Massimo Polito

The Role of Uroflowmetry Biofeedback and Biofeedback Training of the Pelvic Floor Muscles in the Treatment of Recurrent Urinary Tract Infections in Women With Dysfunctional Voiding: A Randomized Controlled Prospective Study

OBJECTIVES To evaluate the efficacy of a training program with uroflowmetry biofeedback and pelvic floor relaxation biofeedback on urodynamic and voiding parameters in women with dysfunctional voiding. METHODS Eighty-six women with recurrent urinary tract infections (UTIs) and dysfunctional voiding were randomly assigned to receive a treatment schedule as follows: uroflowmetry biofeedback (group 1), biofeedback training of the pelvic floor muscles (group 2), uroflowmetry biofeedback combined to biofeedback training of the pelvic floor muscles (group 3), no treatment (group 4). Patients were regularly evaluated by American Urological Association Symptom Index and urodynamics during the study period. All the patients were followed up for 1 year with monthly urine cultures. A further evaluation was done at month 24 by American Urological Association Symptom Index and free uroflowmetry with measurement of residual urine. RESULTS The prevalence of storage and emptying symptoms decreased significantly at 3, 6, and 12 months in the groups 1, 2, and 3, and remained stable during the study period. Mean flow rate, flow time, voiding volume increased significantly, whereas postvoid residual urine decreased. The prevalence of UTI decreased significantly in groups 1, 2, and 3. At month 24, storage and emptying symptoms and voiding patterns were similar to the baseline values in all the patients. The incidence of UTIs was similar to baseline values in groups 1, 2, and 3. CONCLUSIONS Training the voluntary control of the pelvic floor seems essential in obtaining control over the bladder function. These results reinforce the importance of pelvic floor therapy in the resolution of UTIs.

Erectile rehabilitation with intracavernous alprostadil after radical prostatectomy: refusal and dropout rates

Study Type – Therapy (outcomes)

D2-40 immunoreactivity in penile squamous cell carcinoma: a marker of aggressiveness

D2-40 immunohistochemical expression was investigated in tissue specimens from 39 patients with squamous cell carcinoma of the penis who underwent partial or total penectomy between 1987 and 2008. Patient age, tumor size, and grade; D2-40-positive lymphatic vessel density in intratumoral, peritumoral, and normal tissue; cell positivity for D2-40 in intratumoral and normal tissue; and D2-40 staining intensity and distribution were analyzed and correlated with disease-specific survival. Analysis of D2-40-positive lymphatics disclosed that mean lymphatic vessel density was greater in peritumoral tissue than in intratumoral and normal tissue and lower in patients with lymph node metastasis than in those without lymph node metastasis. The receiver operating characteristic curve showed that an intratumoral lymphatic vessel density greater than 2.0 had 83.3% sensitivity and 78% specificity in predicting lymph node metastasis. Analysis of cell immunoreactivity showed cytoplasmic D2-40 positivity in intratumoral and normal tissue in 89.7% and 65.5% of patients, respectively. A strong correlation emerged between grade of cell differentiation and D2-40 immunoreactivity in intratumoral tissue; in particular, 88.9% of tumors with weak podoplanin expression were G1, whereas strong cellular immunoreactivity was detected in 83.3% of G3 patients (P = .003; χ(2) test). A significant correlation was also noted between pattern of reactivity and tumor grade because the basal layer was positive in patients with undifferentiated tumors (100% of G3) and in 72.2% of G1 tumors (P = .021; χ(2) test). D2-40 seems to be a useful marker for the development of node metastasis in squamous cell carcinoma of the penis, although validation in larger series is required to confirm its predictive value.

Comparison between WHO (World Health Organization) 2010 and WHO 1999 parameters for semen analysis – interpretation of 529 consecutive samples

OBJECTIVE To quantify how many men with normal semen according to WHO (WHO - World Health Organization) 1999 criteria, should be considered with abnormal semen according to 2010 criteria and vice versa; to study which parameter of volume, concentration, motility and morphology is the most responsible of this change. MATERIALS AND METHODS We studied, using WHO 1999 parameters, 529 consecutive semen samples from 427 men, collected in our Department from January 2008 to December 2009, then we re-evaluated those results using WHO 2010 parameters; we also studied each parameter to understand how changed the classification from normal (defined normal by all parameters) to abnormal (defined abnormal by at least one parameter) using the two WHO criteria. RESULTS 3 men (0.56%) were azoospermic. Among the remaining 526 samples, 199 (37.83%) were considered normal and 246 (46.76%) abnormal both according to WHO 1999 and WHO 2010 criteria; we found that none of the samples classified normal according to the previous criteria was classified abnormal according the more recent criteria, while 82 (15.58%) evaluated as abnormal according 1999 criteria changed to normal according 2010 criteria. The concordance between 1999 and 2010 evaluation was 84.44%. CONCLUSIONS In this study we noted that the changes from WHO 1999 to WHO 2010 criteria did not modify the interpretation of semen quality, because comparing the two classifications we demonstrated that there is a substantial agreement, considering the three parameters (count, motility and morphology) all together, and also considering each single parameter. Anyhow, almost 16% of the patients considered infertile according to the old criteria, should be evaluated normal by the new classification and they should not need any treatment for infertility.

Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

Do DNA-methylation and histone acetylation play a role in clear cell renal carcinoma? Analysis of radical nephrectomy specimens in a long-term follow-up.

We investigated global methylation and histone acetylation in 50 conventional clear cell renal carcinomas (RCC), treated with radical nephrectomy, to assess their possible role as diagnostic biomarkers. The features considered in this study were patient age, tumor size and grade, percentage and intensity of 5-methylcytosine (5mc) and Acetyl-Histone (Lys 9) expression in tumor tissue. All considered parameters were correlated with patient specific survival. The mean percentage of global cellular methylation in tumoral tissue was significantly higher compared to normal peritumoral tissue (p<0.0001), while the intensity of cellular methylation was significantly higher in normal tissue than in tumoral tissue (p=0.001). The mean percentage of histone cellular acetylation in tumoral tissue was significantly lower compared to normal peritumoral tissue (p=0.0005), while the intensity of mean acetylation in neoplastic tissue was similar to the normal tissue. The percentage of global DNA methylation was significantly higher in grades 3 and 4 tumors (p=0.033). Global DNA methylation and histone acetylation in tumoral tissue did not correlate with survival. Fuhrman grade was statistically significant for prognosis (p=0.031). In conclusion, global hypermethylation and histone hypoacetylation play an important role in RCC carcinogenesis; Fuhrman grade is still considered the most important factor for patient survival; 5mc can have a role as markers of aggressiveness.

Increased Urokinase-Type Plasminogen Activator Receptor and Epidermal Growth Factor Receptor in Serum of Patients With Prostate Cancer

PURPOSE Prostate cancer cell motility and invasion have been linked to the up-regulated signaling of epidermal growth factor receptor and urokinase-type plasminogen activator receptor. We analyzed the expression of serum urokinase-type plasminogen activator receptor and epidermal growth factor receptor in the serum of patients with clinical suspicion of prostate cancer to evaluate the possible role as prostate cancer markers. MATERIALS AND METHODS Serum was collected from 79 consecutive patients referred to our institution for transrectal ultrasound guided prostate biopsy. All blood samples were obtained before prostate biopsy. Total urokinase-type plasminogen activator receptor and epidermal growth factor receptor antigen in serum were measured by specific enzyme-linked immunosorbent assays. Gleason score, the number of positive cores, maximum percent of cancer and inflammation were considered on biopsy. Patients determined to have prostate adenocarcinoma underwent radical retropubic prostatectomy. Gleason score, pathological stage (extraprostatic extension), surgical margins, seminal vesicle involvement, perineural infiltration, lymphovascular invasion and cancer volume were evaluated in radical retropubic prostatectomy specimens. RESULTS The 30 patients with prostate cancer had significantly higher levels of serum urokinase-type plasminogen activator receptor and epidermal growth factor receptor in comparison to those without prostate cancer but not significantly higher levels of prostate specific antigen. Urokinase-type plasminogen activator receptor and epidermal growth factor receptor levels closely correlated in the serum of patients with prostate cancer. In a multivariate model high serum epidermal growth factor receptor increased the probability of positive biopsies by 1.9 times. ROC analysis revealed that serum epidermal growth factor receptor had 93.3% sensitivity and 98% specificity for detecting prostate cancer at a cutoff of 67.9 ng/ml. Urokinase-type plasminogen activator receptor and epidermal growth factor receptor were significantly higher in patients with extraprostatic extension, seminal vesicle involvement and perineural infiltration in the radical retropubic prostatectomy specimens. Serum urokinase-type plasminogen activator receptor was the only independent predictive serum marker of extraprostatic extension, seminal vesicle involvement and perineural infiltration. CONCLUSIONS The measurement of urokinase-type plasminogen activator receptor and epidermal growth factor receptor in the serum of patients with clinical suspicion of prostate cancer might provide clinically relevant information on the state of the prostate gland. Measuring serum epidermal growth factor receptor could help predict which patients have prostate cancer, while serum urokinase-type plasminogen activator receptor over expression seems to be related to tumor extraprostatic spread.

The impact of repeated prostate biopsies on sexual function and urinary symptoms in patients with diagnosis of Atypical Small Acinar Proliferation (ASAP): Can ecoDoppler reduce side effects?

