Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

PDE5is-naïve versus non-naïve patients at first investigation for erectile dysfunction-findings from a long-term, real-life cross-sectional study.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription. OBJECTIVE: We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription. MATERIALS AND METHODS: Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline. RESULTS: Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p < 0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve. CONCLUSIONS: Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use.

Microbiome Profiling in Bladder Cancer Patients Using the First-morning Urine Sample.

Background: Several studies support the interplay between the urinary microbiome (ie, urobiome) and bladder cancer (BCa). Specific urinary bacteria may be responsible for chronic inflammation, which in turn promotes carcinogenesis. Different signatures of urobiome in BCa patients were identified depending on tumor type, geographical area, age, and sex. Objective: We explored the urobiome in BCa patients undergoing transurethral resection of bladder tumor (TURBT), to identify possible predictive biomarkers of cancer. Design setting and participants: The urobiome analysis was conducted in 48 patients (13 females) undergoing TURBT, of whom 30 with BCa (five females) and 18 with benign bladder tumor, analyzing bacterial 16S rRNA by next-generation sequencing in first-morning (FM) urine samples. Forty-three cancer-free individuals and 17 prostate cancer patients were used as controls. Outcome measurements and statistical analysis: First, we identified the better urine collection procedure to perform the urobiome analysis, comparing bacterial composition between catheterized (CAT) and FM urine samples in TURBT patients. Successively, we observed a specific urobiome in BCa patients rather than controls. A combined pipeline including the DESeq2 and linear discriminant analysis effect size tests was used to identify differential urinary taxa, strictly associated with BCa patients. Results and limitations: The bacterial composition of CAT and FM urine samples was comparable, so the latter was used for the following analyses. An increased abundance of Porphyromonas and Porphyromonas somerae was found in BCa patients compared with controls. This signature seems to be more related (p <0.05) to male BCa patients over 50 yr old. Owing to the low biomass of urinary microbiota, several samples were excluded from the study, reducing the number of BCa patients considered. Conclusions: FM urine samples represent a manageable specimen for a urobiome analysis; P. somerae is a specific biomarker of BCa risk. Patient summary: Our study showed an increased abundance of Porphyromonas and Porphyromonas somerae in male bladder cancer (BCa) patients, supporting the use of a first-morning urine sample, a less invasive and low-cost collection method, for the urobiome analysis of patients at risk of BCa.

Unrecognised orgasmic phase disorders in men presenting with new-onset erectile dysfunction-Findings from a real-life, cross-sectional study.

BACKGROUND: Orgasmic phase disorders in men worsen the burden of erectile dysfunction on sexual satisfaction. OBJECTIVES: To investigate the prevalence of and predictors of unreported orgasmic phase disorder in a cohort of men looking for their first urological assessment for new-onset erectile dysfunction in a real-life setting. MATERIALS AND METHODS: Data from 1107 heterosexual, sexually active men consecutively assessed for new-onset erectile dysfunction were analysed. Throughout a comprehensive medical and sexual history, all patients were asked to self-report any orgasmic phase disorder and to complete the International Index of Erectile Function and the Beck's Inventory for Depression (depressive symptoms scored as Beck's Inventory for Depression ≥11). Men self-reporting orgasmic phase disorder during the interview were excluded from further analyses. The median value of the International Index of Erectile Function-orgasmic function domain was arbitrarily used to categorise men with (International Index of Erectile Function-orgasmic function ≤5) and without unreported orgasmic phase disorder (International Index of Erectile Function-orgasmic function >5). Circulating hormones were measured in every patient. Descriptive statistics and logistic regression models were used to test the association between clinical variables and unreported orgasmic phase disorder. RESULTS: Of 1098 patients with non-self-reporting orgasmic phase disorder, 314 (28.6%) had International Index of Erectile Function-orgasmic function ≤5. Patients with erectile dysfunction + unreported orgasmic phase disorder were older (median [interquartile range]: 58 [44-66] years vs. 51 [40-60] years), had higher body mass index [25.8 (23.7-28.1) kg/m2 vs. 25.2 (23.3-27.4) kg/m2 ], higher prevalence of type 2 diabetes (36 [11.5%] vs. 45 [5.7%]) and lower International Index of Erectile Function-erectile function scores (6 [2-10] vs. 18 [11-24]) than men with erectile dysfunction-only (all p < 0.05). Patients with erectile dysfunction + unreported orgasmic phase disorder depicted higher rates of severe erectile dysfunction (75.5% vs. 25%) and Beck's Inventory for Depression ≥11 (22.6% vs. 17.9%) (all p < 0.05). In the multivariable logistic regression analysis, older age (odds ratio: 1.02) and lower International Index of Erectile Function-erectile function scores (odds ratio: 0.83) were independently associated with unreported orgasmic phase disorder (all p < 0.05). CONCLUSIONS: Almost one in three men seeking first medical help for erectile dysfunction depicted criteria suggestive of unreported orgasmic phase disorder. Men with unreported orgasmic phase disorder were older and had higher rates of severe erectile dysfunction and concomitant depressive symptoms. These real-life findings outline the clinical relevance of a comprehensive investigation of concomitant sexual dysfunction in men only complaining of erectile dysfunction to more effectively tailor patient management.

