The role of flower pollen extract in managing patients affected by chronic prostatitis/chronic pelvic pain syndrome. a comprehensive analysis of all published clinical trials

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a challenge to manage for all physicians. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of flower pollen extract would be helpful for physicians who are considering a phytotherapeutic approach to treating patients with CP/CPPS. Methods: A comprehensive search of the PubMed and Embase databases up to June 2016 was performed. This comprehensive analysis included both pre-clinical and clinical trials on the role of flower pollen extract in CP/CPPS patients. Moreover, a meta-analysis of available randomized controlled trials (RCTs) was performed. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and Quality of Life related questionnaires (QoL) were the most commonly used tools to evaluate the therapeutic efficacy of pollen extract. Results: Pre-clinical studies demonstrated the anti-inflammatory and anti-proliferative role of pollen extract. 6 clinical, non-controlled studies including 206 patients, and 4 RCTs including 384 patients were conducted. The mean response rate in non-controlled studies was 83.6% (62.2%-96.0%). The meta-analysis revealed that flower pollen extract could significantly improve patients’ quality of life [OR 0.52 (0.34-.0.81); p = 0.02]. No significant adverse events were reported. Conclusion: Most of these studies presented encouraging results in terms of variations in NIH-CPSI and QoL scores. These studies suggest that the use of flower pollen extract for the management of CP/CPPS patients is beneficial. Future publications of robust evidence from additional RCTs and longer-term follow-up would provide more support encouraging the use of flower pollen extracts for CP/CPPS patients

Pollen extract in association with vitamins provides early pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome

The therapeutic efficacy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is currently unsatisfactory. The aim of the present study was to assess the safety and efficacy of pollen extract in association with vitamins (DEPROX 500®) in males with CP/CPPS. All patients with a diagnosis of CP/CPPS attending the same urologic centre between March and October 2012 were enrolled in this randomised controlled phase III study. Participants were randomised to receive oral capsules of DEPROX 500® (two capsules every 24 h) or ibuprofen (600 mg, one tablet three times a day) for four weeks. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score and Quality of Well-Being (QoL) questionnaires were used. In the intention-to-treat analysis, 87 males (25 class IIIa and 62 class IIIb) with a mean age of 33.6±5.9 years were randomly allocated to the DEPROX 500® (n=41) or ibuprofen (n=46) treatment groups. At the follow-up examination (following one month of treatment), in the DEPROX 500® group, 31/41 patients (75.6%) reported an improvement in quality of life, defined as a reduction of the NIH-CPSI total score by ≥25%, compared with 19/46 (41.3%) in the control group (P=0.002). The greater improvement in the DEPROX 500® group compared with the ibuprofen group was statistically significant (treatment difference in the NIH-CPSI pain domain, -2.14±0.51, P<0.001; QoL scores, P=0.002). All patients were negative at the Meares-Stamey test evaluation. Adverse events were less frequent in the DEPROX 500® group than in the ibuprofen group. The DEPROX 500® treatment significantly improved total symptoms, pain and quality of life compared with ibuprofen in patients with CP/CPPS, without severe side-effects

A Proposal of a New Nomogram to Predict the Need for Testosterone ReplACEment (TRACE): A Simple Tool for Everyday Clinical Practice

International guidelines suggest to use testosterone therapy (TTh) in hypogonadal men presenting symptoms of testosterone deficiency (TD), even if there is no fixed threshold level of T at which TTh should be started. We aimed to develop and validate a nomogram named TRACE (Testosterone ReplACEment) for predicting the need of TTh in patients with “low–normal” total testosterone levels. The following nomogram variables were used: serum T level; serum LH level; BMI; state of nocturnal erections; metabolic comorbidities; and IPSS total score. The nomogram has been tested by calculating concordance probabilities, as well as assaying the calibration of predicted probability of clinical testosterone deficiency and need for TTh, together with the clinical outcome of the TTh. A cohort of 141 patients was used for the development of the nomogram, while a cohort of 123 patients attending another institution was used to externally validate and calibrate it. Sixty-four patients (45.3%) received TTh. Among them, sixty patients (93.7%) reported a significant clinical improvement after TTh. The nomogram had a concordance index of 0.83 [area under the ROC curve 0.81 (95% CI 0.71–0.83)]. In conclusion, the TRACE nomogram accurately predicted the probability of clinical impairment related to TD, and resulted in a simple and reliable method to use to select hypogonadal patients with not clearly pathological testosterone values who will benefit from TTh

Dynamic evaluation of circulating mirna profile in egfr‐ mutated nsclc patients treated with egfr‐tkis

Background: Resistance to EGFR‐TKIs constitutes a major challenge for the management of EGFR‐mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR‐21, miR‐27a and miR‐181a) as a surrogate for predicting EGFR‐TKI performance in EGFR‐mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR‐mutated NSCLC patients treated with EGFR‐TKIs were collected at different points in time and miRNA levels were assessed by RT‐PCR. Results: Higher basal values of miR‐21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR‐21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR‐TKI treatment showed that patients who experienced SD had an increase in miR‐21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR‐27a (FC = 3.1) and miR‐181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR‐21 levels in NSCLC cells that became resistant after exposure to EGFR‐TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR‐21, and their dynamic change over time in predicting EGFR‐TKI response in EGFR‐mutated NSCLC

Monitoring cfDNA in plasma and in other liquid biopsies of advanced EGFR mutated NSCLC patients: A pilot study and a review of the literature

In order to study alternatives at the tissue biopsy to study EGFR status in NSCLC patients, we evaluated three different liquid biopsy platforms (plasma, urine and exhaled breath condensate, EBC). We also reviewed the literature of the cfDNA biological sources other than plasma and compared our results with it about the sensitivity to EGFR mutation determination. Twenty-two EGFR T790M-mutated NSCLC patients in progression to first-line treatment were enrolled and candidate to osimertinib. Plasma, urine and EBC samples were collected at baseline and every two months until progression. Molecular analysis of cfDNA was performed by ddPCR and compared to tissue results. At progression NGS analysis was performed. The EGFR activating mutation detection reached a sensitivity of 58 and 11% and for the T790M mutation of 45 and 10%, in plasma and urine samples, respectively. Any DNA content was recovered from EBC samples. Considering the plasma monitoring study, the worst survival was associated with positive shedding status; both plasma and urine molecular progression anticipated the radiological worsening. Our results confirmed the role of plasma liquid biopsy in testing EGFR mutational status, but unfortunately, did not evidence any improvement from the combination with alternative sources, as urine and EBC

Collagenase clostridium histolyticum for the treatment of Peyronie's disease: a prospective Italian multicentric study

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0–40)° or 42.9 (0–67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three-injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment

Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism : A systematic review by the EAU Sexual and Reproductive Health Guidelines panel

Peer reviewedPostprin

RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients

Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non–small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Panel

The authors acknowledge the participants for their cooperation Conflict of Interest: None of the authors declare any interest. Formatting of funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin