Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer.

PURPOSE: Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of patients who are candidate to radical prostatectomy. METHODS: We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival. RESULTS: 389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small. CONCLUSIONS: Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.

Penile plication for Peyronie's disease: our results with mean follow-up of 103 months on 89 patients.

To evaluate the outcome of the long-term follow-up in patients who underwent corporoplasty-straightening treatment for Peyronie's disease. Between 1990 and 2012, a total of 89 patients underwent corporoplasty-straightening surgery using penile plication for Peyronie's disease. We followed up on all the patients for the following: (a) the correction of the curvature; (b) any penile shortening; (c) sexual function; and (d) complications. The mean follow-up period was 103 months. Complete correction of the curvature was obtained in 81 patients (91%). Shortening of the penis (1.5 to <3 cm) occurred in 20 patients (22.5%) and 79 patients (88.7%) had good erectile function (International Index of Erectile Function (IIEF) 5> 21). The most frequent complication was the sensitivity reduction of the glans in eight patients (8.9%), which was resolved within about a year after surgery (mean 11 months) and the shortening of the penis in 20 patients (22.5%), which, however, did not result in problems during sexual intercourse. Corporoplasty using penile straightening plication is a safe procedure whose results are maintained for even many years after surgery. It is a procedure that can be applied to any type of curvature. Any reduction in the length of the penis, as a result of the surgery procedure, does not lead to difficulties in sexual intercourse.

Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC. METHODS: Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs <3 (Group B). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia and NLR were included in the Cox analysis to investigate their prognostic relevance. RESULTS: Median OS and PFS were 10.6 and 5.3 months, respectively. Median OS was 12.2 months in Group A and 24.4 months in Group B (P=0.001). Median PFS was 3.4 months in Group A and 9.9 months in Group B (P<0.001). At multivariate analysis, only Motzer prognostic group and NLR were independent prognostic factors for OS and PFS. CONCLUSION: Pre-treatment NLR is an independent prognostic factor for patients with mRCC treated with second- or third-line everolimus. This should be investigated and validated in prospective studies.

VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib.

BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.

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.

Angiotensinogen promoter variants influence gene expression in human kidney and visceral adipose tissue.

Human angiotensinogen (AGT) gene promoter polymorphisms (G-217A; A-20C; G-6A) influence AGT transcription in vitro and have been implicated in the genetics of essential hypertension. We analysed the association among AGT promoter variants and AGT mRNA levels in human kidney and visceral adipose tissue (VAT) in vivo. Samples of kidney and VAT were obtained from 35 consecutive patients undergoing renal surgery. The AGT gene promoter of each patient was sequenced to identify variants. AGT gene expression was studied by real-time PCR TaqMan assay. Clinical data obtained before surgery were also considered in the statistical analysis. Two new polymorphisms at -175 and at -163 were identified. Although AGT expression was significantly higher in VAT than in the kidney, when both variants were present together AGT expression in VAT was about fivefold lower (P=0.033) than in the wild haplotype. This lower AGT expression in VAT suggests that the proximity and linkage of -175A and -163A variants might destabilize the binding of specific transcription factors to an acute-phase responsive element 3. Among the known AGT promoter variants, only -20C SNP has an important effect on tissue-specific differential AGT expression in the human tissues studied, inducing a 3.8-fold increase in AGT mRNA localized only in the kidney medulla (P=0.038). The other known polymorphisms (G-6A; G-217A) were not associated with different levels of AGT expression. Our results support the hypothesis that some human AGT promoter variants influence transcriptional activity in a tissue-specific way in humans.

Expression of basic fibroblast growth factor, its receptors and syndecans in bladder cancer.

Basic fibroblast growth factor (bFGF) is a heparin-binding cationic protein involved in a variety of pathological conditions including angiogenesis and solid tumour growth. The basic fibroblast growth factor receptor (FGFR) family comprises at least 4 high affinity tyrosine kinase receptors that require syndecans for their function. Mounting evidence indicates that syndecans, that bind both bFGF and their FGFRs, will act as stimulators, whereas syndecans that only bind bFGF will act as inhibitors of signaling by sequestering the growth factor. Recent findings have highlighted the importance of syndecans in urological cancers. The aim of this study is to investigate the expression of bFGF, its receptors (R1 and R2) and syndecans (1-4) in invasive urothelial carcinoma and normal-looking urothelium by Western blotting, RT-PCR, and immunohistochemistry analyses. Interestingly, bFGF, FGFR1 and FGFR2 protein levels statistically increased in bladder cancer tissues. mRNA of FGFR1 and syndecans (1-4), showed a statistically significant increase while an mRNA increase in the other molecules analysed was not significant. bFGF, its receptors and syndecan immunostaining were mainly present in the urothelium both in normal-looking tissues and urothelial neoplastic cells. In conclusion, our data report that the bFGF, FGFR and syndecan expressions are altered in bladder tumours.

