Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel-Lindau patients.

CONTEXT: Von Hippel-Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death. OBJECTIVE: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients. MATERIALS AND METHODS: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers. RESULTS: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC. DISCUSSION AND CONCLUSION: A1AT and APOH could be promising non-invasive biomarkers.

De Novo Bladder Urothelial Neoplasm in Renal Transplant Recipients: A Retrospective, Multicentered Study.

BACKGROUND AND OBJECTIVES: Renal transplant recipients (RTRs) have a 2- to 7-fold risk of developing a neoplasm compared to general population. Bladder urothelial neoplasms in this cohort has an incidence of 0.4-2%. Many reports describe a more aggressive behavior. The objective of this study is to describe oncologic characteristics of bladder urothelial neoplasms in RTRs and to evaluate its recurrence, progression, and survival rates. METHODS: A retrospective multicentered study was performed evaluating all de novo bladder urothelial neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and evaluation of recurrence, progression, and survival rates were performed. RESULTS: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75, and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60 years was found to be a statistically significant variable for recurrence risk. Progression rate was 14%. Presence of CIS was significantly associated with progression. All cancer-specific deaths were in the high-risk group and all were progressions from non-muscle invasive to muscle invasive bladder cancer. CONCLUSIONS: Bladder urothelial neoplasms following renal transplant is associated with a trend toward worst prognosis. Early aggressive treatments, such as early radical cystectomy, might be advisable to reduce cancer-specific deaths.

H2AX phosphorylation level in peripheral blood mononuclear cells as an event-free survival predictor for bladder cancer.

Bladder cancer (BC) has a typical aetiology characterized by a multistep carcinogenesis due to environmental exposures, genetic susceptibility, and their interaction. Several lines of evidence suggest that DNA repair plays a role in the development and progression of BC. In particular, the study of individual susceptibility to DNA double strand breaks (DSBs) may provide valuable information on BC risk, and help to identify those patients at high-risk of either recurrence or progression of the disease, possibly personalizing both surveillance and treatment. Among the different DSB markers, the most well characterized is phosphorylation of the histone H2AX (γ-H2AX). We assessed any potential role of γ-H2AX as a molecular biomarker in a case-control study (146 cases and 146 controls) to identify individuals with increased BC risk and at high-risk of disease recurrence or progression. We investigated γ-H2AX levels in peripheral blood mononuclear cells before and after their exposure to ionizing radiation (IR). We did not find any significant difference among cases and controls. However, we observed a significant association between γ-H2AX basal levels and risk of disease recurrence or progression. In particular, both BC patients as a whole and the subgroup of non-muscle invasive BC (NMIBC) with high basal H2AX phosphorylation levels had a decreased risk of recurrence or progression (for all BC HR 0.70, 95%CI 0.52-0.94, P = 0.02; for NMIBC HR 0.68, 95%CI 0.50-0.92, P = 0.01), suggesting a protective effect of basal DSB signaling. Our data suggest that γ-H2AX can be considered as a potential molecular biomarker to identify patients with a higher risk of BC recurrence. © 2015 Wiley Periodicals, Inc.

A prospective multicentric international study on the surgical outcomes and patients' satisfaction rates of the 'sliding' technique for end-stage Peyronie's disease with severe shortening of the penis and erectile dysfunction.

OBJECTIVES: To report the results from a prospective multicentric study of patients with Peyronie's disease (PD) treated with the 'sliding' technique (ST). PATIENTS AND METHODS: From June 2010 to January 2014, 28 consecutive patients affected by stable PD with severe penile shortening and end-stage erectile dysfunction (ED) were enrolled in three European PD tertiary referral centres. The validated International Index of Erectile Function (IIEF) questionnaire, the Sexual Encounter Profile (SEP) Questions 2 and 3, and the Peyronie's disease questionnaire (PDQ) were completed preoperatively by all patients. At the follow-up visits (at 3, 6 and 12 months), the IIEF, the SEP Questions 2 and 3, the PDQ, and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) were completed. The outcome analysis was focused on penile length restoration, and intra- and postoperative complications classified according the Clavien-Dindo Classification. RESULTS: The mean (range) follow-up was 37 (9-60) months. A malleable penile prosthesis (PP) was implanted in seven patients, while an inflatable three-pieces PP was placed in the remainder. In the case of inflatable PP implantation, porcine small intestinal submucosa and acellular porcine dermal matrix were used to cover the tunical defects. While in patients undergoing malleable PP implantation, collagen-fibrin sponge was used. The mean operative time was 145 min in the inflatable PP group and 115 min in the malleable PP group. There were no intraoperative complications. Postoperative complications included profuse bleeding requiring a blood transfusion in one patient (3.5%) on anticoagulation therapy for a mechanical heart valve (Grade II) and PP infection requiring the removal of the device (7%) (Grade III). There were no late recurrences of the shaft deformation. The postoperative functional data showed a progressive improvement in the score of all questionnaires, peaking at 12 months postoperatively. The mean (range) penile lengthening was 3.2 (2.5-4) cm and no patient reported recurrence of the curvature. CONCLUSIONS: The present series suggests that, in the hands of experienced high-volume surgeons, penile length restoration with the use of the ST represents an effective option for end-stage PD associated with ED and severe shortening of the shaft. Larger series and longer follow-up will be required to fully establish the efficacy of this procedure.

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.

Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation.

BACKGROUND: Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105(+) CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105(-) TCs) and their EVs. METHODS: Maturation of monocyte-derived DCs was studied in presence of CD105(+) CSCs and CD105(-) TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors. RESULTS: The results obtained demonstrate that both CD105(+) CSCs and CD105(-) TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105(+) CSCs was significantly greater than that of CD105(-) TCs. EVs derived from CD105(+) CSCs and in less extent, those derived from CD105(-) TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation. CONCLUSIONS: In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

Open versus robotic-assisted partial nephrectomy: a multicenter comparison study of perioperative results and complications.

PURPOSE: To compare surgical results, morbidity and positive surgical margins rate of patients undergoing robotic partial nephrectomy (RPN) versus open partial nephrectomy (OPN). METHODS: This is an observational multicenter study promoted by the "Associazione GIovani Laparoscopisti Endoscopisti" (AGILE) no-Profit Foundation, which involved six Italian urologic centers. All clinical, surgical, and pathological variables of patients treated with OPN or RPN for renal tumors were gathered in a prospectively maintained database. Tumor nephrometry was measured with PADUA score, and complications were stratified with modified Clavien system. Differences between RPN and OPN group were assessed with univariate analysis. Perioperative variables independently associated with complications were assessed with multivariate analysis. RESULTS: A total of 198 and 105 patients were enrolled in OPN and RPN group, respectively. Both had similar demographics, indications to surgery, tumor nephrometry, renal function, WIT (18.7 vs. 18.2 min; p = NS), positive margin rate (5.6 vs. 5.7%; p = NS), intraoperative complications, and postoperative medical complications. Compared to OPN, RPN group was significantly more morbid (p = 0.04), included tumors with smaller size (p = 0.002), had longer operative time (p < 0.001), lower blood loss, surgical postoperative complications (5.7 vs. 21.2%, p < 0.001), Clavien 3-4 surgical complications (1 vs. 9.1%, p = 0.001), and shorter hospitalization. The surgical approach resulted independently correlated with surgical complications on multivariate analysis. CONCLUSION: In the present series, RPN was associated with a significant reduction of blood loss, surgical complications, including the reintervention rate for urinary fistula and postoperative bleeding, and with a shorter hospitalization.

Oral mucosa harvest for urologic reconstruction: role of maxillofacial surgeon and donor-site morbidity evaluation.

PURPOSE: The aim of this study was to present retrospective analysis of our experience regarding complications associated with the donor site after oral mucosa harvest for urethral reconstruction. MATERIALS AND METHODS: Between May 2010 and January 2013, a total of 18 patients with recurrent urethral strictures received a buccal mucosal graft for urethral reconstruction at the San Giovanni Battista Hospital, University of Turin, Turin. All operations were performed in a 2-team approach. All patients were retrospectively evaluated by clinical examination and using a questionnaire. RESULTS: Urethroplasty with oral mucosa graft was performed successfully in a 1-step procedure in 17 of 18 patients. No intraoperative complications were observed.The most common complication occurring at the buccal donor site was scarring and contracture (n = 3). CONCLUSIONS: Oral mucosa graft for urethroplasty is a simple and safe method in the interdisciplinary treatment of urethral strictures. Donor-site morbidity measured by clinical assessment and questionnaire is tolerable.

Negative predictive value for cancer in patients with "gray-zone" PSA level and prior negative biopsy: preliminary results with multiparametric 3.0 Tesla MR.