OBJECTIVES To establish whether repeated trans-rectal ultrasound-guided Prostate Needle Biopsies (PNBx) performed in men with diagnosis of Small Acinar Atypical Proliferation (ASAP) predispose these subjects to Erectile Dysfunction (ED) and to evaluate if EcoColorDoppler (ECD) can help to reduce this side effect. MATERIALS AND METHODS We performed a retrospective study regarding 190 men with diagnosis of ASAP detected between January 2001 and December 2011, who underwent to repeated prostate needle biopsies (PNBx). These patients were investigated about Erectile Function (EF) and Lower Urinary tract Symptoms (LUTS) using International Index of Erectile Function (IIEF-5) and International Prostate Symptom Score (IPSS) questionnaires before the first PNBx and 3 months after each other one. In particular, among the 89 men without ED before first PNBx, we compared IIEF-5 score between 64 patients who underwent to standard PNBx and 25 patients submitted to a PNBx done with in addition ECD ultrasound imaging. RESULTS Mean patient age was 65 years (SD 7.7); mean follow-up was 3.2 years (SD 1.8) and the mean number of re-biopsies completed was 2 (SD 1.5). Among the 143 men considered, only 89 resulted with a normal EF (IIEF-5 score > 21): in this group incidence of ED (IIEF-5 score < 21) among patients who underwent to standard PNBx was 4/64 (6.25%) while in patients submitted to a PNBx with ECD was 1/25 (4%). A greater decrease of EF was observed in patients undergone to 3 or more biopsies; no relationship between IPSS score and re-PNBx was identified. CONCLUSION Repeated PNBx done in patients with diagnosis of ASAP appear to get worse EF; number of biopsies seems to increase the risk of ED. Use of ECD in transrectal ultrasound- guided PNBx may have a role to avoid neurovascular bundles (NVBs) and preserve EF; anyway further studies are highly recommended to validate this hypothesis.

Approach for Renal Tumors With Low Nephrometry Score Through Unclamped Sutureless Laparoscopic Enucleation Technique: Functional and Oncologic Outcomes

Purpose: We report an unclamped sutureless laparoscopic simple enucleation (LSE) technique for renal tumors with low nephrometry score and analyze complication rates as well as functional and oncologic outcomes. Patients and Methods: We reviewed the data of 143 consecutive patients who underwent sutureless laparoscopic tumor enucleation with zero ischemia by a single experienced laparoscopic surgeon. The inclusion criteria for LSE with zero ischemia were tumor size ≤ 5 cm and RENAL nephrometry score of 4 to 6. The following data were collected: age, gender, body mass index, tumor side, renal function, tumor characteristics, American Society of Anesthesiologists score, operative time, positive surgical margins, estimated blood loss, and surgical complications. Results: The median RENAL score of patients was 4.7. Median tumor size was 2.7 cm. Conversion to open surgery and hilum vessels clamped were not necessary in any patient. There were no changes in postoperative creatinine values and estimated glomerular filtration rate. The median operation duration time was 78.2 minutes, and median estimated blood loss was 110.2 mL. The median hospital stay was 3.8 days. A total of 2.8% of the patients had positive surgical margins at pathologic examination. Of the 143 patients, 7% developed fever after surgery requiring an adequate antibiotic regimen, 1.4% developed postoperative bleeding requiring blood transfusions, and 0.7% had postoperative urinary leakage from the drainage requiring double‐J stent position. Conclusion: The unclamped sutureless LSE is a rational and safe approach to renal tumors with a low nephrometry score. This surgical technique does not increase the complication rate despite the reduction in parenchymal mass excised and the absence of hilar control.

PPTLBA-01 QUALITY OF LIFE AFTER PENILE PROSTHESIS IMPLANTATION – 1 YEAR FOLLOW-UP DATA OF THE ITALIAN PROSPECTIVE REGISTRY INSIST-ED

Paolo Capogrosso*, Giovanni Alei, Gabriele Antonini, Antonio Avolio, Antonio Barbieri, Carlo Bettocchi, Marco Bitelli, Francesco Boezio, Masssomo Capone, Enrico Caraceni, Maurizio Carrino, Carlo Ceruti, Sandro Ciampalini, Fulvio Colombo, Enrico Conti, Antonio Corvasce, Giuseppe Dachille, Diego Pozza, Stefano Fiordelise, Alessandro Franceschelli, Giulio Garaffa, Nicola Ghidini, FrancoGiorgio, Emilio Italiano, Giuseppe La Pera, Antonino Lagan a, Giovanni Liguori, Lilia Utizi, Matteo Matera, Nicola Mondaini, Alessandro Natali, Carlo Negro, Fabrizio Palumbo, Matteo Paradiso, Edoardo Pescatori, MassimoPolito,GaiaPolloni, AndreaSalonia,MauroSilvani, AldoTamai, Massimiliano Timpano, Francesco Varvello, Patrizio Vicini, Antonio Vitarelli, Antonio Palmieri, Federico Deh o, Milan, Italy