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BACKGROUND: Studies have shown insufficient utilization of care for patients with erectile dysfunction (ED) after radical prostatectomy (RP). AIM: The aim of this study was to evaluate variables associated with barriers to seeking and receiving ED treatment. METHODS: In this multicenter prospective cross-sectional study, the functional outcomes of 936 patients were assessed 10 to 15 years after RP. A total of 525 patients with ED or incontinence were asked about their treatment experiences or lack thereof. The data were analyzed using the chi-square test, t test, and multivariate logistic analyses. OUTCOMES: Patients answered validated questionnaires regarding information sources, communication with their partner and urologist, and barriers to ED treatment. RESULTS: Of the 525 patients, 80 were not available to survey. A total of 304 patients answered the survey (response: 68.0%). A total of 246 patients had ED and were included in this study. The mean age at surgery was 64.4 ± 6.1 years, and the mean age at the time of this survey was 77.1 ± 6.2 years. The mean follow-up duration was 12.7 ± 1.5 years. Forty-six percent (n = 114 of 246) of the patients had never received ED treatment. The most important conversation partners regarding the ED were the partner (69% [n = 169 of 246]) and the urologist (48% [n = 118 of 246]). Patients who never received ED treatment were less likely to have conversations with their urologist (34% vs 60%; P < .001), had less support (51% vs 68%; P = .01), and had less interest in sex from their partner (20% vs 40%; P = .001). Communication with other groups (general practitioners, other physicians, family, friends, and the Internet) had no influence on ED treatment utilization. The most relevant barrier to receiving ED treatment was the belief that treatment would not help (65%). No interest in sex from their partner (odds ratio, 3.9) and no conversation with their urologist about ED (odds ratio, 2.9) were found to be independent predictors of not receiving ED treatment. CLINICAL IMPLICATIONS: Urologists should have enhanced awareness of how to approach patients directly about their ED and actively offer them treatment options. STRENGTHS AND LIMITATIONS: These results should be further validated in a multicenter, prospective study. Response bias may have affected the results. Furthermore, the current cohort was relatively old. CONCLUSION: This study revealed that no interest in sex from one's partner and insufficient communication with a urologist were relevant barriers to insufficient utilization of ED treatment after RP.
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Disfunción Eréctil , Prostatectomía , Humanos , Masculino , Disfunción Eréctil/etiología , Prostatectomía/efectos adversos , Estudios Transversales , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Encuestas y Cuestionarios , Urólogos/estadística & datos numéricos , Comunicación , Relaciones Médico-Paciente , Parejas Sexuales/psicología , Incontinencia Urinaria/etiología , Complicaciones Posoperatorias/terapia , Complicaciones Posoperatorias/etiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Neoplasias de la Próstata/cirugíaRESUMEN
INTRODUCTION: The number of urodynamic studies (UDS) has been declining steadily in recent decades, yet the reasons behind this trend remain poorly understood. This study aims to investigate the structural aspects of UDS in urology and explore the factors contributing to this decline. MATERIAL & METHODS: We surveyed all urological departments performing UDS as well as a representative sample of private practices in Germany in 2023. We examined structural situation, waiting times, capacities and limitations of UDS. All invasive urodynamic examinations were defined as UDS. RESULTS: In 2019, 259/474 (55%) urological departments in Germany performed UDS. 206/259 (80%) urological departments responded to the survey. 163/200 (82%) urological departments stated that their capacities were exhausted, a main reason being lack of medical and nursing staff. 54.8% urological departments performed more than 50% of their UDS for referring physicians. Urological departments with a low number of UDS/year (≤ 100) showed a shorter waiting time (up to 4 weeks: 49% vs. 30%; p = 0.01), reduced UDS capacities (55% vs. 12%; p < 0.001) and these capacities were often not fully utilized (25% vs. 9%; p = 0.007). 122/280 (44%) office urologists responded to the survey. 18/122 (15%) office urologists performed UDS. Main reasons for not offering UDS were lack of personnel and low reimbursement. CONCLUSION: In German urological departments, UDS capacities are consistently fully utilized, primarily due to staffing shortages. This trend towards centralization prompts questions about the role of UDS in urologists' training.
