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There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.
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PURPOSE: Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology. METHODS: To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC. RESULTS: We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade. CONCLUSION: Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/patologia , Estudos Prospectivos , Ureteroscopia/métodos , Biópsia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologiaRESUMO
PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.
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Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Incontinência Urinária , Masculino , Humanos , Próstata/cirurgia , Estudos Retrospectivos , Incidência , Terapia a Laser/métodos , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Lasers de Estado Sólido/efeitos adversos , Resultado do TratamentoRESUMO
Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder cancer (NMIBC), comprising the majority of initial BC presentations, requires accurate risk stratification for optimal management. This review explores the evolving role of programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with a particular focus on its implications in the context of Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests a potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, and disease progression. However, conflicting findings and methodological issues highlight the heterogeneity of PD-L1 assessment in NMIBC, probably due to the complex biological mechanisms that regulate the interaction between PD-L1 and the tumor microenvironment. The identification of PD-L1 as a prognostic biomarker provides ground for tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such as intratumoral heterogeneity and technical issues underscore the need for standardized protocols and larger, homogeneous trials. This review contributes to the ongoing debate on the personalized management of NMIBC patients, focusing on the advances and perspectives of incorporating PD-L1 as a biomarker in this setting.
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Background and objective: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for large or complex renal stones. This study aims to evaluate the outcomes of mini PCNL in obese and nonobese patients and to compare the outcomes of mini and standard PCNL in the obese population. Methods: We retrospectively reviewed our PCNL database to identify patients who had undergone mini (Amplatz sheath size 17.5Ch) or standard (Amplatz sheath size ≥26Ch) PCNL between 2005 and 2022. First, we compared the outcomes of the two procedures in the obese (body mass index [BMI] ≥30) and nonobese (BMI<30) patients. Second, we compared the outcomes of mini and standard PCNL in the obese population. A multivariable logistic regression analysis was performed to assess the variables associated with stone-free rate (SFR) and complications. Key findings and limitations: A total of 781 patients underwent mini PCNL; there was no difference between nonobese (578) and obese (133) patients in surgical time, number of tubeless procedures, postoperative stay, SFR, and overall complication rates. Similar outcomes were also seen in the 356 patients who had undergone standard PCNL, including 276 nonobese and 80 obese patients. The comparison of mini and standard PCNL in the obese population (213 patients) showed that mini PCNL provided significant benefits in surgical time (60 vs 94 min), SFR (85% vs 63.8%), and blood transfusion rate (2% vs 10%). The multivariable analysis confirmed that mini PCNL resulted in significantly higher odds of being stone free (odds ratio [OR] 1.79) and lower odds of having a blood transfusion (OR 0.28). Conclusions and clinical implications: Obese patients can safely undergo either mini or standard PCNL; in this series, mini performed better than standard PCNL in terms of SFR and blood transfusion rates. Patient summary: In this study, we compared the outcomes of mini and standard percutaneous nephrolithotomy (PCNL) in the obese population. We found that mini PCNL had lower surgical time and blood transfusion rate, and better stone-free rate than its standard counterpart in obese patients.
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Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) <30 cm s -1 were considered eligible for Li-ESWT. Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis. After treatment, a significant mean (±standard deviation [s.d.]) PSV increase of 5.0 (±3.4) cm s -1 was recorded and 52/113 (46.0%) patients reached a PSV >30 cm s -1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.
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Tratamento por Ondas de Choque Extracorpóreas , Impotência Vasculogênica , Pênis , Humanos , Masculino , Tratamento por Ondas de Choque Extracorpóreas/métodos , Pessoa de Meia-Idade , Pênis/irrigação sanguínea , Pênis/diagnóstico por imagem , Impotência Vasculogênica/terapia , Adulto , Idoso , Disfunção Erétil/terapia , Disfunção Erétil/etiologia , Resultado do TratamentoRESUMO
Introduction: We aim to review the outcomes of shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotripsy (PCNL) for renal and ureteral stones in spinal cord neuropathy patients (SNP). Material and methods: A literature search was performed on 8th March 2023 using PubMed, EMBASE, and Google Scholar with no date limit. Preclinical/animal studies, reviews, letters to the editor, case reports, and meeting abstracts were excluded. Only English papers were accepted. Results: Thirty-five articles were accepted. Five studies focused on SWL, 17 on PCNL, and 6 on ureteroscopy. The remaining articles employed more than one procedure. Stone composition has shifted from struvite to the more common calcium phosphate. SWL showed a very poor stone-free rate (SFR) likely due to challenges in patient positioning, stone visualization, localization, and inability to pass fragments spontaneously. Flexible ureteroscopy and PCNL were associated with a high incidence of infectious complications, long hospital stays, high blood transfusion rate, and intensive care admissions. There were also cases of death. Both procedures were challenging due to genitourinary reconstruction, scoliosis and kyphosis, rib-cage deformity, lower limb contractures, and severe comorbidity which also affected anesthesia. SFR was lower than in non-neurological patients. Conclusions: SWL, ureterolithotripsy, and PCNL should be considered challenging procedures in SNP due to positioning issues, an increased risk of intra and peri-operative morbidity, and even mortality. Computed tomography should be recommended to assess residual fragments as it becomes imperative to minimize a re-intervention in SNP who should be preferably treated in referral centers.
