Development and validation of a clinical nomogram to predict prostatic inflammation in men with lower urinary tract symptoms.

BACKGROUND: Prostatic inflammation is an important etiological component of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). The Prostatic Inflammation Nomogram Study (PINS) aimed to develop and validate a nomogram for predicting the presence of prostatic inflammation in men with LUTS. METHODS: This non-interventional, cross-sectional, prospective study was conducted in six secondary/tertiary centers across Cyprus, Greece, Italy, Portugal, and Spain. Men (≥40 years) with BPH/LUTS scheduled to undergo prostatic surgery or transrectal ultrasound-guided (TRUS) prostate biopsy were included. Fifteen demographic and clinical participant characteristics were selected as possible predictors of prostatic inflammation. The presence of inflammation (according to Irani score) in the prostatic tissue samples obtained from surgery/TRUS biopsy was determined. The effect of each characteristic on the likelihood a prostate specimen demonstrated inflammation (classified by Irani score into two categories, 0-2 [no/minimal inflammation] or 3-6 [moderate/severe inflammation]) was assessed using multiple logistic regression. A nomogram was developed and its discriminatory ability and validity were assessed. RESULTS: In total, 423 patients (mean age 68.9 years) were recruited. Prostate volume ultrasound (PVUS) > 50 mL, history of urinary tract infection (UTI) treatment, presence of diabetes, and International Prostate Symptom Score (IPPS) Storage score were statistically significant predictors of Irani classification. Logistic regression demonstrated a statistically significant effect for leucocytes detected via urine dipstick, presence of diabetes, PVUS > 50 mL, history of UTIs, and higher IPSS Storage score for the odds of an inflammatory score category of 3-6 versus 0-2. The nomogram had a concordance index of 0.71, and good internal validity. CONCLUSIONS: The nomogram developed from PINS had good predictive ability and identified various characteristics to be predictors of prostatic inflammation. Use of the nomogram may aid in individualizing treatment for LUTS, by identifying individuals who are candidates for therapies targeting prostatic inflammation.

Infectious complications of transrectal prostate biopsy in patients receiving targeted antibiotic prophylaxis after urethral and rectal swab versus standard prophylaxis: A prospective comparative study.

Background: To evaluate the role of targeted antibiotic prophylaxis (TAP) after rectal and urethral swab cultures compared to empiric antibiotic prophylaxis (EAP) for the prevention of infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Methods: We conducted a prospective comparative study on 141 patients who underwent TRUS-Bx and were allocated in two groups. The first group (n = 71) received EAP with ciprofloxacin and the second (n = 70) received TAP according to rectal and urethral cultures. Post-biopsy infectious complications rates were compared between the two groups. Fluoroquinolone resistance (FQ-R) in the urethral and rectal swabs was recorded. Baseline characteristics were analyzed to assess their relationship with infectious complications and antibiotic resistance. Results: A total of 8 infectious complications were observed, 7 of them in the EAP group (9.85%) and 1 in the TAP group (1.4%). There was a statistically significant difference in febrile UTIs between the two groups (6 vs 0, P = 0.028). FQ-R rate was 4.3% and 12.9% for rectal and urethral samples, respectively. Recent antibiotic exposure was associated with higher post-biopsy infection rates for EAP group and FQ-R rates for TAP group. Conclusion: Combination of rectal and urethral swab cultures for TAP was able to detect FQ-R bacteria carriers and was associated with fewer infectious complications compared to EAP.

The effect of pelvic floor muscle training on urodynamic parameters in women with stress urinary incontinence.

Introduction: Pelvic floor muscle training (PFMT) is suggested for women with stress urinary incontinence (SUI). The aim of our study is to examine the effectiveness of PFMT on urodynamic (UDS) parameters. Material and methods: This is a prospective observational study enrolling women with SUI. Pelvic surgery, prolapse, body mass index >30, and cognitive disability were exclusion criteria. Patients had baseline UDS, then PFMT only (Group A) or PFMT plus biofeedback (BFD) (Group B) for 6 months and UDS 3 months after treatment. The primary investigated parameters were the number of pads used per day and Valsalva leak point pressure (VLPP). Results: Forty-six women completed the study, 22 in Group A and 24 in Group B. At baseline, all patients documented SUI with 3 median pads used per day. Urodynamic SUI was documented with a median Valsalva leak point pressure (mVLPP) of 45 cmH2O. At the re-evaluation, 12 women (26.1%) had SUI in BDs with median number pads per day of 1, which was statistically different to baseline (p = 0.02). Urodynamic SUI was reported in 8 (17.4%) women with a mVLPP of 88 cmH2O.Six patients were from Group A and 6 from Group B. In Group A, the median number of pads per day was 1, and urodynamic SUI was found in 3 women. In Group B, the median number of pads per day was 1, and urodynamic SUI was found in 5 women. Thirty-four women (73.9%) were dry - 16 (47.1%) from Group A and 18 (52.9%) from Group B. Conclusions: PFMT improves urodynamic parameters among women with SUI.

