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2.
J Orthop Surg Res ; 19(1): 253, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644485

RESUMO

INTRODUCTION: We present a detailed procedure for the robotic-assisted plate osteosynthesis of an anterior acetabular fracture. The purpose of this work was to describe a robotic-assisted minimally invasive technique as a possible method for reducing complications, pain, and hospitalization. Another goal was to present technical recommendations and to assess potential pitfalls and problems of the new surgical approach. METHODS: Surgery was performed in an interdisciplinary setting by an experienced orthopedic surgeon and a urologist. The DaVinci System with standard instruments was used. Reduction was achieved through indirect traction of a pin that was introduced into the femoral neck and direct manipulation via the plate. The plate position and fixation were achieved through 7 additional minimally invasive incisions. RESULTS: The technique has multiple advantages, such as no detachment of the rectus abdominal muscle, a small skin incision, and minimal blood loss. Furthermore, this approach might lower the incidence of hernia formation, infection, and postoperative pain. DISCUSSION: We see the presented technique as a demanding yet progressive and innovative surgical method for treating acetabular fractures with indications for anterior plate fixation. TRIAL REGISTRATION: The study was approved by the local institutional review board (Nr. 248/18).


Assuntos
Acetábulo , Placas Ósseas , Fixação Interna de Fraturas , Fraturas Ósseas , Procedimentos Cirúrgicos Robóticos , Humanos , Acetábulo/cirurgia , Acetábulo/lesões , Procedimentos Cirúrgicos Robóticos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Feminino , Adulto
3.
BJUI Compass ; 5(1): 90-100, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38179024

RESUMO

Objectives: Most renal tumours can be treated with a partial nephrectomy, with robot-assisted partial nephrectomy becoming the new gold standard. This procedure is challenging to learn in a live setting, especially the enucleation and renorraphy phases. In this study, we attempted to evaluate face, content, and preliminary construct validity of a 3D-printed silicone renal tumour model in robotic training for robot-assisted partial nephrectomy. Materials and Methods: We compared the operative results of three groups of surgeons with different experience levels (>20 partial nephrectomies, 1-20 partial nephrectomies and no experience at all) performing a robotic tumour excision of a newly developed silicone model with four embedded 3D-printed renal tumours. We evaluated the participants' performance using surgical margins, excision time, total preserved parenchyma, tumour injury and GEARS score (as assessed by two blinded experts) for construct validity. Postoperatively, the participants were asked to complete a survey to evaluate the usefulness, realism and difficulty of the model as a training and/or evaluation model. NASA-TLX scores were used to evaluate the operative workload. Results: Thirty-six participants were recruited, each group consisting of 10-14 participants. The operative performance was significantly better in the expert group as compared to the beginner group. NASA-TLX scores proved the model to be of an acceptable difficulty level.Expert group survey results showed an average score of 6.3/10 on realism of the model, 8.2/10 on the usefulness as training model and 6.9/10 score on the usefulness as an evaluation tool. GEARS scores showed a non-significant tendency to improve between trials, emphasizing its potential as a training model. Conclusion: Face and content validity of our 3D renal tumour model were demonstrated. The vast majority of participants found the model realistic and useful for training and for evaluation. To evaluate construct and predictive validity, we require further research, aiming to compare the results of 3D-model trained surgeons with those of untrained surgeons in real-life surgery.

4.
Cancers (Basel) ; 15(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37835449

RESUMO

Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62-71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.

5.
Z Gerontol Geriatr ; 56(4): 324-334, 2023 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-37306771

RESUMO

Prostate cancer is the most frequent cancer in men. For localized prostate cancer, surgery and radiotherapy are the standard treatment, with active surveillance also used in low-risk cases. For advanced/metastatic disease, androgen deprivation treatment is carried out. Further options include inhibitors of the androgen receptor axis and taxane-based chemotherapy. The avoidance of side effects should be considered, e.g., by dose adjustment. New options include poly(ADP-ribose) polymerase (PARP) inhibitors, and radioligand treatment. The existing guidelines only provide a few treatment recommendations for older patients; however, the treatment of older patients should primarily consider not only chronological age but also the patient's psychological and physical condition and preferences. In this context, the geriatric assessment represents an important instrument for determining the treatment strategy.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/efeitos adversos
6.
BMC Urol ; 23(1): 46, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36978025

RESUMO

BACKGROUND: We evaluated the hydrostatic pressure of the renal pelvis (RPP) as a radiation-free alternative to fluoroscopic nephrostogram to assess ureteral patency after percutaneous nephrolithotomy (PCNL). METHODS: Retrospective non-inferiority study analyzing 248 PCNL-patients (86 female (35%) and 162 males (65%)) between 2007 and 2015. Postoperatively, RPP was measured using a central venous pressure manometer in cmH2O. The primary endpoint was to assess RPP depending on the patency of the ureter and the nephrostomy tube removal. Secondary, the upper limit of normal RPP of [Formula: see text] 20 cmH2O was assessed as an indicator of an unobstructed patency. RESULTS: The median procedure duration was 141 min (112-171.5) with a stone free rate of 82% (n = 202). RPP was significantly higher in patients with obstructive nephrostogram with 25.0 mmH2O (21.0-32.0) versus 20.0 mmH2O (16.0-24.0; p < 0.001). The pressure was lower in successful nephrostomy removal with 18 cmH2O (15-21) versus 23 cmH2O (20-29) in the leakage group (p < 0.001). The analysis of a cut-off of [Formula: see text] 20 cmH2O showed a sensitivity of 76.9% (95% CI [60.7%; 88.9%]) and a specificity of 61.5% (95% CI [54.6%; 68.2%]). The negative predictive value was 93.4% (95% CI: [87.9%; 97.0%]) and the positive predictive value 27.3% (95% CI [19.2%; 36.6%]). The accuracy of the model showed an AUC = 0.795 (95% CI [0.668; 0.862]). CONCLUSION: The hydrostatic RPP seems to allow a bedside evaluation of ureteral patency after PCNL.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Masculino , Humanos , Feminino , Nefrolitotomia Percutânea/métodos , Pressão Hidrostática , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Estudos Retrospectivos , Pelve Renal/diagnóstico por imagem , Pelve Renal/cirurgia , Nefrostomia Percutânea/métodos
7.
BMC Urol ; 23(1): 6, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609261

RESUMO

BACKGROUND: To evaluate the incidence of lymph node degeneration and its association with nodal metastatic pattern in prostate cancer. METHODS: A retrospective analysis of the submitted lymph node specimen of 390 prostatectomies in 2011 was performed. All lymph nodes were histologically re-evaluated and the degree of lymph node degeneration e.g. lipomatous atrophy, capsular and framework fibrosis, and calcifications as well as the lymph node size were recorded. Lymph node degeneration was compared in the anatomic regions of the pelvis as well as in lymph nodes with and without metastases of prostatic cancer. RESULTS: Eighty-one of 6026 lymph nodes demonstrated metastases. Complete histologic examination with analysis of a complete cross-section was possible in 5173 lymph nodes including all lymph nodes with metastases. The incidence of lymph node degeneration was different across the various landing sites. Lymph node metastases were primarily detected in less degenerative and therefore more functional lymph nodes. In metastatic versus non-metastatic lymph nodes low lipomatous atrophy was reported in 84.0% versus 66.7% (p = 0.004), capsular fibrosis in 14.8% versus 35.4% (p < 0.001), calcifications in 35.8% versus 46.1% (p = 0.072) and framework fibrosis in 69.8% versus 75.3% (p = 0.53). Metastases were also identified more frequently in larger than in smaller lymph nodes (63.0% vs. 47.5%; p = 0.007). CONCLUSIONS: Degenerative changes in pelvic lymph nodes are commonly detectable but occur with variable frequency in the various nodal landing sites in the pelvis. The degree of lymph node degeneration of single lymph nodes has a significant influence on whether a lymph node is infiltrated by tumor cells and may harbour metastases.


Assuntos
Linfonodos , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Linfonodos/patologia , Neoplasias da Próstata/patologia , Pelve/patologia , Fibrose , Excisão de Linfonodo
8.
Aktuelle Urol ; 54(5): 386-390, 2023 09.
Artigo em Alemão | MEDLINE | ID: mdl-33951740

RESUMO

Cysts in the lesser pelvis are a rare disease and most often an incidental finding from routine diagnostic investigation. Published information is controversial. These cysts are distinguished by localisation, content of the cyst and accompanying anatomical anomalies. In this case, we report a 33 years old man who presented to our clinic due to a large retrovesical cyst. Because of lower abdominal pain and problems with defecation, the cyst was diagnosed by ultrasound. Further radiological diagnostic testing confirmed the presence of a retrovesical cyst of unknown malignancy, which was retrospectively evaluated as a Müllerian duct cyst. Due to symptoms and potential malignancy of the cyst, the decision was made to perform surgery. With the help of the operation robot, this benign cyst was safely and completely removed. In a follow-up, the patient presented free of symptoms and sonographically there was no sign of recurrence. Therefore robotic-assisted resection is a safe procedure to treat large symptomatic Müllerian duct cysts.