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The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.
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BACKGROUND: Recurrent and complex stone disease may be considered a challenging disease. In 2018, the Calculus group of the SIU (Italian Society of Urology) set itself the goal of establishing the minimum requirements for a center that could continuously manage urolithiasis pathology, named a Stone Center. In this study we present the results of a pilot survey carried out in 2019 with the aim of drawing a map of the situation of Italian urological centers dealing with urinary stones. METHODS: A total of 260 national urology departments dealing with urolithiasis surgery were contacted for this study. A survey was issued to each of the centers to determine the number of patients treated for urinary stones and the amount of procedures performed per year: 1) extracorporeal shock wave lithotripsy ESWL; 2) ureterorenoscopy URS; 3) retrograde intrarenal surgery RIRS; 4) percutaneous nephrolithotomy PCNL. RESULTS: Out of 260 centers contacted, 188 fulfilled the survey. Outcomes were quite variable, with approximately 37% of the centers lacking a lithotripter, and 46% of those that did have it performing fewer than 100 treatments per year. In terms of endoscopic procedures, more than 80% of the centers contacted performed URS or RIRS; however, when it came to percutaneous lithotripsy, these numbers dropped significantly; 33% of the centers contacted did not perform PCNL, and of those who did, 18% had less than 5 years of experience as a center. CONCLUSIONS: Our survey shows a very heterogeneous national picture about urolithiasis treatments. Our goal is to create national paradigms to be able to define stone centers where the patient suffering from complex urinary stones can find a network of professionals with an adequate armamentarium suitable for the management of their pathology.
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Cálculos Urinários , Humanos , Itália/epidemiologia , Cálculos Urinários/cirurgia , Cálculos Urinários/terapia , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Procedimentos Cirúrgicos Urológicos/métodos , Litotripsia/métodos , Litotripsia/estatística & dados numéricos , Urolitíase/cirurgia , Urolitíase/terapia , Projetos Piloto , Pesquisas sobre Atenção à Saúde , Inquéritos e Questionários , Nefrolitotomia Percutânea/métodosRESUMO
Background: The use of the new thulium fiber laser in enucleation of the prostate (ThuFLEP) has been introduced recently. Objective: To evaluate complications and urinary incontinence (UI) after ThuFLEP in small and large prostate volume (PV). Design setting and participants: We retrospectively reviewed patients who underwent ThuFLEP in six centers (from January 2020 to January 2023). The exclusion criteria were concomitant lower urinary tract surgery, previous prostate/urethral surgery, prostate cancer, and pelvic radiotherapy. Outcome measurements and statistical analysis: Patients were divided into two groups: group 1: PV ≤80 ml; group 2: PV >80 ml. Univariable and multivariable logistic regression analyses were performed to evaluate the independent predictors of overall UI. Results and limitations: There were 1458 patients in group 1 and 1274 in group 2. There was no significant difference in age. The median PV was 60 (61-72) ml in group 1 and 100 (90-122) ml in group 2. En bloc enucleation was employed more in group 1, while the early apical release technique was used more in group 2. The rate of prolonged irrigation for hematuria, urinary tract infection, and acute urinary retention did not differ significantly. Blood transfusion rate was significantly higher in group 2 (0.5% vs 2.0%, p = 0.001). There was no significant difference in the overall UI rate (12.3% in group 1 vs 14.7% in group 2, p = 0.08). A multivariable regression analysis showed that preoperative postvoiding urine residual (odds ratio 1.004, 95% confidence interval 1.002-1.007, p < 0.01) was the only factor significantly associated with higher odds of UI. A limitation of this study was its retrospective nature. Conclusions: Complications and UI rates following ThuFLEP were similar in patients with a PV up to or larger than 80 ml except for the blood transfusion rate that was higher in the latter. Patient summary: In this study, we looked at outcomes after thulium fiber laser in enucleation of the prostate stratified by PV. We found that blood transfusion was higher in men with PV >80 ml, but urinary incontinence was similar.
