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PURPOSE: There is a paucity of long-term objective and patient-reported outcomes after definitive perineal urethrostomy for complex urethral strictures. Our objective is to determine comprehensive long-term success of perineal urethrostomy with our 15-year experience at a reconstructive referral center. MATERIALS AND METHODS: Patients who underwent perineal urethrostomy between 2009 and 2023 were identified. A comprehensive long-term follow-up was conducted, evaluating both objective outcomes (retreatment-free survival) and subjective outcomes through the use of validated questionnaires. Additionally, to provide further context for our findings, we conducted a scoping review of all studies reporting outcomes following perineal urethrostomy. RESULTS: Among 76 patients, 55% had iatrogenic strictures, with 82% previously undergoing urethral interventions. At a median follow-up of 55 months, retreatment-free survival was 84%, with 16% of patients experiencing perineal urethrostomy recurrent stenosis. Patient-reported outcomes revealed a generally satisfactory voiding function (Urethral Stricture Surgery patient-reported outcome measure Lower Urinary Tract Symptoms score) and continence (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form), with median scores of 4 (range 0-24) and 0 (range 0-21), but with bimodal distributions of sexual function scores (median International Index of Erectile Function-Erectile Function domain: 3.5; median Male Sexual Health Questionnaire-Ejaculation Scale: 21). Treatment satisfaction was very high with a median International Consultation on Incontinence Questionnaire-Satisfaction outcome score of 21 (range 0-24). The scoping review revealed varying success rates ranging from 51% to 95%, highlighting difficulties in comparison due to variable success definitions and patient case mix. CONCLUSIONS: Perineal urethrostomy provides effective treatment for complex anterior urethral strictures, with high patient satisfaction, preserved continence function, and favorable voiding outcomes. It presents a viable option for older and comorbid patients, especially after thorough counseling on expected outcomes and potential risks.
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Background: It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised-compared to routine-intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery. Methods: In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure [MAP] above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7. Results: The primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio [OR]=0.84, 95% confidence interval [CI]: 0.40-1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45-2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04-3.53, P=0.684). Conclusions: Personalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome-delayed neurocognitive recovery and delirium-compared to routine blood pressure management in patients having major noncardiac surgery. Clinical trial registration: ClinicalTrials.gov (NCT03442907).
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BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFRâ <â 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (Pâ =â .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (nâ =â 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCIâ ≥â 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.
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Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.
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OBJECTIVE: To investigate long-term and patient-reported outcomes, including sexual function, in women undergoing urogenital fistula (UGF) repair, addressing the lack of such data in Western countries, where fistulas often result from iatrogenic causes. PATIENTS AND METHODS: We conducted a retrospective analysis at a tertiary referral centre (2010-2023), classifying fistulas based on World Health Organisation criteria and evaluating surgical approaches, aetiology, and characteristics. Both objective (fistula closure, reintervention rates) and subjective outcomes (validated questionnaires) were assessed. A scoping review of patient-reported outcome measures in UGF repair was also performed. RESULTS: The study included 50 patients: 17 (34%) underwent transvaginal and 33 (66%) transabdominal surgery. History of hysterectomy was present in 36 patients (72%). The median (interquartile range [IQR]) operating time was 130 (88-148) min. Fistula closure was achieved in 94% of cases at a median (IQR) follow-up of 50 (16-91) months and reached 100% after three redo fistula repairs. Seven patients (14%) underwent reinterventions for stress urinary incontinence after transvaginal repair (autologous fascial slings). Patient-reported outcomes showed median (IQR) scores on the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) of 5 (3-7) for filling symptoms, 1 (0-2) for voiding symptoms and 4.5 (1-9) for incontinence symptoms. The median (IQR) score on the ICIQ Female Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ-FLUTSsex) was 3 (1-5). The median (IQR) ICIQ Satisfaction (ICIQ-S) outcome score and overall satisfaction with surgery item score was 22 (18.5-23.5) and 10 (8.5-10), respectively. Higher scores indicate higher symptom burden and treatment satisfaction, respectively. Our scoping review included 1784 women, revealing mixed aetiology and methodological and aetiological heterogeneity, thus complicating cross-study comparisons. CONCLUSIONS: Urogenital fistula repair at a specialised centre leads to excellent outcomes and high satisfaction. Patients with urethrovaginal fistulas are at increased risk of stress urinary incontinence, possibly due to the original trauma site of the fistula.
