Role of Contrast-Enhanced Voiding Urosonography in the Evaluation of Renal Transplant Reflux - Comparison with Voiding Cystourethrography and a New Classification.

Vesicoureteral reflux (VUR) is a common urological complication in renal transplant patients. THE AIM: of this study is to evaluate the performance of contrast-enhanced voiding urosonography (CEvUS) in the diagnosis and classification of reflux into the renal allograft, to evaluate and classify VUR into the allograft using voiding cystourethrography (VCUG) and CEvUS, to compare the two methods, and to propose a new classification of reflux into the allograft based on CEvUS and VCUG assessment, in line with the international reflux grading system. MATERIALS AND METHODS: From January 2017 to July 2019, 84 kidney transplant patients were enrolled. All patients underwent VCUG and CEvUS. RESULTS: In 76 cases there was agreement between VCUG and CEvUS (90 %) (Kappa = 0.7). The sensitivity of CEvUS using VCUG as the gold standard was 90 %, and the specificity was 92 %. Of the 7 cases diagnosed by VCUG and not by CEvUS, 6 were grade 1 and 1 was grade 2. CONCLUSION: Transplant patients with reflux symptoms should undergo CEvUS. If the outcome is negative, VCUG should be performed. The classification that we propose is better suited to describe VUR in transplant patients, because it is simpler and takes into account whether reflux occurs not only during urination but also when the bladder is relaxed.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed ("prostatic cancer", "albumin", "globulin", "albumin to globulin ratio") following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients.

Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and BRCA2 mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of BRCA2 was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.

A biofeedback-guided programme or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: A meta-analysis and systematic review.

PURPOSE: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis were conducted to compare different forms of non-invasive treatments for post-RP UI and to analyse whether the addition of biofeedback (BF) and/or pelvic floor muscle electric stimulation (PFES) to PF muscle exercise (PFME) alone can improve results in terms of continence recovery rate. MATERIALS AND METHODS: A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across subgroups during a 12-months follow-up. RESULTS: Twenty-six articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-months intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-months: PFME 111.09 g (95%CI 77.59-144.59), BF 213.81 g (95%CI -80.51-508-13), PFES 306.88 g (95%CI 158.11-455.66), BF + PFES 266.31 g (95%CI 22.69-302.93); P < .01), while at 6- and 12-months differences were similar (P > .04). At 1- and 3-months intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-months: PFME 0.40 (95%CI 0.30-0.49), BF 0.49 (95%CI 0.31-0.67), PFES 0.57 (95%CI 0.46-0.69), BF + PFES 0.75 (95%CI 0.60-0.91); P < .01), while at 6- and 12-months ERs were similar. CONCLUSIONS: Regarding non-invasive treatment of UI secondary to RP, the addition of guided programs using BF or/and PFES demonstrated to improve continence recovery rate, particularly in the first 3-month interval, when compared with the use of PFME alone.

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison.

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65-97) vs. 65 (51-75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes.

Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.

Penoscrotal versus minimally invasive infrapubic approach for inflatable penile prosthesis placement: a single-center matched-pair analysis.

PURPOSE: To compare perioperative results, safety and efficacy profile in patients receiving inflatable penile prosthesis (IPP) via penoscrotal (PS) or minimally invasive infrapubic (MII) approach for erectile dysfunction. METHODS: A matched-pair analysis was performed including 42 patients undergoing IPP implantation via PS (n = 21) or MII (n = 21) between 2011 and 2016. Clinical and surgical data were prospectively collected. Patients' and partners' outcomes were assessed by the International Index of Erectile Function (IIEF), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaires. RESULTS: Mean (SD) operative time was 128 (40.6) min in group PS and 91 (43.0) min in group MII (p = 0.041). Complications occurred in 3/21 (14%) and 2/21 (10%) patients in groups PS and MII (p = 0.832). Overall, no differences were observed concerning the device utilisation (p = 0.275). However, in group MII 4/21 (19%) patients were able to resume sexual activity prior to 4 postoperative weeks, while in group PS no patient was (p = 0.012). Mean (SD) scores for questionnaires were similar between groups PS and MII: IIEF [20.9 (7.3) vs. 20.7 (4.8); p = 0.132], patient EDITS [76.0 (25.6) vs. 74.7 (20.8); p = 0.256] and partner EDITS [72.5 (29.1) vs. 73.1 (21.4); p = 0.114]. Similarly, QoLSPP showed comparable results among the groups PS and MII: functional domain [3.9 (1.4) vs. 4.0 (1.2); p = 0.390], personal [4.0 (1.2) vs. 4.1 (1.0); p = 0.512], relational [3.7 (1.5) vs. 3.9 (1.2); p = 0.462] and social [4.0 (1.2) vs. 3.9 (1.2); p = 0.766]. CONCLUSIONS: PS and MII demonstrated to be safe and efficient techniques, leading to high level of both patients and partners satisfaction. Additionally, the minimally invasive infrapubic approach showed a shorter operative time and a tendency for a faster return to sexual activity.