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Urodinámica , Urología , Humanos , Alemania , Utilización de Procedimientos y Técnicas/estadística & datos numéricosRESUMEN
Serum prostate-specific antigen (PSA), its derivatives, and magnetic resonance tomography (MRI) lack sufficient specificity and sensitivity for the prediction of risk reclassification of prostate cancer (PCa) patients on active surveillance (AS). We investigated selected transcripts in urinary extracellular vesicles (uEV) from PCa patients on AS to predict PCa risk reclassification (defined by ISUP 1 with PSA > 10 ng/mL or ISUP 2-5 with any PSA level) in control biopsy. Before the control biopsy, urine samples were prospectively collected from 72 patients, of whom 43% were reclassified during AS. Following RNA isolation from uEV, multiplexed reverse transcription, and pre-amplification, 29 PCa-associated transcripts were quantified by quantitative PCR. The predictive ability of the transcripts to indicate PCa risk reclassification was assessed by receiver operating characteristic (ROC) curve analyses via calculation of the area under the curve (AUC) and was then compared to clinical parameters followed by multivariate regression analysis. ROC curve analyses revealed a predictive potential for AMACR, HPN, MALAT1, PCA3, and PCAT29 (AUC = 0.614-0.655, p < 0.1). PSA, PSA density, PSA velocity, and MRI maxPI-RADS showed AUC values of 0.681-0.747 (p < 0.05), with accuracies for indicating a PCa risk reclassification of 64-68%. A model including AMACR, MALAT1, PCAT29, PSA density, and MRI maxPI-RADS resulted in an AUC of 0.867 (p < 0.001) with a sensitivity, specificity, and accuracy of 87%, 83%, and 85%, respectively, thus surpassing the predictive power of the individual markers. These findings highlight the potential of uEV transcripts in combination with clinical parameters as monitoring markers during the AS of PCa.
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BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.
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Criptorquidismo , Orquidopexia , Guías de Práctica Clínica como Asunto , Criptorquidismo/cirugía , Humanos , Masculino , Alemania/epidemiología , Niño , Adolescente , Preescolar , Lactante , Factores de Tiempo , Adulto Joven , AdultoAsunto(s)
Terapia de Reemplazo de Hormonas , Disfunciones Sexuales Fisiológicas , Testosterona , Humanos , Masculino , Testosterona/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Disfunción Eréctil/tratamiento farmacológicoRESUMEN
BACKGROUND: Stress urinary incontinence in men is predominantly iatrogenic after radical prostatectomy or transurethral interventions. Current studies show that there is a deficit in the availability of surgical therapy not only in Germany. The aim of this study is to investigate in more detail the structural health care situation of surgical treatment of male stress incontinence in Germany. MATERIALS AND METHODS: The evaluation of the surgical therapy of male stress incontinence in Germany is based on the OPS (Operationen- und Prozedurenschlüssel-German procedural classification) codes from hospital quality reports from 2011-2019. RESULTS: From 2012-2019, the number of male incontinence surgeries declined from 2191 to 1445. The number of departments performing incontinence surgeries decreased from 275 to 244. In the multivariate analysis, a high number (≥â¯50) of radical prostatectomies/year (RPE/year) is an independent predictor of a high-volume centre (≥â¯10 procedures/year; odds ratio [OR] 6.4 [2.3-17.6]; pâ¯< 0.001). The most significant decrease was in sling surgery (from 1091 to 410; pâ¯< 0.001). Here, the number of cases decreased especially in departments that implanted a high number of slings (≥â¯10 slings/year; -69%; -62.4⯱ 15.5 surgeries/year; pâ¯= 0.007). In addition, the number of departments implanting slings decreased over the investigated time period (from 34 to 10; pâ¯< 0.001). This particularly affected departments that also had a low number of RPE/year (from 9 to 0; -100%). CONCLUSION: The situation of surgical treatment of male stress urinary incontinence in Germany shows a clear decline in sling implantation, especially in small departments. On the one hand, this reflects the increasingly differentiated indications for sling implantation. On the other hand, it raises the suspicion that a gap in care has developed, as the decline was not compensated for by other surgical therapies.
