Publications by authors named "Giorgio Ivan Russo"

134 Publications

The relationship between the gut microbiota, benign prostatic hyperplasia, and erectile dysfunction.

Int J Impot Res 2022 Apr 13. Epub 2022 Apr 13.

Urology Unit, Department of Medicine, Surgery, Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Italy.

Microbiota is defined as the group of commensal microorganisms that inhabit a specific human body site. The composition of each individual's gastrointestinal microbiota is influenced by several factors such as age, diet, lifestyle, and drug intake, but an increasing number of studies have shown that the differences between a healthy microbiota and a dysbiotic one can be related to different diseases such as benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). The aim of this review is to give an overview of the role of the gut microbiota on BPH and ED. Gut microbiota modifications can influence prostate health indirectly by the activation of the immune system and the production of proinflammatory cytokines such as IL-17, IL-23, TNF-alpha, and IFN-gamma, which are able to promote an inflammatory state. Gut dysbiosis may lead to the onset of ED by the alteration of hormone levels and metabolic profiles, the modulation of stress/anxiety-mediated sexual dysfunction, the development of altered metabolic conditions such as obesity and diabetes mellitus, and the development of hypertension. In conclusion, much evidence suggests that the intestinal microbiota has an influence on various pathologies including BPH and ED.
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http://dx.doi.org/10.1038/s41443-022-00569-1DOI Listing
April 2022

Preserving Ejaculation: A Guide Through the Landscape of Interventional and Surgical Options for Benign Prostatic Obstruction.

Eur Urol Focus 2022 Mar 23. Epub 2022 Mar 23.

Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany.

Surgical treatment for benign prostatic obstruction in patients wishing to preserve normal ejaculation remains a urological challenge. Standard surgical techniques are associated with high rates of postoperative ejaculatory dysfunction. Research is now concentrating on ejaculation-preserving modifications of standard surgical techniques and on alternative minimally invasive interventional techniques. Ejaculation-preserving modifications seem to be superior to standard techniques for preservation of ejaculation with comparable efficacy in terms of improvement in lower urinary tract symptoms (LUTS). Among the alternative minimally invasive interventional techniques, prostatic artery embolization and prostatic urethral lift provide high success rates for patients wishing to preserve ejaculation but are inferior to standard surgical techniques regarding improvement in LUTS. High-quality studies focusing on ejaculatory function as the primary outcome are still lacking. PATIENT SUMMARY: Benign prostate enlargement can cause obstruction of the lower urinary tract. We reviewed the evidence for techniques that preserve ejaculatory function in treatment of this condition. These ejaculation-preserving treatment techniques may have lower efficacy in improving bothersome urinary symptoms.
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http://dx.doi.org/10.1016/j.euf.2022.03.008DOI Listing
March 2022

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette-Guerin Immunotherapy.

Diagnostics (Basel) 2022 Feb 25;12(3). Epub 2022 Feb 25.

Department of Urology, University of Catania, 95123 Catania, Italy.

Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette-Guérin (BCG) therapy.

Methods: We retrospectively reviewed patient's medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models.

Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression ( = 0.076). Kaplan-Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92-94), in patients with mGPS 0, 82.2% (CI 95% 78.9-85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4-70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97-99) in patients with mGPS 0, 90% (CI 95% 87-94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study.

Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion.
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http://dx.doi.org/10.3390/diagnostics12030586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947693PMC
February 2022

Role of Rezum in the treatment of benign prostate hyperplasia: A review of the literature.

Turk J Urol 2021 Nov;47(6):452-460

Department of Urology, University of Florence, Careggi Hospital, Florence, Italy.

The aim of this study was to review the available literature on the efficacy and safety of the Rezum system for the treatment of symptomatic benign prostatic hyperplasia (BPH). A revision of literature up to January 2021 was carried out. Medline, Scopus, Web of Science, and PubMed archives were screened to identify all the relevant studies investigating the role of Rezum in the treatment of BPH. Randomized controlled trial (RCT), retrospective, prospective, observational, and comparative studies were included. Finally, 17 studies were included, five of which reporting data of a double blind Rezum RCT. Overall, 1,451 patients underwent Rezum procedure. All the studies performed a minimum of 3 months follow-up. Preoperatively, the mean International Prostate Symptom Score (IPSS) score was 19.8, mean Qmax was 9.2mL s1, and mean PVR was 142 cc. At 3 months after surgery, the mean IPSS score was 1.5, mean Qmax was 13.7mL s1, and mean PVR was 74 cc. Six studies investigated sexual function, most of them using the International Index of Erectile Function (IIEF)-5 questionnaire and a few also the Male Sexual Health Questionnaire (MSHQ). Preoperative mean IIEF-5 score was 18.5, and the mean MSHQ score was 7.4. At the 3 months follow-up, the mean IIEF-5 score was 16.4, and the mean MSHQ score was 9.62. None of the studies reported intraoperative complications. Rezum system is a novel minimally invasive treatment for symptomatic BPH using transurethral water vapor thermal energy. It represents a cost-effective and safe procedure with durable relief of lower urinary tract symptom, preservation of sexual function, low complications rate, and short recovery time.
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http://dx.doi.org/10.5152/tud.2021.21128DOI Listing
November 2021

The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis.