Significant increase in detection of prostate cancer recurrence following radical prostatectomy with an early imaging acquisition protocol with ¹8F-fluorocholine positron emission tomography/computed tomography.

PURPOSE: To highlight a new imaging acquisition protocol during (18)F-fluorocholine PET/CT in patients with biochemical recurrence after RP. METHODS: A total of 146 patients with PSA levels between 0.2 and 1 ng/ml with negative conventional imaging who did not receive salvage treatment were prospectively enrolled. Imaging acquisition protocol included an early dynamic phase (1-8 min), a conventional whole body (10-20 min), and a late phase (30-40 min). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were measured. Univariable and multivariable analyses were performed to identify independent predictors of positive PET/CT. RESULTS: The median trigger PSA was 0.6 ng/ml (IQR 0.43-0.76). Median PSA doubling time (PSA DT) was 7.91 months (IQR 4.42-11.3); median PSA velocity (PSAV) was 0.02 ng/ml per month (IQR 0.02-0.04). Overall, (18)F-fluorocholine PET/CT was positive in 111 of 146 patients (76 %). Out of 111 positive examinations, 80 (72.1 %) were positive only in the early dynamic phase. Sensitivity, specificity, PPV, NPV, and accuracy were 78.9, 76.9, 97.2, 26.3, and 78.7 %, respectively. At multivariable logistic regression, trigger PSA ≥ 0.6 ng/ml [odds ratio (OR) 3.13; p = 0.001] and PSAV ≥ 0.04 ng/ml per month (OR 4.95; p = 0.004) were independent predictors of positive PET/CT. The low NPV remains the main limitation of PET/CT in this setting of patients. CONCLUSIONS: The increased sensitivity, thanks to the early imaging acquisition protocol, makes (18)F-fluorocholine PET/CT an attractive tool to detect prostate cancer recurrences in patients with a PSA level <1 ng/ml.

Two-sided urethra-sparing reconstruction combining dorsal preputial skin plus ventral buccal mucosa grafts for tight bulbar strictures.

OBJECTIVES: To report our initial experience with urethra-sparing reconstruction combining dorsal preputial skin and ventral buccal mucosa grafts for tight bulbar urethral strictures. METHODS: Between November 2006 and September 2012, 26 patients with tight bulbar strictures underwent urethroplasty. Using a ventral urethrotomy approach, the two-sided urethral reconstruction was carried out avoiding the transection of urethra and augmenting the preserved urethral plate by dorsal preputial skin plus ventral buccal mucosa grafts. The primary outcome was the objective urinary result, defined as the absence of stricture recurrence. The outcome was considered a failure when any postoperative instrumentation was required. Postoperative sexual dysfunctions were investigated using a validated questionnaire. RESULTS: Mean follow up was 30.1 months (range 12-79 months). Mean stricture length was 3.3 cm (range 1.5-6 cm). Mean length for dorsal preputial skin and ventral buccal mucosa grafts was 3.2 cm (range 2-7 cm) and 4.9 cm (range 4-6 cm), respectively. Of 26 cases, 23 (88.5%) were successful and three (11.5%) were failures with stricture recurrence. Failures were treated with perineal urethrostomy in one case, ventral buccal graft urethroplasty in one case and internal urethrotomy in one case. Among 12 sexually active men preoperatively, none reported postoperative penile curvature/shortening, impaired erection or dissatisfaction regarding erection; sexual activity was unaltered pre- and post-surgery. CONCLUSIONS: In tight bulbar urethra strictures, the two-sided urethroplasty combining dorsal preputial skin and ventral buccal mucosa grafts provides a safe and effective semi-circumferential reconstruction by augmenting the preserved urethral plate, with no impact on sexual function.

Modern extraction techniques and their impact on the pharmacological profile of Serenoa repens extracts for the treatment of lower urinary tract symptoms.

BACKGROUND: Bioactive compounds from plants (i.e., Serenoa repens) are often used in medicine in the treatment of several pathologies, among which benign prostatic hyperplasia (BPH) associated to lower urinary tract symptoms (LUTS). DISCUSSION: There are different techniques of extraction, also used in combination, with the aim of enhancing the amount of the target molecules, gaining time and reducing waste of solvents. However, the qualitative and quantitative composition of the bioactives depends on the extractive process, and so the brands of the recovered products from the same plant are different in terms of clinical efficacy (no product interchangeability among different commercial brands). SUMMARY: In this review, we report on several and recent extraction techniques and their impact on the composition/biological activity of S. repens-based available products.

Bilateral ex vivo repair and kidney autotransplantation for complex renal artery aneurysms: a case report and literature review.

We report the surgical management of a bilateral renal artery aneurysm diagnosed in a 41-year-old patient with a history of recurrent abdominal pain. The preoperative contrast-enhanced computed tomography showed a complex saccular aneurysm on both renal arteries within the renal hilum. The characteristics of aneurysms precluded endovascular procedures, and a double-step bilateral ex vivo reconstruction with kidney autotransplantation was planned. The intra- and postoperative period was uneventful. Imaging and laboratory examinations show preservation of renal function, and patient is symptom-free at 10-month follow up.

Qualitative and quantitative characteristics of CEUS for renal cell carcinoma and angiomyolipoma: a narrative review.

Incidental findings of renal masses are increasing. However, a substantial portion of surgically treated renal masses turn out to be benign on histopathological examination. Thus, there is a clear need for improved pre-surgical assessment to minimize unnecessary invasive procedures. The challenge intensifies when distinguishing between renal cell carcinoma (RCC) and angiomyolipoma (AML) in renal lesions smaller than 4 cm with minimal adipose tissue. In such cases, contrast-enhanced ultrasound (CEUS) has emerged as a valuable diagnostic tool, by utilizing both qualitative and quantitative parameters. Quantitative measures offer objectivity, reliability, and reproducibility compared to qualitative parameters, enabling the characterization of RCC subtypes and differentiation from AML. Qualitative features as enhancement pattern, degree, and peak were less helpful in distinguishing triphasic minimal fat AML (TAML) from epithelioid AML (EAML), with the pseudocapsule sign potentially being the only distinguishing qualitative feature. The pseudocapsule sign was more frequently observed in ccRCCs (38.0%) than in AMLs (15.6%). Moreover, it was detected in 40.0% of EAMLs and 34.5% of ccRCCs but not in TAMLs due to similar growth patterns between EAMLs and low-grade ccRCCs. Quantitative measures such as the time-to-peak (TTP) ratio can further enhance diagnostic accuracy and also TOC ratio should be considered, as it was higher in clear cell RCCs (ccRCCs) and in EAMLs compared to TAMLs, indicating behavior similar to ccRCCs. However, CEUS remains an operator-dependent exam.

Diagnostic Accuracy of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Muscle-Invasive Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. METHODS: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR-), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). RESULTS: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81-0.93) and 0.88 (95% CI: 0.82-0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81-0.98). The pooled PLR+ and PLR- were 7.3 (95% CI: 4.8-11.2) and 0.14 (95% CI: 0.08-0.23), respectively. CONCLUSIONS: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

Mid-term outcomes of minimally invasive infrapubic approach for inflatable penile prosthesis implantation: A single-center study and literature review.

BACKGROUND: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri-operative safety and efficacy profile, but scarce data exist on long-term follow-up. OBJECTIVES: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5-year follow-up. MATERIALS AND METHODS: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan-Meier method was used to analyze IPP survival (defined as a working IPP). RESULTS: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61-70) were included. The median (IQR) follow-up duration was 71 months (63-80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4-96.6), 92.5% (95% CI, 89.7-95.3), and 92.5% (95% CI, 89.7-95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow-up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19-23), personal 16 (15-18), relational 14 (12-15), and social 12 (11-14). DISCUSSION AND CONCLUSION: This study represents the longest follow-up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid-term evaluation.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression.

INTRODUCTION: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). PATIENTS: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. METHODS: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. RESULTS: no significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). CONCLUSIONS: in our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients.

A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary-gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (- 3.25 nmol/L, 95%CI - 0.57 and - 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (- 5.04 nmol/L, 95%CI - 1.26 and - 8.82) but similar for Covid-19 survivors and non-survivors (- 3.04 nmol/L, 95%CI - 2.04 and - 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: -0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy.

Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification into low- and high-risk cases for early progression in metastatic disease is necessary. At present, PSA-DT represents the best parameter to define low- and high-risk BCR PC, but real precision medicine is strongly suggested to define tailored management for patients with BCR. Before defining management, it is necessary to exclude the presence of low-volume metastasis associated with PSA progression using new-generation imaging, preferably with PSMA PET/CT. Low-risk BCR cases should be actively observed without early systemic therapies. Early treatment of low-risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such as the development of castration resistance before the appearance of metastases (non-metastatic castration-resistant PC). Patients with high-risk BCR benefit from early systemic therapy. Even with overall survival (OS) as the primary treatment endpoint, metastasis-free survival (MFS) should be used as a surrogate endpoint in clinical trials, especially in long survival stages of the disease. The EMBARK study has greatly influenced the management of high-risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSIs) and ADT combination therapy. In high-risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining an unchanged quality of life in the asymptomatic phase of the disease. The possibility of using ARSIs alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than with the intensification of the combination therapy. Continued use versus discontinuation of enzalutamide plus leuprolide intensified therapy upon reaching undetectable PSA levels needs to be better defined with further analysis. Real-world analysis must verify the significant results obtained in the context of a phase 3 study.

Extended pelvic lymphadenectomy and various radical prostatectomy techniques: is pelvic drainage necessary?

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The occurence of lymphoceles in patients after radical prostatectomy is well known (2-10%). It appears that patients undergoing open extraperitoneal radical prostatectomy develop more lymphoceles than patients undergoing robot-assisted radical prostatectomy with transperitoneal access. The present study investigates in a prospective randomized manner whether the time of drainage (1 vs 7 days) makes a difference or whether drainage is even necessary. The study data, collected in the same institution, are compared with the incidence of lymphocele in patients treated by robot-assisted radical prostatectomy. OBJECTIVE: To investigate whether routine drainage is advisable after open extended pelvic lymph node dissection (ePLND) and retropubic radical prostatectomy (RRP) by measuring the incidence of lymphoceles and comparing these results with those of a series of robot-assisted radical prostatectomy (RARP) and ePLND. PATIENTS AND METHODS: A total of 331 consecutive patients underwent ePLND and RRP or RARP. The first 132 patients underwent open ePLND and RRP and received two pelvic drains; these patients were prospectively randomized into two groups: group 1 (n = 66), in which the drains were shortened on postoperative (PO) days 3 and 5 and removed on PO day 7, and group 2 (n = 66), in which the drains were removed on PO day 1. The next 199 patients were assigned to two consecutive groups not receiving drainage: group 3 (n = 73) undergoing open ePLND and RRP, followed by group 4 (n = 126) treated by transperitoneal robot-assisted ePLND and RARP. All patients had ultrasonographic controls 5 and 10 days and 3 and 12 months after surgery. RESULTS: Lymphoceles were detected in 6.6% of all patients, 3.3% of whom were asymptomatic and 3.3% of whom were symptomatic. Symptomatic lymphoceles were detected in 0% of group 1, 8% of group 2, 7% of group 3 and 1% of group 4, with groups 2 and 3 differing significantly from group 4 (P < 0.05). In total, 5% of all patients undergoing open RRP (groups 1-3) had symptomatic lymphoceles vs 1% of patients undergoing RARP (group 4) (P = 0.06). Nodal-positive patients had significantly more symptomatic lymphoceles than nodal-negative patients (10% vs 2%) (P < 0.02). CONCLUSIONS: Symptomatic lymphoceles occur less frequently after open RRP and pelvic drainage over 7 days than after open RRP and pelvic drainage over 1 day or without drainage. Patients undergoing RARP without drainage had significantly fewer lymphoceles than patients receiving open RRP without drainage.

Safe digital isolation of the santorini plexus during radical retropubic prostatectomy.

BACKGROUND: We describe a safe and easily reproducible technique to control Santorini plexus during radical retropubic prostatectomy (RRP) which uses simple digital dissection. METHODS: We retrospectively reviewed 56 consecutive patients who underwent RRP for clinically localised prostate cancer from November 2008 to November 2010. Santorini plexus was isolated and secured in all patients using a new technique of simple digital dissection in which the index finger is used not to only localize the catheter inside the urethra, but also to develop the right plane between Santorini plexus and urethra. This is obtained by gentle bilateral digital dissection through the lateral aspects of periprostatic fascia which are eventually breached by the fingers, developing a right plane just above the urethra. Santorini plexus is then easily ligated and divided. Indicators of outcomes included estimated blood loss, transfusion requirements, operative time, positive margins and complication rates of the technique. RESULTS: The maneuver was successful in 53/56 (95%) patients. Mean (range) blood loss and overall operative time for RRP were 620 ml (100-1500) and 130 min. (80-190), respectively. Transfusion rate was 8,9% (5/56). Positive surgical margin rate was 14% (8/56). No complication related to the employed technique was recorded. CONCLUSIONS: Digital dissection of Santorini plexus during RRP is simple and easily feasible. It speeds up the process of finding the right plane just above the urethra allowing good haemostasis in the surgical field and proper apical dissection.