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Incontinencia Urinaria de Esfuerzo , Humanos , Masculino , Incontinencia Urinaria de Esfuerzo/cirugía , Alemania/epidemiología , Prostatectomía/efectos adversos , Anciano , Procedimientos Quirúrgicos Urológicos Masculinos , Persona de Mediana EdadRESUMEN
Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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PURPOSE: We assessed factors that affect the utilization of sperm cryopreservation before 2021, when patients covered expenses, and the influence on quality of life. METHODS: Between 2011 and 2021, testicular cancer survivors (TCS) at our clinic completed a questionnaire, including EORTC QLQ-TC26, covering sperm cryopreservation, sociodemographic details, post-treatment births, and artificial insemination. RESULTS: After 5.7 ± 3.0 years, 279 participants (64%) responded to the questionnaire. Among them, 33% (91/279) of testicular cancer survivors chose sperm cryopreservation prior to treatment, with 11% (10/91) using it for insemination. Conversely, 2% (3/188) without cryopreservation reported unfulfilled desire to have children. Univariate analysis showed TCS with cryopreservation were younger (30.6 ± 7.1 (35 (21-59)) vs. 42.4 ± 10.9 (48 (22-81)) years; p = 0.001), had a lower BMI (24.2 ± 3.3 vs. 26.6 ± 4.6 kg/m2; p = 0.009) and a lower Charlson Score (> 3: 36% vs. 60%; p < 0.001). Multivariate analysis revealed older age (≥ 37 years: OR 13.1 (5.5-31.2), p < 0.001) and lower education (middle school or less: OR 3.3 (1.6-6.9), p = 0.001) as independent factors associated with not undergoing cryopreservation. Regarding quality of life, multivariate analysis identified a lower infertility anxiety score (OR 4.3 (2.0-9.0), p < 0.001) and higher age (≥ 44 years: OR 5.4 (2.6-11.3); p < 0.001) as predictors for the absence of prior cryopreservation. CONCLUSIONS: Age and education seem to impact the choice of undergoing paid sperm cryopreservation. Urologists should inform testicular cancer patients about costs and coverage. Importantly, the occurrence of unmet desires for parenthood is minimal among those who forego cryopreservation.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Niño , Humanos , Masculino , Adulto , Neoplasias Testiculares/terapia , Calidad de Vida , Semen , Criopreservación , EspermatozoidesRESUMEN
PURPOSE: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy. METHODS: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings. RESULTS: A total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17-224.60; p = 0.038). CONCLUSION: Patients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
PURPOSE: The combined approach (CB) of magnetic resonance imaging (MRI)-guided biopsy (TB) and systematic biopsy (SB) is strongly recommended based on numerous studies in biopsy naïve men with suspicion of clinically significant prostate cancer (csPCA). However, the unbalanced accessibility of MRI, challenges related to reimbursement and the scarcity of specialized medical practitioners continue to impede a widespread implementation. Therefore, our objective was to determine a subset of men that could undergo SB without an increased risk of underdiagnosis at reduced expenses. METHODS: A multicenter analysis of 2714 men with confirmed PCA and suspicious MRI who underwent CB were enrolled. Cancer detection rates were compared between the different biopsy routes SB, TB and CB using McNemar paired test. Additionally, Gleason grade up- and down-grading was determined. RESULTS: CB detected more csPCA than TB and SB (p < 0.001), irrespective of MRI findings or biopsy route (transperineal vs. transrectal). Thereby, single biopsy approaches misgraded > 50% of csPCA. TB showed higher diagnostic efficiency, defined as csPCA detection per biopsy core than CB and SB (p < 0.001). For patients with abnormal DRE and PSA levels > 12.5 ng/ml, PSAD > 0.35 ng/ml/cm3, or > 75 years, SB and CB showed similar csPCA detection rates. CONCLUSION: Conducting CB provides the highest level of diagnostic certainty and minimizes the risk of underdiagnosis in almost all biopsy-naive men. However, in patients with suspicious DRE and high PSA levels, PSAD, or advanced age solely using SB leads to similar csPCA detection rates. Thus, a reduced biopsy protocol may be considered for these men in case resources are limited.
