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.

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.

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.

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.

Miliary pulmonary infection after BCG intravesical instillation: a rare, misdiagnosed and mistreated complication.

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy decreases the progression risk of non-muscle-invasive bladder cancer, but potentially yields a broad spectrum of side effects. We report the case of a 73-year-old man affected by miliary pulmonary BCG infection, whose microbiological diagnosis was probably hindered by empiric fluoroquinolones, focusing on imaging and clinical work-up.

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.

Subcapsular Hematoma Causing Anuria After Renal Graft Trauma.

A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.

A Single-center Analysis on the Learning Curve of Male-to-Female Penoscrotal Vaginoplasty by Multiple Surgical Measures.

OBJECTIVE: To asses and quantify the learning curve (LC) of the penoscrotal inversion flap vaginoplasty (PSV). PATIENTS AND METHODS: We retrospectively reviewed clinical records of 69 patients who underwent PSV from January 2005 to January 2015. Two validated methods were used: a scatterplot representation and a splitting group. We selected as primary outcomes the operative time and vaginal depth. Surgical outcomes including blood losses, hospital stay, and postoperative complications such as vaginal stenosis or atresia or urethral meatus stenosis were also evaluated. RESULTS: The overall median operative time was 245 minutes. Severe intraoperative complications were not reported. The overall incidence of postoperative major complications was 21.7 %, most of them being urethral issues. The splitting group analysis revealed a statistically remarkable difference between groups for the operative time (P < .01), the vaginal depth (P = .01), the hospital stay (P < .01), and the intraoperative complication rate (P = .01). On the contrary, no differences were evidenced between the cohorts for the amount of blood loss (P = .08). The scatterplot logarithmic analysis demonstrated a clear visible LC for most parameters. The operative time showed a sharp decrease within the first 20-30 cases, reaching a plateau after 40 cases. Considering the analysis of the vaginal depth, the logarithmic scatterplot curve evidenced a slight increase within the first 10 cases, reaching a clear stabilization after nearly 30-40 cases. CONCLUSION: An evident LC for PSV is detectable, consisting of at least 40 cases needed to the surgical team to develop adequate skills to guarantee a safe and high-quality procedure.

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.

Sentinel lymph node detection during radical prostatectomy for prostate cancer: current evidence and results of our experience.

PURPOSE: A sentinel lymph node (SNL) is the primary landing zone of cancer cells that spreads through the lymphatic vessels. The rational of the detection of sentinel node (SLN) during radical prostatectomy (RP) for prostate cancer (PCa) is the removal of the first nodal stations to provide a restriction of the template of node dissection. A review of the outcomes of SNL detection during RP for PCa was performed. MATERIALS AND METHODS: A systematic review of the literature was conducted, searching on PubMed and Web of Science, using the following keywords: lymph node dissection, prostatic neoplasm, sentinel node. RESULTS: Twenty articles were selected and analyzed including over 2000 PCa patients. Although promising and technically feasible, many points remain to be clarified before clinical application can be recommended. CONCLUSIONS: The technique of SNL detection is feasible and provides a higher sensitivity and detection rate than standard lymphadenectomy, especially for organ-confined tumors. Larger series and long-term follow-up data are mandatory to assess the oncologic effectiveness of the detection of SNL for PCa.

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.

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.

Urological consequences following renal transplantation: a review of the literature.

Renal transplant (RT) represents the treatment of choice for end-stage renal disease (ESRD) but harbours a wide range of possible complications and therapeutic challenges of urological competence. Dialysis years and clinical medical background of these patients are risk factors for sexual dysfunction and lower urinary tract symptoms (LUTS). On the contrary, RT itself may have a number of possible surgical complications such as ureteral stenosis and urinary leakage, while immunosuppressive treatment is a known risk factor for de-novo malignancies.The present review describes the main urologic problems of RT patients and their up-to-date treatment options according to the most recently available literature evidences.

Sexual function after surgical treatment for penile cancer: Which organ-sparing approach gives the best results?

INTRODUCTION: We compared the postoperative sexual function of patients who underwent wide local excision (WLE) and glansectomy with urethral glanduloplasty for penile cancer. METHODS: We retrospectively reviewed clinical data of 41 patients affected by superficial, localized penile cancer (≤cT2a) between 2006 and 2013. Patients with severe erectile dysfunction and not interested in resuming an active sexual life were selected for penile partial amputation. Patients with preoperative satisfying erectile function and concerned about the preservation of their sexual potency were scheduled for WLE (Group A) or glansectomy with urethral glanduloplasty (Group B). Sexual function was assessed with the International Index of Erectile Function (IIEF) questionnaire and the Sex Encounter Profile (SEP). At 1 year, patients were asked to complete the questionnaires again and were questioned about their genital sensibility and ejaculatory reflex persistence. Postoperative complications were reported according to the Clavien-Dindo classification. Statistical analysis was performed by two-tailed test: Student t-test and chi-square. RESULTS: Among the 41 patients enrolled, 12 underwent WLE (29.2%), 23 glansectomy with urethral glanduloplasty (56%) and 6 with penile partial amputation (14.6%). A decrease in postoperative IIEF was recorded in both groups, but was statistically significant only in Group B (p = 0.003). As for the SEP, while no significant changes were recorded postoperatively in Group A, a marked reduction was reported for Group B, with a statistically significant decrease in the possibility of achieving penetrative intercourse (p = 0.006) and in the perceived satisfaction during sexual activity (p = 0.004). CONCLUSIONS: WLE lead to better sexual outcomes and less postoperative complications as compared to glansectomy with urethral glanduloplasty.

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.

[Female incontinence surgery: state of the art]. / Chirurgia dell'incontinenza urinaria femminile: a che punto siamo?

Female urinary incontinence represents a medical and social problem with huge impact regarding both patient's quality of life and social costs. The diagnosis is important for therapeutic choice and should consider some factors: the degree of urethral mobility, urodynamics parameters, patient's will and expectations, information about surgical complications and risks. Nowadays suburethral sling evolution and bulking therapy for selected cases consent to perform miniinvasive surgery; the most relevant problem concerns the management of postoperative complications: in this sense autologous slings are used after urethrolisis. In most difficult cases, it is possible to consider artificial sphincter as the best option.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients.

BACKGROUND: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE: To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS: T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.