Assuntos
Cistos , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Adulto , Ductos Paramesonéfricos/cirurgia , Ductos Paramesonéfricos/patologia , Estudos Retrospectivos , Cistos/cirurgia , Cistos/diagnóstico , Cistos/patologia , Ultrassonografia
9.
Urol Int ; 106(8): 775-783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34963122

RESUMO

INTRODUCTION: The aim of the study was to evaluate the effectiveness of a modified transvesical obturator nerve block (ONB) in the prevention of obturator nerve reflex and consecutive bladder perforations (BPs) during transurethral resection of bladder tumors (TURBTs). MATERIALS AND METHODS: A retrospective analysis of all patients resected in 2014-2015 due to a bladder tumor of the lateral walls, including a follow-up period until December 2018, was performed. Two groups were defined: in the first group, all patients underwent TURBT with a modified transvesical ONB. The second group underwent conventional TURBT with intermittent resection. Primary endpoints were the rates of adductor contractions and BPs. RESULTS: Ninety-four out of 1,145 resected patients presented with tumors on the lateral wall of the bladder and a complete dataset including a long-term follow-up. Thirty-six patients were treated in the ONB group, and 58 patients comprised the control group. The median age in the 2 groups was 70.8 and 71.8 years in the first and second groups, respectively. Adductor spasms were reported in 8.33 versus 25.86% (p = 0.057) and perforation in 2.78 versus 17.24% (p = 0.047) in groups 1 and 2, respectively. After a median follow-up of 32.5 months, there was no significant difference in recurrence rates (52.78 vs. 51.72%, p = 0.672). In a subgroup analysis, lower perforation rates were recorded for the ONB group in patients with tumors <3 cm (0/30 vs. 8/46, p = 0.076) and in patients with unifocal tumors (0/12 vs. 5/23, p = 0.141). DISCUSSION/CONCLUSION: The simplified approach of transvesical ONB demonstrated in this study appears to be an inexpensive, safe, effective, and simple-to-use technique.


Assuntos
Bloqueio Nervoso , Neoplasias da Bexiga Urinária , Idoso , Cistectomia/efeitos adversos , Cistectomia/métodos , Humanos , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Nervo Obturador/patologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
12.
Virchows Arch ; 479(2): 325-335, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33650041

RESUMO

Reliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213-231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/química , Imuno-Histoquímica , Neoplasias da Bexiga Urinária/química , Urotélio/química , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Urotélio/patologia
13.
Urol Oncol ; 39(5): 300.e7-300.e13, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33308977

RESUMO

PURPOSE: Bladder cancer is predominant in the elderly. Up to 70% of geriatric patients with muscle-invasive bladder cancer do not receive curative treatment. We analyzed the outcome of patients managed only by transurethral resection of bladder tumor (TURBT) without chemo- or radio-therapy, and performed a cost analysis of the cumulative inpatient interventions throughout the course of the disease. METHODS: From 2010 to 2016 81 patients ≥75 years with de novo muscle-invasive bladder cancer who were not eligible for curative treatment options were analyzed retrospectively. All patients were treated only with TURBT. Overall survival (OS) was measured by Kaplan-Meier plots (log-rank test) and clinical parameters predicting OS by a multivariate analysis. The cost analysis was based on actual billing from the hospital provider and referenced standardized pricing in Germany for bladder cancer treatment. RESULTS: The median age was 83 years. The OS was 11 months, the 1-year OS was 42%. In the multivariate model Charlson Comorbidity Index <8 (P = 0.016), tumor size ≤3 cm (P = 0.011), complete (T0) tumor resection (P = 0.003), normal C-reactive protein level (P = 0.010), and initial elective surgery (P = 0.035) were shown to be independent predictors of longer OS in palliative TURBT regimes. Median treatment cost for the TURBT regimen was $16,175 vs. $16,467 for a salvage radical cystectomy in this cohort. CONCLUSIONS: In a TURBT-only concept elective surgery, tumor size, Charlson Comorbidity Index, C-reactive protein level and complete TURBT are independent predictors of OS. The treatment-related cumulative cost appears to be higher in patients not managed by cystectomy.


