Quality of life with pharmacological treatment in patients with benign prostatic enlargement: results from the Evolution European Prospective Multicenter Multi-National Registry Study.

BACKGROUND: Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures. METHODS: Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index. RESULTS: The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0-26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients. CONCLUSIONS: After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy.

Contemporary use of phytotherapy in patients with lower urinary tract symptoms due to benign prostatic hyperplasia: results from the EVOLUTION European registry.

BACKGROUND: To use the European Association of Urology Research Foundation (EAURF) registry data to determine the proportion of contemporary Lower Urinary Tract Symptoms associated with Benign Prostatic Enlargement (LUTS/BPE) patients prescribed phytotherapy, and to determine their subjective quality of life and clinical progression responses. METHODS: This was a prospective multicenter multinational observational registry study, conducted over 2 years. Men ≥ 50 years seeking LUTS/BPE were divided at baseline into two cohorts, presently/recently untreated patients (PUP) commencing pharmacotherapy at baseline and presently/recently treated patients (c-PTP) continuing previously received pharmacotherapy, with 24-month follow-up (FU). RESULTS: Overall, 2175 patients were enrolled with 1838 analyzed. Of the PUP cohort (n = 575), 92 (16%) received phytotherapy and 65 (71%, n = 65/92) completed 24-month FU, with France prescribing 34% (n = 30/89) the highest proportion of phytotherapy among all LUTS/BPE medications. In the c-PTP group (n = 1263), only 69 (5%) patients were using phytotherapy, falling to n = 35/69 (51%) at 24-month FU (highest in France 20% (n = 43/210)). Though defined disease progression occurred in ≤ 20%, with only 1% proceeding to surgical intervention, in both groups, clinically meaningful improvement was lower and symptom persistence was higher in PUP but similar in the treated (c-PTP) patients on phytotherapy compared to the other LUTS/BPE medication. CONCLUSION: Low heterogeneous prescribing rates for phytotherapy were reported in both PUP and c-PTP cohorts over the 24-month FU. Although phytotherapy led to subjective improvements, healthcare practitioners should prescribe them with caution until higher quality evidence and guideline recommendations supporting its use are available.

Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE): a cost minimisation analysis.

PURPOSE: A cost minimisation analysis compares the costs of different interventions' to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE). METHODS: The Evolution registry is a prospective, multicentre registry, conducted by the European Association of Urology Research Foundation (EAUrf) for 24 months in 5 European countries. Evolution was designed to register the management of symptomatic BPE in clinical practice settings in 5 European countries. Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed. RESULTS: In total, 1838 men were enrolled with 1246 evaluable at 24 months. Medical therapies were more cost saving than TURP for treatment durations ranging from 2.9 to 70.4 years. Cost saving depended on both medication class and individual country assessed. Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy. Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain. Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany. CONCLUSIONS: BPE medical management was more cost saving than TURP for different specific treatment durations. Information from this study will allow clinicians to convey medical and surgical costs over time, to both patients and payors alike, when considering BPE treatment.

Urinary incontinence in multiple sclerosis: prevalence, severity and impact on patients' quality of life.

BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS) including frequent urination, nocturia and urge urinary incontinence negatively impact quality of life. This project aimed at characterizing the prevalence and severity of urinary incontinence in multiple sclerosis (MS) patients and its association with demographic and clinical features. METHODS: In all, 403 consecutive clinically stable MS patients answered the International Consultation on Incontinence Questionnaire (ICIQ) and the Patient Perception of Bladder Condition (PPBC) questionnaire. Demographic and clinical parameters including the Expanded Disability Status Scale (EDSS) were collected. Statistical analyses were performed using univariate and multivariate linear regression models. RESULTS: Females represented 72%, relapsing-remitting patients 82%. The mean (SD) disease duration and EDSS were 11.8 (8.6) years and 3.1 (1.9) respectively. Approximately 35% of patients reported urine incontinence. ICIQ scores were positively associated with EDSS, female gender, presence of LUTS therapies and absence of disease modifying treatments (P < 0.001). PPBC scores were positively associated with EDSS and the presence of LUTS therapies (P < 0.001). DISCUSSION: Urinary incontinence is frequent in MS, prevailing in more disabled and female patients. Currently available LUTS therapies appear insufficient in the treatment of this symptom. The negative impact of urinary incontinence on quality of life is high and requires more attention in clinical management and research.