PURPOSE: To investigate the negative predictive value (NPV) for malignancy of 3.0 Tesla (T) MRI in patients with "gray zone" PSA level and prior negative biopsies. MATERIALS AND METHODS: We enrolled 26 patients with PSA level between 2.5 and 10 ng/mL and no cancer at previous biopsies. Examinations were performed on a 3.0T system using T2-weighted imaging, diffusion-weighted imaging, spectroscopy, and postcontrast dynamic study. A regional scheme was used to record MRI findings and to perform subsequent transrectal-ultrasonography-guided biopsy. Based on the matching between imaging and biopsy findings we estimated MRI predictive values, sensitivity, specificity and accuracy on a per-patient and per-region basis. RESULTS: On a per patient basis, MRI had five true-positive (5/26; 19.2%), eight true-negative (8/26; 30.8%) and no false-negative cases, corresponding to a NPV and sensitivity of 100% each. Thirteen patients were assessed as false-positive cases (13/26; 50.0%) (specificity of 38.1%). Five of them (5/26; 19.2%) showed high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small-acinar proliferation (ASAP) at biopsy. T2-weighted imaging alone showed per-region NPV (96.8%). CONCLUSION: Because of the high NPV, MRI had the potential to avoid unnecessary biopsy in approximately one-third of "gray-zone" patients with a negative examination. Additionally, MRI was useful to address to biopsy more than one-third of patients with cancer or high-risk lesions as HGPIN and ASAP.

Geometrical stepper-guided navigation system for ProACT implant under transrectal ultrasound control: preliminary data.

PURPOSE: To describe a new geometrical stepper-guided navigation system for positioning ProACT®. METHODS: The sizing of the stepper-guided navigation system was calculated using the distance from the ideal position of the device to anatomic referral points previously measured by ultrasound. The trocar and subsequently the device were maneuvered to the ideal position in accordance with the navigation system. MEASUREMENTS: Treatment efficacy was evaluated with daily pad count, 1-hour pad test, Incontinence Quality of Life questionnaire (IQoL), visual analog scale and overall impression. Complications, balloon volume and number of adjustments were reported at 1, 3, 6 and 12 months follow-up visits. RESULTS: Mean follow-up was 12 (range 3-19) months. Daily pad count showed 30 patients (71%) dry and 9 patients (21%) improved. 1 hour pad test showed 28 patients were dry (66%) and 11 patients improved (26%). IQoL increased from an average of 35.3 to 80. Average visual analog scale score was 8. Complications requiring device removal occurred in 3 patients (7%). Mean balloon volume was 3.1 ml. CONCLUSIONS: The stepper-guided navigation system to implant ProACT is feasible and extremely reproducible making this procedure more standardized.

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.

Is there a prostate-specific antigen upper limit for radical prostatectomy?

OBJECTIVE: • To assess the feasibility of radical prostatectomy (RP) in a series of patients with prostate cancer with very high prostate-specific antigen (PSA) levels by comparing the clinical outcomes of different PSA thresholds (20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL, respectively). PATIENTS AND METHODS: • Within a multicentre European retrospective database of 712 RP in patients with a baseline PSA level >20 ng/mL, we identified 48 patients with prostate cancer with a preoperative PSA level >100 ng/mL, 137 with a PSA level between 50.1 and 100 ng/mL and 527 with PSA values between 20.1 and 50 ng/mL. • Comparisons between groups were performed using chi-square test, analysis of variance and Kaplan-Meier analysis with log-rank test. RESULTS: • Ten-year projected cancer-specific survival (79.8% in the PSA >100 ng/mL group vs 85.4% in the PSA 50.1-99 ng/mL group vs 90.9% in the PSA 20.1-50 ng/mL interval; P = 0.037) but not overall survival (59.6% in the PSA >100 ng/mL group vs 71.8% in the PSA 50.1-99 ng/mL group vs 75.3% in the PSA 20.1-50 ng/mL interval; P = 0.087) appeared significantly affected by the different PSA thresholds. • At a median follow-up of 78.7 months, 25.8%, 6.6% and 8.3% of patients in the PSA level groups for 20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL respectively, were cured by surgery alone. CONCLUSIONS: • Ten-year cancer-specific survival, while showing significant reduction with increasing PSA values intervals, remain relatively high even for PSA levels >100 ng/mL. • As part of a multimodal treatment strategy, RP may therefore be an option, even in selected patients with prostate cancer whose PSA level is >100 ng/mL.

Adjustable continence therapy for severe intrinsic sphincter deficiency and recurrent female stress urinary incontinence: long-term experience.