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Biopsia Guiada por Imagen , Antígeno Prostático Específico , Humanos , Masculino , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: Cabozantinib (CAB) as monotherapy or in combination with immune checkpoint inhibitors is used for systemic treatment of metastatic renal cell carcinoma (mRCC). However, little is known about predictors of treatment response to CAB. For this reason, known genomic drivers were examined to identify potential predictors of treatment response with CAB. METHODS: Twenty mRCC patients receiving monotherapy (≥ first-line) with CAB were prospectively included. DNA was extracted from archived primary tumors or metastatic tissue. Targeted DNA sequencing was performed using a gene panel including 328 genes (QIAseq Targeted DNA V3 Panel, Qiagen). The variant evaluation was performed using Varsome. The endpoints were treatment-failure-free-survival (TFFS) to CAB. RESULTS: 26% of patients received systemic RCC treatment as the primary option. Six patients were treated with CAB in first-line (1L) and 12 patients in ≥ 2L. The median follow-up after initiation of systemic treatment was 26.7 months (mo). The PBRM1 (7 alleles), SETD2 (7 alleles), VHL (11 alleles), and CHEK2 (14 alleles) genes were most frequently altered. The median time to TFFS was 10.5 mo (95% confidence interval (CI) 6.2-14.7 mo). There was a longer treatment response to CAB in patients with alterations of the SETD2 gene (SETD2 alteration median TFFS not reached vs. no SETD2 alterations 8.4 mo (95% CI 5.2-11.6 mo); p = 0.024). CONCLUSION: Pathogenic variant genes may indicate treatment response to systemic therapy in mRCC. Patients with alterations of the SETD2 gene show longer responses to CAB treatment.
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Anilidas , Carcinoma de Células Renales , Neoplasias Renales , Piridinas , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Genómica , ADNRESUMEN
BACKGROUND: Clinical manifestation of prostate cancer (PCa) is highly variable. Aggressive tumors require radical treatment while clinically non-significant ones may be suitable for active surveillance. We previously developed the prognostic ProstaTrend RNA signature based on transcriptome-wide microarray and RNA-sequencing (RNA-Seq) analyses, primarily of prostatectomy specimens. An RNA-Seq study of formalin-fixed paraffin-embedded (FFPE) tumor biopsies has now allowed us to use this test as a basis for the development of a novel test that is applicable to FFPE biopsies as a tool for early routine PCa diagnostics. METHODS: All patients of the FFPE biopsy cohort were treated by radical prostatectomy and median follow-up for biochemical recurrence (BCR) was 9 years. Based on the transcriptome data of 176 FFPE biopsies, we filtered ProstaTrend for genes susceptible to FFPE-associated degradation via regression analysis. ProstaTrend was additionally restricted to genes with concordant prognostic effects in the RNA-Seq TCGA prostate adenocarcinoma (PRAD) cohort to ensure robust and broad applicability. The prognostic relevance of the refined Transcriptomic Risk Score (TRS) was analyzed by Kaplan-Meier curves and Cox-regression models in our FFPE-biopsy cohort and 9 other public datasets from PCa patients with BCR as primary endpoint. In addition, we developed a prostate single-cell atlas of 41 PCa patients from 5 publicly available studies to analyze gene expression of ProstaTrend genes in different cell compartments. RESULTS: Validation of the TRS using the original ProstaTrend signature in the cohort of FFPE biopsies revealed a relevant impact of FFPE-associated degradation on gene expression and consequently no significant association with prognosis (Cox-regression, p-value > 0.05) in FFPE tissue. However, the TRS based on the new version of the ProstaTrend-ffpe signature, which included 204 genes (of originally 1396 genes), was significantly associated with BCR in the FFPE biopsy cohort (Cox-regression p-value < 0.001) and retained prognostic relevance when adjusted for Gleason Grade Groups. We confirmed a significant association with BCR in 9 independent cohorts including 1109 patients. Comparison of the prognostic performance of the TRS with 17 other prognostically relevant PCa panels revealed that ProstaTrend-ffpe was among the best-ranked panels. We generated a PCa cell atlas to associate ProstaTrend genes with cell lineages or cell types. Tumor-specific luminal cells have a significantly higher TRS than normal luminal cells in all analyzed datasets. In addition, TRS of epithelial and luminal cells was correlated with increased Gleason score in 3 studies. CONCLUSIONS: We developed a prognostic gene-expression signature for PCa that can be applied to FFPE biopsies and may be suitable to support clinical decision-making.
