Unraveling the parahormetic mechanism underlying the health-protecting effects of grapeseed procyanidins.

Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable. However, higher molecular weight PACs engage with the colonic microbiota, fostering the production of bioavailable metabolites that undergo metabolic processes, culminating in the emergence of bioactive agents capable of modulating physiological processes. Within this investigation, a GSE enriched with polymeric PACs was employed to explore in detail their impact. Through comprehensive analysis, the present study unequivocally verified the gastrointestinal-mediated transformation of medium to high molecular weight polymeric PACs, thereby establishing the bioaccessibility of a principal catabolite termed 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL). Notably, our findings, encompassing cell biology, chemistry and proteomics, converge to the proposal of the notion of the capacity of VL to activate, upon oxidation to the corresponding quinone, the nuclear factor E2-related factor 2 (Nrf2) pathway-an intricate process that incites cellular defenses and mitigates stress-induced responses, such as a challenge brought by TNFα. This mechanistic paradigm seamlessly aligns with the concept of para-hormesis, ultimately orchestrating the resilience to stress and the preservation of cellular redox equilibrium and homeostasis as benchmarks of health.

Gender and cystectomy for bladder cancer: A high-volume tertiary urologic care center experience.

BACKGROUND: Differences have often been reported in the outcomes of bladder cancer (BC) patients according to gender. OBJECTIVE: This study aims to provide data on patients undergoing radical cystectomy (RC) in a high-volume tertiary urologic center and to assess whether gender discrepancies do exist in terms of surgical options and clinical outcomes. MATERIALS AND METHODS: Consecutive BC patients treated between 2016 and 2020 at a single center (Careggi University Hospital, Florence, Italy) were included in the study. The impact of gender on disease stage at diagnosis, overall survival (OS), and type of surgery was analyzed. RESULTS: The study series comprised 447 patients (85 females and 362 males). At a median follow-up of 28.3 months (IQR: 33.5), OS was 52.6% and cancer-specific survival was 67.6%. Significant differences in OS emerged for age, acute myocardial infarction (AMI), Charlson Comorbidity Index (CCI), pT, and pN. OS rates were higher in patients undergoing robot-assisted surgery and in those receiving open orthotopic neobladder (ONB) (p = 0.0001). No statistically significant differences were found between male and female patients regarding surgical offer in any age group, surgical time, early postoperative complications, pathologic stage, and OS. CONCLUSIONS: After adjustment for pathologic tumor stage and treatment modalities, female and male patients showed similar oncologic outcomes. Further studies should be undertaken to evaluate functional results in women subjected to RC.

Manejo urológico y procedimientos quirúrgicos en migrantes del África Subsahariana con esquistosomiasis urogenital / Urological management and surgical procedures in migrants from Sub-Saharan Africa with urogenital schistosomiasis

Introducción y objetivos: Tras el flujo migratorio procedente del África Subsahariana (ASS) en Europa, el número de diagnósticos de esquistosomiasis urogenital (EUG) es cada vez mayor. Este fenómeno representa un desafío para los urólogos que trabajan en zonas no endémicas. El objetivo de este estudio es describir el tratamiento urológico y los procedimientos quirúrgicos de los pacientes con EUG en un centro de referencia terciarioPacientesTodos los sujetos del ASS diagnosticados con EUG entre enero del 2011 y noviembre del 2018 fueron inscritos retrospectivamente. Se recogió y analizó la información detallada de los pacientes con EUG tratados mediante procedimientos urológicos.ResultadosTreinta pacientes fueron diagnosticados con EUG, 12 (42,8%) fueron tratados mediante cirugía. El procedimiento quirúrgico más común fue la resección transuretral de vejiga (RTUV) para las lesiones sospechosas persistentes después del tratamiento con praziquantel administrado en 7 casos (58%). Otros procedimientos quirúrgicos (realizados una vez) fueron RTUV combinada con ureteroscopia láser por sospecha de neoplasia de vejiga con cálculos renales, litotricia endoscópica y nefrolitotomía percutánea para cálculos vesicales y renales, nefrectomía laparoscópica para enfermedad renal terminal, colocación de nefrostomía bilateral para hidroureteronefrosis, cirugía testicular exploratoria por sospecha de torsión testicular. Cuatro pacientes (33%) se perdieron en el seguimiento.ConclusiónSe ha observado un número cada vez mayor de migrantes del ASS diagnosticados con EUG. Algunos pacientes requirieron intervención quirúrgica por sospecha de lesiones neoplásicas o daños en órganos en fase terminal. En varios pacientes fue particularmente difícil realizar un seguimiento regular. Se necesitan más estudios multicéntricos para lograr un manejo estándar en términos de diagnóstico, tratamiento y seguimiento de los sujetos con EUG. (AU)