Emerging Role of YAP and the Hippo Pathway in Prostate Cancer.

The Hippo pathway regulates and contributes to several hallmarks of prostate cancer (PCa). Although the elucidation of YAP function in PCa is in its infancy, emerging studies have shed light on the role of aberrant Hippo pathway signaling in PCa development and progression. YAP overexpression and nuclear localization has been linked to poor prognosis and resistance to treatment, highlighting a therapeutic potential that may suggest innovative strategies to treat cancer. This review aimed to summarize available data on the biological function of the dysregulated Hippo pathway in PCa and identify knowledge gaps that need to be addressed for optimizing the development of YAP-targeted treatment strategies in patients likely to benefit.

Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis.

An emerging theory regarding the potentially autoimmune nature of painful bladder syndrome/interstitial cystitis (PBS/IC) had led to several studies being conducted to assess the possible therapeutic effect of immunotherapeutic options for PBS/IC. This review presents the available evidence regarding the potential autoimmunity-based pathogenesis of PBS/IC and focuses on a main representative of the immunotherapeutic modalities for PBS/IC, aiming to summarize, evaluate, and present available data regarding the potential therapeutic role of monoclonal antibodies for PBS/IC patients. A non-systematic narrative and interpretative literature review was performed. The monoclonal antibodies included in the review were the anti-tumor necrosis factor-α (anti-TNF-α) agents adalimumab, which showed no difference compared to placebo, and certolizumab pegol, which showed statistically important differences in all outcome measures compared to placebo at the 18-week follow-up visit. Anti-nerve growth factor (anti-NGF) agents were also reviewed, including tanezumab, which showed both positive and negative efficacy results compared to placebo, and fulranumab, the study of which was discontinued owing to adverse events. In summary, monoclonal antibody therapy remains to be further researched in order for it to be proposed as a promising future treatment option for PBS/IC.

Efficacy of fesoterodine fumarate (8 mg) in neurogenic detrusor overactivity due to spinal cord lesion or multiple sclerosis: A prospective study.

AIMS: Antimuscarinic drugs are the first-line choice in the treatment of patients with neurogenic Detrusor Overactivity (nDO). Fesoterodine fumarate is the newest antimuscarinic drug. Limited data are published about the use of fesoterodine fumarate in patients suffering from neurogenic lower urinary tract dysfunction. Our study aims to determine the efficacy of fesoterodine fumarate on patients with nDO due to spinal cord lesion or multiple sclerosis (MS). METHODS: This is an open-label prospective interventional study. Eligible patients were 18-80 years old with SCL or MS and nDO confirmed by a urodynamic study (UDS). At baseline, patients underwent a UDS to confirm nDO. Quality of life (QoL) was assessed by the Short-Form (SF) Qualiveen questionnaire. Patients received fesoterodine 8 mg/day for 3 months and were re-evaluated with UDS and SF-Qualiveen. The primary endpoint was the confirmation of the maximum detrusor pressure (Pdetmax ) reduction after treatment. Secondary endpoints were: evaluation of maximum bladder capacity and compliance and QoL effect. Statistical analysis included Wilcoxon-test using SPSSv26. RESULTS: One hundred and twenty-four patients completed the study. Ninety-five of them (76.6%) had SCL, while 29 (23.4%) had MS. Pdetmax , maximum bladder capacity, and compliance had significant reduction after treatment (p < .001) in the whole group and each subgroup. SF-Qualiveen revealed a significant increase in QoL in each group (p < .001). CONCLUSIONS: Fesoterodine fumarate (8 mg) is an efficacious drag in patients with SCL and MS, as it significantly decreases the detrusor pressure, increases the bladder capacity and compliance, and improves the QoL.

The Clinical Impact of Hexanic Extract of Serenoa repens in Men with Prostatic Inflammation: A Post Hoc Analysis of a Randomized Biopsy Study.

