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Resistance to antiandrogens and chemotherapy (Cx) limits therapeutic options for patients with hormone-sensitive and hormone-resistant prostate cancer (mCRPC). In this context, up-regulation of the glucocorticoid receptor has been identified as a potential bypass mechanism in mCRPC, and a combination of docetaxel and mifepristone (Doc + RU-486), an inhibitor of the glucocorticoid receptor, re-sensitized docetaxel-resistant cell models to Cx. This study was designed to elucidate the molecular mechanisms responsible for this phenomenon. RNA sequencing was performed in docetaxel-resistant prostate cancer cell models after Doc + RU-486 treatment with consecutive functional assays. Expression of selected proteins was verified in prostatic tissue from prostate cancer patients with progressive disease. Treatment with Doc + RU-486 significantly reduced cancer cell viability, and RNA sequencing revealed sterol regulatory element of binding transcription factor 1 (SREBF-1), a transcription factor of cholesterol and lipid biosynthesis, as a significantly down-regulated target. Functional assays confirmed that SREBF-1 down-regulation is partially responsible for this observation. In concordance, SREBF-1 knockdown and pharmacologic sterol regulatory element binding protein inhibition, together with other key enzymes in the cholesterol pathway, showed similar results. Furthermore, SREBF-1 expression is significantly elevated in advanced prostate cancer tissues, showing its potential involvement in tumor progression and emerging therapy resistance. Therefore, specific inhibition of cholesterol and lipid biosynthesis might also target Cx-resistant cancer cells and represents a potential additive future therapeutic option to improve mCRPC therapy.
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BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.
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PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.
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Neoplasias da Próstata , Melhoria de Qualidade , Masculino , Humanos , Estudos de Coortes , Prostatectomia , Medidas de Resultados Relatados pelo Paciente , Neoplasias da Próstata/cirurgiaRESUMO
PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.
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Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Estudos Prospectivos , Biópsia Guiada por Imagem/métodos , Idoso , Pessoa de Meia-Idade , Próstata/patologia , Próstata/diagnóstico por imagem , Método Simples-CegoRESUMO
PURPOSE: Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment. METHODS: We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression. RESULTS: Median follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence. CONCLUSION: HIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.
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Neoplasias da Próstata , Ultrassom Focalizado Transretal de Alta Intensidade , Masculino , Humanos , Idoso , Antígeno Prostático Específico , Estudos Prospectivos , Resultado do Tratamento , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/cirurgia , Próstata/patologiaRESUMO
PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.
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Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Etoposídeo/uso terapêutico , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Orquiectomia , Seminoma/patologia , Neoplasias Testiculares/patologiaRESUMO
OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. METHODS: In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. RESULTS: 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). CONCLUSION: The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.
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COVID-19 , Padrões de Prática Médica , Triagem , Neoplasias Urológicas , Procedimentos Cirúrgicos Urológicos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Saúde Global/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Oncologia/métodos , Oncologia/organização & administração , Oncologia/tendências , Avaliação das Necessidades , Inovação Organizacional , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/tendências , SARS-CoV-2 , Tempo para o Tratamento/estatística & dados numéricos , Triagem/organização & administração , Triagem/tendências , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/terapia , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricosAssuntos
COVID-19 , Educação de Pós-Graduação em Medicina , Internato e Residência , Procedimentos Cirúrgicos Urológicos/educação , Urologistas/educação , Urologia/educação , Carga de Trabalho , Competência Clínica , Currículo , Humanos , Curva de Aprendizado , Estudos Retrospectivos , Fatores de TempoRESUMO
We present a case of bladder cancer with a singular cardiac metastasis. A 51-year-old female patient was referred to our department for painless macrohematuria. We confirmed the diagnosis of muscle-invasive urothelial carcinoma of the urinary bladder with partial squamous cell differentiation. Computed tomography (CT) staging demonstrated a singular cardiac metastasis. Two months after receiving six cycles of chemotherapy control CT scan revealed massive tumour progression. The singular cardiac metastasis size increased to approximately two thirds of right ventricle size. Singular cardiac metastases of urothelial carcinoma are extremely rare and show rapid progression, hence introduction to therapy should not be delayed.
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BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.
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BACKGROUND: The SARS-CoV-2 pandemic presents an unprecedented challenge to health care systems worldwide. Data on SARS-CoV-2 transmission in a hospital is rare and outbreaks among health care professionals are complex to control. MATERIAL AND METHODS: Over the course of 6 consecutive weeks we recorded data on an exponential outbreak of SARS-CoV-2 within our department. We reconstructed the assumed route of the spread of infection, and the employees' acute and late symptoms. Increasing preventive measures (mandatory face masks, intense training in hygiene, physical distancing whenever possible, and termination of visits from outside the hospital) were implemented. RESULTS: Within 6 weeks, 13 employees were tested positive for SARS-CoV-2. All individuals had a moderate course, not resulting in hospitalization. The majority of infections was discovered after testing contacts of known cases, prior to their onset of symptoms and was predominantly related to removal of face masks during breaks. Increasing preventive measures resulted in a decline and finally containment of transmission rates amongst the staff, confirmed by mass testing at week 6, with no further SARS-CoV-2 infection. Three individuals, all in their late 40s or older, have lasting or newly onset neurological symptoms 8 months after their infection. CONCLUSIONS: Outbreaks of SARS-CoV-2 are particularly difficult to contain in a medical setting, where employees work in close physical proximity. Adherence to preventive measures, particularly face masks, seem to be effective.
