The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Impact of operator expertise on transperineal free-hand mpMRI-fusion-targeted biopsies under local anaesthesia for prostate cancer diagnosis: a multicenter prospective learning curve.

PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Penile injection of aedile silicone: A dangerous shortcut.

INTRODUCTION: The size of penis can cause concern in patients, even if the organ is clinically normal. Additionally, the cost of phosphodiesterase 5 inhibitors (iPDE5) and long waiting lists to access penile prosthesis placement can lead patients to resort to non-medical and potentially dangerous alternatives. One of these dangerous alternatives is the injection of building silicone at the level of the subcutis of the penis or the corpora cavernosa causing the formation of a granuloma that increases the girth and consistency of the penis. CASE REPORT: The article describes the case of a 43-year-old patient who self-injected aedile silicone at the level of his penis in an attempt to achieve greater penile size and greater rigidity. The patient reported that he could not economically afford the iPDE5.The persistence of severe pain in the penis forced the patient to go to a urological examination. The patient subsequently underwent the penile granuloma exeresis procedure and skin reconstruction with scrotal flap. CONCLUSION: The pursuit of sexual well-being can lead some patients to rely on unconventional and potentially harmful techniques. The role of the andrologist and of the scientific society should be to dissuade the patient from using these dangerous methods and to provide valid alternatives accessible to the patient. The economic difficulty in purchasing drugs that facilitate erection or the long waiting lists for the placement of penile prostheses can favor dangerous methods such as penile injection of silicon. There is therefore a clear need to facilitate access to drugs and surgical techniques that favor the patient's sexual well-being.

Transperineal freehand multiparametric MRI fusion targeted biopsies under local anaesthesia for prostate cancer diagnosis: a multicentre prospective study of 1014 cases.

OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.

Pain in Men Undergoing Transperineal Free-Hand Multiparametric Magnetic Resonance Imaging Fusion Targeted Biopsies under Local Anesthesia: Outcomes and Predictors from a Multicenter Study of 1,008 Patients.

PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.

68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

OBJECTIVES: The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. MATERIALS AND METHODS: Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6 months; (6) PSA < 1.5 ng/mL or any PSA in case of negative choline-PET/CT (n = 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n = 25); first-time BCR (group-2, n = 121); BCR after salvage therapy (group-3, n = 77). RESULTS: Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65 ng/mL (0.2-8.9) and median PSAdt = 9.3 months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p < 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. CONCLUSION: This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo.

Cancer stem cells (CSCs) are considered as responsible for initiation, maintenance and recurrence of solid tumors, thus representing the key for tumor eradication. The antitumor activity of extracellular vesicles (EVs) derived from different stem cell sources has been investigated with conflicting results. In our study, we evaluated, both in vitro and in vivo, the effect of EVs derived from human bone marrow mesenchymal stromal cells (MSCs) and from a population of human liver stem cells (HLSCs) of mesenchymal origin on renal CSCs. In vitro, both EV sources displayed pro-apoptotic, anti-proliferative and anti-invasive effects on renal CSCs, but not on differentiated tumor cells. Pre-treatment of renal CSCs with EVs, before subcutaneous injection in SCID mice, delayed tumor onset. We subsequently investigated the in vivo effect of MSC- and HLSC-EVs systemic administration on progression of CSC-generated renal tumors. Tumor bio-distribution analysis identified intravenous treatment as best route of administration. HLSC-EVs, but not MSC-EVs, significantly impaired subcutaneous tumor growth by reducing tumor vascularization and inducing tumor cell apoptosis. Moreover, intravenous treatment with HLSC-EVs improved metastasis-free survival. In EV treated tumor explants, we observed both the transfer and the induction of miR-145 and of miR-200 family members. In transfected CSCs, the same miRNAs affected cell growth, invasion and survival. In conclusion, our results showed a specific antitumor effect of HLSC-EVs on CSC-derived renal tumors in vivo, possibly ascribed to the transfer and induction of specific antitumor miRNAs. Our study provides further evidence for a possible clinical application of stem cell-EVs in tumor treatment.

Transperineal Free-hand mpMRI Fusion-targeted Biopsies Under Local Anesthesia: Technique and Feasibility From a Single-center Prospective Study.

OBJECTIVE: To evaluate the feasibility of "in-office" TPFBx under local anesthesia (LA). MATERIALS AND METHODS: We prospectively screened for eligibility data of 724 consecutive men undergoing either TPFBx (target and systematic cores) or TPSBx (systematic cores only) from September 2016 to June 2018 due to suspicion of prostate cancer (CaP), according to predefined exclusion criteria. RESULTS: We included 459 men (TPFBx n = 279 including n = 338 mpMRI lesions, Pi-RADS 4 in 63.6%; TPSBx n = 180). Median procedural time and maximum pain were 19 minutes and 5 numeric rating scale (NRS) points; pain was highest at the time of LA. Only 1 major complication occurred (Clavien 3a). Hematuria and hematospermia were frequent (72.6% and 54.2%). Vaso-vagal reactions and AUR were rare (0.7% and 0.4%). No cases of UTI and 1 case of fever were recorded. No significant changes in erectile and urinary functions were noted from baseline compared to 40 days after TPFBx (P = .86 and P = .89). In comparison with TPSBx the sole differences were pain during prostatic sampling (P = .03), duration of hematospermia (P <.0001) and procedural time (P <.001) all higher for TPFBx. Clinically significant (cs) CaP was detected in n = 150 (53.8%) patients in the TPFBx group (34.9%, 51.7%, and 75% of Pirads 3, 4, and 5, respectively). Addition of systematic cores detected n = 25 csCaP that were missed by targeted cores (17.4% of all csCaP). CONCLUSION: TPFBx under LA are feasible, yielding high tolerability, low complications, no impact on erectile and urinary function and good csCaP detection. Addition of systematic to targeted cores remains recommended. Further studies are needed to confirm our findings.

The association of Boswellia resin extract and propolis derived polyphenols can improve quality of life in patients affected by prostatitis-like symptoms.

OBJECTIVES: Chronic prostatitis syndrome is a bothering and poorly understood condition. Many patients report genitourinary pain and Lower Urinary Tract Symptoms as a main complaint. Many different pharmacological or behavioural therapies are prescribed in daily clinical practice, but efficacy data are still lacking. The aim of our study was to test the efficacy and safety of a transrectal delivered association of Boswellia resin extract and propolis derived polyphenols for the relief of prostatitis - like symptoms. MATERIALS AND METHODS: Patients affected by chronic/recurrent prostatitis - like symptoms were prospectively enrolled in our study from December, 2016 to December, 2018. Patients were screened at baseline through clinical examination and validated questionnaires administration: Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF). Inclusion criteria were: age ≥ 18; prostatitis symptoms persisting for at least 3 of the last 6 months; CPSI pain domain score ≥ 5; previous negative Meares-Stamey test. Treatment consisted on the administration of 1 suppository containing Boswellia resin extract and propolis derived polyphenols, once a day for 20 days. The primary endpoint of the study was the improvement of quality of life after treatment, defined by a reduction of ≥ 2 points, or ≥ 25%, of mean CPSI pain domain score, compared to baseline. Secondary endpoints were the improvement of post-treatment CPSI total score and the analysis of treatment - related adverse events. All patients were re-evaluated 1 month after treatment. RESULTS: 40 patients were enrolled in our study. Median age (Inter - Quartile Range IQR) was 51.5 (41.5-63.2) years. Mean baseline CPSI scores were: 22.15 (total score), 9.67 (pain domain), 5.15 (micturition domain) and 7.35 (quality of life domain), respectively. No significant adverse events were reported. At 1 month follow-up, CPSI scores appeared modified as follows: 16.40 (total score, p = 0.001); 6.92 (pain domain; p = 0.001; 4.02 (micturition domain, p = 0.09); 5.45 (quality of life domain, p = 0.002). Mean CPSI pain domain score reduction was -2.75 points (-28.5%). Mean CPSI total score reduction was -5.75 points (-26%). CONCLUSIONS: The association of Boswellia resin extract and propolis derived polyphenols can reduce genitourinary pain and then improve quality of life of men affected by bothersome prostatitis - like symptoms.

Hyperthermia for non-muscle invasive bladder cancer.

Recurrent non muscle invasive bladder cancer (NMIBC) represents a therapeutic challenge, especially in the case of Bacillus Calmette Guerin (BCG)-failures. Chemohyperthermia (CHT) has been tested as adjuvant therapy in selected categories of patients with promising results. The aim of this systematic review is to explore the current role of CHT and its future perspectives. The review process was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. After the selection process, 30 articles were used in this review. Treatment with CHT is safe and quite well tolerated. CHT seems to be effective in low and intermediate risk bladder cancer. Moreover CHT could be offered to selected categories of high risk patients and BCG failures NMIBC. Further trials are needed in order to better identify the categories of patients which could benefit from this therapy and to standardise the right schedule of treatment.

Systematic review of lower urinary tract symptoms/benign prostatic hyperplasia surgical treatments on men's ejaculatory function: Time for a bespoke approach?

Although ejaculatory dysfunction is common for patients undergoing benign prostatic hyperplasia surgery, no clear evidence is present to counsel men seeking to preserve ejaculation. Our aim was to evaluate ejaculatory dysfunction in relation to benign prostatic hyperplasia surgery. We carried out a web and manual search using MEDLINE and Embase including randomized controlled trials reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery: 42 randomized controlled trials comprising a total of 3857 patients were included. Only one study had ejaculatory dysfunction as a primary outcome, and just 10 evaluated ejaculatory dysfunction before and after surgery. The definition of ejaculatory dysfunction was not standardized. Similarly, just seven studies used internationally validated questionnaires to address ejaculatory dysfunction. The reported rates of ejaculatory dysfunction after resectional electrosurgery, laser procedures, coagulation, ablation and implant techniques were assessed and compared. Transurethral resection of the prostate and recent laser procedures including holmium, thulium and GreenLight cause similar rates of ejaculatory dysfunction, occurring in almost three out of four to five men. Although providing less symptomatic benefit compared with transurethral resection of the prostate, transurethral incision of the prostate, transurethral needle ablation and transurethral microwave thermotherapy should be considered for men aiming to maintain normal ejaculation. UroLift is also a recent promising option for this category of patients. The vast majority of studies reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery used poor methodology to investigate this complication. Future studies able to address clear hypothesis and considering ejaculatory dysfunction anatomical and pathophysiological features are required to develop ejaculation preserving techniques and to increase the evidence to counsel men aiming to preserve ejaculation.

Efficacy and safety of a new device for intravesical thermochemotherapy in non-grade 3 BCG recurrent NMIBC: a phase I-II study.

PURPOSE: We report for the first time the activity and safety of Unithermia(®) (Elmedical Ltd, Hod-Hasharon, Israel), a novel device for administration of MMC-C with hyperthermia (HT), that employs conductive heating, in a series of non-grade 3 non-muscle-invasive bladder cancer (NMIBC) that failed Bacillus Calmette-Guerin (BCG). METHODS: Patients with non-grade 3 NMIBC recurring after at least a full induction course of BCG were eligible for this phase I-II prospective single-arm study. Six weekly instillations with Unithermia(®) were scheduled following complete TUR. Primary end points were treatment safety and response rate (RR), and the latter defined as the absence of any unfavourable outcome at 12 months. Any grade 3 and/or muscle-invasive (T > 1) recurrence was considered disease progression. Kaplan-Meier estimation of the time to recurrence and progression, cancer-specific survival and overall survival was taken as secondary end points. RESULTS: Thirty-four eligible patients entered the study between January 2009 and April 2011. RR was documented in 20/34 (59%). Among the 14/34 (41%) non-responders, four developed G3 disease, one developed carcinoma in situ, and one progressed to muscle-invasive bladder cancer, with an overall 18% progression rate at 1 year. At a median follow-up of 41 months, recurrence and progression rates were 35.3 and 23.5%, respectively. Toxicity did not go beyond grade 2 except in five cases. CONCLUSIONS: Initial experience with MMC-HT with Unithermia(®) showed an interesting activity and safety profile in non-grade 3 NMIBC recurring after BCG, suggesting a role as second-line therapy in this selected subgroup of NMIBC.

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

BACKGROUND: Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). METHODS: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS: Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 µM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION: Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.

Intravesical thermo-chemotherapy based on conductive heat: a first pharmacokinetic study with mitomycin C in superficial transitional cell carcinoma patients.

PURPOSE: To evaluate, for the first time, the mitomycin C (MMC) pharmacokinetics during intravesical hyperthermia treatment based on conductive heat and the stability and recovery of the drug at the end of the instillation period. METHODS: Eleven patients with recurrent intermediate-risk superficial transitional cell carcinoma of the bladder were treated weekly for six cycles with intravesical MMC (40 mg MMC in 50 ml) in local hyperthermia (45 °C) with Unithermia(®) system. Each instillation lasted 45 min, with the solution being replaced after the first 22 min. The MMC recovery at the end of the two instillation period and the plasmatic pharmacokinetics of MMC were evaluated by high-pressure liquid chromatography. RESULTS: Nine patients completed all the six planned cycles, whereas two patients missed the last cycle because of allergic reactions. No other systemic toxicity was observed, and the local toxicities were mild. Median MMC concentration in the instillation residual solution decreases from the initial 0.8 to 0.22 mg/ml for the 0-22-min instillation period and to 0.38 mg/ml for the 22-45-min instillation period; the median percentage of MMC recovered after instillation was 66.2 and 99.6, respectively. In all patients, MMC plasmatic C max resulted considerably lower than the toxic threshold (400 ng/ml). CONCLUSIONS: The MMC is stable during the instillation, and its absorption occurs mainly during the first minutes of the treatment. The plasmatic MMC concentration is always well below the threshold level for myelosuppression, as confirmed by the total lack of hematological toxicity evidenced by the patients. In order to evaluate the efficacy of the treatment performed with UniThermia(®) in reducing the disease recurrence rate in short- and long-term follow-up, we are currently carrying out a clinical multicentric study involving a larger number of patients.

The impact of prior TURP on radical prostatectomy surgical margins: a multicenter analysis.

OBJECTIVE: To analyze positive surgical margins (PSM) after radical prostatectomy (RP) in the overall population and in patients previously treated with transurethral resection of the prostate (TURP). MATERIALS AND METHODS: 2,408 patients treated with RP for clinically localized prostate cancer (PCa) were consecutively enrolled in 135 departments. We correlated PSM rates and all preoperative, surgical and pathological features. We stratified the site of PSM as unique or multifocal. Moreover, we analyzed differences between 75 patients who had undergone previous TURP and the remaining 2,333 patients. RESULTS: In the entire study population, we identified 702 patients with PSM (29%). Using univariate analysis, we reported a significant correlation between overall PSM and prostate-specific antigen (PSA), stage cT, biopsy Gleason score, number of biopsy cores, number of positive cores, percentage of positive cores and nerve-sparing approach. PSM proved to be strongly dependent on pT in particular in patients with pT2 PCa. When we compared the data from 75 patients previously treated with TURP and those from 2,333 without previous prostatic surgery, a statistically significant difference in margin localization was found. Moreover, we analyzed the 75 patients mentioned above, stratified in incidental PCa diagnosed at TURP or PCa detected with prostate biopsy for PSA rising during the post-TURP follow-up: no statistical differences were found between the 2 groups regarding margin status, even if PSM were more frequent in incidental PCa with no significance deriving from the stratification for PSM location at the apex or base. CONCLUSION: Men treated with TURP before RP presented an overall incidence of PSM similar to those without previous TURP, but with a higher risk of PSM at the bladder neck and a lower risk of PSM at the prostatic apex.