Cancers (Basel) 2021 Dec 31;14(1). Epub 2021 Dec 31.

STLab s.r.l., Via Anapo 53, 95126 Catania, Italy.

Liquid biopsy is emerging as a potential diagnostic tool for prostate cancer (PC) prognosis and diagnosis. Unfortunately, most circulating tumor cells (CTC) technologies, such as AdnaTest or Cellsearch, critically rely on the epithelial cell adhesion molecule (EpCAM) marker, limiting the possibility of detecting cancer stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this context, dielectrophoresis (DEP) is an epCAM independent, label-free enrichment system that separates rare cells simply on the basis of their specific electrical properties. As compared to other technologies, DEP may represent a superior technique in terms of running costs, cell yield and specificity. However, because of its higher complexity, it still requires further technical as well as clinical development. DEP can be improved by the use of microfluid, nanostructured materials and fluoro-imaging to increase its potential applications. In the context of cancer, the usefulness of DEP lies in its capacity to detect CTCs in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotype forms, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and diagnosis.
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http://dx.doi.org/10.3390/cancers14010198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750463PMC
December 2021

Assessment of Conservative Combination Therapies for Active and Stable Peyronie's Disease: A Systematic Review and Meta-analysis.

Eur Urol Focus 2021 Dec 17. Epub 2021 Dec 17.

Department of Urology, 'Martha-Maria' Hospital Nuremberg, Nuremberg, Germany. Electronic address:

Context: In patients with Peyronie's disease (PD), oral, injected, or topical agents provide limited efficacy. In this setting, combination of two or more conservative treatments may improve symptoms further.

Objective: To explore the effects of available conservative combination therapies for active and stable PD through a systematic review and meta-analysis.

Evidence Acquisition: We searched multiple databases and sources of gray literature until June 2021. We included randomized or observational comparative studies assessing any conservative combination therapies for PD. We undertook a random-effect meta-analysis when at least two studies employed the same treatment modality (PROSPERO: CRD42021224517).

Evidence Synthesis: Overall, 13 studies on active PD and ten on stable PD (1962 participants) were included. Most included studies raised methodological concerns. In patients with active or stable PD, the available evidence is inconclusive to support the use of any combination treatment modality, such as intralesional verapamil injections, antioxidants, and other oral, injected, or topical agents. Based on data availability, we performed a meta-analysis to compare the effect of collagenase Clostridium histolyticum (CCH) plus adjunctive mechanical therapies (penile traction or vacuum pump) versus CCH monotherapy on penile curvature and length in patients with stable PD. CCH and adjunctive mechanical therapies resulted in an additional decrease of 0.3° in penile curvature (95% confidence interval [CI]: -3.97 to 4.49, I = 0%) and in an increase of 0.5 cm in penile length (95% CI: -0.32 to 1.4, I = 70%) compared with CCH monotherapy.

Conclusions: The available combination treatment modalities, including the addition of adjunctive mechanical therapies to CCH, do not improve symptoms further compared with monotherapy and should not be implemented in patients with active or stable PD. Further high-quality randomized trials combining only recommended treatments are mandatory.

Patient Summary: Despite the interest in and optimism for combination treatment modalities, the road to an effective conservative therapy for Peyronie's disease still seems long.
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http://dx.doi.org/10.1016/j.euf.2021.12.003DOI Listing
December 2021

Relationship between Dietary Patterns with Benign Prostatic Hyperplasia and Erectile Dysfunction: A Collaborative Review.

Nutrients 2021 Nov 19;13(11). Epub 2021 Nov 19.

Urology Section, San Marco Hospital, 95100 Catania, Italy.

Interest in the role of dietary patterns has been consistently emerging in recent years due to much research that has documented the impact of metabolism on erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH). We conducted a non-systematic review of English articles published from 1964 to September 2021. The search terms were: ("dietary patterns" OR "diet") AND/OR ("erectile dysfunction") AND/OR ("benign prostatic hyperplasia"). In the present review, we have highlighted how the association between dietary patterns and two of the most frequent pathologies in urology, namely erectile dysfunction and benign prostatic hyperplasia, is present in the literature. The data suggested that a diet that is more adherent to the Mediterranean diet or that emphasizes the presence of vegetables, fruits, nuts, legumes, and fish or other sources of long-chain (n-3) fats, in addition to reduced content of red meat, may have a beneficial role on erectile function. At the same time, the same beneficial effects can be transferred to BPH as a result of the indirect regulatory effects on prostatic growth and smooth muscle tone, thus determining an improvement in symptoms. Certainly, in-depth studies and translational medicine are needed to confirm these encouraging data.
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http://dx.doi.org/10.3390/nu13114148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618879PMC
November 2021

The Impact of SARS-CoV-2 Pandemic on Time to Primary, Secondary Resection and Adjuvant Intravesical Therapy in Patients with High-Risk Non-Muscle Invasive Bladder Cancer: A Retrospective Multi-Institutional Cohort Analysis.

Cancers (Basel) 2021 Oct 21;13(21). Epub 2021 Oct 21.

Department of Urology, University of Bologna, S-Orsola-Malpighi Hospital, 40138 Bologna, Italy.

Background: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC).

Methods: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG.

Results: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups ( = 453, 86% vs. = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, < 0.0001).

Conclusions: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.
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http://dx.doi.org/10.3390/cancers13215276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582553PMC
October 2021

Sexual Behaviour and Fantasies in a Group of Young Italian Cohort.

J Clin Med 2021 Sep 23;10(19). Epub 2021 Sep 23.

Department of Urology, University of Florence, 50100 Florence, Italy.

Over the years, sexual behaviour has changed due to the growing interest in everything related to the sexual sphere. The purpose of the study was to collect information on the sexual habits and behaviours of Italian people of all ages, sexes and sexual orientations and to describe the patterns of sexual behaviour, with the aim of gaining a representative picture of sexuality in Italy, before the COVID-19 pandemic. Participants completed a survey with 99 questions about their sexual habits. In our group first sexual experiences occurred on average around the age of 15, whilst the median age of the first sexual intercourse was 17. The fantasies that most stimulated and excited our group (Likert scale ≥ 3) was having sex in public (63.9%), having sex with more than one person at the same time (59.4%), blindfolded sex (64.9%), being tied up (56.3%) and observing a naked person (48.6%). As for pornography, we have shown that 80% of our group watched porn at home, alone or from their smartphones. Our results have several practical implications for the areas of sex education and sexual health. It is necessary to safeguard the health of young people and support them increasing their sexual well-being.
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http://dx.doi.org/10.3390/jcm10194327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509395PMC
September 2021

New Ultra-minimally Invasive Surgical Treatment for Benign Prostatic Hyperplasia: A Systematic Review and Analysis of Comparative Outcomes.

Eur Urol Open Sci 2021 Nov 22;33:28-41. Epub 2021 Sep 22.

Department of Oncology, Division of Urology, University of Turin, Turin, Italy.

Context: Benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) is diagnosed in up to 80% of men during their lifetime. Several novel ultra-minimally invasive surgical treatments (uMISTs) for BPH/benign prostatic obstruction (BPO) have become available over the past 5 yr.

Objective: To evaluate the perioperative and functional outcomes of recently introduced uMISTs for BPH/BPO, including Urolift, Rezūm, temporary implantable nitinol device, prostatic artery embolization (PAE), and intraprostatic injection.

Evidence Acquisition: A systematic literature search was conducted in December 2020 using Medline (via PubMed), Embase (via Ovid), Scopus, and Web of Science (registered on PROSPERO as CRD42021225014). The search strategy used PICO criteria and article selection was conducted in accordance with the PRISMA guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest. Pooled and cumulative analyses were performed to compare perioperative and functional outcomes between study groups. A random-effects model using the DerSimonian and Laird method was used to evaluate heterogeneity. Stata version 15.0 software was used for all statistical analyses.

Evidence Synthesis: The initial electronic search identified 3978 papers, of which 48 ultimately met the inclusion criteria and were included in the analysis. Pooled analysis revealed a uMIST benefit in terms of International Prostate Symptom Score (IPSS; -9.81 points, 95% confidence interval [CI] -11.37 to -8.25 at 1 mo; -13.13 points, 95% CI -14.98 to -11.64 at 12 mo), maximum flow rate (from +3.66 ml/s, 95% CI 2.8-4.5 to +4.14 ml/s, 95% CI 0.72-7.56 at 12 mo), and postvoid residual volume (-10.10 ml, 95% CI -27.90 to 7.71 at 12 mo). No negative impact was observed on scores for the International Index of Erectile Function-5, Male Sexual Health Questionnaire-Ejaculatory Dysfunction bother and function scales (overall postintervention change in pooled median score of 1.88, 95% CI 1.34-2.42 at the start of follow-up; and 1.04, 95% CI 0.28-1.8 after 1 yr), or the IPSS-Quality of Life questionnaire.

Conclusions: Novel uMISTs can yield fast and effective relief of LUTS without affecting patient quality of life. Only Rezūm, UroLift, and PAE had a minimal impact on patients' sexual function with respect to baseline, especially regarding preservation of ejaculation.

Patient Summary: We reviewed outcomes for recently introduced ultra-minimally invasive surgical treatments for patients with lower urinary tract symptoms caused by benign prostate enlargement or obstruction. The evidence suggests that these novel techniques are beneficial in terms of controlling symptoms while preserving sexual function.

Take Home Message: Novel ultra-minimally invasive treatments can yield fast and effective relief of lower urinary tract symptoms without affecting a patient's quality of life.
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http://dx.doi.org/10.1016/j.euros.2021.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473553PMC
November 2021

Is there a line between ethics and market competition? Lights and shades of the withdrawal of collagenase treatment for Peyronie's disease.

Int J Impot Res 2021 Sep 22. Epub 2021 Sep 22.

Villa Donatello, Private Hospital, Florence, Italy.

Peyronie's disease treatments is changing again due the interruption of Xiapex® distrubution in Europe. There are many reasons that can be referred to this event. In this editorial we would like to shed light on the current cost items relating to treatment with collagenase clostridium histolyticum (CCH). The inaccessibility of the drug has seen both an increase in surgery for the treatments of both PD and Dupuytren's disease and an interruption of therapies in patients who had not completed their therapeutic cycle. Considering the aforementioned concerns, we would like to invite researchers dealing with PD to conduct studies with the available CCH products in collaboration with the drug companies in order to give again an efficacious treatment for PD.
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http://dx.doi.org/10.1038/s41443-021-00469-wDOI Listing
September 2021

European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility.

Eur Urol 2021 11 10;80(5):603-620. Epub 2021 Sep 10.

Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy.

Context: The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021.

Objective: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health, including advances and areas of controversy in male infertility.

Evidence Acquisition: The panel performed a comprehensive literature review of novel data up to January 2021. The guidelines were updated and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable.

Evidence Synthesis: The male partner in infertile couples should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors causing fertility impairment. Infertile men are at a higher risk of harbouring and developing other diseases including malignancy and cardiovascular disease and should be screened for potential modifiable risk factors, such as hypogonadism. Sperm DNA fragmentation testing has emerged as a novel biomarker that can identify infertile men and provide information on the outcomes from assisted reproductive techniques. The role of hormone stimulation therapy in hypergonadotropic hypogonadal or eugonadal patients is controversial and is not recommended outside of clinical trials. Furthermore, there is insufficient evidence to support the widespread use of other empirical treatments and surgical interventions in clinical practice (such as antioxidants and surgical sperm retrieval in men without azoospermia). There is low-quality evidence to support the routine use of testicular fine-needle mapping as an alternative diagnostic and predictive tool before testicular sperm extraction (TESE) in men with nonobstructive azoospermia (NOA), and either conventional or microdissection TESE remains the surgical modality of choice for men with NOA.

Conclusions: All infertile men should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors. Increasing data indicate that infertile men are at higher risk of cardiovascular mortality and of developing cancers and should be screened and counselled accordingly. There is low-quality evidence supporting the use of empirical treatments and interventions currently used in clinical practice; the efficacy of these therapies needs to be validated in large-scale randomised controlled trials.

Patient Summary: Approximately 50% of infertility will be due to problems with the male partner. Therefore, all infertile men should be assessed by a specialist with the expertise to not only help optimise their fertility but also because they are at higher risk of developing cardiovascular disease and cancer long term and therefore require appropriate counselling and management. There are many treatments and interventions for male infertility that have not been validated in high-quality studies and caution should be applied to their use in routine clinical practice.
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http://dx.doi.org/10.1016/j.eururo.2021.08.014DOI Listing
November 2021

Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).

Transl Res 2021 12 24;238:25-35. Epub 2021 Jul 24.

Department of Surgery, Urology Section, University of Catania, Catania, Italy. Electronic address:

In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR)  α and β, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. We constructed tissue microarray for immunohistochemistry (IHC) analysis. In the final cohort (76 BPH and 284 PC), 57 (15.8%) patients had diabetes, 17 (22.37%) in BPH and 40 (14.08%) in PC (P = 0.08). IR-α was more expressed in patients with PC compared to the BPH Group (95.96% vs 4.04%; P <0.01). We found that AR was associated with increased risk of International Society of Urological Pathology (ISUP) score ≥4 (OR: 2.2; P <0.05), higher association with Ki-67 (OR: 2.2; P <0.05) and IR-α (OR: 5.7; P <0.05); IGF-1 receptor was associated with PSMA (OR: 2.8; P <0.05), Ki-67 (OR: 3.5; P <0.05) and IR-β (OR: 5.1; P <0.05). Finally, IGF-1 receptor was predictive of ISUP ≥ 4 (OR: 16.5; P =0.017) in patients with PC and diabetes. In the present study we highlighted how prostate cancer patients have a different protein expression in the tissue. This expression, and in particular that relating to IGF-1R, is associated with greater tumor aggressiveness in those patients with diabetes. We suppose that these results are attributable to an alteration of the insulin signal which therefore determines a greater mitogenic activity that can influence tumor progression.
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http://dx.doi.org/10.1016/j.trsl.2021.07.002DOI Listing
December 2021

A risk-group classification model in patients with bladder cancer under neoadjuvant cisplatin-based combination chemotherapy.

Future Oncol 2021 Oct 19;17(30):3987-3994. Epub 2021 Jul 19.

Department of Urology, Humanitas Gavazzeni, Bergamo, Italy.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.
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http://dx.doi.org/10.2217/fon-2020-1298DOI Listing
October 2021

Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy.

Future Sci OA 2021 Aug 20;7(7):FSO709. Epub 2021 Apr 20.

Department of Emergency & Organ Transplantation-Urology, Andrology & Kidney Transplantation Unit, University of Bari, Bari, Italy.

Aim: To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).

Patients & Methods: 213 patients were included.

Inclusion Criteria: Nonmetastatic, MIBC (cT2-T4aN0M0), at least three cycles of NAC, undergone RC and with blood count within 30 days before NAC.

Results: Five-years overall survival (OS) with NPAR >18 was 34.06% (95% CI: 18.3-50.5) and 65.37% (95% CI: 52.4-75.6) with NPAR <18. Five years cancer-specific survival (CSS) with NPAR >18 was 42.9% (95% CI: 23.9-60.7) and 74.5% (95% CI: 62.6-83.1) with NPAR <18 (p < 0.001). In multivariable analysis, NPAR increased OS of 1.3 points and CSS of 4.37 points.

Conclusion: High NPAR prior to NAC seems to be a strong predictor of OS and CSS in MIBC patients treated with NAC and RC.
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http://dx.doi.org/10.2144/fsoa-2021-0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256323PMC
August 2021

Reply to 'Penile length and circumference dimensions: A large study in young Italian men'.

Andrologia 2021 10 11;53(9):e14161. Epub 2021 Jul 11.

Department of Urology, University of Florence, Firenze, Italy.

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http://dx.doi.org/10.1111/and.14161DOI Listing
October 2021

SRSF-1 and microvessel density immunohistochemical analysis by semi-automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study).

Prostate 2021 09 1;81(12):882-892. Epub 2021 Jul 1.

Urology Section, Department of Surgery, University of Catania, Catania, Italy.

Objective: To study the association between insulin receptors (isoforms α and β), insulin growth factor-1 (IGF1) and serine/arginine splicing factor 1 (SRSF-1) in patients with prostate cancer (PC) and diabetes.

Materials And Methods: We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor-α and -β, IGF1 (IGF1-R), Ki-67, and prostate specific membrane antigen (PSMA) expression using validated score.

Results: The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF-1 expression was associated with AR (odds ratio [OR]: 1.66), PSMA (OR: 2.13), Ki-67 (OR: 5.99), insulin receptor (IR)-α (OR: 2.38), IR-β (OR: 3.48), IGF1-R (OR: 1.53), and microvascular density (MVD) was associated with PSMA (OR: 3.44), Ki-67 (OR: 2.23), IR-α (OR: 2.91), IR-β (OR: 3.02), IGF1-R (OR: 2.95), and SRSF-1 (OR: 2.21). In the sub cohort of PC patients, we found that SRSF-1 expression was associated with AR (OR: 2.34), Ki-67 (OR: 6.77), IR-α (OR: 2.7), and MVD (OR: 1.98). At the Kaplan-Meier analysis, SRSF-1 patients had worse 5- and 9-year biochemical recurrence (36% and 6%) respect to SRSF-1 (67% and 7%; p < .01) and similarly MVD patients (44% and 7%) respect to MVD (64% and 8%; p < .01). Restricting the analysis only in patients with PC and diabetes, we found that SRSF-1 was associated with Ki-67 (OR: 8.75; p < .05) and MVD (OR: 7.5; p < .05).

Conclusions: PC exhibits widespread heterogeneity in protein expression. In particular, the expressions of the SRSF-1 protein and of the MVD are associated with a worse prognosis and in particular with a greater cell proliferation. These results, although preliminary, may offer new future scientific insights with the aim of highlighting possible genetic alterations linked to a greater expression of SRSF-1 and associated with a worse prognosis.
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http://dx.doi.org/10.1002/pros.24185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362056PMC
September 2021

European Association of Urology Guidelines on Sexual and Reproductive Health-2021 Update: Male Sexual Dysfunction.

Eur Urol 2021 09 26;80(3):333-357. Epub 2021 Jun 26.

Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK.

Context: The present summary of the European Association of Urology (EAU) guidelines is based on the latest guidelines on male sexual health published in March 2021, with a last comprehensive update in January 2021.

Objective: To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health.

Evidence Acquisition: A literature review was performed up to January 2021. The guidelines were updated, and a strength rating for each recommendation was included based on either a systematic review of the evidence or a consensus opinion from the expert panel.

Evidence Synthesis: Late-onset hypogonadism is a clinical condition in the ageing male combining low levels of circulating testosterone and specific symptoms associated with impaired hormone production and/or action. A comprehensive diagnostic and therapeutic work-up, along with screening recommendations and contraindications, is provided. Erectile dysfunction (ED) is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Along with a detailed basic and advanced diagnostic approach, a novel decision-making algorithm for treating ED in order to better tailor therapy to individual patients is provided. The EAU guidelines have adopted the definition of premature ejaculation (PE), which has been developed by the International Society for Sexual Medicine. After the subtype of PE has been defined, patient's expectations should be discussed thoroughly and pharmacotherapy must be considered as the first-line treatment for patients with lifelong PE, whereas treating the underlying cause must be the initial goal for patients with acquired PE. Haemospermia is defined as the appearance of blood in the ejaculate. Several reasons of haemospermia have been acknowledged; the primary goal over the management work-up is to exclude malignant conditions and treat any other underlying cause.

Conclusions: The 2021 guidelines on sexual and reproductive health summarise the most recent findings, and advise in terms of diagnosis and treatment of male hypogonadism and sexual dysfunction for their use in clinical practice. These guidelines reflect the multidisciplinary nature of their management.

Patient Summary: Updated European Association of Urology guidelines on sexual and reproductive health are presented, addressing the diagnosis and treatment of the most prevalent conditions in men. Patients must be fully informed of all relevant diagnostic and therapeutic options and, together with their treating physicians, decide on optimal personalised management strategies.
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http://dx.doi.org/10.1016/j.eururo.2021.06.007DOI Listing
September 2021

Development of a nomogram predicting the probability of stone free rate in patients with ureteral stones eligible for semi-rigid primary laser uretero-litothripsy.

World J Urol 2021 Nov 26;39(11):4267-4274. Epub 2021 Jun 26.

Department of Urology, "Sant'Andrea" Hospital, "La Sapienza" University, Rome, Italy.

Purpose: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones.

Methods: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success.

Results: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74.

Conclusions: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.
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http://dx.doi.org/10.1007/s00345-021-03768-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571227PMC
November 2021

Development of a nomogram predicting the probability of stone free rate in patients with ureteral stones eligible for semi-rigid primary laser uretero-litothripsy.

World J Urol 2021 Nov 26;39(11):4267-4274. Epub 2021 Jun 26.

Department of Urology, "Sant'Andrea" Hospital, "La Sapienza" University, Rome, Italy.

Purpose: Few tools are available to predict uretero-lithotripsy outcomes in patients with ureteral stones. Aim of our study was to develop a nomogram predicting the probability of stone free rate in patients undergoing semi-rigid uretero-lithotripsy (ULT) for ureteral stones.

Methods: From January 2014 onwards, patients undergoing semi-rigid Ho: YAG laser uretero-lithotripsy for ureteral stones were prospectively enrolled in two centers. Patients were preoperatively evaluated with accurate clinical history, urinalysis and renal function. Non-contrast CT was used to define number, location and length of the stones and eventually the presence of hydronephrosis. A nomogram was generated based on the logistic regression model used to predict ULT success.

Results: Overall, 356 patients with mean age of 54 years (IQR 44/65) were enrolled. 285/356 (80%) patients were stone free at 1 month. On multivariate analysis single stone (OR 1.93, 95% CI 1.05-3.53, p = 0.034), stone size (OR 0.92, 95% CI 0.87-0.97, p = 0.005), distal position (OR 2.12, 95% CI 1.29-3.48, p = 0.003) and the absence of hydronephrosis (OR 2.02, 95% CI 1.08-3.78, p = 0.029) were predictors of success and these were used to develop a nomogram. The nomogram based on the model presented good discrimination (area under the curve [AUC]: 0.75), good calibration (Hosmer-Lemeshow test, p > 0.5) and a net benefit in the range of probabilities between 15 and 65%. Internal validation resulted in an AUC of 0.74.

Conclusions: The implementation of our nomogram could better council patients before treatment and could be used to identify patients at risk of failure. External validation is warranted before its clinical implementation.
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http://dx.doi.org/10.1007/s00345-021-03768-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571227PMC
November 2021

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis.

Front Oncol 2021 11;11:651745. Epub 2021 May 11.

Division of Urology of European Institute of Oncology (IEO), IRCCS, Milan, Italy.

Background: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes.

Methods: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B.

Results: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis.

Conclusions: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting.
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http://dx.doi.org/10.3389/fonc.2021.651745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144638PMC
May 2021

SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, 71122 Foggia, Italy.

Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4-5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 score followed by a positive SelectMDx.
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http://dx.doi.org/10.3390/cancers13092047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122883PMC
April 2021

Mechanical and Ablative Minimally Invasive Techniques for Male LUTS due to Benign Prostatic Obstruction: A Systematic Review according to BPH-6 Evaluation.

Urol Int 2021 13;105(9-10):858-868. Epub 2021 Apr 13.

Department of Urology, University of Catania, Catania, Italy.

The treatment of male lower urinary tract symptoms (LUTS) due to benign prostatic obstruction represents one of the major interesting aspects in urological clinical practice. Although transurethral resection of the prostate is still considered the surgical gold standard for treatment of benign prostatic hyperplasia with prostate volume <80 mL, various minimally invasive surgical treatments (MITs) have been developed to overcome the limitations of the "conventional" surgery. To date, there are no validated tools to evaluate the surgical outcomes of MITs; however, in the past, BPH-6 has been used for this purpose. In this systematic review, we evaluated the efficacy and safety of MITs according to BPH-6 score system. We focused our attention on MITs based on mechanical devices (prostatic urethral lift and the temporary implantable nitinol device) and techniques for prostate ablation (image guided robotic waterjet ablation and convective water vapor energy ablation). Evidence shows that MITs are capable of leading to an improvement in LUTS without having an overwhelming impact on complications and are a valid alternative to other treatments in patients who wish to preserve their sexual function or in case of inapplicability of conventional surgery. However, comparative studies between these techniques are still missing.
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http://dx.doi.org/10.1159/000514438DOI Listing
January 2022

Penile length and circumference dimensions: A large study in young Italian men.

Andrologia 2021 Jul 21;53(6):e14053. Epub 2021 Mar 21.

Centro Integrato di Sessuologia Il Ponte, Florence, Italy.

The aim of the present study was to evaluate the size of the penis in flaccidity and in erection of Italian men. A total of 4,685 men living in Italy and who have been visited at the Italian urology operating units were involved in the study between January 2019 and January 2020. Each patient was given details on how to measure their penis (erect length and circumference) in flaccidity and in erection, from the lower base to the distal penile tip. Mean (standard deviation [SD]) flaccid penis length was 9.47 (2.69), mean (SD) flaccid penis circumference was 9.59 (3.08), mean (SD) erect penis length was 16.78 (2.55) and mean (SD) erect penis circumference was 12.03 (3.82). At the linear regression analysis, height was associated with flaccid penis length (β = 0.04; p-value = .01), and erect penis length was (β = 0.05; p-value < .01) and erect penis circumference was (β = 0.06; p-value < .01). Height is proportional to the length of the penis in flaccidity and in erection, and to the circumference in erection. The increase in BMI leads to a reduction in the length of the erect penis, as well as weight gain reduces the length of the flaccid penis.
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http://dx.doi.org/10.1111/and.14053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243978PMC
July 2021

Penile Rehabilitation and Treatment Options for Erectile Dysfunction Following Radical Prostatectomy and Radiotherapy: A Systematic Review.

Front Surg 2021 2;8:636974. Epub 2021 Mar 2.

Urology Department, University of Catania, Catania, Italy.

After radical prostatectomy (RP) or radiotherapy (RT) for prostate cancer, erectile dysfunction (ED) is the main complication next to urinary incontinence, affecting quality of life. The pathophysiology of ED after these treatments is believed to include neuropraxia causing reduced oxygenation and structural changes of the tissue in the corpora cavernosa. Next to the option of sparing the nerves during RP, research has been focusing on methods for penile rehabilitation after RP and RT, since it occurs often, even after nerve-sparing techniques were used. In animal studies, the use of phosphodiesterase type 5 inhibitors (PDE5i) after cavernous nerve damage is supported, but results in human studies are contradictory. Non-medical treatment options such as vacuum device therapy, hyperbaric oxygen therapy, yoga, aerobic, or pelvic floor training may be helpful, but evidence is scarce. Clear guidelines for penile rehabilitation are not yet available. However, care and support for ED after RP and RT is highly demanded by a large group of patients, so measures have to be taken even though the evidence is not strong yet. In this systematic review, an overview of the literature for penile rehabilitation and treatment options for ED after RP and RT is provided, using only randomized controlled trials (RCT).
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http://dx.doi.org/10.3389/fsurg.2021.636974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961076PMC
March 2021

Systemic combining inflammatory score (SCIS): a new score for prediction of oncologic outcomes in patients with high-risk non-muscle-invasive urothelial bladder cancer.

Transl Androl Urol 2021 Feb;10(2):626-635

Department of Neurosciences, Sciences of Reproduction and Odontostomatology, Urology Unit, University of Naples "Federico II", Naples, Italy.

Background: An accurate and early diagnosis of bladder cancer (BC) is essential to offer patients the most appropriate treatment and the highest cure rate. For this reason, patients need to be best stratified by class and risk factors. We aimed to develop a score able to better predict cancer outcomes, using serum variables of inflammation.

Methods: A total of 1,510 high-risk non-muscle invasive bladder cancer (NMIBC) patients were included in this retrospective observational study. Patients with pathologically proven T1 HG/G3 at first TURBT were included. Systemic combined inflammatory score (SCIS) was calculated according to systemic inflammatory markers (SIM), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) dichotomized (final score from 0 to 3).

Results: After 48 months of follow-up (IQR 40.0-73.0), 727 patients recurred (48.1%), 485 progressed (32.1%), 81 died for cancer (7.0%), and 163 died for overall causes (10.8%). Overall, 231 (15.3%) patients had concomitant Cis, 669 (44.3%) patients had multifocal pathology, 967 (64.1%) patients had tumor size >3 cm. Overall, 357 (23.6%) patients received immediate-intravesical therapy, 1,356 (89.8%) received adjuvant intravesical therapy, of which 1,382 (91.5%) received BCG, 266 (17.6%) patients received mitomycin C, 4 (0.5%) patients received others intravesical therapy. Higher SCIS was independently predictive of recurrence (hazard ratio HR 1.5, 1.3 and 2.2) and cancer specific mortality for SCIS 0 and 3 (HR: 1.61 and 2.3), and overall mortality for SCIS 0 and 3 (HR: 2.4 and 3.2). Conversely, SCIS was not associated with a higher probability of progression.

Conclusions: The inclusion of the SCIS in clinical practice is simple to apply and can help improve the prediction of cancer outcomes. It can identify patients with high-grade BC who are more likely to experience disease mortality.
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http://dx.doi.org/10.21037/tau-20-1272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947442PMC
February 2021

Assessment of PSIM (Prostatic Systemic Inflammatory Markers) Score in Predicting Pathologic Features at Robotic Radical Prostatectomy in Patients with Low-Risk Prostate Cancer Who Met the Inclusion Criteria for Active Surveillance.

Diagnostics (Basel) 2021 Feb 20;11(2). Epub 2021 Feb 20.

Department of Urology, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

Background: circulating levels of lymphocytes, platelets and neutrophils have been identified as factors related to unfavorable clinical outcome for many solid tumors. The aim of this cohort study is to evaluate and validate the use of the Prostatic Systemic Inflammatory Markers (PSIM) score in predicting and improving the detection of clinically significant prostate cancer (csPCa) in men undergoing robotic radical prostatectomy for low-risk prostate cancer who met the inclusion criteria for active surveillance.

Methods: we reviewed the medical records of 260 patients who fulfilled the inclusion criteria for active surveillance. We performed a head-to-head comparison between the histological findings of specimens after radical prostatectomy (RP) and prostate biopsies. The PSIM score was calculated on the basis of positivity according to cutoffs (neutrophil-to-lymphocyte ratio (NLR) 2.0, platelets-to-lymphocyte ratio (PLR) 118 and monocyte-to-lymphocyte-ratio (MLR) 5.0), with 1 point assigned for each value exceeding the specified threshold and then summed, yielding a final score ranging from 0 to 3.

Results: median NLR was 2.07, median PLR was 114.83, median MLR was 3.69.

Conclusion: we found a significantly increase in the rate of pathological International Society of Urological Pathology (ISUP) ≥ 2 with the increase of PSIM. At the multivariate logistic regression analysis adjusted for age, prostate specific antigen (PSA), PSA density, prostate volume and PSIM, the latter was found the sole independent prognostic variable influencing probability of adverse pathology.
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http://dx.doi.org/10.3390/diagnostics11020355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924196PMC
February 2021
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