gravitational loading, enhanced proprioceptive input, and trunk stabilization; however, its role in post-prostatectomy incontinence has not been investigated. This prospective pilot study evaluated the feasibility, safety, and clinical outcomes associated with hydrokinesitherapy in men with persistent SUI following RARP. Methods: Men with persistent pure SUI after rArP despite three months of standardized conservative management, including PFMT and biofeedback, were prospectively enrolled between January and May 2023. Participants underwent a five-week hydrokinesitherapy program consisting of ten supervised 40-minute sessions performed twice weekly. outcomes included the 24-hour pad test, International Consultation on Incontinence Questionnaire-short Form (ICIQ-sF), Incontinence Quality of Life questionnaire (I-QoL), International Prostate symptom score (IPSS), IPSS quality-of-life item, and Patient Global Impression of Improvement (PGI-I), assessed at baseline, end of treatment (5 weeks), and 12-week follow-up. Results: Twenty patients completed the rehabilitation program without treatment-related adverse events or dropouts. significant improvements were observed at the end of treatment in pad weight, IPSS, IPSS-QoL, ICIQ-SF, and I-QoL scores (all p ≤ 0.01). These improvements were maintained or further improved at 12 weeks, particularly for pad weight, QoL, and incontinence-related symptom scores. overall patient satisfaction was high according to PGI-I. Two patients (10%) subsequently underwent male sling surgery because of persistent bothersome sUI. Conclusions: Hydrokinesitherapy was feasible, safe, and associated with clinically meaningful improvements in urinary continence and health-related QoL in men with persistent SUI after RARP who had not achieved satisfactory recovery following initial conservative rehabilitation. These findings should be considered hypothesis-generating and warrant confirmation in adequately powered randomized controlled trials.