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BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.
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Antígeno B7-H1 , Carcinoma de Células de Transição , Inibidores de Checkpoint Imunológico , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Antígeno B7-H1/análise , Antígeno B7-H1/biossíntese , Masculino , Feminino , Prognóstico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/metabolismo , Idoso , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso de 80 Anos ou mais , Estudos RetrospectivosRESUMO
INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.
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Cistectomia , Complicações Pós-Operatórias , Potássio , Período Pré-Operatório , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/sangue , Masculino , Feminino , Estudos Retrospectivos , Idoso , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/sangue , Pessoa de Meia-Idade , Potássio/sangue , Resultado do Tratamento , Prognóstico , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/sangue , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidadeRESUMO
OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cistectomia , Quimioterapia de Indução , Metástase Linfática , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Gencitabina , Cisplatino/administração & dosagem , Excisão de Linfonodo , Metotrexato/administração & dosagem , Linfonodos/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagemRESUMO
BACKGROUND AND OBJECTIVE: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. METHODS: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data. KEY FINDINGS AND LIMITATIONS: The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8+ cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8+ T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells. CONCLUSIONS AND CLINICAL IMPLICATIONS: The density of intraepithelial CD8+ T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8+ cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8+ T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index. PATIENT SUMMARY: Quantification of intraepithelial CD8+ T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T CD8-Positivos/imunologia , Imuno-Histoquímica , Masculino , Feminino , Análise Serial de Tecidos , Urotélio/imunologia , Urotélio/patologia , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Idoso , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/análise , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Urethral strictures, particularly those refractory to endoscopic interventions, are commonly treated through open urethroplasty. However, predicting recurrence in homogeneous patient populations remains challenging. METHODS: To address this, we developed an intraoperative urethral stricture assessment tool aiming to identify comprehensive risk predictors. The assessment includes detailed parameters on stricture location, length, urethral bed width, spongiosum thickness, obliteration grade, and spongiofibrosis extension. The tool was prospectively implemented in 106 men with anterior one-stage augmentation urethroplasty from April 2020 to October 2021. RESULTS: An intraoperative granular assessment of intricate stricture characteristics is feasible. Comparative analyses revealed significant differences between bulbar and penile strictures. Bulbar strictures exhibited wider urethral beds and thicker spongiosum compared to penile strictures (all p < 0.001). The assessment showed marked variations in the degree of obliteration and spongiofibrosis extension. CONCLUSION: Our tool aligns with efforts to standardize urethral surgery, providing insights into subtle disease intricacies and enabling comparisons between institutions. Notably, intraoperative assessment may surpass the limitations of preoperative imaging, emphasizing the necessity of intraoperative evaluation. While limitations include a single-institution study and limited sample size, future research aims to refine this tool and determine its impact on treatment strategies, potentially improving long-term outcomes for urethral strictures.
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Estudo de Prova de Conceito , Uretra , Estreitamento Uretral , Procedimentos Cirúrgicos Urológicos Masculinos , Estreitamento Uretral/cirurgia , Humanos , Masculino , Estudos Prospectivos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Pessoa de Meia-Idade , Uretra/cirurgia , Adulto , Cuidados Intraoperatórios , Idoso , Período IntraoperatórioRESUMO
BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.
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Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Comorbidade , Morbidade , Indicadores Básicos de Saúde , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.