Which inflammatory marker, between systemic immune-inflammation index and neutrophil to eosinophil ratio, is associated with Peyronie's disease and are there any implications for a better understanding of its mechanisms?

BACKGROUND: Peyronie's disease affects up to 9% of men and is often accompanied by pain and/or erectile dysfunction. It is characterized by an inflammatory process that is the grassroots of the subsequent fibrosis stage. There is an unmet need to evaluate its onset and progression. Among the newly proposed biomarkers of inflammation, authors developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts. Similarly, a recent study reported that a neutrophil-to-eosinophil ratio (NER) represents systemic inflammation. RESULTS: A 49-patient group with Peyronie's disease as confronted with 50 well-matched for age and BMI controls. As laboratory evaluation of inflammation, SII, NER and the eosinophil to neutrophil ratio (ENR) were studied. As a likely risk factor for the presence of Peyronie's disease, a higher prevalence of hypercholesterolemia, hyperglycemia and hypertension was discovered in the patients compared to controls. A significant difference was found in the median values of the NER between the two selected groups, i.e., 32.5 versus 17.3 (p = 0.0021). As expected, also ENR was significantly different. The receiver operating characteristic curves for SII, ENR and NER were 0.55, 0.32 and 0.67, respectively, highlighting the best performance of NER. The cut-off for NER was 12.1, according to the Youden test. CONCLUSIONS: According to our results, any evaluation of circulating eosinophil, evaluated as NER, beyond being a signature of immuno-inflammatory response, help assess tissue homeostasis, since eosinophils are now considered multifunctional leukocytes and give a picture of the inflammatory process and repair process belonging to Peyronie's disease.

RéSUMé: CONTEXTE: La maladie de La Peyronie touche jusqu'à 9% des hommes et s'accompagne souvent de douleurs et/ou de dysfonction érectile. Elle se caractérise par un processus inflammatoire qui est. à la base de l'étape de fibrose ultérieure. Il existe un besoin non satisfait d'en évaluer son apparition et sa progression. Parmi les biomarqueurs de l'inflammation nouvellement proposés, les auteurs ont développé un nouvel indice d'inflammation immunitaire systémique (SII) basé sur le nombre de lymphocytes, de neutrophiles et de plaquettes. De même, une étude récente a rapporté qu'un rapport neutrophiles/éosinophiles (NER) représente une inflammation systémique. RéSULTATS: Un groupe de 49 patients atteints de la maladie de La Peyronie a été confronté à 50 témoins étroitement appariés sur l'âge et l'IMC. Dans le cadre de l'évaluation de l'inflammation au laboratoire, le SII, le NER et le rapport éosinophiles/neutrophiles (ENR) ont été étudiés. En tant que facteur de risque probable de la présence de la maladie de La Peyronie, une prévalence plus élevée d'hypercholestérolémie, d'hyperglycémie et d'hypertension a été découverte chez les patients par rapport aux témoins. Une différence significative a été constatée pour les valeurs médianes du NER entre les deux groupes sélectionnés, c'est-à-dire 32,5 contre 17,3 (p = 0,0021). Comme on pouvait s'y attendre, le ERN était également significativement différent. Les courbes caractéristiques de fonctionnement du récepteur pour le SII, l'ENR et le NER étaient respectivement de 0,55, 0,32 et 0,67, ce qui met en évidence les meilleures performances du NER. Le seuil pour le NER était de 12,1 (test de Youden). CONCLUSIONS: D'après nos résultats, toute évaluation de l'éosinophilie circulante, sous la forme NER, au-delà d'être une signature de la réponse immuno-inflammatoire, permet d'évaluer l'homéostasie tissulaire, puisque les éosinophiles sont maintenant considérés comme étant des leucocytes multifonctionnels, et donne une image du processus inflammatoire et du processus de réparation appartenant à la maladie de La Peyronie. MOTS-CLéS: Maladie de La Peyronie Rapport Neutrophiles/Eosinophiles Rapport Eosinophiles/Neutrophiles Indice d'Inflammation immunitaire systémique Réponse Immuno-inflammatoire.

