Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.288
Filtrar
1.
Arch. esp. urol. (Ed. impr.) ; 73(5): 374-383, jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-189694

RESUMO

OBJETIVOS: Las directrices y recomendaciones de la buena práctica clínica se han visto trastocadas por las nuevas y urgentes prioridades, marcadas po rla pandemia COVID-19. El carcinoma urotelial es una enfermedad de prevalencia significativa en España, cuya población se ha visto muy afectada por la COVID-19, directamente por la enfermedad e indirectamente por el confinamiento. El objetivo de este trabajo es ofrecer recomendaciones sobre protocolos y circuitos asistenciales ajustados a diferentes fases de la pandemia. MATERIAL Y MÉTODOS: El presente documento sobre el manejo del carcinoma vesical, se basa en la escasa evidencia sobre la práctica oncológica urológica durante los primeros meses de la pandemia y en la experiencia de los autores en esta patología durante la crisis del COVID-19. En ella, han participado expertos hospitalarios en patología infecciosa y radiodiagnóstico para diseñar una estrategia común y reorganizar así la actividad. RESULTADOS: Se presentan distintas propuestas de tratamiento y seguimiento de los pacientes diagnosticados de cáncer vesical ajustados al riesgo oncológico en las diferentes fases de la pandemia. CONCLUSIONES: La velocidad de expansión de la pandemia era inimaginable hace solo unos meses. Los sistemas sanitarios se han visto sacudidos por la enfermedad en las fases más críticas. Es necesario, en estos momentos, realizar un esfuerzo más para desarrollar herramientas que puedan facilitar la asistencia del carcinoma vesical y minimizar el impacto y los riesgos para los pacientes y los profesionales de la salud en el futuro


OBJECTIVES: The guidelines and recommendations of good clinical practice have been disrupted by new and urgent policies, marked by the COVID-19 pandemic. Urothelial carcinoma has a significant prevalence in Spain, whose population has been greatly affected by COVID-19, directly by the disease and indirectly by the confinement. The objective of this work is to offer recommendations on protocols and guidelines adjusted to different phases of the pandemic. MATERIAL AND METHODS: This document on the management of bladder carcinoma is based on few evidence on urological oncological practice during the first months of the pandemic and on the authors' experience in this pathology during the crisis of COVID-19. Hospital experts in infectious disseases and radiology have participated to design a common strategy to reorganize the activity. RESULTS: Different proposals for treatment and follow-up of patients diagnosed with bladder cancer adjusted for oncological risk and the different phases of the pandemic are presented. CONCLUSIONS: The pandemic's spread was unimaginable just a few months ago. Health systems have been shaken by the disease in the most critical phases. It is necessary, at this time, to make an additional effort to develop tools that can facilitate the care of bladder carcinoma and minimize the impact and risks for patients and health professionals in the future


Assuntos
Humanos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Prioridades em Saúde , Guias de Prática Clínica como Assunto , Fatores de Risco , Prognóstico
2.
Arch Esp Urol ; 73(5): 374-383, 2020 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-32538807

RESUMO

OBJECTIVES: The guidelines and recommendation sof good clinical practice have been disrupted by new and urgent policies, marked by the COVID-19 pandemic. Urothelial carcinoma has a significant prevalence in Spain, whose population has been greatly affected by COVID-19, directly by the disease and indirectly by the confinement. The objective of this work is to offer recommendations on protocols and guidelines adjusted to different phases of the pandemic. MATERIAL AND METHODS: This document on the management of bladder carcinoma is based on few evidence on urological oncological practice during the first months of the pandemic and on the authors' experience in this pathology during the crisis of COVID-19. Hospital experts in infectious disseases and radiology have participated to design a common strategy to reorganize the activity. RESULTS: Different proposals for treatment and follow-up of patients diagnosed with bladder cancer adjusted for oncological risk and the different phases of the pandemic are presented. CONCLUSIONS: The pandemic's spread was unimaginable just a few months ago. Health systems have been shaken by the disease in the most critical phases. It is necessary, at this time, to make an additional effort to develop tools that can facilitate the care of bladder carcinoma and minimize the impact and risks for patients and health professionals in the future.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Neoplasias da Bexiga Urinária , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Pneumonia Viral/epidemiologia , Espanha , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia
3.
Analyst ; 145(12): 4173-4180, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32490854