PURPOSE: ACT was developed to treat female stress urinary incontinence resulting from intrinsic sphincter deficiency by increasing urethral resistance. We evaluated the implantation procedure and assessed patient outcomes at our center. MATERIALS AND METHODS: The adjustable continence device consists of 2 silicone balloons on either side of the proximal urethra under the bladder neck, each attached to a titanium port buried in the labia to allow postoperative titration. Urodynamic assessment was done in 57 female patients in whom previous pelvic surgery had failed. Pad use and an incontinence quality of life questionnaire were evaluated before ACT implantation, postoperatively at 1, 3, 6 and 12 months, and annually thereafter. Patients recorded the overall impression and percent of improvement postoperatively based on the Patient Global Impression Index and a visual analog scale. RESULTS: Mean followup was 72 months (range 12 to 84). At 6-year followup in 29 patients mean pad use improved from 5.6 daily at baseline to 0.41 and intrinsic sphincter deficiency improved from 27.2 to 78.6 (p <0.001). As measured on the visual analog scale, 68% of patients considered themselves dry. On the Patient Global Impression Index questionnaire 64% were very much improved, 23% were much improved and 13% were only minimally improved or unchanged. No patients considered themselves worse after the procedure. Complications necessitating device removal developed in 21.1% of patients. CONCLUSIONS: Relative ease of insertion and the ability to tailor this therapy to individual needs makes this an attractive option for the challenging treatment for recurrent stress urinary incontinence due to intrinsic sphincter deficiency.

Prognostic factors in a prospective series of papillary renal cell carcinoma.

OBJECTIVE: To prospectively assess the clinical outcome of a series of papillary renal cell carcinomas (PRCCs) to identify possible prognostic clinical variables and tumour markers, as previous retrospective series of PRCC do not provide unanimous results on the prognostic utility of clinicopathological variables. PATIENTS AND METHODS: Forty-six patients with PRCC (median follow-up 40 months) diagnosed in one institution from 1989 to 2002 were prospectively followed until May 2006. The pathology was reviewed, the PRCC subtyped (type 1 and 2) and immunohistochemistry assessed for MIB-1, vascular endothelial growth factor (VEGF), CD31 and c-met oncogenic protein, by a referee pathologist. Prognostic values were estimated by fitting a Cox model. RESULTS: The 5-year survival rate was 49.5%; type 2 histology was predominant and was almost significant in the univariate analysis. Stage and MIB-1 were significant prognostic factors only in the univariate model, while the Cox model identified only the Fuhrman grade as an independent predictor of survival (hazard ratio 3.054; P = 0.007). MET expression, CD31 and VEGF had no prognostic utility. CONCLUSION: These patients with PRCC followed prospectively fared worse than in previously reported series. The Fuhrman grade was the sole independent predictor of survival.

Adjustable continence therapy (ProACT) and bone anchored male sling: Comparison of two new treatments of post prostatectomy incontinence.

OBJECTIVES: To compare the efficacy of two surgical treatments for male urinary stress incontinence: adjustable continence therapy (ProACT) and bone anchored male sling (BAMS). METHODS: Eighty-four consecutive post radical prostatectomy incontinent patients received ProACT (n = 46) or BAMS (n = 38) implantation by two different operators in two different centres. Eighty of them had a complete follow up. Both groups were prospectively assessed by number of pads per day and a validated questionnaire (UCLA/RAND). Complications rate and mean operating times were compared. All comparisons were analyzed using the t test, Fischer's exact test and chi(2) analysis (significance P < 0.05). RESULTS: At a mean follow up of 19 and 33 months respectively, 30/44 (68%) patients treated with ProACT were dry (0/1 safety pad) in comparison with 23/36 (64%) patients treated with BAMS (P > 0.05). Stratifying the results, ProACT had 33/39 (85%) dry patients in severe (more than three pads/day) preoperative incontinence, in comparison with 21/26 (81%) for BAMS (P > 0.05). The UCLA/RAND questionnaire showed an average increase of 11.7 points (from 10.2 to 21.9) for ProACT and of 10 points (from 11.9 to 21.9) for BAMS (P > 0.05). Complications included removal of ProACT and BAMS in 6/44 (14%) and 2/36 (6%), respectively. Mean operating time was 18 min and 45 min (P < 0.05) for ProACT and BAMS, respectively. CONCLUSIONS: ProACT and BAMS are both associated with a satisfactory rate of success. ProACT results seem to be better for severe incontinence and BAMS for mild incontinence. The operation time of ProACT is shorter.

Role of perioperative dynamic sentinel node biopsy for cN0 penile cancer management: experience from an Italian tertiary referral center.