Prognostic role of global DNA-methylation and histone acetylation in pT1a clear cell renal carcinoma in partial nephrectomy specimens.

Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin-embedded sections, using anti-5-methylcytosine (5mc) and anti-Acetyl-Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P = 0.033), whereas the percentage of histone acetylation was significantly lower (P = 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.

Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up.

Angiogenesis is a critical step in the growth, invasive progression and metastatic spread of solid tumors. We investigated the importance of tumor necrosis, and microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1alpha (HIF-1alpha) immunohistochemical expression in a large series of clear cell renal carcinomas treated with radical nephrectomy and assessed the prognostic value of their expression in terms of patient survival at long-term followup. Fifty patients with clear cell RCC were examined. The features considered when evaluating the patients were age, tumor size and grade, intratumoral vascular and renal capsula invasion, histological necrosis, and MVD, vascular and tumoral cell VEGF, and vascular, tumoral cytoplasmic and nuclear HIF-1alpha expression on the histologic specimens. All considered parameters were correlated with patient specific survival. Mean age was 62.06 +/- 6.8 years. Median follow-up was 191.66 months; median survival was 120.86 months. Twenty-one patients developed metastases in the follow-up. Tumor necrosis, microvascular invasion and renal capsula infiltration are more likely to occur in high stage and grade RCC; cytoplasmic HIF-1alpha is highly expressed in high grade RCC. Survival is dependent upon tumor stage and grade, the presence of intratumoral vascular invasion and capsular infiltration, and tumor necrosis; MVD also resulted as being an important prognostic factor. VEGF and HIF-1alpha correlate with prognosis in high stage tumors where VEGF is the most important independent prognostic factor for cancer specific death. The histological and immunohistochemical parameters considered in our study can influence disease recurrence and survival in RCC.

Effects of fluoroquinolones on bacterial adhesion and on preformed biofilm of strains isolated from urinary double J stents.

The activity of levofloxacin and ulifloxacin on biofilm formation and persistence was evaluated on microorganisms isolated from urinary double-J-stents. We analyzed 51 bacterial strains and their susceptibility to different antimicrobial classes was determined. We evaluated the bacterial ability to form biofilm and the effects of different concentrations of levofloxacin and ulifloxacin on bacterial adhesion and biofilm persistence. Most of the strains were biofilm producers with no relevant difference in biofilm production at 24 or 48 hours. The fluoroquinolones were able to prevent biofilm formation, but not to eradicate the preformed biofilm. On the basis of our data we advise that antibiotic prophylaxis with fluoroquinolones may be most helpful if given at the time of stent insertion and at high dosage.

Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice.

Accumulation of visceral fat is a key phenomenon in the onset of obesity-associated metabolic disorders. Macrophage infiltration induces chronic mild inflammation widely considered as a causative factor for insulin resistance and eventually diabetes. We previously showed that >90% of macrophages infiltrating the adipose tissue of obese animals and humans are arranged around dead adipocytes, forming characteristic crown-like structures (CLS). In this study we quantified CLS in visceral and subcutaneous depots from two strains of genetically obese mice, db/db and ob/ob. In both strains, CLS were prevalent in visceral compared with subcutaneous fat. Adipocyte size and CLS density exhibited a positive correlation both in visceral and in subcutaneous depots; however, the finding that adipocyte size was smallest and CLS density highest in visceral fat suggests a different susceptibility of visceral and subcutaneous adipocytes to death. Visceral fat CLS density was 3.4-fold greater in db/db than in ob/ob animals, which at the age at which our experimental strain was used are more prone to glucose metabolic disorders.

Activity and expression of nitric oxide synthase in rat bladder after sacral neuromodulation.

The aim of our study is to investigate the effects of chronic sacral neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female Sprangue-Dawley rats were considered: group I, normal control rats; group II, a sham treatment, in whom catheters for electrical stimulation were placed in the S1 foramen bilaterally and left in place for 21 days, without performing neuromodulation; group III in whom electrical sacral neuromodulation was performed for 21 days. Finally a cystectomy was performed and the bladder biopsy specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and immunohistochemical analysis was carried out, and evaluated in urothelial cells, endothelial cells and muscle fibers of the muscularis propria. Differences between the 3 groups were analyzed by Student Newman-Keuls test. We could observe that urothelial and endothelial i-NOS (37.00+/-4.69 and 59.00+/-7.42 respectively) and urothelial n-NOS (36.80+/-7.85) expression are significantly increased in neuromodulated rats, compared to groups 1 and 2 (p<0.005). In conclusion, the increase of i-NOS expression on endothelial cells after sacral neuromodulation could be in some way related to angiogenetic responses in the microvascular structures; the increase of n-NOS and i-NOS expression on urothelial cells can suggest that NO is able to influence the plasticity of bladder response, inducing the release of messengers within the urothelium. This study can therefore improve our understanding of the mechanisms of sacral neuromodulation on chronic bladder dysfunction; further studies will need to better demonstrate the role of angiogenesis in the bladder after sacral neuromodulation and to investigate the effects of neuromodulation in rats with chronically induced bladder dysfunction.

Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth.

OBJECTIVE: Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion. METHODS: Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, 'surmountable' AT1 antagonist devoid of peroxisome proliferator-activated receptor gamma agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression. RESULTS: Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10-11 M) and inhibited by ANP (already at 10-13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor. CONCLUSION: A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.

Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma.

The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CC-RCC development, we examined whether the 5-Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)-reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5-LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO up-regulation is an important step in renal cancer progression.

Rapid, economical treatment of large impacted calculi in the proximal ureter with ballistic ureteral lithotripsy and occlusive, percutaneous balloon catheter: the high pressure irrigation technique.

PURPOSE: We describe our innovative technique for the treatment of large calculi (greater than 1.5 cm) of the proximal ureter. MATERIALS AND METHODS: Between 2003 and 2005 we positioned an 8Ch pyelostomy in 25 patients diagnosed with impacted calculi of the proximal ureter greater than 1.5 cm on ultrasound, direct x-ray of the abdomen, and/or computerized tomography and subsequent retrograde pyelography. After 30 days all patients underwent combined treatment in the Valdivia supine position, including positioning a 0.035-inch guidewire through the pyelostomy into the ureter up to above the calculus, pyelostomy removal and insertion onto the guide of a 7Ch balloon occlusion catheter, which was inflated in the ureter immediately above the calculus. Ureteral lithotripsy was done with an 8.5 to 11.5Ch ureteroscope (Wolf, Dudley, Massachusetts) with a 6Ch operating channel and a Calcusplit ballistic probe, alternating high antegrade pressure by the balloon catheter and retrograde pressure using the ureteroscope, as required. After lithotripsy and fragment dislocation the ureteroscope was retracted with rapid flow antegrade irrigation. At the end of the procedure after antegrade contrast medium followup the balloon catheter was retracted as far as the pelvis as a nephrostomy. We analyzed operative time, the number of postoperative recovery days, the incidence of complications during and after surgery, and the stone-free rate immediately, after 5 days and after 1 month. RESULTS: Average calculus size was 1.7 cm. Ten patients presented with multiple ureteral bending upon diagnosis, which was no longer found at surgery with a consequent lack of difficult ureteroscope feeding. Significant edema downstream of the calculus was present in all cases. High pressure irrigation, a rigid ballistic probe and retrieving forceps enabled the dislocation of even larger fragments from the original calculous site in all cases. Antegrade high pressure irrigation after lithotripsy enabled the complete clearance of calcareous fragments as far as the bladder without the need for ancillary maneuvers. We observed no cases of calcareous fragment push-back. No retroperitoneal extravasation, or pyelolymphatic or pyelovenous backflow was observed. Average procedure time was 33 minutes. The renal-ureteral stone-free rate was 100% at the end of the procedure and all calcareous fragments were in the bladder. We did not observe any ureteral lesions. In no case was there onset of fever. Average postoperative hospitalization was 2 days. Followup with contrast material after 5 days showed a renal-ureteral stone-free rate of 100% and a bladder stone-free rate of 84%. The nephrostomy was removed at an average of 5.5 days. CONCLUSIONS: Compared to the techniques described in the medical literature our method appears to have certain advantages, including a mini-invasive approach to the renal pelvis compared to that of percutaneous nephrolithotomy with protection of the renal parenchyma from high pressure, rigid ureteroscope use, which provides a high level of maneuverability and low operating costs, ballistic probe use, which provides lower costs and higher speeds than the laser, and balloon catheter use, which removes the risk of push-back and enables push-down of the fragments without any further ancillary maneuvers. The balloon catheter also enables contrast medium followup and immediate postoperative drainage. The speed of the procedure and the ability to adjust antegrade or retrograde flow with variable pressure and direction make this technique highly suitable for the complete resolution of large, impacted calculi of the proximal ureter.

Correlation between urodynamics and perineal ultrasound in female patients with urinary incontinence.