RESUMO

Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


Assuntos
MicroRNA Circulante/sangue , Corantes Fluorescentes/química , Análise Espectral Raman , Neoplasias da Bexiga Urinária/diagnóstico , Betacoronavirus/isolamento & purificação , Biomarcadores Tumorais/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Ouro/química , Humanos , Limite de Detecção , Microscopia Confocal , Nanoestruturas/química , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
4.
DNA Cell Biol ; 39(6): 1072-1089, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32352838

RESUMO

The roof plate-specific spondin (RSPO) family of proteins has critical roles in the tumorigenesis and progression of several carcinomas; however, little is known about their functions in bladder cancer (BLCA). This study aimed to investigate RSPO in terms of their expression levels, prognostic value, and potential mechanisms of action in BLCA. mRNA expression profiles and clinical information of BLCA patients were collected from The Cancer Genome Atlas database. Genetic alteration and DNA methylation data were obtained from cBioPortal and MethHC databases, respectively, and SurvExpress was used to determine the prognostic risk score of each RSPO. R software was used to analyze the expression levels and prognostic roles of RSPOs in BLCA. The effects of RSPO2 overexpression in BLCA cells were detected using MTT, colony formation, and Transwell invasion assays. Gene set enrichment analysis (GSEA) was used to analyze the functions of RSPOs and associated signaling pathways in BLCA. All members of the RSPO family were differentially expressed in BLCA cells compared with normal control cells. Aberrant RSPO expression levels were associated with higher histological stages and worse prognosis. The frequency of genetic alterations in RSPO genes was very high, which was related to a less favorable prognosis. Moreover, the effects of mutations in the RSPO2 gene were reversed using a Wnt/ß-catenin inhibitor, IWP-2. In addition, GSEA demonstrated that RSPOs were associated with focal adhesion and immune cell infiltration, which was then confirmed by tumor immune cell infiltration analysis. RSPOs are potential biomarkers for predicting the prognosis of patients with BLCA and may serve as novel therapeutic targets. Moreover, overexpressed RSPO2 promoted BLCA cell growth and invasion through the Wnt/ß-catenin pathway. In addition, RSPOs may regulate the progression of BLCA through modulating cell adhesion, focal adhesion, and CD4+ T cell and macrophage infiltration.


Assuntos
Regulação Neoplásica da Expressão Gênica , Trombospondinas/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Linhagem Celular Tumoral , Metilação de DNA , Humanos , Mutação , Prognóstico , RNA Mensageiro/genética , Análise de Sobrevida
5.
Med Sci Monit ; 26: e920504, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277695

RESUMO

BACKGROUND Evidence indicates that there is an important role for long non-coding RNAs (lncRNA) in numerous cellular processes and that lncRNAs dysregulation contributes to tumor progression. Improved insight into the molecular characteristics of bladder cancer is required to predict outcomes and to develop a new rationale for targeted therapeutic strategies. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information about differentially expressed genes (DEGs) in bladder cancer. This study aimed to explore the role of lncRNAs and their regulation network in bladder cancer. MATERIAL AND METHODS We analyzed bladder cancer data by The Cancer Genome Atlas profiling to identify differentially expressed lncRNAs in bladder cancer. The genes involved in the circlncRNAnet database were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), evolutionary relationship analysis, and protein-protein interaction (PPI) networks. RESULTS Two new lncRNAs, ADAMTS9-AS1 and LINC00460, were shown to be differentially expressed in bladder cancer. Patients were divided into 2 groups (high expression and low expression) according to their median expression values. The overall survival and disease-free survival of patients with high ADAMTS9-AS1 bladder cancer were significantly shorter; the expression of LINC00460 had no significant correlation with survival. GO and KEGG analysis of the 2 lncRNA-related genes revealed that these lncRNAs played a vital role in tumorigenesis. Bioinformatics analysis showed that key genes related to LINC00460, including CXCL, CCL, and CSF2, may be related to the development of bladder cancer. The low expression of ADAMTS9-AS1 may influence the survival rate of bladder cancer with the hub gene as a target. CONCLUSIONS LncRNA, including LINC00460 and ADAMTS9-AS1, might play a crucial role in the biosynthesis network of bladder cancer. Differential expression results of ADAMTS9-AS1 suggests it may be correlated with a worse prognosis and a shorter survival time. We outlined the biosynthesis network that regulates lncRNAs in bladder cancer. Further experimental data is needed to validate our results.