Is there a link between overactive bladder and the metabolic syndrome in women? A systematic review of observational studies.

OBJECTIVES: To conduct a systematic review to determine whether there is an association between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) or overactive bladder (OAB) in women. METHODS: We systematically reviewed English language observational studies on the effect of MetS (or component factors) on the presence of OAB or LUTS in women. We searched PubMed, Web of Science and The Cochrane Library with no date restrictions, checked reference lists and undertook citation searches in PubMed and Google Scholar. Studies were assessed for risk of bias. Because of heterogeneity, results were not pooled, but are reported narratively. RESULTS: Of 27 included studies, only three looked at the link between MetS and OAB. The rest looked at links between OAB and components of MetS such as obesity or insulin resistance (n = 10), between MetS and urinary symptoms (n = 3) and between urinary symptoms and components of MetS, such as obesity (n = 14). Evidence is currently limited, but it does suggest that there may be important links between MetS and OAB and components of MetS such as obesity. CONCLUSIONS: The literature on MetS and OAB or LUTS in women is limited, and poor quality. However, the evidence available on obesity appears to support MetS as a contributor and predictor of LUTS in women. Many of the women with LUTS will be overweight and will have features of the MetS, if looked for. This provides not only an opportunity to encourage weight loss as an adjunct to therapy for the OAB symptoms but also a window of opportunity to address cardiovascular risk factors and prevent future cardiovascular morbidity and mortality.

Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.

BACKGROUND AND PURPOSE: Posterior tibial nerve stimulation (PTNS) is an effective treatment option for lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients. METHODS: Patients with MS and LUTS unresponsive to medical treatment received PTNS for 12 weeks after saline urodynamics to evaluate the prevalence of motor, sensory and combined responses during PTNS and to determine whether the type of response can predict treatment outcome. LUTS were also assessed using a 3-day bladder diary, patient perception of bladder condition (PPBC) questionnaire, patient perception of intensity of urgency scale (PPIUS), Kings Health QOL questionnaire (KHQ) and Overactive Bladder Questionnaire (OAB-q) before and after treatment. Patients were considered as "responders" if they reported an improvement >50% in their LUTS according to the PPBC. Sensory, motor and combined sensory/motor responses were compared between responders and non-responders. RESULTS: Eighty-three patients were included. 61% (51/83) of patients were responders. Sensory, motor and combined sensory/motor responses were found in 64% (53/83), 6% (5/83) and 30% (25/83) of patients respectively. A sensory response alone, or in combination with a motor response, was better associated with a successful outcome than the presence of a motor response alone (P = 0.001). CONCLUSIONS: A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone.

Urgency and pain in patients with overactive bladder and bladder pain syndrome. What are the differences?

BACKGROUND: The Overactive Bladder Syndrome (OAB) and the Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) are different urological conditions sharing 'urgency' as a common symptom. The aim of this review is to address our existing knowledge and establish how these symptoms are interrelated and to determine whether or not there is a common link between both symptoms complexes that help to distinguish one from the other. METHODS: Pubmed was used to obtain references for this non-systematic review aiming to discuss differences between OAB and BPS/IC. Guidelines of several professional associations and discussions based on expert opinion from the authors were implemented. RESULTS: Whilst in BPS the hallmark symptom is pain on bladder filling, urgency is the defining symptom of OAB. Whilst it is likely that the pain in BPS/IC arises from local inflammation in the bladder wall, the nature of urgency as a symptom, its origin, and the relationship between urgency and pain, as well as the different afferent mechanisms associated with the genesis of these sensory symptoms, remains unknown. Although the aetiology of both OAB and PBS/IC is unclear, the influence of environmental factors has been suggested. Both are chronic conditions with very variable symptom resolution and response to therapy. The relationship with voiding dysfunction, gynaecological causes of chronic pelvic pain or the possible alteration of the hypothalamic-pituitary-adrenal axis and psychological disorders has not been established. Inflammation has been suggested as the common link between OAB and BPS/IC. CONCLUSIONS: OAB and BPS/IC are different symptoms complexes that share urgency as a common symptom. None of them have a specific symptom although pain on bladder filling is the hallmark symptom in BPS/IC. Bladder pain with urgency should be a trigger for referral to the provider with appropriate knowledge and expertise in this disease state, whereas the management of OAB should be part of normal routine care in the community.