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Neoplasias de la Próstata , Transcriptoma , Masculino , Humanos , Adhesión en Parafina , Perfilación de la Expresión Génica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Factores de Riesgo , Formaldehído , ARN , BiopsiaRESUMEN
BACKGROUND: Metastasis-directed therapy (MDT) in oligometastatic prostate cancer (omHSPC) is playing an increasingly important role in therapy with the aim of delaying disease progression, the start of systemic treatment or switching systemic treatment to improve the patient's overall prognosis. Molecular imaging as prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging allows metastases to be detected with a higher sensitivity and specificity. This means that they can be detected early and made accessible for treatment. RESULTS: The standard therapy for oligo-mHSPC is androgen deprivation (ADT), which is supplemented by novel hormonal therapeutics (NHT). A few small prospective trials have shown an extension of the ADT-free interval and progression-free survival (PFS), particularly in metachronous oligo-mHSPC, by MDT, usually radiotherapy. Additional ADT can further extend the PFS in particular. There are hardly any prospective data for synchronous oligo-mHSPC. CONCLUSION: Despite the currently still poor evidence, MDT is playing an increasingly important role. The still unclear definition of oligometastasis and the large number of influencing factors make it difficult to compare current data. Large multicenter prospective data are still pending. It is also important to clarify the effect of limited ADT in combination with NHT in the treatment of synchronous and metachronous oligo-mHSPC with MDT. In synchronous oligo-mHSPC in particular, further benefit of additional local therapy of the primary in combination with MDT should also be investigated.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Antagonistas de Andrógenos/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Tomografía Computarizada por Rayos X , Estudios Multicéntricos como AsuntoRESUMEN
INTRODUCTION: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology. METHODS: Patients with PCa, diagnosed by targeted biopsy after mpMRI and undergoing RP, were included. The predictive accuracy of mpMRI for extraprostatic extension (ECE), seminal vesicle infiltration (SVI), and lymph node positivity was calculated from the final histopathology. RESULTS: 846 patients were involved. Independent risk parameters include imaging findings such as ECE (OR 3.12), SVI (OR 2.55), and PI-RADS scoring (4: OR 2.01 and 5: OR 4.34). mpMRI parameters such as ECE, SVI, and lymph node metastases showed a high prognostic accuracy (73.28% vs. 95.35% vs. 93.38%) with moderate sensitivity compared to the final histopathology. The ROC analysis of our combined scoring system (D'Amico classification, PSA density, and MRI risk factors) improves the prediction of adverse pathology (AUC: 0.73 vs. 0.69). CONCLUSION: Our study supports the use of mpMRI for comprehensive pretreatment risk assessment in PCa. Due to the high accuracy of factors like ECE, SVI, and PI-RADS scoring, utilizing mpMRI data enabled accurate prediction of unfavorable pathology after RP.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Imagen por Resonancia Magnética/métodos , Vesículas Seminales/diagnóstico por imagen , Vesículas Seminales/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Estadificación de Neoplasias , Prostatectomía/métodos , Estudios RetrospectivosRESUMEN