AIMS: We performed urodynamics and perineal ultrasound in female patients with urinary incontinence to assess morphology and function of the bladder base-urethra complex and of the detrusor muscle, and to find the correlation between these investigations in the diagnosis of (a) bladder neck and urethral hypermobility and (b) detrusor overactivity; we wanted to compare the tolerabililty of the urodynamic investigation and of the perineal ultrasound. METHODS: We considered 66 female patients referred to our outpatient clinic for urinary incontinence; we also studied 14 healthy control patients. After accurate case-history collection and physical examination, urodynamic investigation and perineal ultrasound were performed, with recording of parameters specific to both investigations. The statistical analysis was performed by ANOVA, Bonferroni post hoc test, and Spearman correlation test. The tolerability index between the diagnostic investigations performed was assessed by a 3-point scale suggested by the patient. RESULTS: In patients with stress incontinence the posterior urethro-vesical angle, the angle of urethral inclination, and the proximal pubo-urethral distance are significantly different under stress compared to the resting phase; in patients with urge incontinence, the detrusor wall is thicker and is accompanied by an increase in opening detrusor pressure and detrusor pressure at maximum flow; it is also accompanied by detrusor overactivity with increased urethral functional length. Increased urethral functional length is suggested on axial US images by alteration of its normal characteristic target-like appearance with four concentric rings of different echogenicity. In all cases the tolerability of perineal ultrasound has been higher than that of urodynamics. CONCLUSIONS: There is a good correlation between urodynamic and perineal ultrasound in the diagnosis of bladder neck and urethral hypermobility; perineal ultrasound can also be useful in the diagnosis of urge incontinence. Functional compressive urethral obstruction can be diagnosed on the basis of the ultrasound aspect of the urethral sphincter.

Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens.

PURPOSE: Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup. MATERIALS AND METHODS: A total of 48 patients with a mean age +/- SD of 58.2 +/- 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 +/- 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186). RESULTS: Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival. CONCLUSIONS: Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.

Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5).

Erectile dysfunction (ED) is frequent in patients with essential hypertension (EH); a likely common pathogenetic pathway could be a reduced ability of arteriolar vascular smooth muscle (VSM) to relax. Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. The PDE5A gene represents a good candidate for the intermediate phenotype EH/ED: genetic variants of the PDE5A may predispose to EH and ED and could affect the local and systemic response to sildenafil administration. Thus, a functionally relevant portion of PDE5 5'-flanking promoter region was analyzed by PCR and direct sequencing in patients with EH and idiopathic ED. The sequences obtained showed a T/G polymorphism at position -1142, near an AP1 regulatory element, that was not apparently associated with the intermediate phenotype. We also studied the relationship between this polymorphism and the effects of oral sildenafil on blood pressure (BP) and heart rate (HR) in men with ED. Sildenafil caused a significant decrease of BP, but had no effects on HR; statistical analysis showed no differences in BP and HR variations among PDE5A genotypes. In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration. Further studies are necessary to define the role of this polymorphism and to study the genetic predisposition for EH with ED.

Detectable serum PSA after radical prostatectomy. Clinical and pathological relevance of perianastomotic biopsies.

BACKGROUND: Few reports have detailed the histopathological results of biopsies of the vesicourethral anastomosis or prostatic bed in patients with a detectable postoperative PSA. PATIENTS AND METHODS: Among a series of 153 patients who underwent radical retropubic prostatectomies, we analyzed the results of 64 perianastomotic biopsies performed in 17 men with a detectable PSA and no evidence of local recurrence or distant metastases. RESULTS: Fourteen of the 17 patients had a relapse of prostatic carcinoma; the results of histology in the three pT2bN0M0 patients revealed the presence of benign prostatic hyperplasia in 2 patients and atypical cribriform proliferation in 1 patient. The first two patients are free from prostatic cancer recurrence 36 months after perianastomotic biopsies; a further biopsy performed 6 months after in the third patient showed the presence of prostatic carcinoma. CONCLUSION: The present study raises the possibility that residual benign tissue, resulting from unintentional disruption of the prostatic capsule during surgery, may be responsible for a detectable postoperative PSA. These cases comprise a histopathological classification described as "intraprostatic surgical margin".

Percutaneous therapy of varicocele: effects on semen parameters in young adults.

BACKGROUND: In spite of many years of debate, the impact of varicocele on male infertility is still controversial since its pathogenetic role on the impairment of semen quality has never been fully demonstrated. METHODS: In the present work, a series of 426 young adult males undergoing percutaneous treatment of varicocele were studied and semen parameters were evaluated at baseline and 12 months of follow-up. RESULTS: A significant increase in sperm cell concentration and a decrease in immotile spermatozoa were found after varicocele repair, but we failed to detect any significant positive change in progressive motility as well in sperm morphology after treatment. Similar results were also obtained when semen parameters were correlated with the degree of varicocele. CONCLUSION: Since a spontaneous improvement in semen quality has been mathematically established as a model of regression toward the mean, we conclude that the correction of varicocele in young adults is not a major indication when semen alteration is the only clinical problem.