Introduction and objectives: An increasing number of urogenital schistosomiasis (UGS) is being diagnosed in Europe following the unprecedented migratory flux from Sub-Saharan Africa (SSA). This phenomenon represent a challenge for urologists working in a non-endemic area. The aim of this study is to describe the urological management and the surgical procedures of patients with UGS in a tertiary referral centre.PatientsAll subjects from SAA diagnosed with UGS from January 2011 to November 2018 were enrolled retrospectively. Detailed data of patients with UGS undergoing to urological procedures were collected and analysed.ResultsThirty patients were diagnosed with UGS, among them 12 (42.8%) were submitted to surgery. The most common surgical procedure was trans urethral resection of bladder (TURB) for suspected lesions persisted after praziquantel treatment performed in 7cases (58%). Other surgical procedure were TURB and concomitant ureteroscopy with laser fragmentation for suspected bladder neoplasm with renal stone, endoscopic lithotripsy and percutaneous nephrolithotomy for bladder and renal stones, laparoscopic nephrectomy for end-stage kidney disease, placement of bilateral nephrostomy for hydroureteronephrosis, explorative testicular surgery for a suspected testicular torsion in one case each. Four patients (33%) were lost at the follow up.ConclusionAn increasing number of migrants from SSA diagnosed with UGS has been observed. Some patients required a surgical intervention for suspected neoplastic lesions or end-stage organ damage. It was particularly difficult to perform a regular follow-up in several patients. Further multicentric studies are needed to reach a proper standard in diagnosis, treatment and follow-up of subjects with UGS. (AU)

Water vapor therapy (Rezum) for lower urinary tract symptoms related to benign prostatic hyperplasia: early results from the first Italian multicentric study.

PURPOSE: Rezum is the latest developed minimally invasive treatment for benign prostatic hyperplasia (BPH). We aimed to carefully assess the functional outcomes of patients treated with Rezum for BPH. METHODS: We prospectively followed 135 consecutive patients treated by Rezum at 5 institutions from June 2019 to August 2020. The International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF), the Overactive Bladder Questionnaire-Short Form (OAB-q SF) score, the International Index of Erectile Function (IIEF-5) and questions 9 and 10 to assess ejaculatory dysfunction were recorded. Election criteria were age > 18, no prior prostate interventions, IPSS ≥ 13, post-void residual ≤ 250 mL, prostate volume between 30 and 120 cc. RESULTS: The median operative time was 10.5 (IQR 8.7-15) min. All patients were dismissed few hours after surgery with indwelling urinary catheter that was removed after a median of 7 (IQR 7-10) days. A significantly decrease of IPSS from baseline at first (p = 0.001) and third (p < 0.0001) month after surgery was reported. No difference was reported in terms of ICIQ-UI SF score postoperatively. A mild reduction of the OAB-q SF score was reported at 1 month from surgery (p = 0.06) that turned significant at 3 months postoperatively (p < 0.0001). A slight but statistically significant increase of the IIEF-5 score was reported from baseline at 6 months (p = 0.04). Postoperatively, patients reported a significantly decrease of ejaculatory dysfunction after alpha-blocker interruption. CONCLUSION: Rezum treatment is a feasible minimally invasive option for patients with BPH symptoms and showed optimal early functional outcomes.

Urological management and surgical procedures in migrants from Sub-Saharan Africa with urogenital schistosomiasis. / Manejo urológico y procedimientos quirúrgicos en migrantes del África Subsahariana con esquistosomiasis urogenital.