PURPOSE: Inguinal lymphadenectomy (iLAD) reduces mortality in patients with cN0 penile cancer but yields high complication rates. Thus, its prophylactic role has been questioned and dynamic sentinel node biopsy (DSNB) was introduced to select men who should undergo the procedure. Our aim was to investigate the accuracy of a contemporary DSNB cohort. METHODS: We performed a retrospective analysis of ≥T1 or ≥G2 cN0 penile cancer undergoing perioperative DSNB from June 2009 to June 2015 at a tertiary referral center. We excluded men with <18 months follow-up or with local recurrence after primary curative treatment. Complications were graded according to the Clavien-Dindo classification. RESULTS: Thirty-five men underwent DSNB; 85.71% had ≤T2 penile cancer with ≤G2a histology. Per groin detection rate was 80% (scintigraphy being positive bilaterally in 60% and unilaterally in 20.0%). In no cases did DSNB prolong the postoperative course compared to primary surgery. Nine men (n = 15/109 nodes removed) had positive results, 8 of whom underwent iLAD. Among negative DSNB patients, 2 developed nodal penile cancer recurrence; none of them had node biopsy due to inconclusive scintigraphy. At a median follow-up of 42 months (interquartile range 30-78 months), if considering only men with scintigraphy detected inguinal nodes, per-patient sensitivity and specificity were 50% and 80% whereas positive predictive value and negative predictive value were 25% and 92.3%, respectively. CONCLUSIONS: Perioperative DSNB is a safe procedure, yielding promising results when performed at a tertiary referral center. Future prospective large studies are needed to investigate how to optimize detection rate and reduce false-negative rates.

Lipoid-cell variant of urothelial carcinoma: report of a new case of the urinary bladder.

We report a new case of urothelial lipoid carcinoma of the urinary bladder, occurring in a 71 year-old woman. The tumor presented with metastatic involvement of the left axillary and supraclavicular lymph nodes. Clinical work up revealed a large infiltrating bladder tumor microscopically featuring poorly differentiated, pleomorphic cells with nuclear pleomorphism and frequent mitoses. Large, optically clear intracytoplasmic vacuoles imparting an adipocytic or signet-ring cell appearance could be noticed. Areas of conventional urothelial carcinoma were present as well. Due to the extensive invasion of the bladder coat, distant metastases as well as poor performance status radical cystectomy was not performed. The patient was treated with multimodality conservative therapy and is alive 9 months after the diagnosis.

Quality of life evaluation by the EORTC QLQ-C30 questionnaire in patients treated with hormonal treatment in Italy. A QuABIOS group study.

OBJECTIVES: An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities. METHODS: Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment. RESULTS: 587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide. CONCLUSIONS: Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.

The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury.

BACKGROUND: Mesenchymal stromal cells (MSCs) and renal stem/progenitors improve the recovery of acute kidney injury (AKI) mainly through the release of paracrine mediators including the extracellular vesicles (EVs). Several studies have reported the existence of a resident population of MSCs within the glomeruli (Gl-MSCs). However, their contribution towards kidney repair still remains to be elucidated. The aim of the present study was to evaluate whether Gl-MSCs and Gl-MSC-EVs promote the recovery of AKI induced by ischemia-reperfusion injury (IRI) in SCID mice. Moreover, the effects of Gl-MSCs and Gl-MSC-EVs were compared with those of CD133+ progenitor cells isolated from human tubules of the renal cortical tissue (T-CD133+ cells) and their EVs (T-CD133+-EVs). METHODS: IRI was performed in mice by clamping the left renal pedicle for 35 minutes together with a right nephrectomy. Immediately after reperfusion, the animals were divided in different groups to be treated with: Gl-MSCs, T-CD133+ cells, Gl-MSC-EVs, T-CD133+-EVs or vehicle. To assess the role of vesicular RNA, EVs were either isolated by floating to avoid contamination of non-vesicles-associated RNA or treated with a high dose of RNase. Mice were sacrificed 48 hours after surgery. RESULTS: Gl-MSCs, and Gl-MSC-EVs both ameliorate kidney function and reduce the ischemic damage post IRI by activating tubular epithelial cell proliferation. Furthermore, T-CD133+ cells, but not their EVs, also significantly contributed to the renal recovery after IRI compared to the controls. Floating EVs were effective while RNase-inactivated EVs were ineffective. Analysis of the EV miRnome revealed that Gl-MSC-EVs selectively expressed a group of miRNAs, compared to EVs derived from fibroblasts, which were biologically ineffective in IRI. CONCLUSIONS: In this study, we demonstrate that Gl-MSCs may contribute in the recovery of mice with AKI induced by IRI primarily through the release of EVs.