A randomized biopsy study showed that hexanic Serenoa repens (HESr) treatment resulted in prostatic inflammation reduction. This post-hoc analysis evaluated the clinical impact of HESr and investigated correlations between baseline parameters and treatment response. Patients were randomized to receive HESr 320mg/day for six months or no therapy. Assessment included International Prostate Symptoms Score (IPSS), prostate volume (PV), and maximum flow rate (Qmax). Baseline characteristics were recorded, including body mass index (BMI) and metabolic syndrome (MetS) components. In patients under α1-adrenoceptor antagonists (α1-blockers), the addition of HESr resulted in statistically significant IPSS improvement after 6 months (p = 0.006). IPSS remained stable in patients under a1-blockers only (p = 0.346). Patients treated only with HESr reported a significant IPSS amelioration (p = 0.001). In the control group of naïve patients, no significant IPSS change was detected (p = 0.298). Baseline PV showed fair correlation (r = -0.20) with inflammation reduction in the HESr patients. BMI (r = 0.40), diabetes mellitus (r = 0.40), and PV (r = 0.23) showed fair correlation with Qmax increase but without reaching statistical significance. MetS (p = 0.06) was an influent biomarker for Qmax improvement. Treatment with HESr (as monotherapy or add-on therapy to a-blockers) may improve urinary symptoms in terms of IPSS in patients with prostatic inflammation.

Cefixime versus prulifloxacin as a prophylactic treatment for prostate biopsy: a randomized study.

INTRODUCTION: Urinary tract infections may be a severe complication after prostate biopsy. The aim of our study is to investigate the efficacy of cefixime versus prulifloxacin, as a prophylactic treatment in the era of fluoroquinolone resistance. MATERIAL AND METHODS: In this prospective randomized trial, patients were allocated into two groups. In Group A, patients received cefixime 400 mg p.o./day, while in Group B, prulifoxacin 600 mg p.o./day, both for three days, starting the day before procedure. Eligible for the study were men with a high prostate-specific antigen (PSA) and/or a positive rectal examination. Exclusion criteria were allergy to cefixime or fluoroquinolones, low glomerular filtration rate and drug-resistance to these antibiotics. Patients were followed-up for seven days. RESULTS: Finally, 120 patients were divided into 2 groups of 60 patients with a mean age of 68.6 years. A total of 16 (13.3%) men had already undergone another biopsy in the past, while 18 (15%) had received prulifloxacin and 8 (6.67%) cefixime, at least once in the last three months. During follow-up, hospital admission due to a severe urinary tract infection (UTI) was required in 2 of 60 (1.3%) and 1 of 60 (1.67%) patients from Group B and A respectively. The bacterial specimens detected in those urine cultures were resistant to prulifloxacin or cefixime. Among the remaining 117 patients (97.5%), nobody presented with a UTI. CONCLUSIONS: Prophylactic cefixime could be suggested as effective in preventing severe UTIs after prostate biopsy in the era of high bacterial resistance to fluoroquinolones.

The effect of hexanic extract of Serenoa repens on prostatic inflammation: results from a randomized biopsy study.

PURPOSE: To evaluate the effect of hexanic extract of Serenoa repens (HESr) on prostatic inflammation in patients with diagnosed prostatic inflammation. METHODS: Patients with prostatic inflammation histologically confirmed by TRUS prostatic biopsy were randomized either to receive HESr (320 mg/day) or no treatment. A second biopsy was performed 6 months later according to standard clinical practice. Inflammation was assessed by the Irani's score and immunohistochemical staining using the CD3, CD4 and CD8 (for T-leucocytes), CD20 (for B-leucocytes) and CD163 (for macrophages) antibodies. RESULTS: Overall 97 patients were eligible for analysis. In the HESr group the mean inflammation grading and aggressiveness grading score significantly decreased from 1.55 and 1.55 at baseline to 0.79 (p = 0.001) and 0.87 (p = 0.001) at the second biopsy, respectively. In the control group the mean inflammation grading score was 1.44 at first biopsy and 1.23 at the second biopsy. The mean aggressiveness gradings core was 1.09 and 0.89, respectively. No statistical significance was found (p = 0.09 and p = 0.74).The mean decrease in all inflammation scores was statistically higher in the HESr patients compared to controls. The immunohistochemical staining showed a significant change in the expression of the analyzed antibodies for the HESr patients compared to the first biopsy. In the nontreatment group, no significant difference was found at the second biopsy. The change in expression of each antibody in the HESr group was statistical significant compared to control. CONCLUSIONS: HESr seems to reduce prostatic inflammation in terms of histological and immunohistochemical parameters in this specific patients population.

Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications.