Assuntos
RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida , Transcriptoma , Neoplasias da Bexiga Urinária/diagnóstico
8.
Curr Urol Rep ; 21(5): 19, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32248340

RESUMO

PURPOSE OF REVIEW: It has been firmly established that hexaminolevulinate-assisted blue light cystoscopy (HAL-BLC) reduces cancer recurrence rates. This review explores the impact of HAL-BLC on other meaningful outcomes in patients with bladder cancer, including disease progression, and earlier detection of disease at the time of surveillance cystoscopy. RECENT FINDINGS: A randomized clinical trial confirmed earlier implementation of HAL-BLC at the time of surveillance cystoscopy increased identification of cancerous lesions, including those of high grade, when compared with white light cystoscopy. In addition, the evidence is evolving that the use of HAL-BLC at the time of endoscopic treatment of high-risk tumors may lead to lower rates of progression to muscle invasion, and this in part may be due to better risk stratification leading to changes in treatment plan. The clinical contexts for the use of HAL-BLC are broader than prior knowledge. It is also becoming more clear that the positive impact of HAL-BLC is likely more than just reducing cancer recurrence rates, and patients would benefit from the technology at many time points in the management and follow-up of their disease.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Cistoscopia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Ácido Aminolevulínico/administração & dosagem , Progressão da Doença , Humanos , Luz , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(2): 97-103, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32314705

RESUMO

Objective To study the infiltration pattern of bladder cancer immune cells and explore the relationship between immune cells and tumor prognosis. Methods The bladder cancer transcript data and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA). CIBERSORT software deconvolution method was used to calculate the proportions of 22 kinds of immune cells. R software was used to analyze the immune cell infiltration pattern in each clinical stage. The relationship between each immune cell and prognosis was analyzed by Kaplan-Meier survival. Results A total of 433 cases of gene transcript data were downloaded from the TCGA database, including 414 cases of bladder cancer tissues and 19 normal tissues. After the data were corrected, the proportions of immune cells were calculated using CIBERSORT software. Screening was performed, and 146 cases of bladder cancer tissue and 4 cases of normal bladder tissue were obtained. Activated CD4+ memory T cells and CD8+ T cells had the lowest expression and M0 macrophages had the highest expression in clinical stage IV of bladder cancer. The bladder cancer patients with high expression of activated CD4+ memory T cells, CD8+ T cells and low expression of M0 macrophages had beneficial prognosis. Conclusion The bladder cancer patients with high expression of activated CD4+ memory T cells, CD8+ T cells and low expression of M0 macrophages might have better clinical prognosis.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Macrófagos/imunologia , Neoplasias da Bexiga Urinária/imunologia , Humanos , Memória Imunológica , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico
10.
Urologe A ; 59(6): 731-732, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32242269

RESUMO

The annual symposium of the German Research Association for Bladder Carcinoma (DFBK) was organized on February 7th and 8th, 2020, in Düsseldorf. On the first day, eight international guest speakers invited by the DFBK and the Department of Urology of the Heinrich Heine University Düsseldorf presented the current state of research on bladder cancer (BC). Topics were genomic changes and molecular classification in non-muscle-invasive and muscle-invasive BC, prospects and limits of proteome technology in urine diagnostics, function of chromatin regulators in bladder carcinogenesis, cellular reactions to aneuploidy, organoid technology and biobanking, as well as novel aspects of immunotherapy for BC. The second day was dedicated to new results and ideas of the DFBK members on BC pathomechanisms, diagnostics and therapeutic approaches, and most importantly, discussions on the further development of collaborative projects. Additional information is available at http://www.forschungsverbund-blasenkarzinom.de.