A systematic review of robot-assisted partial nephrectomy outcomes for advanced indications: Large tumors (cT2-T3), solitary kidney, completely endophytic, hilar, recurrent, and multiple renal tumors.

Objective: Robot-assisted partial nephrectomy (RAPN) has become widely used for treatment of renal cell carcinoma and it is expanding in the field of complex renal masses. The aim of this systematic review was to analyze outcomes of RAPN for completely endophytic renal masses, large tumors (cT2-T3), renal cell carcinoma in solitary kidney, recurrent tumors, completely endophytic and hilar masses, and simultaneous and multiple tumors. Methods: A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed in December 2022 for English language papers. The primary endpoint was to evaluate the role of RAPN in the setting of each category of complex renal masses considered. The secondary endpoint was to evaluate the surgical and functional outcomes. Results: After screening 1250 records, 43 full-text manuscripts were selected, comprising over 8500 patients. Twelve and thirteen studies reported data for endophytic and hilar renal masses, respectively. Five and three studies reported outcomes for cT2-T3 and solitary kidney patients, respectively. Four studies focused on redo-RAPN for recurrent tumors. Two studies investigated simultaneous bilateral renal masses and five reports focused on multiple tumor excision in ipsilateral kidney. Conclusion: Over the past decade, evidence supporting the use of RAPN for the most challenging nephron-sparing surgery indications has continuously grown. Although limitations remain including study design and lack of detailed long-term functional and oncological outcomes, the adoption of RAPN for the included advanced indications is associated with favorable surgical outcomes with good preservation of renal function without compromising the oncological result. Certainly, a higher likelihood of complication might be expected when facing extremely challenging cases. However, none of these indications should be considered per se an exclusion criterion for performing RAPN. Ultimately, a risk-adapted approach should be employed.

The relationship between the history of PDE5-inhibitors assumption and melanoma: a systematic review.

INTRODUCTION: Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association. CONTENT: A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis. SUMMARY AND OUTLOOK: Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma.

The spreading information of YouTube videos on Phosphodiesterase 5 inhibitors: a worrisome picture from one of the most consulted internet source.