Sandwich ELISA assay for the quantitation of palytoxin and its analogs in natural samples.

Palytoxins are potent marine biotoxins that have recently become endemic to the Mediterranean Sea, and are becoming more frequently associated with seafood. Due to their high toxicity, suitable methods to quantify palytoxins are needed. Thus, we developed an indirect sandwich ELISA for palytoxin and 42-hydroxy-palytoxin. An intralaboratory study demonstrated sensitivity (limit of detection, LOD = 1.1 ng/mL; limit of quantitation, LOQ = 2.2 ng/mL), accuracy (bias of 2.1%), repeatability (RSDr = 6% and 9% for intra- and interassay variability, respectively) and specificity: other common marine toxins (okadaic acid, domoic acid, saxitoxin, brevetoxin-3, and yessotoxin) do not cross-react in this assay. It performed well in three different matrices: observed LOQs were 11.0, 9.6, and 2.4 ng/mL for mussel extracts, algal net samples and seawater, respectively, with good accuracy and precision. The LOQ in seafood is 11 µg palytoxin/kg mussel meat, lower than that of the most common detection technique, LC-MS/MS.

The treatment of lower urinary tract symptoms in patients with multiple sclerosis: a systematic review.

This is a systematic review on the treatment of lower urinary tract symptoms (LUTS) in patients with multiple sclerosis (MS). The heterogeneity of the outcome criteria did not allow a meta-analysis of the published evidence. In the last few decades, the therapeutic options for neurogenic bladder dysfunction have broadened. Despite this, no consensus has been reached as to the management of LUTD and LUTS in patients with MS, and the subject remains controversial. Bladder dysfunction is common in MS, affecting 80 %-100 % of patients during the course of the disease. Several studies have shown that urinary incontinence has a severe effect on patients' quality of life, with 70 % of patients classifying the impact bladder symptoms had on their life as "high" or "moderate." Moreover, the progressive feature of MS makes its treatment complex, since any achieved therapeutic result may be short-lived, with the possibility that symptoms will recur or develop de novo.

Asymptomatic bacteriuria in candidates for active treatment of renal stones: results from an international multicentric study on more than 2600 patients.

The occurrence of asymptomatic bacteriuria concomitant to urolithiasis is an issue for patients undergoing renal stone treatment. Disposing of a preoperative urine culture is essential to reduce the risk of septic events. The endpoint of the study is to report which characteristics of candidates for renal stone treatment are frequently associated with positive urine culture. 2605 patients were retrospectively enrolled from 14 centers; inclusion criteria were age > 18 and presence of a single renal stone 1-2 cm in size. The variables collected included age, gender, previous renal surgery, comorbidities, skin-to-stone distance, stone size, location, density, presence of hydronephrosis. After a descriptive analysis, the association between continuous and categorical variables and the presence of positive urine culture was assessed using a logistic regression model. Overall, 240/2605 patients (9%) had preoperative bacteriuria. Positive urine culture was more frequent in females, patients with previous renal interventions, chronic kidney disease, congenital anomalies, larger stones, increased density. Multivariate analysis demonstrated that previous renal interventions (OR 2.6; 95% CI 1.9-3.4; p < 0.001), renal-related comorbidities (OR 1.31; 95% CI 1.19-1.4; p < 0.001), higher stone size (OR 1.06; 95% CI 1.02-1.1; p = 0.01) and density (OR 1.00; 95% CI 1.0-1.00; p = 0.02) were associated with bacteriuria; male gender and lower caliceal location were inversely related to it. Beyond expected risk factors, such as female gender, other parameters are seemingly favoring the presence of positive urine culture. The awareness of variables associated with bacteriuria allows to assess which individuals are at increased risk of presenting bacteriuria and reduce the rate of septic complications.

Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma.

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.

Efficacy and efficiency of Green-Light XPS 180-watt laser system for benign prostatic enlargement in patients treated with 5α-reductase inhibitors.

OBJECTIVE: Aim of the study was to evaluate efficacy and efficiency of 180-watt Green-Light XPS (GL-XPS) laser photoselective vaporization of the prostate (PVP) in patients under 5-Alpha-Reductase Inhibitors (5ARI) treatment. PATIENTS AND METHODS: A consecutive series of patients with lower urinary tract symptoms due to benign prostatic enlargement treated by PVP with the GL-XPS were enrolled. Patients were divided in two groups according to the chronic use (>6 months) of 5ARI. These two groups were compared on lasing density (kilojoules per prostate volume), vaporization efficiency (prostate volume per lasing time), vaporization power (kilojoules per lasing time), Prostate Specific Antigen (PSA) reduction from baseline, symptom score change from baseline and uroflowmetry parameters improvement. Follow-up was performed at 3, 6 and 12 months with International Prostate Symptom Score, Uroflowmetry parameters and PSA. RESULTS: Overall 193 patients were enrolled. Out of them 87/193 (45%) were on 5ARI treatment. No significant differences were recorded between the two groups at baseline. Median age was 68 years old and median prostate volume was 60 ml. In terms of laser efficiency, no statistically significant differences were recorded in terms of lasing time (25 min vs. 24.5 min; p>0.05); energy used (250 kJ vs. 221 kJ; p>0.05), lasing density (6.8 kJ/ml vs. 6.6 kJ/ml, p>0.05), vaporization efficiency (1.4 ml/min vs. 1.3 ml/min, p>0.05) and vaporization power (9.6 kJ/min vs. 9.4 kJ/min; p>0.05). Finally, no significant differences were also recorded postoperatively in the two groups in terms of PSA reduction, improvement in symptom score and uroflowmetry parameters (p>0.05). CONCLUSIONS: Thirty-seven efficacy and efficiency outcomes were not statistically different between the two groups. 5ARI does not reduce the performance and ability of the 180-watt Green-Light XPS laser system.

Pelvic organ prolapse and overactive bladder.

AIMS: In this review we try to shed light on the following questions: *How frequently are symptoms of overactive bladder (OAB) and is detrusor overactivity (DO) present in patients with pelvic organ prolapse (POP) and is there a difference from women without POP? *Does the presence of OAB symptoms depend on the prolapsed compartment and/or stage of the prolapse? *What is the possible pathophysiology of OAB in POP? *Do OAB symptoms and DO change after conservative or surgical treatment of POP? METHODS: We searched on Medline and Embase for relevant studies. We only included studies in which actual data about OAB symptoms were available. All data for prolapse surgery were without the results of concomitant stress urinary incontinence (SUI) surgery. RESULTS: Community- and hospital-based studies showed that the prevalence of OAB symptoms was greater in patients with POP than without POP. No evidence was found for a relationship between the compartment or stage of the prolapse and the presence of OAB symptoms. All treatments for POP (surgery, pessaries) resulted in an improvement in OAB symptoms. It is unclear what predicts whether OAB symptoms disappear or not. When there is concomitant DO and POP, following POP surgery DO disappear in a proportion of the patients. Bladder outlet obstruction is likely to be the most important mechanism by which POP induces OAB symptoms and DO signs. However, several other mechanisms might also play a role. CONCLUSIONS: There are strong indications that there is a causal relationship between OAB and POP.

Ultrastructural damage to heart tissue from repeated oral exposure to yessotoxin resolves in 3 months.

Yessotoxin (YTX), an algal toxin contaminating edible shellfish, was previously shown to induce ultrastructural changes in some cardiac muscle cells of mice after acute (1 and 2mg/kg) or daily repeated oral exposure (1 and 2mg/kg/day, for 7 days). Therefore, the temporal evolution of the ultrastructural myocardial alterations and the development of other signs of toxicity induced by a repeated daily oral administration of YTX (1mg/kg/day, for 7 days) to mice were evaluated within 3 months after the treatment. Symptoms, food consumption, body weight, gross pathology and histopathology of the main organs and tissues were observed, and plasma levels of transaminases, lactate dehydrogenase, creatinine and creatinine phosphokinase were measured. Heart, liver, kidneys and cerebellum were also analysed by transmission electron microscopy. In addition, the blood concentration of YTX was determined by a direct enzyme linked immunosorbent assay (ELISA) 24h after the last toxin administration. No mortality or other treatment-related changes, including histological or hematoclinical parameters, were recorded in mice administered with YTX. Similarly, electron microscopy did not reveal any ultrastructural alteration in the liver, kidneys, and cerebellum associated with YTX treatment. In contrast, changes in cardiac muscle cells near to the capillaries (clusters of rounded mitochondria and disorganization of myofibrils) were observed 24h after the treatment. These changes were also noted 30 days after the toxin administration, while after 90 days no differences in cardiac muscle cells between control and YTX-treated mice were observed, which indicated a recovery of the ultrastructural alterations induced by the toxin.

Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, -2 and -3 in mice.

Azaspiracids (AZAs) are marine algal toxins that can be accumulated by edible shellfish to cause a foodborne gastrointestinal poisoning in humans. In the European Union, only AZA1, -2 and -3 are currently regulated and their concentration in shellfish is determined through their toxic equivalency factors (TEFs) derived from the intraperitoneal lethal potency in mice. Nevertheless, considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data. Thus, the acute oral toxicity of AZA1, -2 and -3 was investigated in female CD-1 mice treated with different doses (AZA1: 135-1100µg/kg; AZA2 and AZA3: 300-1100µg/kg) and sacrificed after 24h or 14days. TEFs derived from the median lethal doses (LD50) were 1.0, 0.7 and 0.5, respectively for AZA1, -2 and -3. In fact, after 24h from gavage administration, LD50s were 443µg/kg (AZA1; 95% CL: 350-561µg/kg), 626µg/kg (AZA2; 95% CL: 430-911µg/kg) and 875µg/kg (AZA3; 95% CL: 757-1010µg/kg). Mice dead more than 5h after the treatment or those sacrificed after 24h (doses: ≥175µg AZA1/kg, ≥500µg AZA2/kg and ≥600µg AZA3/kg) showed enlarged pale liver, while increased serum markers of liver alteration were recorded even at the lowest doses. Blood chemistry revealed significantly increased serum levels of K+ ions (≥500mg/kg), whereas light microscopy showed tissue changes in the gastrointestinal tract, liver and spleen. No lethality, macroscopic, tissue or haematological changes were recorded two weeks post exposure, indicating reversible toxic effects. LC-MS/MS analysis of the main organs showed a dose-dependency in gastrointestinal absorption of these toxins: at 24h, the highest levels were detected in the stomach and, in descending order, in the intestinal content, liver, small intestine, kidneys, lungs, large intestine, heart as well as detectable traces in the brain. After 14days, AZA1 and AZA2 were still detectable in almost all the organs and intestinal content.

Meta-analysis of metabolic syndrome and prostate cancer.

BACKGROUND: Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features. METHODS: A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4-5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml-1 after radical prostatectomy) was evaluated. RESULTS: 24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00-1.36), P=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50-2.38), P<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34-2.34); P<0.01), extra-capsular extension (OR=1.13 (1.09-1.18); P<0.01), seminal vesicle invasion (OR=1.09 (1.07-1.12); P<0.01), positive surgical margins (OR=1.67 (1.47-1.91); P<0.01) and biochemical recurrence (OR=1.67 (1.04-2.69); P<0.01). CONCLUSIONS: The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.

Anti-inflammatory and anti-oxidant activity of a new class of phenyl-pyrazolone derivatives.

The anti-inflammatory activity of a new class of phenyl-pyrazolone derivatives, structurally related to phenidone, has been evaluated using the Croton oil ear test in mice as model of acute inflammation. Derivative 5h reduces the percentage of oedema similarly to indomethacin and more efficiently than phenylbutazone. The anti-inflammatory activity of these two reference drugs depends on their COX inhibition, but for the synthesized derivatives it has not been demonstrated a significant COX or LOX inhibition, as previously reported. While the anti-inflammatory activity of phenidone is correlated to its anti-oxidant properties, the redox potential of these compounds appears not decisive in the inflammatory process inhibition. In order to investigate the mechanism of action for these compounds, we quantified their anti-oxidant activity and the lipophilicity, and a relationship between the calculated logP and the percentage of oedema reduction was found. We hypothesize that the anti-inflammatory activity, recorded in vivo, could be related to lipophilic parameter of these compounds.

Local activation of immune response in bladder cancer patients treated with intraarterial infusion of recombinant interleukin-2.