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Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Linfonodos/cirurgia , Linfonodos/patologia , CistectomiaRESUMO
BACKGROUND: Little is known about patients' pre-treatment expectations in Peyronie's disease (PD). OBJECTIVE: To evaluate in detail patients' expectations of conservative therapy and surgery. PATIENTS AND METHODS: This multi-center study prospectively enrolled 317 PD patients, who were scheduled to receive conservative therapy or surgery between 2019 and 2022 at the Department of Urology of the University Medical Center Hamburg-Eppendorf, and the Center of Reproductive Medicine and Andrology, University Medical Center Muenster, both Germany. The primary end-point was patients' pre-treatment expectations of conservative therapy and surgery, measured with the Stanford Expectations of Treatment Scale (SETS). Secondary end-points included patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function, measured with the Peyronie's disease questionnaire (PDQ) and International Index of Erectile Function Erectile Function Domain (IIEF-EF). RESULTS: In total, 239 (75%) and 78 (25%) patients were scheduled for the conservative therapy and surgery, respectively. Patients undergoing surgery had higher positive and negative mean SETS expectations scores (14 vs. 11, p < 0.001; 9.6 vs. 6.0, p < 0.001). In multivariable analysis, surgery was an independent predictor of positive and negative patients' pre-treatment expectations (all p ≤ 0.001). In thematic analysis, patients undergoing surgery emphasized distinct themes of pre-treatment expectations. Patients undergoing surgery had higher mean PDQ symptom bother as well as higher psychological and physical symptom scores (14 vs. 10, p < 0.001; 9.2 vs. 7.1, p = 0.001). There were significant positive correlations between SETS negative expectation score and PDQ symptom bother (|ρ| = 0.25; p < 0.001) as well as PDQ psychological and physical symptoms score, respectively (|ρ| = 0.21; p = 0.001). CONCLUSION: PD patients expect both more benefit and more harm from surgery. In addition, patients undergoing surgery have more psychological and physical symptoms and more symptom bother. To set realistic expectations, it is of pivotal importance to assess patients' expectations before starting treatment.
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Disfunção Erétil , Induração Peniana , Masculino , Humanos , Induração Peniana/cirurgia , Induração Peniana/diagnóstico , Estudos Prospectivos , Resultado do Tratamento , Ereção Peniana , PênisRESUMO
BACKGROUND: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder. METHODS: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data. RESULT: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers. CONCLUSIONS: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Bexiga Urinária/patologia , Uroplaquina Ia/metabolismo , Uroplaquina Ib/metabolismo , Biomarcadores Tumorais/metabolismoRESUMO
Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.
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Doenças Cardiovasculares , Síndrome Metabólica , Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Androgênios , Hormônio Liberador de Gonadotropina/uso terapêutico , Síndrome Metabólica/epidemiologiaRESUMO
OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.
Assuntos
Neoplasias da Bexiga Urinária , Derivação Urinária , Incontinência Urinária , Humanos , Feminino , Cistectomia/efeitos adversos , Bexiga Urinária/cirurgia , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Micção , Derivação Urinária/efeitos adversos , Resultado do TratamentoRESUMO
In light of recently published international guidelines concerning the diagnosis, treatment, and aftercare of urethral strictures and stenoses, the objective of this study was to synthesize an overview of guideline recommendations provided by the American Urological Association (AUA, 2023), the Société Internationale d'Urologie (SIU, 2010), and the European Association of Urology (EAU, 2023). The recommendations offered by these three associations, as well as the guidelines addressing urethral trauma from the EAU, AUA, and the Urological Society of India (USI), were assessed in terms of their guidance on posterior urethral stenosis. On the whole, the recommendations from the various guidelines exhibit considerable alignment. However, SIU and EAU place a stronger emphasis on the role of repeated endoscopic treatment compared to AUA. The preferred approach for managing radiation-induced bulbomembranous stenosis remains a subject of debate. Furthermore, endoscopic treatments enhanced with intralesional therapies may potentially serve as a significant treatment modality for addressing even fully obliterated stenoses.
Assuntos
Estreitamento Uretral , Urologia , Humanos , Estados Unidos , Uretra/lesões , Estreitamento Uretral/diagnóstico , Constrição Patológica/diagnóstico , EndoscopiaRESUMO
In recent years, several international urological societies have published guidelines on the diagnosis, treatment, and follow-up of urethral strictures, but a guideline for the German-speaking region has not been available to date. This summary provides a detailed comparison of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA) and the Société Internationale d'Urologie (SIU) with regard to the treatment of anterior urethral strictures, i.e. from the bulbar urethra to the meatus. In the following work, differences and specific recommendations in the guidelines are highlighted. In particular, the three guidelines largely agree with regard to diagnostic workup and follow-up. However, divergences exist in the management of anterior urethral strictures, particularly with regard to the use of endoscopic therapeutic approaches and the use of urethral stents. In addition, the EAU provides more comprehensive and detailed recommendations on urethroplasty techniques and specific patient follow-up. The EAU guidelines are the most current and were the first to include instructions for urethral strictures in women and individuals with gender incongruence after genital approximation surgery. Reconstructive urology is a rapidly evolving specialty and, thus, the clinical approach has been changing accordingly. Although guideline recommendations have become more inclusive and comprehensive, more high-quality data are needed to further improve the level of evidence.