Arcangelo Sebastianelli

Metabolic syndrome and lower urinary tract symptoms: the role of inflammation.

Background:Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities.Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens.Methods:A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker.Results:Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm3 (hazard ratio (HR)=3.268, P<0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Qmax): 8.6 vs 10.1, P=0.008 and average flow rate (Qave): 4.6 vs 5.3, P=0.033, respectively), and higher obstructive urinary symptoms score (P=0.064). A positive correlation among both IS–GD and IPSS Score was also observed (adjusted r=0.172, P=0.008 and adjusted r=0.128, P=0.050).Conclusions:MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.

PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS

Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH)/low urinary tract symptoms (LUTS) are often comorbid. Chronic inflammation is one of the putative links between these diseases. Phosphodiesterase type 5 inhibitors (PDE5i) are recognized as an effective treatment of BPH‐related LUTS. One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation. In this study we investigate whether PDE5i could blunt inflammation in the human prostate.

Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal cell carcinoma after tumor enucleation

OBJECTIVE To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically intracapsular renal cell carcinomas (RCCs). METHODS AND MATERIALS PC status was analyzed in 304 consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were evaluated. Mean (median, range) follow-up was 49 months (46, 25-69). Local recurrence rate, progression-free survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. RESULTS Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC-), 34.9% had capsular penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side (PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC-, PCK, and PCF were 97.5%, 96.7%, and 77.1%, respectively (P<0.0001). The multivariate Cox model showed PCF to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a significant increased risk in developing recurrence. CONCLUSIONS Tumor enucleation is an oncologically safe nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the risk of recurrence.

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.

Male Lower Urinary Tract Symptoms and Cardiovascular Events: A Systematic Review and Meta-analysis

CONTEXT The correlation among metabolic syndrome, lower urinary tract symptoms (LUTS), and cardiovascular disease (CVD) is well established. In particular, CVD has been proposed as a potential risk factor for both LUTS progression and severity. OBJECTIVE To evaluate whether LUTS severity can be considered as a significant risk factor of major adverse cardiac events (MACE) in the male population. EVIDENCE ACQUISITION A systematic literature search was performed using PubMed, Google Scholar, and Scopus. The combination of the following keywords was adopted in a free-text strategy: benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) and cardiovascular, cardio, major adverse cardiac events, MACE, heart disease, heart, myocardial infarction, myocardial, infarction, stroke, ischemic events, ischemic, cardiac death, coronary syndrome. We included all cross-sectional and longitudinal trials enrolling men and comparing the prevalence or incidence of MACE in men with moderate to severe LUTS compared with those without LUTS or with mild LUTS. The studies in which only nocturia was evaluated were excluded from the analysis. EVIDENCE SYNTHESIS Of 477 retrieved articles, 5 trials longitudinally reported the incidence of MACE in patients with moderate to severe LUTS in comparisons to those with mild or no LUTS and 10 studies reported the prevalence of history of MACE at enrollment. All were included in the present meta-analysis. Among cross-sectional studies, 38 218 patients and 2527 MACE were included in the meta-analysis. The mean age of enrolled patients was 62.2±8.0 yr. Presence of moderate to severe LUTS significantly increased the risk of reported history of MACE (p<0.001). Metaregression analyses showed that the risk of MACE was lower in older patients and higher in those with diabetes. The association between LUTS-related MACE and diabetes was confirmed in a multivariate regression model after adjusting for age (adjusted r=0.498; p<0.0001). Longitudinal trials included 25 494 patients and 2291 MACE. The mean age of enrolled patients was 52.5±5.5 yr, and mean follow-up was 86.8±22.1 mo. Presence of moderate to severe LUTS was associated with an increased incidence of MACE compared with the rest of the sample (odds ratio: 1.68; 95% confidence interval, 1.13-2.50; p=0.01). CONCLUSIONS Men with moderate to severe LUTS seem to have an increased risk of MACE. A holistic approach in considering the morbidities of aging men should be strongly encouraged and represents an important role for the practicing urologist. PATIENT SUMMARY We evaluated whether the severity of lower urinary tract symptoms could be considered as a significant risk factor for major adverse cardiac events (MACE) in the male population. We demonstrated that men with moderate to severe LUTS have an increased risk of MACE.