Prostate cancer is the most common cancer among men and androgen deprivation therapy (ADT) is the most effective treatment for this disease. The cornerstone of the treatment of prostate cancer is inhibition of testosterone production which interrupts testosterone-induced growth of the prostate tumor. The dramatic decrease in testosterone levels, however, has several undesirable effects on the metabolic profile and bone metabolism and can also lead to fatigue, loss of libido, gynecomastia, and anemia, provoke vasomotor flushing, and generally affect the quality of life. Due to the long-term survival rates of patients with prostate cancer, treatment-related adverse effects are highly relevant and thus, in each clinical setting, the benefits of ADT must be weighed against treatment-related adverse effects. The current review focuses on the more recently described metabolic complications of androgen deprivation therapy, including obesity, diabetes, lipid alterations, metabolic syndrome, and cardiovascular disease. In addition, it provides practical management recommendations drawn from the available guidelines issued by the American Diabetes Association and American Heart Association.

Ultrasound-guided radiofrequency ablation for cT1a renal masses in poor surgical candidates: mid-term, single-center outcomes.

OBJECTIVES: Surgical management of small renal masses can be challenging in frail patients and thus modalities such as radiofrequency ablation (RFA) have emerged as valid alternative options. The aim of the current study was to present mid-term oncological and functional results on a series of patients with cT1a renal cell carcinomas (RCCs) who were unfit for surgery and underwent RFA using ultrasound guidance under local anesthesia. METHODS: Data from patients fulfilling the study selection criteria were retrospectively collected. RENAL nephrometry score was used for tumor description. Parametric tests were used for data analysis and survival curves were estimated using the Kaplan-Meier method. RESULTS: Overall, 32 patients (mean±standard deviation age, 72.4 ± 7.6 years) with biopsy-proven RCCs (tumor size, 23.75 ± 10.44 mm and RENAL score, 5.28 ± 1.33) underwent 32 RFA sessions. Twenty-seven patients (84.4%) had low complexity masses and five patients had masses of intermediate complexity (15.6%) according to RENAL score categorization. Over a follow-up period of 22.1 ± 13.7 months, one case of primary treatment failure was recognized (primary technical success 97.0%), and overall, three patients were diagnosed with residual disease (primary technique effectiveness 90.6%). No major complications occurred during the postprocedure 90-day follow up, while no difference was found in serum creatinine and estimated glomerular filtration rate pre and post procedure. Patients with intermediate-complexity renal lesions had shorter time to recurrence in comparison to low-complexity masses (p = 0.002). All patients were alive at the time of study data analysis without diagnosed metastases. CONCLUSIONS: Percutaneous RFA of small RCCs using ultrasound-based guidance under local anesthesia can be an effective alternative method for managing patients who are unfit for surgery.

Optimal bladder diary duration for patients with suprapontine neurogenic lower urinary tract dysfunction.

PURPOSE: To identify the minimum bladder diary's length required to furnish reliable documentation of LUTS in a specific cohort of patients suffering from neurogenic urinary dysfunction secondary to suprapontine pathology. MATERIALS AND METHODS: From January 2008 to January 2014, patients suffering from suprapontine pathology and LUTS were requested to prospectively complete a bladder diary form for 7 consecutive days. Micturitions per day, excreta per micturition, urgency and incontinence episodes and voided volume per day were evaluated from the completed diaries. We compared the averaged records of consecutive days (2-6 days) to the total 7 days records for each patient's diary, seeking the minimum diary's length that could provide records comparable to the 7 days average, the reference point in terms of reliability. RESULTS: From 285 subjects, 94 male and 69 female patients enrolled in the study. The records of day 1 were significantly different from the average of the 7 days records in every parameter, showing relatively small correlation and providing insuficiente documentation. Correlations gradually increased along the increase in diary's duration. According to our results a 3-day duration bladder diary is efficient and can provide results comparable to a 7 day length for four of our evaluated parameters. Regarding incontinence episodes, 3 days seems inadequate to furnish comparable results, showing a borderline difference. CONCLUSIONS: A 3-day diary can be used, as its reliability is efficient regarding number of micturition per day, excreta per micturition, episodes of urgency and voided volume per day.

