Salvatore Blanco

Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa

BackgroundRhoA-Rho kinase complex contributes to keep the cavernosus smooth muscle contracted and its inhibition is considered a potential strategy for the therapy of erectile dysfunction (ED).MethodsWe compared the effects of SAR407899, the Rho-kinase inhibitor Y-27632 and the PDE5 inhibitor sildenafil for their ability to relax corpus cavernosum strips contracted with phenylephrine in healthy and diabetic animals. Strips were obtained from WKY, spontaneous hypertensive (SHR), control CD, and diabetic CD rats, humans, control and diabetic rabbits. Diabetes was induced by streptozotocin or alloxan injection. In vivo penile erection (length) induced by drugs was measured in conscious rabbits.ResultsSAR407899 dose-dependently relaxed the pre-contracted corpora cavernosa in all species, with similar potency and efficacy in healthy vs diabetic rats, WKY vs SHR rats, healthy vs diabetic rabbits (IC50 range from 0.05 to 0.29 μM, Emax range 89 to 97%). In the presence of the NO-synthase (NOS) inhibitor, L-NAME, the SAR407899 response did not decrease in any of the species or experimental conditions. The effect was confirmed in human strips where sildenafil was significantly less potent and effective, with IC50 respectively 0.13 and 0.51 μM; Emax 92 and 43%. Unlike SAR407899, the potency and efficacy of sildenafil and Y27632 were significantly reduced by diabetes and L-NAME. In vivo, SAR407899 dose-dependently induced rabbit penile erection, with greater potency and longer duration of action than sildenafil. Sildenafil, but not SAR407899, was less effective in alloxan-induced diabetes.ConclusionThe induction of penile erection by SAR407899, unlike that by sildenafil, is largely independent of e-NO activity. This suggests its use in erectile dysfunction for diabetic and hypertensive patients where e-NO activity is impaired.

Early detection of urothelial premalignant lesions using hexaminolevulinate fluorescence cystoscopy in high risk patients

BackgroundTo evaluate fluorescence cystoscopy with hexaminolevulinate (HAL) in the early detection of dysplasia (DYS) and carcinoma in situ (CIS) in select high risk patients.MethodsWe selected 30 consecutive bladder cancer patients at high risk for progression. After endoscopic resection, all patients received (a) induction BCG schedule when needed, and (b) white light and fluorescence cystoscopy after 3 months. HAL at doses of 85 mg (GE Healthcare, Buckinghamshire, United Kingdom) dissolved in 50 ml of solvent to obtain an 8 mmol/L solution was instilled intravesically with a 12 Fr catheter into an empty bladder and left for 90 minutes. The solution was freshly prepared immediately before instillation. Cystoscopy was performed within 120 minutes of bladder emptying. Standard and fluorescence cystoscopy was performed using a double light system (Combilight PDD light source 5133, Wolf, Germany) which allowed an inspection under both white and blue light.ResultsThe overall incidence was 43.3% dysplasia, 23.3% CIS, and 13.3% superficial transitional cell cancer. In 21 patients, HAL cystoscopy was positive with one or more fluorescent flat lesions. Of the positive cases, there were 4 CIS, 10 DYS, 2 association of CIS and DYS, 4 well-differentiated non-infiltrating bladder cancers, and 1 chronic cystitis. In 9 patients with negative HAL results, random biopsies showed 1 CIS and 1 DYS. HAL cystoscopy showed 90.1% sensitivity and 87.5% specificity with 95.2% positive predictive value and 77.8% negative predictive value.ConclusionPhotodynamic diagnosis should be considered a very important tool in the diagnosis of potentially evolving flat lesions on the bladder mucosa such as DYS and CIS. Moreover, detection of dysplasic lesions that are considered precursors of CIS may play an important role in preventing disease progression. In our opinion, HAL cystoscopy should be recommended in the early follow-up of high risk patients.

Preservation of Cavernosal Erectile Function after Soft Penile Prosthesis Implant in Peyronie's Disease: Long-Term Followup

The aim of this retrospective study is to evaluate the long-term followup of soft penile SSDA prosthesis, without plaque surgery in the treatment of Peyronies disease. This study included 12 men with Peyronies disease who underwent placement of a penile prosthesis. All patients were followed for at least 6 years. Prosthesis straightened the penile shaft in all cases, restoring patient sexual satisfaction. No operative or postoperative complications occurred, and no reoperations were needed. All patients have undergone further examination with basal and dynamic eco color Doppler. The findings are encouraging as the penis preserves the ability to enhance the tumescence and penile girth. We can conclude that SSDA penile prosthesis is safe and effective in Peyronies disease.

Vesicoureteral reflux in the child with lazy bladder syndrome: the infrequent voider.

The Infrequent Voider Syndrome or Lazy Bladder Syndrome in children is characterized by a large capacity bladder, frequently associated with a significant volume of residual urine. Usually these patients arrive at medical examination with a history of recurrent urinary infections but without anomalies in the upper urinary tract. We report about a young girl affected by one-sided 2° degree vesico-ureteral reflux due to Lazy Bladder Syndrome that had never been diagnosed before. This patient has been submitted to a prompt bladder training and seems presently to have at last gained a physiological micturition after 9 months of follow-up, without actual evidence of vesicoureteral reflux. Therefore we must stress that it is prominently important considering about infrequent micturition in a paediatric case history or a large capacity bladder, possible presence of bladder dysfunction and vesicoureteral reflux too.

Reduction in PSA messenger-RNA expression and clinical recurrence in patients with prostatic cancer undergoing neoadjuvant therapy before radical prostatectomy

BackgroundWe assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose.Methods29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM.Results64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence.ConclusionsQrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT.

Lower urinary tract symptoms associated with neurological conditions: Observations on a clinical sample of outpatients neurorehabilitation service

OBJECTIVES The overall aims of this study were to investigate the lower urinary tract symptoms (LUTS) associated with neurological conditions and their prevalence and impact on a clinical sample of outpatients of a neurorehabilitation service. MATERIALS AND METHODS We reviewed the files of 132 patients treated in our neurorehabilitation service from December 2012 to December 2013. Patients were divided into several subgroups based on the neurological diagnosis: Multiple Sclerosis (MS), other demyelinating diseases, Peripheral Neuropathy, neurovascular disorders (ND), neoplastic disease, traumatic brain injury (TBI), Parkinson and Parkinsonism, spinal cord injuries (SCI). Urinary status was based on medical evaluations of history of LUTS, type, degree, onset and duration of symptoms. We tried to analyze prevalence, kind of disorder, timing of presentation (if before or after the neurological onset) and eventual persistence of urological disorders (in the main group and in all subgroups). RESULTS At the time of admission to our rehabilitation service, LUTS were observed in 14 out of 132 cases (11%). A high proportion of these outpatients (64.2%) presented bothersome urinary symptoms such as incontinence, frequency and urgency (storage LUTS). The most frequent symptom was urinary urge incontinence (42.8%). This symptom was found to be prevalent in the multiple sclerosis and neurovascular disorders. In 93% the urinary symptoms arose as a result of neurologic conditions and 78.5% did not present a complete recovery of urological symptoms in spite of improved self-reported functional activity limitations. None of these patients performed urological rehabilitation. CONCLUSIONS Neurological disorders are a significant issue in rehabilitation services and it can lead to lower tract dysfunction, which causes LUTS. Storage symptoms are more common, especially urge incontinence. Current literature reports that a further optimization of the rehabilitation potential of neurologically ill patients is possible through an implementation of urological basic measures into the neurological treatment routine.

Efficacy of spermatic vein ligation in patients affected by high grade left varicocele.

PURPOSE To study the effect of high grade varicocele treatment in infertile patients. MATERIALS AND METHODS Seventy-five patients were selected by the following criteria: infertility persisting for more than 1 year; abnormal semen parameters; no other infertility-related disease; no obvious causes of infertility in the subjects partner; basal eco-color Doppler ultrasound demonstrating continuous reflux in the spermatic vein. All patients considered for the study had at least a six months period from the diagnosis to the surgery due to waiting list, choice of the patient or time needed to complete diagnostic evaluation of the couple. The surgical procedure was performed through an inguinal approach. All enrolled patients were counseled to have unprotected intercourse during the ovulation period in order to maximize the probability of pregnancy within the 6-month preoperative period. The achievement of pregnancy and semen parameters were recorded during the preoperative and postoperative period. RESULTS Two of the seventy-five patients were excluded because of persistent varicocele after surgery. The preoperative pregnancy rate was 1.3% (1 couple). The postoperative pregnancy rate was 42.5%. The stratification of pregnancies by semester showed a significantly higher rate in the first postoperative period (p = 0.0012). Mean time to conception was 13.5 months. Mean preoperative sperm count was 17.6x10(6)/mL compared to 19.7x10(6)/mL in the postoperative period (p < 0.0001). Mean percentage of progressive sperm motility was 13.7%, compared to 17.6% in the postoperative period (p < 0.0001). Mean percentage of normal sperm morphology was 7.6%, compared to 15.2% postoperatively (p < 0.0001). CONCLUSION Surgical treatment of high grade varicocele proved to effectively treat associa¬ted infertility by improving seminal parameters and pregnancy rate in our patient cohort.