Role of abdominal obesity for functional outcomes and complications in men treated with radical prostatectomy for prostate cancer: Results of the Multicenter Italian Report on Radical Prostatectomy (MIRROR) study

Abstract Objective. This study aimed to evaluate the impact of abdominal obesity on preoperative features, complications and functional outcomes of men treated with radical prostatectomy (RP) for prostate cancer. Material and methods. In 2006 a multicentre Italian report on RP evaluated the surgical and functional characteristics of prostate cancer and RP outcomes. Age and waist circumference (WC) were recorded. Abdominal obesity was defined as a WC of at least 102 cm. International Index of Erectile Function (IIEF) score, prostate-specific antigen, prostate volume, tumour characteristics, presence/absence of perioperative complications and the number of blood units transfused were recorded. Preoperative and postoperative continence status was evaluated. Spearman correlation coefficient and binary logistic regression analyses were conducted. Results. In total, 470 men were recruited. A significant negative correlation between WC and preoperative IIEF scores was observed (r = –0.032, p < 0.001). Non-obese patients presented a preoperative IIEF score of 18.8 ± 6.0 and obese patients an IIEF score of 16.0 ± 7.0 (p < 0.001). Obese men are at three-fold greater risk of intraoperative complications and blood transfusions than those with a WC below 102 cm [adjusted odds ratio (OR) = 3.116, 95% confidence interval (CI) 0.281–16.348, p < 0.001, and OR = 2.763, 95% CI 0.518–3.843, p < 0.050, respectively]. A significant positive correlation between WC and postprostatectomy incontinence severity was observed. The risk of needing at least two pads per day is two and a half times greater in men with a WC of at least 102 cm than in those with a WC below 102 cm (adjusted OR = 2.435, 95% CI 0.321–7.668, p = 0.007). Conclusion. Abdominal obesity in a multicentre Italian cohort of patients treated with RP was associated with an increased risk of intraoperative and perioperative complications and with a worse functional outcome.

Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study.

To evaluate the impact of components of metabolic syndrome (MetS) on urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), as central obesity can be associated with the development of BPE and with the worsening of LUTS.

Management of Benign Prostatic Hyperplasia: Role of Phosphodiesterase-5 Inhibitors

Several studies have highlighted a strong association between benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED), particularly in elderly men. Many epidemiological trials, such as in vitro and in vivo studies, have reported the emerging role of metabolic syndrome, including abdominal obesity, impaired glucose metabolism, hypertriglyceridemia, low high-density lipoprotein cholesterol, and hypertension, in the development and progression of urinary and sexual symptoms. Moreover, many authors have focused their studies on the identification of all the shared pathogenetic mechanisms of LUTS/BPH and ED, including alteration of cyclic guanosine monophosphate and RhoA-ROCK pathways or vascular and neurogenic dysfunction. All these are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Therefore, several trials have recently been designed to evaluate the role of PDE5-Is alone or in combination with conventional treatment for BPH, such as α-adrenergic blockers, in men affected by LUTS/BPH, with or without ED. Different PDE5-Is are in clinical use worldwide and currently six of them are licensed for the oral treatment of ED. All these compounds differ in pharmacokinetic factors, with influence on drug action, and subsequently in the overall safety and efficacy profile.

The use of a single daily dose of tadalafil to treat signs and symptoms of benign prostatic hyperplasia and erectile dysfunction

A strong and independent association between lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and erectile dysfunction (ED) has been widely evidenced in several clinical epidemiologic studies. Preclinical animal models have provided a great deal of information on potential common pathogenic mechanisms underlying these two clinical identities. Although the efficacy of the most commonly used treatments for LUTS/BPH is well defined, the negative impact of these treatments on sexual function – in particular, on ED – has triggered the search for new treatment options. In this regard, a new role for phosphodiesterase type 5 inhibitors in the treatment of LUTS/BPH and ED has been claimed. Tadalafil is one of the most extensively investigated phosphodiesterase type 5 inhibitors for this new indication. All evidence reported to date suggests that tadalafil 5 mg once daily is a safe and effective treatment option for both LUTS/BPH and ED.

The Impact of Central Obesity on Storage Luts and Urinary Incontinence After Prostatic Surgery

In the developed and developing countries, the overall prevalence of central obesity in the elderly men is growing. In addition, the progressive aging of male population increased the possibilities of coexisting morbidities associated with obesity such as lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) or to prostate cancer (PCa) needing primary treatment, including radical prostatectomy (RP), which can further adversely affect the quality of life. Simple and radical prostatectomy are the most common surgical procedures in urologic unit all over the world for BPE and PCa, respectively. After both interventions, patients can present bothering storage LUTS that can worsen all the other clinical outcomes. Preset study will review the role of central obesity as a risk factor for storage LUTS or urinary incontinence, after prostatic surgery for BPE or PCa.