Assuntos
Custos e Análise de Custo , Cistectomia/economia , Cistectomia/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento , Uretra , Neoplasias da Bexiga Urinária/patologia
14.
Urol Oncol ; 38(11): 851.e19-851.e25, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32739227

RESUMO

PURPOSE: To examine survival rates and to calculate the risk of disease recurrence, progression, overall, and cancer-specific mortality in patients diagnosed with high-risk NMIBC using a multi-institutional dataset to evaluate differences between the guidelines of the European Association of Urology and the guidelines of the National Comprehensive Cancer Network (NCCN) with regard to tumor size in risk stratification. METHODS AND MATERIAL: In total 1,116 individuals diagnosed with high-risk NMIBC between 2001 and 2013 were included in the analysis. Patients were stratified to NCCN guideline recommendations (high-grade T1, high-grade Ta ≤ 3 cm, and high-grade Ta > 3 cm). Recurrence and progression rates were calculated. Kaplan-Meier curves were fitted to examine differences in recurrence-free (RFS) and progression-free survival (PFS). Multivariable Cox proportional hazards regression models were employed to calculate differences in the RFS, PFS, overall, and cancer-specific survival (CSS). RESULTS: The majority of patients were diagnosed with high-grade T1 disease (N = 576, 51.6%), while 34.2% and 14.2% of patients were diagnosed with high-grade Ta ≤ 3 cm and Ta > 3 cm NMIBC, respectively. The 1- and 5-year RFS (1-year: 80.5% vs. 64.9%; 5-year: 58.6% vs. 48.3%, P = 0.048) and PFS (1-year: 99.1% vs. 98.6%; 5-year: 97.7% vs. 92.4%, P = 0.054) rates were higher in patients with Ta ≤ 3 cm. Patients diagnosed with high-grade Ta > 3 cm experienced unfavorable progression-free, and cancer-specific survival compared to high-grade Ta ≤ 3 cm, respectively (PFS: 2.41, 95% confidence interval [CI] 1.05-5.56, P = 0.038; CSS: hazard ratios [HR] 2.22, 95% CI 1.02-4.89, P = 0.048). CONCLUSION: Patients diagnosed with high-grade Ta NMIBC ≤3 cm demonstrated a favorable progression-free, and cancer-specific survival compared to patients diagnosed with high-grade Ta > 3 cm and high-grade T1 NMIBC.


Assuntos
Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Carga Tumoral , Neoplasias da Bexiga Urinária/classificação
15.
Oncogene ; 39(40): 6387-6392, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32820250

RESUMO

After publication of this Article, the Authors noticed errors in some of the Figures. In Figures 2e, 2f-g, 4a, 4j, 5a and 6b, unmatched ß-actin was inadvertently used as loading control for the immunoblots. These have been corrected using repeat data from a similar set of samples and the revised Figures containing matched ß-actin and their respective quantification data are included below. In Figure 7a, the same image was inadvertently used to represent tumors 3 and 5 in the control group. This error has been corrected using original images of tumors 3 and 5 in the control group. Additional corrections have been made in the Article and Figure legends to enhance the clarity of the description. NAD was replaced by NADP. NAD/NADP was replaced by NADP/NADPH. The description of the antibody source and dilution for the antigens PFKFB4 (Abcam, 1:1000), G6PD, and HK1 (Cell Signaling, 1:1,000) have been included in the Methods section for Western Blot. The legend for Figure 4e and 4j has been updated. The HTML and PDF versions of this Article have been corrected. The scientific conclusions of this paper have not been affected.

16.
Eur Urol Open Sci ; 22: 45-50, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34337476

RESUMO

BACKGROUND: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. OBJECTIVE: The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. DESIGN SETTING AND PARTICIPANTS: An online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons' experience and caseloads with pIVC utilization. RESULTS AND LIMITATIONS: Overall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7-10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%). CONCLUSIONS: Our research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted. PATIENT SUMMARY: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

17.
Oncogene ; 39(40): 6265-6285, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31383940

RESUMO

Advanced Bladder Cancer (BLCA) remains a clinical challenge that lacks effective therapeutic measures. Here, we show that distinct, stage-wise metabolic alterations in BLCA are associated with the loss of function of aldehyde oxidase (AOX1). AOX1 associated metabolites have a high predictive value for advanced BLCA and our findings demonstrate that AOX1 is epigenetically silenced during BLCA progression by the methyltransferase activity of EZH2. Knockdown (KD) of AOX1 in normal bladder epithelial cells re-wires the tryptophan-kynurenine pathway resulting in elevated NADP levels which may increase metabolic flux through the pentose phosphate (PPP) pathway, enabling increased nucleotide synthesis, and promoting cell invasion. Inhibition of NADP synthesis rescues the metabolic effects of AOX1 KD. Ectopic AOX1 expression decreases NADP production, PPP flux and nucleotide synthesis, while decreasing invasion in cell line models and suppressing growth in tumor xenografts. Further gain and loss of AOX1 confirm the EZH2-dependent activation, metabolic deregulation, and tumor growth in BLCA. Our findings highlight the therapeutic potential of AOX1 and provide a basis for the development of prognostic markers for advanced BLCA.


Assuntos
Aldeído Oxidase/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária/patologia , Aldeído Oxidase/metabolismo , Animais , Linhagem Celular Tumoral , Progressão da Doença , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Cinurenina/metabolismo , Masculino , Metabolômica , Camundongos , NADP/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Nucleotídeos/biossíntese , Via de Pentose Fosfato/genética , RNA-Seq , Análise Serial de Tecidos , Triptofano/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Urology ; 137: 84-90, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31877313

RESUMO

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.


Assuntos
Citocromo P-450 CYP2D6/genética , Qualidade de Vida , Fibrose Retroperitoneal , Tamoxifeno , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos/métodos , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fibrose Retroperitoneal/diagnóstico por imagem , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/genética , Fibrose Retroperitoneal/psicologia , Espaço Retroperitoneal/diagnóstico por imagem , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Resultado do Tratamento
19.
J Vasc Interv Radiol ; 31(3): 378-387, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31735482

RESUMO

PURPOSE: To determine if cone-beam CT and digital subtraction angiography analysis of pelvic arterial anatomy has predictive value for radiation exposure and technical success of prostatic artery embolization (PAE). MATERIALS AND METHODS: This prospective, nonrandomized, single-center study included 104 consecutive patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Cone-beam CT was performed in 160/208 (76.9%) hemipelves to determine prostatic artery (PA) origin. Classification of pelvic arterial tortuosity was possible in 73/104 (70.2%) patients. Learning curves of 2 interventionalists who performed 86.5% of PAEs were analyzed. RESULTS: Tortuosity of pelvic arteries was classified as mild in 25 (34.2%) patients median age 64 years, moderate in 40 (54.8%) patients median age 69 years, and severe in 8 (11.0%) patients median age 70 years (mild vs moderate, P = .002; mild vs severe, P = .019); median fluoroscopy times were 24, 36, and 46 minutes (P = .008, P = .023); median contrast volumes were 105, 122.5, and 142 mL (P = .029, P = .064); and bilateral PAE rates were 84.0%, 77.5%, and 62.5% (P = .437), respectively. PA origin from superior vesical artery was most frequent (27.5%) and showed higher dose area product (median 402.4 vs 218 Gy ∙ cm2, P = .033) and fluoroscopy time (median 42.5 vs 27 min, P = .01) compared with PA origin from obturator artery, which was least frequent. Interventionalist experience revealed significant impact on procedure times (median 159 vs 130 min, P = .006). CONCLUSIONS: Tortuosity of pelvic arteries was more frequent in older patients and predicted worse technical outcomes of PAE. PA origin from obturator artery was associated with lower dose area product and fluoroscopy time, especially compared with PA origin from superior vesical artery. Interventionalist experience showed significant influence on technical outcome.


Assuntos
Angiografia Digital , Artérias/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Embolização Terapêutica , Sintomas do Trato Urinário Inferior/terapia , Próstata/irrigação sanguínea , Hiperplasia Prostática/terapia , Idoso , Idoso de 80 Anos ou mais , Artérias/anormalidades , Competência Clínica , Embolização Terapêutica/efeitos adversos , Humanos , Curva de Aprendizado , Sintomas do Trato Urinário Inferior/diagnóstico por imagem , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/fisiopatologia , Radiologistas , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
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