Several previous studies on YouTubeTM information on medical topics have already been published. The current study aimed to evaluate the quality information of YouTubeTM videos on Phosphodiesterase 5 inhibitors (PDE5-is). A systematic search on YouTube™ was conducted using 30 keyword combinations. For each keyword's combination, the first 50 videos were recorded. The quality of videos on YouTube™ was assessed with Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V), DISCERN score and a specified created Misinformation tool. According to the selection criteria, 229 YouTube™ videos were suitable for the analyses. Videos were stratified according to the five main identified topics: sildenafil [n = 98; 42.79%] vs tadalafil [n = 50; 21.83%] vs vardenafil [n = 44;19.21%] vs avanafil [n = 17; 7.42%] vs PDE5-is in general [n = 20; 8.73%]. The median overall PEMAT A/V Understandability score and Actionability score were 55% (interquartile range [IQR]: 42-75) and 0% (IQR = 0-67), respectively. Specifically, according to our stratification, YouTube Videos on avanafil reached higher values of both Understandability and Actionability (72.7% and 66.7, respectively) in contrast to other categories. According to DISCERN tool, the total overall median score was 29.5 (IQR = 18-41). According to Misinformation scale, the item 1 ('sexual stimulation') harboured an overall median score of 2 (IQR = 1-2); the item 2 ('side effects') an overall median score of 2 (IQR = 1-3); the item 3 ('treatment choices') an overall median score of 1 (IQR = 1-2); the item 4 ('contraindications') an overall median score of 2 (IQR = 1-2). YouTube™ is a fast and open-access source for mass information. The overall quality of the PDE5-is contents provided is sadly unsatisfactory. Nowadays, YouTube™ cannot be recommended as a reliable source of information on PDE5-is.

Robotic partial nephrectomy for large renal Leiomyoma: first case report

ABSTRACT Aim: Renal leiomyoma is a rare benign mesenchymal tumor arising from the smooth muscle cells of the kidney. Renal capsule is its most common location (1). Large tumor may require surgical excision which can be challenging in case of proximity to major vessels (2). Indications of robotic partial nephrectomy (RPN) have exponentially expanded over the past few years (3). We aim to report a case of large renal leiomyoma successfully managed with RPN. Methods: A 59-year-old female patient with BMI 51 presented with chief complaint of abdominal discomfort. The patient underwent a CT scan that revealed a massive circumscribed exophytic complex solid cystic mass of 4.5 × 7.7 × 6.2 cm, arising from the lower pole of right kidney and abutting the inferior vena cava. RENAL score was 11ah (high complexity). Past surgical history included mid-urethral sling, breast reduction, and hysterectomy with salpingectomy. Preoperative creatinine and eGFR were 0.9 (mg/dL) and 77 (mL/min), respectively. A robotic excision of this mass was successfully performed by using Da Vinci Xi platform. Main steps of the procedure are illustrated in the present video. Results: Dissection and isolation of the tumor were carefully performed after identifying key anatomical structures such as the ureter, the IVC and the renal hilum. Intraoperative ultrasound was used to confirm the margins of the mass. The renal artery was clamped and then the tumor was resected/enucleated. Renal parenchyma was re-approximated with a single layer of interrupted CT-1 Vicryl 0 with sliding clip technique. Warm ischemia time was 19 min. Estimated blood loss (EBL) was 250 ml. Operative time was 165 min. No intraoperative complications occurred. No drain was placed. Patient was discharged on postoperative day 2. Post-operative hypotension was managed with fluid bolus. Postoperative creatinine and eGFR were 1,0 (mg/dL) and 69 (mL/min/1.72m2), respectively. Pathology revealed a leiomyoma of genital stromal origin with hyalinization and calcification. Conclusions: To the best of our knowledge, this is the first description of RPN for the management of a large (about 8 cm) renal leiomyoma. Robotic assisted surgery allows to expand the indications of minimally invasive conservative renal surgery whose feasibility becomes even more clinically significant in case of benign masses which can be managed without sacrificing healthy renal parenchyma.

Novel Key Ingredients in Urinary Tract Health-The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®).

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.

Robotic partial nephrectomy for large renal Leiomyoma: first case report.