Relationship between sun exposure and kidney cancer: preliminary experience with the evaluation of recreational UV exposure

Introduction Recent findings reported an inverse relationship between solar ultraviolet-B (UV-B) exposure and mortality from various types of cancers, including renal cancer. Methods We reviewed the literature concerning the relationship between sun exposure and incidence of kidney cancer. We performed a case-control study, evaluating recreational sun exposure in 50 kidney cancer patients and 50 controls. A questionnaire concerning sun exposure habits during childhood, adult life and in the previous 2 years was filled in by every patient. The questionnaire focused on: hours/day spent in the sun during summer; hours/day spent sunbathing (considering as well which kind of UV protection was used); sunburns; holidays in tropical countries. Results We found and analyzed few articles concerning the relationship between kidney cancer and sunlight exposure. The two cohorts of patients we evaluated were homogeneous for age, phototype, origin and living area. We found no statistically significant differences between sun exposure in patients affected by kidney cancer and controls, both during childhood and adult life; no differences were found in the use of sunscreens either. Conclusions Recreational sunlight exposure does not differ in our cohorts of patients and controls; studies on greater cohorts are needed to evaluate the effect of recreational sun exposure in the development of kidney cancer.

Simultaneous management of renal carcinoma with caval vein thrombosis and double coronary artery disease

INTRODUCTION Recent advances in surgical and anesthesiology techniques allow simultaneous thoracic and abdominal operations to be performed for severe heart disease and benignant or malignant abdominal diseases. CASE REPORT The simultaneous surgical management in a 75-year-old patient suffering from severe double coronary artery disease and a renal cell carcinoma with extended intravascular growth into the inferior vena cava is reported. CONCLUSION The postoperative course was uneventful. Simultaneous surgery proved to be beneficial and safe, showing optimal results in our patient.

PREOPERATIVE BLOOD DONATION PROGRAM AND POSTOPERATIVE LOW MOLECULAR WEIGHT HEPARINE (LMWH) PROPHYLAXIS IN PATIENTS UNDERGOING RADICAL PROSTATECTOMY

OBJECTIVE The need and timing of perioperative heparin prophylaxis is matter of debate. The aim of our work is to review the incidence of venous thromboembolism (VTE) after radical retro pubic prostatectomy (RRP) in patients undergoing preoperative blood donation, compressive stockings, haemodilution, surgical prevention of lymphocoele and postoperative low molecular weight heparin therapy as prophylaxis for thrombotic events. METHODS This is a retrospective analysis considering a series of 500 RRP performed between 1999 and 2006 by the same Surgeon (MG) at the Urological Unit, Desio, Hospital, Milan, Italy. All the patients were enrolled in an auto transfusion program and were subjected to autologous blood donation. Low molecular weight heparin (.04 ml of Calcic Nadroparin 3800 UI s.c. daily) was administrated within 24 hours following surgery until the 11th post-operative. Age, PSA, basal, preoperative and postoperative haemoglobin values were assessed in each patient. The incidence of venous thromboembolism was calculated taking into consideration occurrences of both pulmonary embolism and deep venous thrombosis. RESULTS In this retrospective analysis we did not observe any major event including intra- or peri-operative deaths. There was one occurrence of pulmonary microembolism and one sural phlebitis that were treated with prolonged heparin and dicumarol therapy. Two significant haemorrhagic events occurred in the postoperative period requiring surgical revision. CONCLUSION These data suggest that low weight heparin prophylaxis starting with 24 hours following radical prostatectomy, associated with preoperative blood donation, intra-operative haemodilution, compression stockings, surgical care to avoid lymphocoele and early mobilization in preventing venous thromboembolism.