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"Gacci, Mauro"
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Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia
by
De Nunzio Cosimo
,
Salonia Andrea
,
Gacci Mauro
in
Adrenergic receptors
,
Antagonists
,
Genital diseases
2020
PurposeTo review the role of a persistent prostatic inflammatory status (PIS) in the development and progression of benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) and which medical therapies approved for LUTS/BPH may reduce persistent PIS.MethodsLiterature search in PubMed up to July 2019.ResultsThe cause of histologically defined persistent PIS or chronic prostatic inflammation is multifactorial. It is evident in many men with LUTS/BPH, particularly in older men and in men with a large prostate volume or more severe (storage) LUTS. Additionally, persistent PIS is associated with an increased risk of acute urinary retention and symptom worsening. Of medical therapies approved for LUTS/BPH, the current evidence for a reduction of persistent PIS is greatest for the hexanic extract of Serenoa repens (HESr). This treatment relieves LUTS to the same extent as α1-adrenoceptor antagonists and short-term 5α-reductase inhibitors. Limited evidence is available on the effect of other mainstream LUTS/BPH treatments on persistent PIS.ConclusionsPersistent PIS plays a central role in both the development and progression of LUTS/BPH. In men with LUTS/BPH who have a high chance of harbouring persistent PIS, HESr will not only improve LUTS, but also reduce (underlying) inflammation. Well-designed clinical studies, with a good level of evidence, are required to better evaluate the impact of BPH/LUTS medical therapies on persistent PIS.
Journal Article
Reappraising the microscopic anatomy of human testis: identification of telocyte networks in the peritubular and intertubular stromal space
2018
Telocytes are a recently described stromal cell type widely distributed in various organs including the female and male reproductive systems. This study was aimed to investigate for the first time the existence, distribution and characteristics of telocytes in normal human testis by an integrated morphological approach (immunohistochemistry, immunofluorescence and transmission electron microscopy). We found that telocytes displaying typical long and moniliform prolongations and coexpressing CD34 and PDGFRα formed networks in the outer layer of peritubular tissue and around Leydig cells and vessels in the intertubular stroma. Testicular telocytes were immunophenotypically negative for CD31, c-kit/CD117 as well as α-SMA, thus making them clearly distinguishable from myoid cells/myofibroblasts located in the inner layer of peritubular tissue. Transmission electron microscopy confirmed the presence of cells ultrastructurally identifiable as telocytes (
i.e
. cells with telopodes alternating podomers and podoms) in the aforementioned locations. Intercellular contacts between neighboring telocytes and telopodes were observed throughout the testicular stromal compartment. Telopodes intimately surrounded and often established close contacts with peritubular myoid cells/myofibroblasts, Leydig cells and vessels. Extracellular vesicles were also frequently detected near telopodes. In summary, we demonstrated that telocytes are a previously neglected stromal component of human testis with potential implications in tissue homeostasis deserving further investigation.
Journal Article
Best practice in the management of storage symptoms in male lower urinary tract symptoms: a review of the evidence base
by
Sebastianelli, Arcangelo
,
Gravas, Stavros
,
Spatafora, Pietro
in
Agonists
,
Reviews
,
Urogenital system
2018
Storage lower urinary tract symptoms (LUTS) are characterized by an altered bladder sensation, increased daytime frequency, nocturia, urgency and urgency incontinence. Some evidence underlines the role of metabolic factors, pelvic ischemia, prostatic chronic inflammation and associated comorbidities in the pathophysiology of storage LUTS. A detailed evaluation of the severity of storage LUTS, and the concomitance of these symptoms with voiding and postmicturition symptoms, is mandatory for improving the diagnosis and personalizing treatment.
A detailed medical history with comorbidities and associated risk factors, a physical examination, a comprehensive analysis of all the features of LUTS, including their impact on quality of life, and a frequency–volume chart (FVC) or bladder diary, are recommended for men with storage LUTS.
Several drugs are available for the treatment of LUTS secondary to benign prostatic obstruction (BPO). Alpha-blockers (α-blockers), 5-α-reductase inhibitors and phosphodiesterase type 5 inhibitors are commonly used to manage storage LUTS occurring with voiding symptoms associated with BPO.
Muscarinic receptor antagonists and Beta 3-agonists (β3-agonists) alone, or in combination with α-blockers, represent the gold standard of treatment in men with predominant storage LUTS. There is no specific recommendation regarding the best treatment options for storage LUTS after prostatic surgery.
Journal Article
Training and external validation of machine learning supervised prognostic models of upper tract urothelial cancer (UTUC) after nephroureterectomy
2026
The European association of Urology (EAU) suggests a prognostic stratification of Upper Tract Urothelial Cancer (UTUC) based on high and low risk patients, with Radical nephroureterectomy (RNU) and bladder cuff resection being the gold standard for the treatment of non-metastatic High risk UTUC. However, no consensus on post-operative patient management or tools that predict who would benefit the most from a close follow-up rather than adjuvant chemotherapy regimen exist. in Machine Learning (ML) is gaining interest in Urology providing models for prognostic prediction purpose; It’s role in UTUC has not yet been investigated. We aim to develop and validate multiple supervised ML models based on patient- and tumor- related features to predict prognosis in patients with preoperative Histological or Imaging proved UTUC treated with RNU within a multiethnic large cohort. Data from an international multicenter large cohort of histologically proven UTUC patients from Asia and Europe treated with RNU were retrospectively collected. Twenty different ML-supervised predictive models were first trained and then external validate with two separate set. Nomograms were constructed based on 8 independent prognostic factors (age, gender, grading, pT, pN, presence of Carcinoma in Situ (CIS), multifocality and Lymphovascular invasion(LVI)) to predict 6 Outcomes (Overall Survival (OS), Cancer Specific Survival (CSS) and Disease Free Survival (DFS) at 3 and 5 year). Performances were compared using Area-under-curve (AUC) of Receiver-Operating Characteristics (ROC). A total of 3129 patients were enrolled: 637 Asian Patients (training cohort) and 2492 European patients (validation cohort). Upon training assessment, LR models achieved the best results, being the best model for prediction of 4/6 outcomes, with the best result in CSS both at 3 and 5 years (AUC: 0.85, 0.84, 0.81 for CSS-3y, CSS-5y and DFS-3y respectively). Upon external validation, LR(CSL) models achieve the best results, being the number 1 model for prediction of 3/6 outcomes (AUC: 0.84, 0.79, 0.77 for CSS-3y, OS-3y and OS-5y respectively). ML is a promising technology in the field of UTUC. Our model achieve favorable results in terms of prediction of prognosis after RNU, especially in terms of CSS at 3 and 5 years, moreover is the first model of prognosis taking into account the differences in epidemiology existing between European and Asian patients. Further clinical validation and verification of its reliability for the case selection of adjuvant therapy are needed to assess its use in clinical practice linked to clinical decision making. ML is an advancing technology in the field of medicine and urology, which can also be applied to the definition of the prognosis of patients with UTUC undergoing RNU. Our study represents the first experience investigating this potential.
Journal Article
Correction to: Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia
2020
The article “Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia”, written by Cosimo De Nunzio, Andrea Salonia, Mauro Gacci and Vincenzo Ficarra was originally published electronically on the publisher’s internet portal on 14 February 2020 without open access.