INTRODUCTION AND OBJECTIVES: An increasing number of urogenital schistosomiasis (UGS) is being diagnosed in Europe following the unprecedented migratory flux from Sub-Saharan Africa (SSA). This phenomenon represent a challenge for urologists working in a non-endemic area. The aim of this study is to describe the urological management and the surgical procedures of patients with UGS in a tertiary referral centre. PATIENTS: All subjects from SAA diagnosed with UGS from January 2011 to November 2018 were enrolled retrospectively. Detailed data of patients with UGS undergoing to urological procedures were collected and analysed. RESULTS: Thirty patients were diagnosed with UGS, among them 12 (42.8%) were submitted to surgery. The most common surgical procedure was trans urethral resection of bladder (TURB) for suspected lesions persisted after praziquantel treatment performed in 7cases (58%). Other surgical procedure were TURB and concomitant ureteroscopy with laser fragmentation for suspected bladder neoplasm with renal stone, endoscopic lithotripsy and percutaneous nephrolithotomy for bladder and renal stones, laparoscopic nephrectomy for end-stage kidney disease, placement of bilateral nephrostomy for hydroureteronephrosis, explorative testicular surgery for a suspected testicular torsion in one case each. Four patients (33%) were lost at the follow up. CONCLUSION: An increasing number of migrants from SSA diagnosed with UGS has been observed. Some patients required a surgical intervention for suspected neoplastic lesions or end-stage organ damage. It was particularly difficult to perform a regular follow-up in several patients. Further multicentric studies are needed to reach a proper standard in diagnosis, treatment and follow-up of subjects with UGS.

hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma.

BACKGROUND: In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia. METHODS: A monocentric study on 30 consecutive surgical samples from surgically-treated ccRCC patients with a 10-year follow up was performed. The following proteins were analysed by immunohistochemistry: Vascular Endothelial Growth Factor- A (VEGF-A), Platelet-Derived Growth Factor ß Receptor (PDGFRß), VEGF-receptor 1 (Flt1), VEGF-receptor 2 (KDR), Glucose Transporter 1 (GLUT1), Carbonic anhydrase IX (CA-IX) and the hERG1 potassium channel. Data were analysed in conjunction with the clinico-pathological characteristics of the patients and follow up. RESULTS: All the proteins were expressed in the samples, with statistically significant associations of VEGF-A with PDGFRß and Flt1 and hERG1 with CA IX. Notably, hERG1 and CAIX co-immunoprecipitated in primary ccRCC samples and survival analysis showed that the positivity for hERG1 and CA IX had a negative impact on Recurrence Free Survival (RFS) at the univariate analysis. At the multivariate analysis only hERG1 maintained its statistically significant negative impact. CONCLUSIONS: hERG1 expression can be exploited to predict recurrence in surgically-treated ccRCC patients. hERG1 channels form a multiprotein complex with the pH regulator CA IX in primary ccRCC samples their potential use as therapeutic target might be suggested.

Robotic correction of iatrogenic ureteral stricture: preliminary experience from a tertiary referral centre.

Objective: Iatrogenic stenosis is a relatively common complication and it could happen after urological procedures in the entire course of the ureter. The aim of this study is to report the surgical outcomes of 36 consecutive patients (period April 2013-November 2018) submitted to robot-assisted correction of benign stricture with previous urological surgery in a tertiary referral center.Methods: Elective criteria were to have had a benign ureteral stricture development after at least one urological procedure. Patients were classified as failures in the event of post-operative ultrasound demonstrating persistent hydronephrosis with or without symptoms or persistent symptoms with renal scan evidence of obstruction or redo procedures.Results: Eighteen patients (50%) were treated for calculosis, seven (19.4%) patients were submitted to double J ureteral stenting and previous pyeloplasty was performed in 11 (30.5%) patients. Overall median operative time was 160 min (IQR = 120-180). Five (13.8%) complications with three (8.3%) surgical post-operative complications occurred. Length of stay was 6 (IQR = 5-7) days. At last follow-up, ranging between 7-60 months, the overall success rate was 86.1% (31/36): three of them (8.3%) were submitted to retrograde holmium laser endopyelotomy, while two (5.5%) underwent a redo robot-assisted correction.Conclusions: Robot-assisted correction procedures can be done safely with good perioperative outcomes and a high post-operative success rate in a tertiary referral center. Further randomized clinical trials are mandatory to confirm the safety of this procedure.

Influence of male human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection on the reproductive outcomes in serodiscordant couples: a case-control study.