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Objective: Sepsis is the most serious complication of flexible ureteroscopy (F-URS) and laser lithotripsy. We assessed the influence of positive stone culture (SC) on major infectious complications (sepsis, septic shock). Methods: This prospective study enrolled adult patients deemed suitable for F-URS and laser lithotripsy from nine centers (January 2022-August 2023). Inclusion criteria were as follows: kidney stone(s), preoperative midstream urine culture (MSUC), stone(s) assessed at computed tomography scan, and SC. Exclusion criteria were as follows: bilateral procedures, ureteral stones, and children. Group 1 included patients with sterile SC. Group 2 included patients with positive SC. Data are presented as median (interquartile range). A multivariable logistic regression analysis was performed to evaluate factors associated with having a positive SC. Results: In total, 293 patients were included. Median age was 51.0 (24) years. There were 167 (57.0%) males. Group 2 included 32 (2.5%) patients. Group 2 patients were significantly older [75.0 (14) vs 51.0 (23) years, p = 0.02]. Stone features were similar. Major infectious complications were higher in Group 2 (15.6% vs 0.4%). One patient died because of sepsis in Group 2. Two out of 6 (33.3%) patients with major infectious complications had the same pathogen in MSUC and SC. In the multivariable regression analysis, diabetes (OR 3.23), symptomatic urinary infections within 3 months before operation (OR 4.82) and preoperative stent/nephrostomy (OR 2.92) were factors significantly associated with higher odds of positive SC. Conclusions: Patients with positive SC have a higher incidence of major infectious complications after F-URS lithotripsy. SC should be performed whenever feasible because there is a poor correlation between MSUC and SC.
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Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group ( P = 0.0186). Total sperm count also significantly increased in the supplemented group ( P = 0.0117), as did sperm motility ( P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration ( P = 0.0352), while a body mass index (BMI) above 25 kg m -2 had a negative effect on sperm concentration ( P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.
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Antioxidantes , Índice de Massa Corporal , Carnitina , Contagem de Espermatozoides , Varicocele , Humanos , Masculino , Varicocele/complicações , Varicocele/tratamento farmacológico , Antioxidantes/uso terapêutico , Adulto , Método Duplo-Cego , Carnitina/uso terapêutico , Motilidade dos Espermatozoides/efeitos dos fármacos , Suplementos Nutricionais , Análise do Sêmen , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Fatores Etários , Estresse Oxidativo/efeitos dos fármacos , Oligospermia/tratamento farmacológico , Vitaminas/uso terapêutico , Acetilcarnitina/uso terapêutico , Astenozoospermia/tratamento farmacológico , Espermatozoides/efeitos dos fármacosRESUMO
INTRODUCTION: Inflatable penile prosthesis are the definitive treatment for erectile dysfunction. The two most used surgical approaches to position the implants are the penoscrotal and the infrapubic. Current trends showed that the penoscrotal approach is extensively preferred however, there is not conclusive evidence demonstrating the superiority of one technique over the other. The aim of this review is to summarize the scientific evidence available and to underline strengths and weaknesses of the two techniques. EVIDENCE ACQUISITION: We conducted a comprehensive search of MEDLINE, Cochrane Library, and National Center for Biotechnology Information PubMed to identify relevant published articles. The included studies had to explicitly examine the use of three-piece inflatable penile prosthesis with a focus on the surgical access method and complications. EVIDENCE SYNTHESIS: Twenty-six articles were included in the review: seven narrative reviews, five retrospective observational studies, five prospective observational studies, and nine mixed methodology studies. The most frequent approach was the penoscrotal, which was also found more comfortable (RG1) by the operators in one study. The infrapubic approach lasts less and one study demonstrated higher satisfaction by the patients. CONCLUSIONS: There is no evidence of significant differences in complications among the penoscrotal and infrapubic approaches. While the infrapubic approach is faster and patients were more satisfied, the penoscrotal approach is the most used by far. This is likely related to the more straightforward procedure through this access and the excellent surgical field exposure. For these reasons, it is also preferred in the most complex cases.