AIM: Renal leiomyoma is a rare benign mesenchymal tumor arising from the smooth muscle cells of the kidney. Renal capsule is its most common location (1). Large tumor may require surgical excision which can be challenging in case of proximity to major vessels (2). Indications of robotic partial nephrectomy (RPN) have exponentially expanded over the past few years (3). We aim to report a case of large renal leiomyoma successfully managed with RPN. METHODS: A 59-year-old female patient with BMI 51 presented with chief complaint of abdominal discomfort. The patient underwent a CT scan that revealed a massive circumscribed exophytic complex solid cystic mass of 4.5 x 7.7 x 6.2 cm, arising from the lower pole of right kidney and abutting the inferior vena cava. RENAL score was 11ah (high complexity). Past surgical history included mid-urethral sling, breast reduction, and hysterectomy with salpingectomy. Preoperative creatinine and eGFR were 0.9 (mg/dL) and 77 (mL/min), respectively. A robotic excision of this mass was successfully performed by using Da Vinci Xi platform. Main steps of the procedure are illustrated in the present video. RESULTS: Dissection and isolation of the tumor were carefully performed after identifying key anatomical structures such as the ureter, the IVC and the renal hilum. Intraoperative ultrasound was used to confirm the margins of the mass. The renal artery was clamped and then the tumor was resected/enucleated. Renal parenchyma was re-approximated with a single layer of interrupted CT-1 Vicryl 0 with sliding clip technique. Warm ischemia time was 19 min. Estimated blood loss (EBL) was 250 ml. Operative time was 165 min. No intraoperative complications occurred. No drain was placed. Patient was discharged on postoperative day 2. Post-operative hypotension was managed with fluid bolus. Postoperative creatinine and eGFR were 1,0 (mg/dL) and 69 (mL/min/1.72m2), respectively. Pathology revealed a leiomyoma of genital stromal origin with hyalinization and calcification. CONCLUSIONS: To the best of our knowledge, this is the first description of RPN for the management of a large (about 8 cm) renal leiomyoma. Robotic assisted surgery allows to expand the indications of minimally invasive conservative renal surgery whose feasibility becomes even more clinically significant in case of benign masses which can be managed without sacrificing healthy renal parenchyma.

Functional and oncological outcomes after radical prostatectomy in patients with history of surgery for lower urinary tract symptoms related to benign prostatic enlargement: A systematic review with meta-analysis.

BACKGROUND: Outcomes of radical prostatectomy (RP) in men with history of lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) surgery represents a controversial issue. We performed an updated systematic review and meta- analysis evaluating oncological and functional outcomes of RP in this subset of patients. METHODS: Eligible studies were identified from MEDLINE, Web of Science and the Scopus databases. The following outcomes were evaluated: incidence of positive surgical margins (PSM), incidence of biochemical recurrence (BCR), 3-mo and 1-year urinary continence (UC) rates, incidence of nerve-sparing (NS) procedures, 1-year erectile function (EF) recovery rates. We estimated pooled Odds ratios (OR) and 95% confidence intervals (CI) using random effects models. Sub-analyses were performed according to the type of RP and LUTS/BPE surgery. RESULTS: Twenty-five retrospective studies including 11,101 patients undergoing RP were included in the analysis (2113 with history of LUTS/BPE surgery, and 8898 controls). PSM rate was significantly higher in patients with history of LUTS/BPE surgery (OR 1.39, 95% CI 1.18-1.63, p < 0.001). No statistically significant difference in terms of BCR emerged between patients with or without history of LUTS/BPE surgery (OR 1.46, 95% CI 0.97-2.18, p = 0.066). Three-months and 1-year UC rates were significantly lower in patients with previous LUTS/BPE surgery (OR 0.48, 95% CI 0.34-0.68, p < 0.001 and OR 0.44, 95% CI 0.31-0.62, p < 0.001; respectively). Although not statistically significant differences between the two groups emerged in terms of adoption of NS procedures (OR 0.59, 95% CI 0.32-1.12, p = 0.107), 1-year EF recovery was significantly lower in patients with history of LUTS/BPE procedures (OR 0.60, 95% CI 0.40-0.89, p = 0.010). CONCLUSIONS: In conclusions, RP in patients with history of previous LUTS/BPE surgery is associated with increased incidence of PSM, lower UC rates at both 3-months and 1-year follow-up as well as lower rates of EF recovery at 1-year follow-up.

Two-Stage Penile Reconstruction after Paraffin Injection: A Case Report and a Systematic Review of the Literature.