BACKGROUND: Nowadays, serodiscordant couples (SDCs) with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)-infected men have the chance to conceive safely, giving birth with a minimum risk of cross-infection. OBJECTIVE: To assess the impact of male HIV and HCV infection on the assisted reproductive technologies (ART) outcomes in SDCs, with HIV or HCV seropositive men and negative partners. MATERIALS AND METHODS: Of 153 couples: 24 in Group 1 (HIV-seropositive men), 60 in Group 2 (HCV-seropositive men) and 69 in Group 3 (controls). Sperm-washing procedure was performed using a three-step system. Fresh ICSI cycles were carried out in HIV SDCs, HCV SDCs and controls. Seminal parameters, fertilization rate (FR), cleavage rate (CR), pregnancy rate per cycle (PR/C), miscarriage rate, implantation rate (IR) and live birth rate were evaluated. RESULTS: All the seropositive men have undetectable viral loads at the time of insemination, and both partners were free from co-morbid infections. The median number of embryos transferred was 2.0 (IQR 1.0-3.0), with no differences among groups. FR was significantly reduced in HIV and HCV SDCs compared to the controls (66%, 61% and 75%, respectively; p < 0.01). CR was similar between groups (p = 0.3). IR was 12.1%, 11.1% and 14.1%, respectively, in the three groups (p = 0.30). PR/C was 21.7%, 17.6% and 20.2% in HIV, HCV and controls, respectively. Live birth rate per cycle was 17.4%, 15.7% and 15.9%, respectively. There were no significant differences in clinical pregnancies per cycle, as well as miscarriages and live births (p = 0.30; 0.30; 0.60, respectively). CONCLUSIONS: The sperm-washing technique with ICSI may generate a promising way to improve pregnancy outcomes and to reduce the risk of viral transmission in these couples. In this setting, we can correctly counsel HIV- and HCV-infected men of SDCs with regard to the likelihood of father their own biological child.

Are hormone measurements and ultrasounds really predictors of sperm retrieval in testicular sperm extraction? A case report and literature review.

Azoospermia can be diagnosed in about 10%-15% of the infertile male population. To overcome the problem of failure to produce spermatozoa in the ejaculate in patients with nonobstructive azoospermia (NOA), testicular sperm extraction (TESE) may be performed to find the focal area of spermatogenesis. A 47-year-old man with NOA presented for treatment of secondary couple infertility. The patient underwent a first TESE 7 years earlier with cryopreservation, and an intracytoplasmic sperm injection-embryo transfer ended in a term pregnancy. He reported a history of repeated testicular traumas. At the present time, a complete medical workup was carried out, including clinical history, general and genital physical examination, scrotal and transrectal ultrasounds. Hormone measurements showed follicle-stimulating hormone level of 42.7 IU/L, luteinising hormone of 11.4 IU/L, total testosterone of 2.6 ng/ml and right and left testicular volume, respectively, of 4 and 3.9 ml. He underwent a second TESE, with successful sperm retrieval and cryopreservation. The histological pattern was hypospermatogenesis. In cases of extreme testicular impairment, although in the presence of very high follicle-stimulating hormone value and small testicular volume, estimating poor sperm recovery potential, the integration of clinical and anamnestic data, could help the surgeon to practise the more appropriate method of treatment.

Testicular sperm extraction after laparoscopic orchiectomy for bilateral postpubertal intra-abdominal cryptorchidism: What chance of sperm retrieval?

Infertility occurs in up to 54% of men with bilateral undescended testes. Orchiectomy is considered the best therapeutic approach, especially when cryptorchidism is diagnosed in adulthood, due to a high risk of malignancy. A 33-year-old man was referred with a clinical presentation of empty scrotum and an ultrasonography and magnetic resonance imaging evaluation of intra-abdominal bilateral cryptorchidism. Follicle-stimulating hormone was 23.20 IU/L, luteinising hormone was 14.10 IU/L, total testosterone was 12.1 nmol/L, and 17-beta-oestradiol was 0.16 nmol/L. Semen analysis showed absolute azoospermia. Tumour marker levels were in the normal range. Testicular volume was 4.0 ml for right testis and 4.6 ml for left testis. The patient underwent a laparoscopy bilateral orchiectomy and subsequently a testicular sperm extraction (TESE), in the purpose to finding mature spermatozoa. The biological examination revealed the presence of immature sperm cells, not efficient for a cryopreservation. The histologic analyses show a pattern of Sertoli cell-only syndrome and maturation arrest. TESE might be a good option for patients with absolute azoospermia and cryptorchidism, especially if bilateral. The procedure, performed after orchiectomy, is safe and does not have any impact on patient's health, although it is important to clarify the very low potential of sperm recovery.

Pharmacokinetic profile of bilberry anthocyanins in rats and the role of glucose transporters: LC-MS/MS and computational studies.