Rationale: Current therapies for metastatic osseous disease frequently fail to provide a durable treatment response. To date, there are only limited therapeutic options for metastatic prostate cancer, the mechanisms that drive the survival of metastasis-initiating cells are poorly characterized, and reliable prognostic markers are missing. A high aldehyde dehydrogenase (ALDH) activity has been long considered a marker of cancer stem cells (CSC). Our study characterized a differential role of ALDH1A1 and ALDH1A3 genes as regulators of prostate cancer progression and metastatic growth. Methods: By genetic silencing of ALDH1A1 and ALDH1A3 in vitro, in xenografted zebrafish and murine models, and by comparative immunohistochemical analyses of benign, primary tumor, and metastatic specimens from patients with prostate cancer, we demonstrated that ALDH1A1 and ALDH1A3 maintain the CSC phenotype and radioresistance and regulate bone metastasis-initiating cells. We have validated ALDH1A1 and ALDH1A3 as potential biomarkers of clinical outcomes in the independent cohorts of patients with PCa. Furthermore, by RNAseq, chromatin immunoprecipitation (ChIP), and biostatistics analyses, we suggested the molecular mechanisms explaining the role of ALDH1A1 in PCa progression. Results: We found that aldehyde dehydrogenase protein ALDH1A1 positively regulates tumor cell survival in circulation, extravasation, and metastatic dissemination, whereas ALDH1A3 plays the opposite role. ALDH1A1 and ALDH1A3 are differentially expressed in metastatic tumors of patients with prostate cancer, and their expression levels oppositely correlate with clinical outcomes. Prostate cancer progression is associated with the increasing interplay of ALDH1A1 with androgen receptor (AR) and retinoid receptor (RAR) transcriptional programs. Polo-like kinase 3 (PLK3) was identified as a transcriptional target oppositely regulated by ALDH1A1 and ALDH1A3 genes in RAR and AR-dependent manner. PLK3 contributes to the control of prostate cancer cell proliferation, migration, DNA repair, and radioresistance. ALDH1A1 gain in prostate cancer bone metastases is associated with high PLK3 expression. Conclusion: This report provides the first evidence that ALDH1A1 and PLK3 could serve as biomarkers to predict metastatic dissemination and radiotherapy resistance in patients with prostate cancer and could be potential therapeutic targets to eliminate metastasis-initiating and radioresistant tumor cell populations.
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Neoplasias de la Próstata , Receptores Androgénicos , Masculino , Humanos , Animales , Ratones , Pez Cebra/metabolismo , Línea Celular Tumoral , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Neoplasias de la Próstata/genética , Biomarcadores , Familia de Aldehído Deshidrogenasa 1 , Retinal-DeshidrogenasaRESUMEN
PURPOSE: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). METHODS: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months. Functional outcome after 1 year was investigated by IIEF-5 and IPSS questionnaires. Progression was defined as the evidence3 of ISUP ≥ 2 PCa. RESULTS: At any control biopsy (n = 46) after VTP, only 37% of patients showed no evidence of PCa. Recurrence-free survival was 20 months (95% CI 4.9-45.5) and progression-free survival was 38.5 months (95% CI 33.5-43.6 months). In-field and out-field recurrent PCa occurs in 37% (55% ISUP ≥ 2 PCa) and 35% (56% ISUP ≥ 2 PCa). Seventy-nine percent of patients preserved erectile function, respectively. Ten percent of patients presented long-term bladder outlet obstruction. None of the patients presented incontinence. CONCLUSION: Due to the high-recurrence in- and out-field recurrence rate in a mainly low-risk prostate cancer cohort, VTP has to be regarded critically as a therapy option in these patients. Pre-interventional diagnostic evaluation is the main issue before focal therapy to reduce the risk of tumor recurrence and progression.
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Fotoquimioterapia , Neoplasias de la Próstata , Masculino , Humanos , Estudios de Seguimiento , Resultado del Tratamiento , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patologíaRESUMEN
Digitalization is changing medicine. In Germany these changes are not highly accepted yet. Medical pathways should be supported and become safer by digital transformation. Furthermore, artificial intelligence (AI) applications are increasingly used in medicine. Only time will tell whether these will decrease the workload and make patient treatment easier, while increasing precision and individualization.. Urology must accept the upcoming new challenges. This can best be done by participating in the development.