Optimal bladder diary duration for patients with suprapontine neurogenic lower urinary tract dysfunction

ABSTRACT Purpose: To identify the minimum bladder diary's length required to furnish reliable documentation of LUTS in a specific cohort of patients suffering from neurogenic urinary dysfunction secondary to suprapontine pathology. Materials and Methods: From January 2008 to January 2014, patients suffering from suprapontine pathology and LUTS were requested to prospectively complete a bladder diary form for 7 consecutive days. Micturitions per day, excreta per micturition, urgency and incontinence episodes and voided volume per day were evaluated from the completed diaries. We compared the averaged records of consecutive days (2-6 days) to the total 7 days records for each patient's diary, seeking the minimum diary's length that could provide records comparable to the 7 days average, the reference point in terms of reliability. Results: From 285 subjects, 94 male and 69 female patients enrolled in the study. The records of day 1 were significantly different from the average of the 7 days records in every parameter, showing relatively small correlation and providing insufficient documentation. Correlations gradually increased along the increase in diary's duration. According to our results a 3-day duration bladder diary is efficient and can provide results comparable to a 7 day length for four of our evaluated parameters. Regarding incontinence episodes, 3 days seems inadequate to furnish comparable results, showing a borderline difference. Conclusions: A 3-day diary can be used, as its reliability is efficient regarding number of micturition per day, excreta per micturition, episodes of urgency and voided volume per day.

A single dose of meropenem is superior to ciprofloxacin in preventing infections after transrectal ultrasound-guided prostate biopsies in the era of quinolone resistance.

PURPOSE: To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance. METHODS: This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained. RESULTS: A total of 110 patients, 52-75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine. CONCLUSIONS: A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.

Generalized Lymphadenopathy of Prostate Adenocarcinoma Origin. A Case Series.

Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. We report on 2 cases of prostate adenocarcinoma, which clinically manifested as generalized lymphadenopathy. The origin of the primary tumor was confirmed by transrectal ultrasound-guided prostate biopsy. We underline the fact that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate and complete diagnostic and therapeutic approach.

Tumor size and T stage correlate independently with recurrence and progression in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant BCG.

We conducted a retrospective study to determine the prognostic significance of age, gender, associated carcinoma in situ, stage, number of tumors, and tumor size for patients with high-risk non-muscle-invasive bladder tumors treated with bacillus Calmette-Guérin (BCG). Data were evaluated on 144 high-risk patients with non-muscle-invasive bladder cancer treated with BCG immunotherapy after the initial treatment with transurethral resection. According to their response to BCG, patients were divided into groups, and the differences in factors, associated with recurrence and progression, were evaluated. Patients were categorized into two groups: group A, complete responders without recurrence and without progression, and group B, patients with recurrence and with progression. Furthermore, group B was divided into two subgroups: group B1, patients with recurrence, and group B2, patients with progression. Univariate analysis of group B showed that only tumor size of >3 cm diameter (hazard ratio (HR) 11.99; 95% confidence interval (CI) range 5.69-25.3; p < 0.001) is associated with recurrence. After multivariate analysis, the same factor appeared to be prognostic for recurrence as well. In addition, group B2 was statistically correlated with group B1. Univariate analysis proved that tumor stage (Ta or T1) is the unique factor associated with progression (HR 6.4; 95% CI 1.29-31.9; p = 0.02). Tumor stage seems to be associated with disease's progression after the multivariate analysis too. Tumor size and stage may serve as prognostic factors, because of its independent correlation with recurrence and progression for patients with high-risk non-muscle-invasive bladder tumors treated with BCG.

Two-step minipercutaneous ureterolithotripsy under multimodal analgesia for complicated impacted calculi in proximal ureter.

OBJECTIVE: To suggest minipercutaneous ureterolithotripsy using the mininephroscope as an alternative process for impacted stones of the upper ureter because these stones can be challenging to treat and can produce severe symptoms. MATERIALS AND METHODS: We report our results of cases in which the percutaneous approach using 2-step minipercutaneous ureteroscopy with the mininephroscope was used to achieve relief from the stone, with minimal anesthesia risks. A total of 54 patients (33 men and 21 women) presented with impacted stones in the proximal ureter. The mean stone size was 16.2 mm (range 10-21). All patients were treated with 2-step minipercutaneous antegrade ureterolithotripsy under multimodal analgesia. RESULTS: The mean operative time was 49 minutes (range 40-110). Placement of the percutaneous drainage tube was quick and was performed with the patient under local anesthesia. The minipercutaneous session followed several days later, with the patient under multimodal anesthesia. The initial stone-free rate was 94%. The stone-free rate 2 months after the procedure was 100%. All procedures were well tolerated by the patients (group mean visual analog scale score 3.1 ± 0.7 standard deviation). No severe adverse events were noted. The mean hospital stay was 5.3 days (range 3-12). CONCLUSION: In selected emergency cases of impacted proximal ureteral stones, the approach of the initial insertion of a nephrostomy tube followed by a second session of antegrade ureterolithotripsy using the mininephroscope is a safe and effective alternative treatment, especially, because it can be accomplished with minimal anesthesia requirements.