Journal Article
Contrast-enhanced ultrasound (CEUS) imaging for active surveillance of small renal masses
by
Nicoletti Rossella
,
Agostini, Simone
,
Baldi, Irene
in
Adverse events
,
Computed tomography
,
Growth rate
2021
PurposeTo assess the safety and efficacy of contrast-enhanced ultrasound (CEUS) imaging for monitoring small (< 4 cm) renal masses (SRM) in patients undergoing active surveillance (AS).MethodsWe retrospectively selected all consecutive patients with SRMs who underwent AS for at least 6 months at our Institution between January 2014 and December 2018. CEUS imaging was performed by two experienced genitourinary radiologists at established time points. The accuracy of CEUS for monitoring SRM size was compared with that of CT scan. For solid SRMs, four enhancement patterns (EP) were recorded. Radiological progression was defined as SRM growth rate ≥ 5 mm/year.ResultsOverall, 158/1049 (15.1%) patients with SRMs underwent AS. At a median follow-up of 25 months (IQR 13–39), no patient died due to renal cell carcinoma (RCC). No patients experienced CEUS-related adverse events. There was a large variability in the pattern of growth of SRMs (overall median growth rate: 0.40 mm/year), with 9.5% of SRMs showing radiological progression. The median SRM size was comparable between CEUS and CT scan examinations at all time points. The vast majority (92.7%) of SRMs did not show a change in their EP over time; and there was no association between the SRM’s EP and radiological progression or SRM size. Overall, 43 (27.2%) patients underwent delayed intervention (DI); median SRM size, and median growth rate were significantly higher in these patients as compared to those continuing AS.ConclusionIn experienced hands, CEUS is a safe and effective strategy for active monitoring of SRMs in well-selected patients undergoing AS.
Journal Article
Metabolic syndrome and prostate abnormalities in male subjects of infertile couples
2014
No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05-3.33), P < 0.05), with calcification size (Wald = 3.11, P< 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia.
Journal Article
Physical Inactivity, Metabolic Syndrome and Prostate Cancer Diagnosis: Development of a Predicting Nomogram
2023
Insufficient physical activity (PA) may be a shared risk factor for the development of both metabolic syndrome (MetS) and prostate cancer (PCa). To investigate this correlation and to develop a nomogram able to predict tumor diagnosis. Between 2016 and 2018, a consecutive series of men who underwent prostate biopsy at three institutions were prospectively enrolled. PA was self-assessed by patients through the Physical Activity Scale for the Elderly (PASE) questionnaire; MetS was assessed according to Adult Treatment Panel III criteria. A logistic regression analyses was used to identify predictors of PCa diagnosis and high-grade disease (defined as International Society of Uro-Pathology grade >2 tumors). A nomogram was then computed to estimate the risk of tumor diagnosis. A total of 291 patients were enrolled; 17.5% of them (n = 51) presented with MetS. PCa was diagnosed in 110 (38%) patients overall while 51 presented high-grade disease. At multivariable analysis, age (OR 1.04; 95%CI: 1.00–1.08; p = 0.048), prostate volume (PV) (OR 0.98; 95%CI: 0.79–0.99; p = 0.004), suspicious digital rectal examination (OR 2.35; 95%CI: 1.11–4.98; p = 0.02), total PSA value (OR 1.12; 95%CI: 1.05–1.2; p < 0.001), and PASE score (OR 0.99; 95%CI: 0.98–0.99; p = 0.01) were independent predictors of tumor diagnosis. The latter two also predicted high-grade PCa. MetS was not associated with PCa diagnosis and aggressiveness. The novel nomogram displayed fair discrimination for PCa diagnosis (AUC = 0.76), adequate calibration (p > 0.05) and provided a net benefit in the range of probabilities between 20% and 90%. reduced PA was associated with an increased risk of PCa diagnosis and high-grade disease. Our nomogram could improve the selection of patients scheduled for prostate biopsy at increased risk of PCa.
Journal Article
Diagnostic and prognostic factors in patients with prostate cancer: a systematic review
by
Devecseri, Zsuzsanna
,
MacLennan, Steven
,
Van Hemelrijck, Mieke
in
Bias
,
Biomarkers
,
Clinical Medicine
2022
ObjectivesAs part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa).DesignWe performed a systematic review to identify validated and non-validated studies.Data sourcesMEDLINE, Embase and the Cochrane Library were searched on 21 January 2020.Eligibility criteriaOnly quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded.Data extraction and synthesisAfter initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2.ResultsThe search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability.ConclusionMost of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies.Ethics and disseminationThere are no ethical implications.
Journal Article