The aim of the present investigation was to better understand the pharmacokinetic profile of bilberry (Vaccinium Myrtillus) anthocyanins and the role of glucose transporters (sGLT1 and GLUT2) on their absorption. In particular, the absorption of 15 different anthocyanins contained in a standardized bilberry extract (Mirtoselect®) was measured in rats by a validated LC-ESI-MS/MS approach. The plasma concentration peak (Cmax) of 11.1ng/mL was reached after 30min and fasting condition significantly increased the bioavailability of anthocyanins by more than 7 fold in respect to fed rats. Glucose co-administration did not interfere with the overall anthocyanin uptake. Bioavailability of each anthocyanin was then estimated by comparing the relative content in plasma vs extract. The 15 anthocyanins behaved differently in term of bioavailability and both the aglycone and the sugar moiety were found to affect the absorption. For instance, arabinoside moiety was detrimental while cyanidin enhanced bioavailability. Computational studies permitted to rationalize such results, highlighting the role of glucose transporters (sGLT1 and GLUT2) in anthocyanins absorption. In particular a significant correlation was found for the 15 anthocyanins between sGLT1 and GLUT2 recognition and absorption.

Nanocrystalline cellulose-fullerene: Novel conjugates.

The covalent grafting of two amino-fullerene C60 derivatives (C60-LC-NH2 and C60-SC-NH2, LC=long chain and SC=short chain) onto the surface of TEMPO oxidized nanocrystalline cellulose (NCC-COOH) has been reported for the first time. These hybrids (NCC-LC-C60 and NCC-SC-C60) form stable colloidal suspensions at concentrations up to 0.5mg/mL and act as effective photosensitizers for singlet oxygen production as demonstrated by the oxidation of L-methionine-methyl ester to the corresponding sulphoxide. Using the same approach, in a one-pot reaction both a fluorescent target molecule (FITC-LC-NH2) and the C60-LC-NH2 derivative have been successfully attached covalently onto the NCC-COOH surface. These hybrids, which showed no cytotoxicity on MCF-7 human breast cancer cells could be good candidates in photodynamic cancer therapy.

Predictive factors of overall and major postoperative complications after partial nephrectomy: Results from a multicenter prospective study (The RECORd 1 project).

INTRODUCTION AND OBJECTIVES: To analyze postoperative complications and to assess for significant predictive factors during partial nephrectomy (PN) using a large multicenter dataset. METHODS: Patients who underwent PN for clinical T1 renal tumors at 19 urological Italian centers (Registry of Conservative Renal Surgery [RECORd] project) were evaluated between 2009 and 2012. Anthropometric data, comorbidities and perioperative outcomes were analyzed. Complications were divided as intra- and postoperative, medical and surgical, as appropriate. The severity of postoperative complications was graded according to the modified Clavien classification system. Patients who experienced intraoperative complications were excluded from the analyses for the potential confounding effect in the evaluation of predicting factors for postoperative complications. RESULTS: Overall, 979 patients were analyzed: open, laparoscopic and robot-assisted (available since 2011) surgical approaches were used in 522 (56.4%), 286 (30.9%) and 117 (12.6%) cases, respectively. Surgical postoperative complications were reported in 121 (13.1%) cases (32 (3.5%) were Clavien 3), medical were reported in 52 (5.6%) cases (3 (0.3%) were Clavien 3). No Clavien 4 complications were reported. At multivariable analysis, ECOG score ≥1 (OR 1.98; p = 0.002), lower preoperative hemoglobin (OR 0.71; p < 0.0001) and open surgical approach (2.91; p = 0.02) were significant predictive factors of overall surgical postoperative complications, ECOG score ≥1 (OR 1.93; p = 0.04) and surgical approach (p = 0.05) were significant predictive factors of Clavien 3 either surgical or medical postoperative complications. CONCLUSIONS: Comorbidities and surgical approach should be considered in preoperative evaluation of patients undergoing PN, as they resulted to play a significant role in the occurrence of postoperative complications.

CyberKnife stereotactic radiotherapy for isolated recurrence in the prostatic bed.

PURPOSE: To report a clinical experience of stereotactic body radiation therapy (SBRT) for isolated recurrence in the prostatic bed from prostate cancer. MATERIALS AND METHODS: Between November 2011 and November 2013, 16 patients were treated with SBRT for a macroscopic isolated recurrence of prostate cancer in the prostatic bed. All patients were initially treated with radical prostatectomy, and half of them also received radiotherapy. Two schedules of SBRT were used: 30 Gy in 5 fractions in previously irradiated patients, 35 Gy in five fractions in radiotherapy-naïve patients. RESULTS: At a median follow-up of 10 months (range 2-21 months), a significant biochemical response was found in all but one patient. At imaging evaluation, no local progression was noted: 10 patients showed partial response while four stable disease. At the moment of analysis, all 16 patients were alive. Seven of them experienced distant relapse, while nine maintained biochemical control, with no further therapy. Median time to relapse was 9.3 months (range 3-15.2 months). The treatment was well tolerated: One patient experienced G2 acute genitourinary and gastrointestinal toxicity. CONCLUSIONS: Our experience shows that SBRT with CyberKnife for isolated nodal relapse is a safe and well-tolerated treatment.

Simple enucleation for the treatment of highly complex renal tumors: Perioperative, functional and oncological results.

AIM: To assess the role of simple enucleation (SE) for the treatment of highly complex renal tumors. METHODS: Overall, 96 Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score 10 to 13 renal tumors were treated with SE at our institution. All conventional perioperative variables, surgical, functional and oncological results were gathered in a prospectively maintained database. Survival curves were generated using a Kaplan-Meier method. Univariate analysis assessed the outcome differences. RESULTS: Mean (± 1s.d.) clinical tumor diameter was 4.8 (± 1.6 cm). 70.8% of patients had ≥ cT1b stage. The PADUA score was recorded as 10, 11, 12 and 13 in 57.3%, 29.2%, 11.5%, and 2.1% of tumors respectively. Overall, 76 patients were treated with an open approach and 20 robotically. Mean warm ischemia time (WIT) was 19.2 min, and WIT greater than 25 min occurred in 14.6% of cases. Positive surgical margin (PSM) rate was 3.6% and trifecta was achieved in 64.3% of patients. Postoperative surgical complications occurred in 24% of patients, with 14.6% Clavien-Dindo grade 1-2, 8.3% grade 3, and 1% grade 4. Five-year cancer specific survival (CSS), recurrent free survival (RFS), and overall survival (OS) rates resulted 96.1%, 90.8% and 88.0%, respectively. Overall, 4.2% of patients experienced progressive disease. At follow-up, the mean decrease of eGFR from preoperative value was 13.9 ml/min. This was not significantly correlated with PADUA score (p = 0.69). The surgical approach was neither a predictor of Trifecta outcome, nor of postoperative complications, WIT > 25 min or PSM rate. CONCLUSIONS: SE is an effective treatment for highly-complex renal tumors, with a potential key role to widen the NSS (nephron sparing surgery) indications according to guidelines.

Cyberknife treatment for low and intermediate risk prostate cancer.

Cyberknife is an emerging treatment for early stage prostate cancer. Between October 2012 and January 2014, 32 patients were treated in our institution. Prescribed dose was 35-36.25 Gy in five fractions. Biochemical response was observed in 22 patients. Four patients experienced G2 acute genitourinary toxicity and in two cases we recorded G3 acute GU toxicity. 5 patients experienced G2 acute proctitis. At last follow up visit, all patients were still alive. 29 remained free of disease at last follow up appointment, while three developed a biochemical recurrence. Our experience confirms the efficacy and safety of Cyberknife for localized prostate cancer.

A snapshot of nephron-sparing surgery in Italy: a prospective, multicenter report on clinical and perioperative outcomes (the RECORd 1 project).

INTRODUCTION: Nephron-sparing surgery (NSS) has become the standard of care for the surgical management of small and clinically localized renal cell carcinoma (RCC). The conservative management of those RCCs is increasing over time. Aim of this study was to report a snapshot of the clinical, perioperative and oncological results after NSS for RCC in Italy. MATERIAL AND METHODS: We evaluated all patients who underwent conservative surgical treatment for renal tumours between January 2009 and December 2012 at 19 urological Italian Centers (RECORd project). Perioperative, radiological and histopathological data were recorded. Surgical eras (2009 vs 2012 and year periods 2009-2010 vs 2011-2012) were compared. RESULTS: Globally, 983 patients were evaluated. More recently, patients undergoing NSS were found to be significantly younger (p = 0.05) than those surgically treated in the first study period, with a significantly higher rate of NSS with relative and imperative indication (p < 0.001). More recently, a higher percentage of procedures for cT1b or cT2 renal tumours was observed (p = 0.02). Utilization rate of open partial nephrectomy (OPN) constantly decreased during years, laparoscopic partial nephrectomy (LPN) remained almost constant while robot-assisted partial nephrectomy (RAPN) increased. The rate of clampless NSS constantly increased over time. The use of at least one haemostatic agent has been significantly more adopted in the most recent surgical era (p < 0.001). CONCLUSIONS: The utilization rate of NSS in Italy is increasing, even in elective and more complex cases. RAPN has been progressively adopted, as well as the intraoperative utilization of haemostatic agents and the rate of clampless procedures.