Tumor regression induced in cancer patients by i.v. infusion of interleukin-2 (IL-2) is often accompanied by severe side effects. To investigate whether local administration would affect immune response without the side effects, two 5-day cycles of continuous intraarterial [internal iliac artery] infusion of recombinant interleukin-2 (rIL-2) were performed in 12 patients with transitional cell carcinoma (tumor stage 1, node stage 0, metastasis stage 0, and grade 1-2) of the bladder. Four groups of 3 patients were treated at each of 4 escalating doses of rIL-2 (18 x 10(3), 18 x 10(4), 18 x 10(5), and 18 x 10(6) IU/m2/day) throughout the course of the two IL-2 cycles. This treatment was effective in inducing a marked intratumor inflammatory response, consisting mainly of T-lymphocytes and macrophages. A remarkable dose-dependent increase in the levels of soluble CD25 was observed in the urine of all patients, which was associated constantly with an enhanced number of intratumor CD25+ cells. Intratumor macrophages were often immunoreactive for interleukin-1 and/or tumor necrosis factor, suggesting an activated status. Increased levels of soluble CD25 and CD25+ lymphocytes were observed in peripheral blood only at the two highest doses of rIL-2, while increased percentages of circulating HLA-DR+ and CD71+ lymphoid cells and enhancement of CD3+/CD16+ T-lymphocytes were found at lower doses. Peripheral blood eosinophils were augmented in almost all patients but were rarely increased in situ. We provide evidence that continuous intraarterial infusion of rIL-2 activates host immune response, acting preferentially at the tissue level.

Combination therapies for improved management of lower urinary tract symptoms/benign prostatic hyperplasia.

Several urological and non-urological conditions can contribute to the onset of lower urinary tract symptoms (LUTS), including benign prostatic hyperplasia (BPH), which is one of the main underlying causes in male patients. Six pharmacological classes (alpha-adrenoceptor blockers [ABs], 5alpha-reductase inhibitors [5ARIs], phytotherapeutics, antimuscarinics [AMs], beta3-adrenoceptor agonists and phosphodiesterase type 5 inhibitors [PDE5Is]) are available, alone or in combination, for the treatment of male LUTS. The aim of this review is to summarize the latest evidence on combination medical treatments for male patients with LUTS/BPH. Standard combinations include AB + 5ARI (for patients with increased prostate volume who are at risk for BPH progression); AB + PDE5I (for patients with concomitant erectile dysfunction); and AB + AM or beta3 agonist (for patients with persistent storage symptoms and not at risk for acute urinary retention). Other possible multidrug treatments have been proposed in preliminary studies, but further randomized controlled trials are needed to determine whether these putative strategies will eventually be considered a new standard for patients with LUTS/BPH. The possibility of tailoring BPH treatment according to different patient characteristics and expectations, using two or more drugs, seems a promising path in the field of LUTS/BPH management; however, physicians should consider the risk of increasing costs without proven long-term efficacy with most of these combination treatments.

Metabolic abnormalities linked to an increased cardiovascular risk are associated with high-grade prostate cancer: a single biopsy cohort analysis.

BACKGROUND: Smoking, hypertension, abdominal obesity and metabolic abnormalities have been considered individual factors involved in prostate cancer (PCa) pathogenesis. All of these factors are used to define the individual cardiovascular risk (CVR). The aim of our study was to evaluate the association between CVR and PCa diagnosis and grade among a consecutive series of men undergoing prostate biopsy. METHODS: From 2010 onwards, consecutive patients undergoing 12-core prostate biopsy were enrolled. Body mass index was measured before the biopsy. Blood samples were collected and tested for: PSA, fasting glucose, triglycerides and high-density lipoproteins. Blood pressure was also recorded. Metabolic syndrome was defined according to the Adult Treatment Panel III and CVR according to the European Association of Cardiologist Guidelines. We evaluated the association between CVR and PCa biopsy Gleason score using logistic regression analyses. RESULTS: Five hundred and eighty-four patients were enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with moderate/high CVR and 80 with low/no CVR (P=0.11). Out of the 237 patients with PCa, 113 had a Gleason score 6 and 124 a Gleason score ⩾7. Out of them, 92/124 (75%) presented a moderate/high CVR (P=0.004). Moderate/high CVR was not associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence interval (CI): 0.474-1.156; P=0.186) but with an increased risk of Gleason score ⩾7 (OR: 2.154, CI: 1.076-4.314; P=0.030). CONCLUSIONS: In our study, a moderate/high CVR is associated with an increased risk of a high-grade Gleason score when PCa is diagnosed on biopsy. Although these results should be confirmed in multicentre studies, patients with moderate/high CVR should be carefully evaluated for PCa diagnosis.