Microwave-induced thermoablation with Amica-probe is a safe and reproducible method to treat solid renal masses: results from a phase I study.

Microwave thermal ablation (MWTA) could be considered in the future for treating small solid renal masses. The aim of the present study was to determine both the tolerability of the new Amica-probe applicator-induced MWTA used in vivo on patients with solid renal masses and the effects of heating on renal tumors and normal renal parenchyma. Fourteen patients with renal masses eligible for open radical nephrectomy were enrolled in this phase I study. All patients underwent MWTA of renal masses during the open surgery procedure before clamping of renal vascular pedicle. The effects of MWTA on patients' coagulation and tumor/renal vasculature were investigated. The histological effects of MWTA on the tumor and intralesional vital tumor cell skipping were also evaluated. The MWTA-induced lesion diameters were measured to calculate both the overall ablation volume and the lesion sphericity index (SI). The Clavien-Dindo classification was used. In all patients the RENAL score was 9.4 (8-12) and the Charlson comorbidity index was 4.8 (3-7). MWTA-induced lesion size was 44.14 mm (±22.59). Mean SI was 1.08 (±0.2). No significant differences among coagulation clinical parameters were found. No local bleeding after MWTA treatment was reported. According to the Clavien-Dindo classification, there were two grade II perioperative complications due to the tumor extent but not related with the MWTA treatment. No residual vital tumor cells inside the MWTA-induced lesions were found. Telephone interview at 27.4 (±4.2) months mean follow-up did not find any long-term adverse events due to previous MWTA treatment. Amica-Probe applicator-induced MWTA is a safe and reproducible method to treat solid renal masses.

Inguinal versus subinguinal varicocele vein ligation using magnifying loupe under local anesthesia: which technique is preferable in clinical practice?

OBJECTIVES: To compare the intraoperative results of inguinal versus subinguinal varicocelectomy using magnifying loupe, in terms of vein ligation and arterial preservation, recurrence rate, and patient tolerability. METHODS: Ninety-nine patients were randomized to undergo a varicocele repair with an inguinal or a subinguinal approach under local anesthesia. Data concerning the number of veins ligated and arterial preservation were recorded during each procedure. The amount of intraoperative and postoperative pain was assessed by means of visual analogue scale (VAS) scores. The recurrence rate was documented by color Doppler ultrasound examination. RESULTS: The average number of ligated veins was 5.6 with a subinguinal dissection and 4.4 with the inguinal approach. Inadvertent injury of the spermatic artery occurred in 6 of 47 subinguinal and 3 of 50 inguinal dissections; the artery could not be identified during 2 subinguinal and 1 inguinal dissection. Recurrent varicocele was detected in 8% and 14.9% of patients after an inguinal and a subinguinal approach, respectively. The intraoperative VAS score was significantly higher in the inguinal than in the subinguinal patients (P = 0.008). CONCLUSIONS: In our hands, the inguinal approach to the spermatic cord showed a trend toward an easier preservation of the artery and a reduced incidence of persistent pathologic vein reflux. The subinguinal approach had a lower degree of intraoperative pain. On the whole, an inguinal repair might be preferable when magnifying loupe are used for varicocelectomy.

Sacral neuromodulation for urinary retention in a kidney-transplant patient.

Bladder outlet obstruction can negatively affect renal function in the kidney transplant population. Functional obstruction represents a clinical challenge as conventional treatments are either ineffective or not recommended. Sacral neuromodulation was successfully used in functional voiding dysfunction in a kidney transplant patient. This is the first case to be reported in the literature.