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Medicina , Urología , Humanos , Inteligencia Artificial , Alemania , Carga de TrabajoRESUMEN
PURPOSE: To assess differences in the length of hospital stay (LOS) in patients who present emergently versus electively for a symptomatic ureteral stone and to explore underlying risk factors. METHODS: Billing data were analyzed from patients with symptomatic ureteral calculi at our department from 2010 to 2021. Statistical analysis (U test, logistic regression) was performed. RESULTS: 2274 patients (72% male, 28% female) with ureteral stones were analyzed (mean age of 52.9y). 1578 patients (69.4%) presented in an emergency setting and 696 patients (30.6%) electively. Arterial hypertension was seen in 31%, diabetes mellitus in 11% and hyperuricemia in 5% of the whole cohort. 46.5% of emergency patients were desobstructed (DJ/PCN), 35.4% underwent emergency ureteroscopy (URS), 13.4% had spontaneous passage (SP), and 4.8% underwent emergency shock wave lithotripsy (SWL). Of the electively treated patients, 58.6% underwent URS, 21.3% SWL, 18.5% DJ/PCN, and 1.6% had SP. Emergency stone treatment was associated with a significantly longer LOS when compared to primary desobstruction for patients admitted emergently. Also, LOS was significantly longer for each intervention of stone treatment in emergency patients vs. electively treated patients. Arterial hypertension was associated with a 1.8-fold increased risk of a hospital stay longer than 3 days, irrespective of hospital admission mode, whereas metabolic disorders did not influence LOS in this cohort. CONCLUSION: For emergency patients in contrast to the electively treated patients, the type of procedure had a significant impact on the length of hospital stay. Arterial hypertension is an independent significant risk factor for prolonged hospital stay.
Asunto(s)
Hipertensión , Litotricia , Cálculos Ureterales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cálculos Ureterales/complicaciones , Cálculos Ureterales/cirugía , Tiempo de Internación , Resultado del Tratamiento , Litotricia/métodos , Ureteroscopía/métodos , Tratamiento de Urgencia , Hipertensión/epidemiologíaRESUMEN
PURPOSE: Retroperitoneal lymph node dissection (RPLND) for germ cell tumours is a challenging procedure that may present relevant complications. The purpose was to analyse postoperative complications and identify risk factors for major complications. METHODS: This is a retrospective unicentric analysis of a large cohort of 295 RPLNDs from 1992 to 2020. Early complications (30 days) and late complications (31-180 days) were classified according to the ClavienâDindo classification. The influence of surgical, patient-specific, and tumour-specific parameters on grade III-V complications was analysed in univariate and multivariate logistic regression models. RESULTS: A total of 232 were postchemotherapy RPLNDs, and 63 were primary RPLNDs. Early postoperative complications were found to be grades I-II in 58.6% (173/295), grades III-IV in 9.8% (29/295), and grade V in 0.3% (1/295). In 20% (58/295), additional surgical procedures were needed. Grade III-V complications were associated with ≥ 4 cycles of preoperative chemotherapy (OR 3.7 (1.5-8.9); p = 0.004), RPLND specimen (nonseminoma or immature teratoma) (OR 3.1 (1.4-6.6); p = 0.005), transfusions (OR 2.4 (1.1-5.4); p = 0.03), salvage RPLND (OR 4.1 (1.8-9.3); p < 0.001), and preoperatively elevated AFP (OR 5 (2.2-11.7); p < 0.001). In multivariate analysis, the only independent predictor for grade III-V complications was preoperative AFP elevation (OR 3.3 (1.2-9.2); p = 0.02). Limitations include the retrospective study design. CONCLUSIONS: Our results demonstrate that RPLND is a demanding surgical procedure. Patients with a complex tumour history have a higher risk of complications. We recommend treatment of these complex cases in high-volume centres.