BACKGROUND: Penile injection of foreign materials is an obsolete practice often performed by non-medical personnel in order to enlarge penile size. METHODS: A systematic review of the literature from 1956 to 2022 was conducted in accordance with the general guidelines recommended by the Primary Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included full papers published from 1956 to 2022. We also described a case report of a 23 year old Bulgarian male affected by penile paraffinoma who underwent a 2-stages surgical technique. RESULTS: A total of 152 cases have been reported, with a median age of 37.9 ranging from 18 to 64 years. Six different techniques have been described in the whole literature: bilateral scrotal flap, simple excision of the paraffinoma with primary closure, two-stage scrotum skin flap, medial prepuce-soprapubic advancement flap technique and penile reconstruction using split thickness skin graft (STSG) or full thickness skin graft (FTSG). An analysis of the distribution among early and late complications was then carried out. CONCLUSION: In our experience, among the variety of surgical techniques described, a two-stage penile reconstruction using scrotal skin results in excellent cosmetic and functional outcomes, with a low rate of complications.

Effect of the new 75-mg orodispersible film of sildenafil on erection and sexual quality of life: insights from an observational study.

Background: The newly devised orodispersible film (ODF) of sildenafil is the first phosphodiesterase type 5 inhibitor (PDE5i) available in a 75-mg dose. This intermediate dose and the particular properties of the ODF formulation can improve the clinical management of erectile dysfunction (ED) patients. Aim: We investigated the effects of the sildenafil ODF 75-mg dose on both sexual quality of life and erectile function based on the results from an observational study in daily practice in Italy. Methods: This study was a post hoc analysis of results from an observational, real-life study carried out in ED patients at 6 treatment centers in Italy. All subjects were asked to take the prescribed dose of sildenafil ODF at inclusion (visit 1) and to return for a control visit (visit 2) to confirm or adapt the prescribed dose after a minimum of 4 weeks. An end of study control visit (visit 3) was performed after additional 4 weeks. Outcomes: Erectile function, assessed by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain; sexual quality of life, measured using the sexual quality of life instrument for men (SQoL-M). Results: Among the 36 subjects initially recruited for the 75-mg dose, 5 patients dropped out of the study (2 at visit 2 and 3 at visit 3), none of whom due to treatment inefficacy or serious adverse events. At visit 2, the mean (SD) IIEF-EF scores significantly increased (∆ = 7.97 [4.71], P < 0.0001) as SQoL-M scores also did (∆ = 10.76 [10.46], P < 0.0001). At visit 3, IIEF-EF and SQoL-M scores were still significantly improved compared to baseline (∆ = 10.64 [7.01], P < 0.0001, and ∆ = 18.15 [12.32], P < 0.0001, respectively). By ANCOVA, we found no significant effects for age, BMI, previous use of PDE5i, presence of metabolic comorbidities, or smoking habits on study outcomes at both visits 2 and 3. Clinical implication: The new 75-mg ODF sildenafil formulation is a safe and effective treatment for ED, significantly improving both erectile function and sexual quality of life in patients undergoing treatment. Strengths and limitations: This is the first study assessing the efficacy of the sildenafil ODF 75-mg dose in a real-life setting. However, the small sample size, possible underlying cultural factors, and limited availability of clinically relevant data may have affected the reliability of our results. Conclusion: The use of the 75 mg ODF formulation for sildenafil represents an effective and safe novel treatment option for ED patients.

Bladder Cancer and Risk Factors: Data from a Multi-Institutional Long-Term Analysis on Cardiovascular Disease and Cancer Incidence.

Background: Bladder cancer (BCa) is a heterogeneous disease with a variable prognosis and natural history. Cardiovascular disease (CVD), although completely different, has several similarities and possible interactions with cancer. The association between them is still unknown, but common risk factors between the two suggest a shared biology. Materials and Methods: This was a retrospective study that included patients who underwent transurethral resection of bladder tumor at two high-volume institutions. Depending on the presence of a previous history of CVD or not, patients were divided into two groups. Results: A total of 2050 patients were included, and 1638 (81.3%) were diagnosed with bladder cancer. Regarding comorbidities, the most common were hypertension (59.9%), cardiovascular disease (23.4%) and diabetes (22.4%). At univariate analysis, independent risk factors for bladder cancer were age and male sex, while protective factors were cessation of smoking and presence of CVD. All these results, except for ex-smoker status, were confirmed at the multivariate analysis. Another analysis was performed for patients with high-risk bladder cancer and, in this case, the role of CVD was not statistically significant. Conclusions: Our study pointed out a positive association between CVD and BCa incidence; CVD was an independent protective factor for BCa. This effect was not confirmed for high-risk tumors. Several biological and genomics mechanisms clearly contribute to the onset of both diseases, suggesting a possible shared disease pathway and highlighting the complex interplay of cancer and CVD. CVD treatment can involve different drugs with a possible effect on cancer incidence, but, to date, findings are still inconclusive.

Incidence and Predicting Factors of Histopathological Features at Robot-Assisted Radical Prostatectomy in the mpMRI Era: Results of a Single Tertiary Referral Center.

Background and Objectives: To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018-2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D'Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results: Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p-value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions: RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications.

There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements in the promoter regions of TH-related genes, such as deiodinases and TH receptor isoforms, has been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of PCa and hyperthyroidism. This article aims to review the role of androgen-TH crosstalk in PCa and its implication in clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.

A Novel Low-Cost Uroflowmetry for Patient Telemonitoring.

Uroflowmetry (UF) is a crucial guideline-recommended tool for men with benign prostatic obstruction (BPO). Moreover, UF is a helpful decision-making tool for the management of patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). In the last few years, telemedicine and telehealth have increased exponentially as cost-effective treatment options for both patients and physicians. Telemedicine and telehealth have been well positioned during the COVID-19 pandemic to prevent healthcare system overload and to ensure adequate management of patients through screening, diagnosis, and follow-up at home. In the present manuscript, the main characteristics and performance of a novel and low-cost device for home-based UF have been analyzed. The simple weight-transducer method has been applied to perform UF. An inexpensive load cell connected to a 24 bit analogic digital converter (ADC) sends data to a cloud server via SIM card or home Wi-Fi. Data are processed and shown in graphics with both volume and flow rate as a function of time, allowing for measurement of average flow rate, maximum flow rate, voided volume, and voiding time. A numerical algorithm allows for filtering of the dynamic effect due to the urine gravity acceleration and for removing the funnel to simplify the home measurement procedure. Through an online platform, the physician can see and compare each UF data. The device's reliability has been validated in a first laboratory setting and showed excellent performance. This approach based on domiciliary tests and an online platform can revolutionize the urologic clinic landscape by offering a constant patient cost-effective follow-up, eliminating the time wasted waiting in the office setting.

The symptomatic burden of Peyronie's disease at presentation according to patient age: A critical analysis of the Peyronie's disease questionnaire (PDQ) domains.

BACKGROUND: Peyronie's disease (PD) has a huge impact on patients' physical and psychological wellbeing. OBJECTIVES: To investigate whether patients' age has an impact on PD symptomatic burden at first presentation. MATERIALS AND METHODS: Data from 129 consecutive heterosexual patients seeking first medical attention for PD at a single andrological tertiary-referral centre were collected. All patients completed the International Index for Erectile Function (IIEF) and the PD questionnaire (PDQ). Descriptive statistics were used to compare clinical features between younger (≤40years) and older (>40 years) patients. Multivariable linear model assessed the impact of age, the degree of penile curvature and their impact on PDQ (total scores and its domains), after adjusting for PD duration and IIEF-erectile function domain scores. RESULTS: Of 129, 24 (18.6%) patients were ≤40 years old. Young patients presented with a less severe curvature than older patients (median [interquartile ranges] 20° [15-36] vs. 50° [40-80]; p = 0.04). However, younger age was associated with higher psychological and physical symptoms, PDQ-penile pain and PDQ-symptom bother scores (Coeff -0.11, -0.21 and -0.17, respectively) (all p < 0.05). Moreover, the greater the degree of curvature, the higher the PDQ-psychological and physical symptoms and the PDQ-symptom bother scores (Coeff. 0.21 and 0.22, respectively; all p < 0.05). CONCLUSION: Around one in five men seeking first medical help for PD is younger than 40 years at presentation in the real-life setting. PD-related distress varies according to patients' age, with younger men presenting with a greater risk of penile pain and symptom bother despite lower curvature.