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COVID-19 , SARS-CoV-2 , Surtos de Doenças , Pessoal de Saúde , Humanos , PandemiasRESUMO
INTRODUCTION & OBJECTIVES: Percutaneous nephrostomy [1] has emerged as a pivotal approach in the therapeutic management of the obstructed urinary tract. A consecutive incorporation of ultrasonic and radiographic guidance, the approach experienced an almost ubiquitious distribution while most centers currently applying either one or both of these tools jointly. However, success of ultrasound-guidance is limited in obese patients and non-dilated uropathy. In turn, fluoroscopy usually requires an opacification of the urinary collecting system by intravenous or antegrade contrast media injection, which might be harmful for already impaired renal function, raise intrapelvic pressure and augment the risk of sepsis and hemorrhage. CT-guided PCN aids in overcoming these limitations. In the current study, we present the experience of a tertiary referral center with this technique. MATERIALS & METHODS: Epidemiological and clinical data of all patients treated with a CT-guided PCN of native kidneys at the University Hospital Frankfurt between October 2003 and October 2013 were retrospectively collected from the patient charts. Procedural parameters including radiological aspects, technical and therapeutic success, complication and mortality rate have been analyzed statistically. RESULTS: In total, 140 PCN procedures have been performed in 77 patients with a median age of 69 (± 13). The median body mass index was 27 with 66.6% of patients being overweight or obese. Charlson comorbidity index was 7 ranging 0-16. Indications for PCNs were obstructive uropathy (62.9), urine extravasation (22.9%), urinary tract fistulas (11.4%) and technical reasons (2.8%). In 68.8% of patients, initial diagnosis was malignancy. 56.4% of kidneys were non-dilated before puncture. In 78.4% prone position, otherwise supine oblique position (17.3%) or supine position (4.3%) was used. 71.4% of PCNs were carried out solely under local anesthesia. Technical success has been achieved in 90% with a complication rate of 3.6% (all grade minor B) and was not significantly different between dilated and non-dilated kidneys. 42.9% of fistulas and 64.3% of urinary tract leakages, healed after PCN placement. 30 days mortality rate was 5.2% without being directly associated with the PCN procedure itself. CONCLUSION: CT-guided PCN is a feasible approach associated with low morbidity. It is particularly useful in complex clinical scenarios e.g. critically ill, newly operated or obese patients as well as non-dilated kidneys. Moreover, it represents a minimally-invasive option for treating leakages and fistulas of the urinary tract.
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Nefrostomia Percutânea/métodos , Doenças Urológicas/cirurgia , Idoso , Anestesia Local , Dilatação Patológica/cirurgia , Estudos de Viabilidade , Feminino , Fluoroscopia/métodos , Humanos , Rim/diagnóstico por imagem , Masculino , Obesidade/complicações , Sobrepeso/complicações , Radiografia Intervencionista , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia de Intervenção , Doenças Uretrais/cirurgiaRESUMO
INTRODUCTION: We investigated the incidence, clinical course and risk factors for symptomatic lymphoceles after radical retropubic prostatectomy with pelvic lymph node dissection. Moreover, we explored parameters for the failure of percutaneous lymphocele drainage. METHODS: The incidence of symptomatic lymphoceles in patients with prostate cancer who underwent radical retropubic prostatectomy with pelvic lymph node dissection in our department between 2008 and 2013 was investigated retrospectively. The occurrence of lymphoceles was correlated with several clinical and histopathological parameters. In addition, logistic regression analysis was performed to assess the value of independent variables with regard to the development of symptomatic lymphoceles and failure of percutaneous drainage. RESULTS: A total of 599 consecutive patients treated with radical retropubic prostatectomy with pelvic lymph node dissection were included in the study, of whom symptomatic lymphocele had developed in 5%. Median time to diagnosis of symptomatic lymphocele was 22.5 days. Median time of percutaneous drainage was 16 days. Overall 43% of patients required surgical unroofing. On multivariate analysis age greater than 67 years (OR 3.27, p=0.005) and removal of more than 10 lymph nodes (OR 2.57, p=0.018) were independent predictors for the development of symptomatic lymphoceles. A significantly increased risk of percutaneous drainage failure was observed in patients who had a body mass index greater than 27 kg/m2 (OR 7.0, p=0.03), followed by a trend for those with a drainage volume of more than 375 ml 24 hours after puncture (OR 3.89, p=0.12). CONCLUSIONS: Symptomatic lymphocele will develop in 1 of 20 patients after radical retropubic prostatectomy with pelvic lymph node dissection. The number of lymph nodes removed constitutes an independent risk factor. Percutaneous drainage failure is associated with high body mass index and high drainage volume within the first 24 hours after puncture.
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Nine out of ten metastatic prostate cancer (PCa) patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE). SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC) patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ). Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.