Assuntos
Bancos de Espécimes Biológicos , Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Congressos como Assunto , Humanos , Pesquisa , Sociedades Médicas , Neoplasias da Bexiga Urinária/diagnóstico , Urologia/tendências
11.
Med Sci Monit ; 26: e921087, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147666

RESUMO

BACKGROUND We sought to investigate the expression of KPNA2 in bladder cancer (BC) and its relationship with prognosis, and to analyze the potential mechanism of KPNA2 in promoting BC progression. MATERIAL AND METHODS The RNA-seq data on BC from The Cancer Genome Atlas (TCGA) database were imported into R statistical software for differential analysis. The clinical data for patients with BC were screened and analyzed with R software. The survival curve was drawn with the Kaplan-Meier Plotter. The expression of KPNA2 in 4 human BC cell lines and a human bladder epithelial cell line was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The proliferation of BC cells was detected with Cell Counting Kit-8 (CCK8), detection of apoptosis, and flow cytometry, and the migration and invasion of BC cells were detected through Transwell assays. WB was used to detect proteins involved in the P53 pathway. RESULTS The expression of KPNA2 was higher in BC. The difference in KPNA2 expression was associated with many clinicopathological factors, and high expression of KPNA2 was associated with shorter survival time. After KPNA2 knockout, the proliferation, migration, and invasion ability decreased significantly, the cell cycle was clearly arrested in the G0/G1 phase, and the number of apoptotic cells increased. Moreover, CyclinD1, BCL2, and pro-caspase3 decreased significantly, whereas P53, P21, BAX, and cleaved-caspase3 increased significantly. The results in the overexpression group were the opposite of results in the knockdown group. CONCLUSIONS KPNA2 is an oncogenic factor that facilitates BC tumorigenicity through the P53 pathway.


Assuntos
Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/patologia , alfa Carioferinas/genética , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética
12.
PLoS One ; 15(3): e0230417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203532

RESUMO

PURPOSE: To assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: A retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death. RESULTS: Among 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; p<0.001). Risk of death from bladder cancer did not differ significantly by low (cumulative incidence [CIn] 8.4% [95% CI 6.5-10.9) at 5 years) vs. high-intensity surveillance (CIn 9.1% [95% CI 7.4-11.2) at 5 years, p = 0.61). Low vs. high-intensity surveillance was not associated with increased risk of bladder cancer death among patients with Ta (CIn 5.7% vs. 8.2% at 5 years p = 0.24) or T1 disease at diagnosis (CIn 10.2% vs. 9.1% at 5 years, p = 0.58). Among patients with Ta disease, low-intensity surveillance was associated with decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (CIn 19.3% vs. 31.3% at 5 years, p = 0.002). CONCLUSIONS: Patients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC.


Assuntos
Carcinoma de Células de Transição/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/patologia , Cistoscopia/métodos , Feminino , Humanos , Masculino , Músculo Esquelético/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia
13.
Curr Oncol Rep ; 22(1): 9, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989430

RESUMO

PURPOSE OF REVIEW: The aim of this review is to sum up the state of the art of urachal carcinoma (UC) in order to easily guide clinicians. RECENT FINDINGS: UC is a rare and aggressive disease with consequent few data about diagnosis and treatment. Dates are mainly based on retrospective trial and case reports with limited prospective trial. Clinical presentation is not specific, often with urinary symptoms. Diagnosis is mainly based on CT scan and MRI, useful to evaluate local invasion and nodal status and to detect the presence of distant metastases. Therefore, biopsy is needed to obtain histological confirmation. Surgery is the gold standard for localized disease, while different chemotherapy schemes have been used in metastatic setting. Novel findings based on mutational analysis of the tumor include the use of biological treatment, such as cetuximab, and immunotherapy, such as atezolizumab, with satisfactory responses, suggesting that personalized treatment could be the most suitable option for UC.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Cistectomia/métodos , Humanos , Imunoterapia , Terapia de Alvo Molecular , Prognóstico , Neoplasias da Bexiga Urinária/patologia
14.
BMC Cancer ; 20(1): 8, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900121

RESUMO

BACKGROUND: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. METHODS: Study design: "RACE IT" (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11-15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. DISCUSSION: This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. TRIAL REGISTRATION: Protocol Code RACE IT: AB 65/18; EudraCT: 2018-001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018.