A comparison of different oral therapies versus no treatment for erectile dysfunction in 196 radical nerve-sparing radical prostatectomy patients.

We retrospectively analyzed the effects on the erectile function (EF) of no treatment (NT), and an oral therapy (OT; on-demand therapy (OD) or a regimented rehabilitation (RR) program with phosphodiesterase type 5 inhibitors (PDE5-Is)), in a cohort of 196 consecutive patients following nerve-sparing radical retropubic prostatectomy (NSRRP). Patients undergoing bilateral NSRRP (BP; n = 147) and unilateral NSRRP (UP; n = 49), chose between OT (PDE5-Is OD or RR program) and NT. Patients who chose OD therapy received PDE5-Is (100 mg sildenafil, 20 mg tadalafil and vardenafil), whereas patients who chose the RR program received 100 mg sildenafil or 20 mg vardenafil three times a week, or 20 mg tadalafil twice a week at bedtime. The t-test for unpaired data and Fisher test were used for univariate analyses, logistic regression multivariate analysis was used to test the accuracy of available variables to predict EF recovery after radical prostatectomy. Potency rates were significantly correlated with the surgical technique and with OT when compared to NT (P < 0.02), respectively 68.7% for BP (61% with no therapy and 71% with PDE5-Is) and 44% for UP (29% with no therapy and 51% with PDE5-Is), while no statistically significative differences were found between OD and rehabilitation protocols (72% with rehabilitation and 70% with OD therapy in BP, 52% with rehabilitation and 50% with OD therapy in UP; P = NS). Early OT with PDE5-Is (OD or RR program) was superior to NT in recovery of EF in NSRRP. Furthermore, an RR program with PDE5-Is did not appear to be superior to OD therapy.

Hypofractionation in prostate cancer: radiobiological basis and clinical appliance.

External beam radiation therapy with conventional fractionation to a total dose of 76-80 Gy represents the most adopted treatment modality for prostate cancer. Dose escalation in this setting has been demonstrated to improve biochemical control with acceptable toxicity using contemporary radiotherapy techniques. Hypofractionated radiotherapy and stereotactic body radiation therapy have gained an increasing interest in recent years and they have the potential to become the standard of care even if long-term data about their efficacy and safety are not well established. Strong radiobiological basis supports the use of high dose for fraction in prostate cancer, due to the demonstrated exceptionally low values of α / ß . Clinical experiences with hypofractionated and stereotactic radiotherapy (with an adequate biologically equivalent dose) demonstrated good tolerance, a PSA control comparable to conventional fractionation, and the advantage of shorter time period of treatment. This paper reviews the radiobiological findings that have led to the increasing use of hypofractionation in the management of prostate cancer and briefly analyzes the clinical experience in this setting.

Management of benign prostatic hyperplasia: role of phosphodiesterase-5 inhibitors.

Several studies have highlighted a strong association between benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED), particularly in elderly men. Many epidemiological trials, such as in vitro and in vivo studies, have reported the emerging role of metabolic syndrome, including abdominal obesity, impaired glucose metabolism, hypertriglyceridemia, low high-density lipoprotein cholesterol, and hypertension, in the development and progression of urinary and sexual symptoms. Moreover, many authors have focused their studies on the identification of all the shared pathogenetic mechanisms of LUTS/BPH and ED, including alteration of cyclic guanosine monophosphate and RhoA-ROCK pathways or vascular and neurogenic dysfunction. All these are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Therefore, several trials have recently been designed to evaluate the role of PDE5-Is alone or in combination with conventional treatment for BPH, such as α-adrenergic blockers, in men affected by LUTS/BPH, with or without ED. Different PDE5-Is are in clinical use worldwide and currently six of them are licensed for the oral treatment of ED. All these compounds differ in pharmacokinetic factors, with influence on drug action, and subsequently in the overall safety and efficacy profile.