Assuntos
Radioterapia Adjuvante , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Cistectomia , Feminino , Humanos , Imunoterapia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Resultado do Tratamento
15.
Acta Cytol ; 64(1-2): 182-192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31060038

RESUMO

Aside from its diagnostic importance, urinary tract endoscopy is an uncomfortable, expensive, and time-consuming procedure. Patients with a history of urothelial carcinoma remain at an increased risk for recurrence and the development of de novo disease; most have had exposure to carcinogenic risk factors for decades prior to their first diagnosis that have bathed the entire urothelial tract. Consequently, monitoring these patients over their lifetime has made urothelial carcinoma one of the most expensive cancers for the US healthcare system. This expense has provided a financial incentive for academic and commercial groups to develop a test with a sufficient negative predictive value to reduce the frequency of surveillance procedures. Slide-based tests require a separate slide prepared from a split urine sample or from an additional urinary tract specimen. This process can place an additional burden on the laboratory due to changes in the workflow, especially if the split specimens need to be stored until a cytologic diagnosis is rendered (i.e., when used as a reflex test). Importantly, slide-based tests allow for the result to be directly correlated with cytomorphologic findings; however, these tests require the cells of interest to be present. Thus, slide-based tests suffer from the same sensitivity issues as urinary tract cytology. In contrast, slide-free tests do not require an additional slide to be prepared, and laboratory testing may be centralized to a core facility or performed on-site. Some tests detect the expression of altered or abnormally expressed subcellular material (proteins, DNA, etc.) in urothelial neoplasms, which are found in tumor cells and/or in the urine specimen when the proteins are either excreted or leaked from degenerating tumor cells. Slide-free tests may also be developed into point-of-care tests, meaning that the result may be available to the urologist but not to the cytopathologist. Since these proteins are often disassociated from the tumor cells that produce them, such tests may have a positive result even if tumor cells are absent in the tested specimen. Here we review critical concepts as well as several ancillary tests that have been developed for urinary tract specimens.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Citodiagnóstico/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Urotélio/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Análise Mutacional de DNA/métodos , Humanos , Hibridização in Situ Fluorescente/métodos , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Sistema Urinário/metabolismo , Sistema Urinário/patologia , Urotélio/metabolismo
17.
Am J Clin Pathol ; 153(2): 274-284, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31732739

RESUMO

OBJECTIVES: Our aim was to predict progression of non-muscle-invasive bladder urothelial carcinomas (NMIUCs) into muscle-invasive disease by assessing cytogenetic abnormality of tumors with a new UroVysion scoring system. METHODS: Seventy-five bladder cancer cases (including 57 NMIUCs) were classified according to the quantitatively assessed degree of UroVysion-detected chromosomal abnormalities into urine fluorescence in situ hybridization score (UFS) groups: UFS I, II, and III. Cox time-to-event, Kaplan-Meier, and C-statistics analyses were performed. RESULTS: UFS proved to be an independent prognostic factor of progression-free survival (PFS) and time to progression (TTP). NMIUCs with UFS III had a 34.05-fold increased hazard for progression to muscle-invasive cancer (TTP; 95% confidence interval, 5.841-198.5; P < .001) in comparison with UFS I to II cases. The addition of UFS to conventional risk scores increased the C-index for PFS and TTP. CONCLUSIONS: UFS can indicate an increased risk for progression into muscle-invasive disease in patients with NMIUC and improves prognostic accuracy of the current clinical risk assessment systems.


Assuntos
Hibridização in Situ Fluorescente/métodos , Neoplasias da Bexiga Urinária/genética , Progressão da Doença , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade
18.
J Urol ; 203(5): 902-909, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31821066

RESUMO

PURPOSE: Rescue intravesical therapies for patients with bacillus Calmette-Guérin failure nonmuscle invasive bladder cancer remain a critical focus of ongoing research. Sequential intravesical gemcitabine and docetaxel therapy has shown safety and efficacy in 2 retrospective, single institution cohorts. This doublet has since been adopted as an intravesical salvage option at multiple institutions. We report the results of a multi-institutional evaluation of gemcitabine and docetaxel. MATERIALS AND METHODS: Each institution retrospectively reviewed all records of patients treated with intravesical gemcitabine and docetaxel for nonmuscle invasive bladder cancer between June 2009 and May 2018. Only patients with recurrent nonmuscle invasive bladder cancer and a history of bacillus Calmette-Guérin treatment were included in the analysis. If patients were disease-free after induction, maintenance was instituted at the treating physician's discretion. Posttreatment surveillance followed American Urological Association guidelines. Survival analysis was performed using the Kaplan-Meier method and risk factors for treatment failure were assessed with Cox regression models. RESULTS: Overall 276 patients (median age 73 years, median followup 22.9 months) received treatment. Nine patients were unable to tolerate a full induction course. One and 2-year recurrence-free survival rates were 60% and 46%, and high grade recurrence-free survival rates were 65% and 52%, respectively. Ten patients (3.6%) had disease progression on transurethral resection. Forty-three patients (15.6%) went on to cystectomy (median 11.3 months from induction), of whom 11 (4.0%) had progression to muscle invasion. Analysis identified no patient, disease or prior treatment related factors associated with gemcitabine and docetaxel failure. CONCLUSIONS: Intravesical gemcitabine and docetaxel therapy is well tolerated and effective, providing a durable response in patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin therapy. Further prospective study is warranted.


Assuntos
Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Biópsia , Canadá/epidemiologia , Cistoscopia , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade
19.
Virchows Arch ; 476(3): 423-429, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31482302

RESUMO

Urine cytology is an essential element of the diagnostic work up of hematuria. A significant proportion of cases continue to be placed in the "atypical" or "suspicious" categories of the Paris system for urine cytology, posing difficulty in patient management. We report on the performance of our recently described urine-based assay "UroSEEK" in cases with equivocal diagnosis in patients who are investigated for bladder cancer. Urine samples were collected from two cohorts. The first consisted of patients who presented with hematuria or lower urinary tract symptoms (early detection cohort) and the second of patients that are in follow-up for prior bladder cancer (surveillance cohort). Urine samples were analyzed for mutations in 11 genes and aneuploidy. In the early detection setting, we found high sensitivity and specificity (96% and 88%, respectively) and a strong negative predictive value of 99%. The assay performance was less robust in the surveillance cohort (sensitivity of 74%, specificity of 72%, and negative predictive value of 53%). UroSEEK demonstrated a notable lead time to cancer diagnosis. Seven cases in the early detection cohort and 71 surveillance cases were detected at least 6 months prior to clinical diagnosis. Our results suggest a potential role for UroSEEK assay in guiding management of patients with atypical urine cytology if confirmed in future prospective trials.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Urinálise/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
20.
Neoplasma ; 67(1): 137-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31777254

RESUMO

Cell-free circular RNAs (circRNAs) stably and abundantly exist in body fluids. In this study we aimed to investigate the potential of urinary cell-free circRNAs as a novel class of noninvasive disease biomarkers for diagnosis of bladder cancer. Differentially expressed circRNAs from 10 normal and 10 bladder cancer urine samples were firstly detected by microarray. Hsa_circ_0137439 was then screened and validated in 30 normal and 116 bladder cancer samples. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0137439. The Kaplan-Meier method was used to evaluate the significance of hsa_circ_0137439 in the prognosis of bladder cancer. We found that hsa_circ_0137439 was significantly upregulated in bladder cancer samples. Moreover, increased expression of hsa_circ_0137439 was correlated with higher tumor stage, higher tumor grade, higher lymph node status, and history of muscle-invasive bladder cancer (MIBC). Also, urinary cell-free hsa_circ_0137439 could not only differentiate bladder cancer from normal controls but also distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). Additionally, hsa_circ_0137439 in urine supernatant could serve as an independent prognostic predicator of recurrence-free survival and overall survival for patients with bladder cancer. Cell assays showed that hsa_circ_0137439 knockdown contributed to the inhibition of cell proliferation and migration via hsa_circ_0137439/miR-142-5p/ MTDH axis. In conclusion, urinary cell-free hsa_circ_0137439 could be a promising biomarker for tumor diagnosis and prognostic assessment of bladder cancer patients.


Assuntos
Biomarcadores Tumorais/urina , RNA Circular/urina , Neoplasias da Bexiga Urinária/diagnóstico , Moléculas de Adesão Celular , Proliferação de Células , Humanos , Proteínas de Membrana , Prognóstico , Proteínas de Ligação a RNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA