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1.
Cell ; 173(2): 515-528.e17, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29625057

RESUMO

Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine.


Assuntos
Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Mutação , Organoides/citologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Medicina de Precisão , Transplante Heterólogo , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo
2.
Int Urogynecol J ; 32(11): 2959-2967, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34570246

RESUMO

INTRODUCTION AND HYPOTHESIS: To evaluate whether the studies contributing to the national treatment guidelines on pelvic organ prolapse adequately represent the racial and/or ethnic makeup of the American population. METHODS: This analysis examines the racial and ethnic makeup of all primary study cohorts contributing to the American College of Obstetricians and Gynecologists/American Urogynecologic Society Practice Bulletin No. 214 on pelvic organ prolapse. References were excluded if they lacked a primary patient population or were from outside the US. Mean proportional representation of racial/ethnic groups was compared to the 2018 United States Census data on race/ethnicity. The representation quotient was also calculated to evaluate for relative representation of each group. Descriptive statistics were used. RESULTS: Of the 110 references, 53 primary studies were included in the final analysis with 30 studies reporting on race/ethnicity. On average, 82% (SD = 15%) of study populations were White, while Blacks, Hispanics, and Asians represented 67% (SD = 7%), 4% (SD = 8%), and < 1% (SD = 1%), respectively, differing significantly from the 2018 US Census (p < 0.01.) The representation quotients for White women was 1.36, demonstrating a 36% overrepresentation, while Black, Hispanic, and Asian women were underrepresented among studies of all evidence levels, with representative quotients of 0.50, 0.23, and 0.09, respectively. CONCLUSIONS: Our study demonstrates a significant underrepresentation of non-White populations in primary cohorts of studies contributing to the ACOG/AUGS Practice Bulletin No. 214 on POP. This analysis reinforces that more efforts are required to include and report on racial and ethnically diverse cohorts to better serve all patients.


Assuntos
Etnicidade , Prolapso de Órgão Pélvico , Negro ou Afro-Americano , Feminino , Hispânico ou Latino , Humanos , Prolapso de Órgão Pélvico/terapia , Guias de Prática Clínica como Assunto , Estados Unidos
3.
J Urol ; 206(5): 1266-1267, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34372684
4.
J Urol ; 195(6): 1704-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26807928

RESUMO

PURPOSE: We compared the pathological and survival outcomes of patients who underwent radical cystectomy soon after bacillus Calmette-Guérin failure with those of patients who received additional salvage intravesical chemotherapy before cystectomy for nonmuscle invasive bladder cancer. We also identified predictors of prognosis in the entire cohort. MATERIALS AND METHODS: We retrospectively analyzed the records of 117 patients who underwent radical cystectomy for recurrent nonmuscle invasive bladder cancer at our institution from 1990 to 2012. The cohort was divided into group 1 of 61 patients treated only with bacillus Calmette-Guérin with or without interferon-α and group 2 of 56 who received at least 1 additional salvage intravesical chemotherapy after bacillus Calmette-Guérin. RESULTS: Final pathology and survival outcomes did not differ significantly between the groups. Five-year overall and cancer specific survival was similar in groups 1 and 2 at 80% and 85%, respectively, at approximately equivalent followups. Median bladder retention was 1.7 years longer in group 2 (p <0.001). On multivariate Cox regression analysis delayed cystectomy in group 2 did not convey a significant hazard for all cause mortality after cystectomy (HR 1.08, p = 0.808). Only up-staging to cT1 (HR 1.88, p = 0.045), lymph node invasion (HR 2.58, p = 0.023) and prostatic urethra involvement (HR 1.95, p = 0.029) achieved significance. CONCLUSIONS: With appropriate selection for salvage intravesical chemotherapy patients who elect bladder sparing treatment instead of earlier radical cystectomy after bacillus Calmette-Guérin fails do not sacrifice positive pathological or oncologic outcomes while retaining bladder function for a significantly longer duration.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Cistectomia/métodos , Terapia de Salvação/efeitos adversos , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cistectomia/efeitos adversos , Progressão da Doença , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mycobacterium bovis , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação/métodos , Taxa de Sobrevida , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade
5.
J Urol ; 192(6): 1633-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24996128

RESUMO

PURPOSE: Response rates to current second line intravesical therapies for recurrent nonmuscle invasive bladder cancer range between 10% and 30%. Nanoparticle albumin bound (nab-)paclitaxel has increased solubility and lower toxicity compared to other taxanes. Results of the phase I intravesical trial of this compound demonstrated minimal toxicity during dose escalation. We now report the results of a phase II trial to assess efficacy. MATERIALS AND METHODS: This study was an investigator initiated, single center, single arm, phase II trial investigating the use of nab-paclitaxel in patients with recurrent Tis, T1 and Ta urothelial carcinoma in whom at least 1 prior regimen of intravesical bacillus Calmette-Guérin failed. Patients received 500 mg/100 ml nab-paclitaxel administered in 6 weekly intravesical instillations. Efficacy was evaluated with cystoscopy, biopsy, cytology and imaging. If complete response was achieved, patients were treated with full dose monthly maintenance treatments for 6 months. RESULTS: A total of 28 patients were enrolled in the study. Of these patients 10 (35.7%) exhibited a complete response after initial treatment. At 1 year all of these responses remained durable after maintenance therapy. At a mean followup of 21 months (range 5 to 47) 19 of 28 (67.8%) patients retained their bladders without progression or distant metastases. A single patient had progression to muscle invasive disease at radical cystectomy. Treatment related adverse events were noted in 9 of 28 (32.1%) patients and were limited to grade 1 or 2. CONCLUSIONS: Intravesical nab-paclitaxel has minimal toxicity and a 35.7% response rate in patients with nonmuscle invasive bladder cancer and previous bacillus Calmette-Guérin failure. Complete response remained durable at 1 year followup in this heavily pretreated patient population.


Assuntos
Albuminas/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia
6.
J Urol ; 189(3): 834-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23123371

RESUMO

PURPOSE: Docetaxel is a safe agent for intravesical therapy. Adding monthly maintenance treatments can extend response durability. We report our cumulative experience with intravesical docetaxel in a larger cohort with extended followup. MATERIALS AND METHODS: A total of 54 patients received salvage intravesical docetaxel for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer between 2003 and 2012, including 18 treated during the original phase I trial. All patients received 6 weekly instillations of intravesical docetaxel. After the phase I trial, those with a complete response to induction treatment were offered single dose monthly maintenance treatments for a total of up to 12 months of docetaxel therapy. Recurrence was defined as positive biopsy or urine cytology. Recurrence-free, disease specific and overall survival was determined by Kaplan-Meier analysis. RESULTS: Median followup was 39.1 months. Of the 54 patients 32 (59%) had a complete initial response after induction therapy, including 18 who received additional monthly maintenance treatments. Median time to recurrence in initial responders treated with vs without docetaxel maintenance was 39.3 vs 19.0 months. One and 3-year recurrence-free survival rates for the entire cohort were 40% and 25%, respectively. Of the 54 patients 17 (24%) underwent radical cystectomy at a median of 24 months of followup. Five-year disease specific and overall survival rates were 85% and 71%, respectively. CONCLUSIONS: Intravesical docetaxel appears to be a promising agent with significant efficacy and durability for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. Adding maintenance treatments may increase the duration of recurrence-free survival.


Assuntos
Vacina BCG/administração & dosagem , Invasividade Neoplásica , Taxoides/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/patologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Docetaxel , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/patologia
7.
Curr Urol Rep ; 14(2): 65-70, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23378162

RESUMO

The definitive treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical bacillus Calmette-Guérin (BCG) is cystectomy. However, many patients who experience recurrence after BCG are either poor operative candidates or refuse surgery due to the long-term impact on their quality of life. In the last decade, there has been an increased interest in alternative intravesical therapies, and several novel chemotherapeutics have emerged as promising agents for high-risk NMIBC patients unable or unwilling to undergo cystectomy. Additionally, extended treatment regimens with combined induction and maintenance therapy have been investigated, and may increase the durability of response to these new agents, as has been shown for conventional intravesical therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Humanos , Mitomicina/uso terapêutico , Paclitaxel/uso terapêutico , Taxoides/uso terapêutico , Tiotepa/uso terapêutico , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia , Gencitabina
8.
Cancer Res ; 83(4): 506-520, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36480186

RESUMO

Mutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited. Here, we showed that transgenic expression of human APOBEC3G promotes mutagenesis, genomic instability, and kataegis, leading to shorter survival in a murine bladder cancer model. Acting as mutagenic fuel, APOBEC3G increased the clonal diversity of bladder cancer, driving divergent cancer evolution. Characterization of the single-base substitution signature induced by APOBEC3G in vivo established the induction of a mutational signature distinct from those caused by APOBEC3A and APOBEC3B. Analysis of thousands of human cancers revealed the contribution of APOBEC3G to the mutational profiles of multiple cancer types, including bladder cancer. Overall, this study dissects the mutagenic impact of APOBEC3G on the bladder cancer genome, identifying that it contributes to genomic instability, tumor mutational burden, copy-number loss events, and clonal diversity. SIGNIFICANCE: APOBEC3G plays a role in cancer mutagenesis and clonal heterogeneity, which can potentially inform future therapeutic efforts that restrict tumor evolution. See related commentary by Caswell and Swanton, p. 487.


Assuntos
Desaminase APOBEC-3G , Evolução Clonal , Mutagênese , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Desaminase APOBEC-3G/genética , Desaminase APOBEC-3G/metabolismo , Evolução Clonal/genética , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Instabilidade Genômica , Antígenos de Histocompatibilidade Menor/genética , Mutagênese/genética , Mutagênicos , Neoplasias da Bexiga Urinária/genética
9.
Cancer ; 118(2): 358-64, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21717438

RESUMO

BACKGROUND: Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2-T4aN0-N2M0 bladder cancer. METHODS: In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum-based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin-based chemotherapy compared with carboplatin-based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin-based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01-112.2). CONCLUSION: In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum-based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin- or carboplatin-based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
10.
BJU Int ; 109(3): 379-83, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21851533

RESUMO

OBJECTIVE: To examine the relationship between tumour diameter and estimated GFR (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC were identified in the Columbia Urologic Database. eGFR was calculated using the modification of diet in renal disease equation using demographic data and preoperative serum creatinine values. Data on patient demographics, tumour characteristics, and comorbidities were analyzed using univariate and multivariate regression analysis. RESULTS: Mean (sd, range) tumour diameter was 5.29 (3.8, 0.3-29) cm. Mean (sd, range) eGFR was 75 (23.4, 3-173) mL/min per 1.73 m(2) . In multivariate regression analysis, tumour diameter independently predicted decreased preoperative eGFR (coefficient, -0.513; P= 0.008) when controlling for hypertension and race. Consistent with this, decreased preoperative eGFR independently predicted increased tumour diameter (coefficient, -0.013; P= 0.007) when controlling for race, histology and smoking status. CONCLUSION: Tumour diameter and decreased preoperative eGFR are independently correlated in patients with RCC.


Assuntos
Carcinoma de Células Renais/patologia , Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/fisiopatologia , Neoplasias Renais/patologia , Carga Tumoral/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/fisiopatologia , Feminino , Humanos , Falência Renal Crônica/complicações , Neoplasias Renais/etiologia , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Retrospectivos
11.
Urology ; 162: 63-69, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34380056

RESUMO

OBJECTIVE: To determine if there is an association between patient race and physician time spent with the patient during outpatient urology consultations. METHODS: We identified all adult urology new outpatient visits in the National Ambulatory Medical Care Survey dataset for 2012-2016. Patient race was dichotomized as White or non-White. Our primary outcome was time spent during the visit between the patient and urologist. Using population-level weighting, we compared differences in mean time spent during visits with White and non-White patients. Mixed-effects linear regression was used to adjust for confounding factors and to account for clustering among individual physicians. Secondary outcomes included number of services provided and if ancillary providers were seen. RESULTS: Over the 5 year period, 1668 raw visits met criteria and were used to estimate 21million new outpatient urology visits nationwide. 80% of all visits were with White patients. Mean physician time spent among visits with white patients was 23.9 minutes and 24.4 minutes for non-White patients. There was no difference in number of services provided but visits with non-white patients were less likely to include an ancillary provider. After adjustment, there was no significant difference in mean time spent with the urologist among visits with White and non-White patients (difference 0.9 minutes, 95% CI: -0.6-2.4). There were also no differences in adjusted mean time spent among return visits or new visits for hematuria, urologic cancers, or BPH. CONCLUSION: We found no statistically significant difference in time spent with a urologist during outpatient office consultations between White and non-White patients.


Assuntos
Médicos , Urologia , Adulto , Humanos , Visita a Consultório Médico , Pacientes Ambulatoriais , Encaminhamento e Consulta
12.
J Urol ; 186(2): 448-51, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21680003

RESUMO

PURPOSE: Up to 50% of patients treated with intravesical agents for high grade nonmuscle invasive bladder cancer will have disease recurrence. Response rates to current second line intravesical therapies are low and for these high risk patients novel agents are necessary. Our previously completed phase I trial showed docetaxel was a safe agent for intravesical use. Nanoparticle albumin-bound paclitaxel (Abraxane®, ABI-007) has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy. Thus, we assessed the dose limiting toxicity and maximum deliverable dose of intravesical nanoparticle albumin-bound paclitaxel. MATERIALS AND METHODS: Inclusion criteria for this institutional review board approved phase I trial were recurrent high grade Ta, T1 and Tis transitional cell carcinoma of the bladder for which at least 1 prior standard intravesical regimen failed. Six weekly instillations of nanoparticle albumin-bound paclitaxel were administered with a modified Fibonacci dose escalation model used until the maximum deliverable dose was achieved. The primary end point was dose limiting toxicity and the secondary end point was response rate. RESULTS: A total of 18 patients were enrolled in the study. One patient demonstrated measurable systemic absorption after 1 infusion. Grade 1 local toxicities were experienced by 10 (56%) patients with dysuria being the most common, and no grade 2, 3 or 4 drug related local toxicities were encountered. Of the 18 patients 5 (28%) had no evidence of disease at posttreatment evaluation. CONCLUSIONS: Intravesical nanoparticle albumin-bound paclitaxel exhibited minimal toxicity and systemic absorption in the first human intravesical phase I trial to our knowledge. A larger phase II study has begun to formally evaluate the activity of this regimen.


Assuntos
Carcinoma de Células de Transição/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Paclitaxel Ligado a Albumina , Albuminas/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas , Invasividade Neoplásica , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia
13.
BJU Int ; 106(4): 489-92, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20039869

RESUMO

OBJECTIVE: To examine the functional outcomes after radical (RN) and partial nephrectomy (PN) stratified by variables before and after surgery, using estimated glomerular filtration rate (eGFR), as nephrectomy is the standard treatment for localized renal tumours, but the risk of developing chronic kidney disease (CKD) increases after surgery. PATIENTS AND METHODS: We retrospectively analysed patients treated with PN or RN for renal cancer at one institution from 1988 to 2008. Chronic renal function before and after surgery was measured using the eGFR computed using the Modification of Diet in Renal Disease equation. Four outcomes were measured: (i) presence of new-onset renal insufficiency (eGFR <60 mL/min/1.73m(2)); (ii) the percentage change in eGFR; (iii) the change in CKD stage; and (iv) the presence of CKD upstaging. Regression models were used to determine the effect of surgical procedure (RN vs PN), access technique (open vs laparoscopic) and several preoperative characteristics on functional outcomes. RESULTS: In all, 276 patients met the inclusion criteria (174 RN and 102 PN) of whom 209 had a preoperative eGFR of >60 mL/min/1.73m(2). After >or=3 months from surgery, 108/209 (52%) patients developed new-onset eGFR of <60 mL/min/1.73m(2). On multivariate analysis, preoperative CKD stage (P < 0.001) and procedure (P= 0.001) were both independent predictors of all four functional outcomes measured. Also, hypertension was an independent predictor of CKD upstaging (P= 0.02). Surgical access technique was not an independent predictor of any of the renal functional outcomes measured. CONCLUSION: Patients undergoing renal surgery have a high rate of new-onset CKD afterward. After controlling for preoperative risk factors, patients undergoing RN are at greater risk of a decline in renal function. However, surgical access technique was not a significant predictor for renal impairment.


Assuntos
Carcinoma de Células Renais/cirurgia , Córtex Renal/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Insuficiência Renal Crônica/etiologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Córtex Renal/fisiopatologia , Neoplasias Renais/complicações , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
BJU Int ; 105(12): 1646-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19863523

RESUMO

OBJECTIVES: To evaluate the effects of age at radical prostatectomy (RP) on recurrence-free survival (RFS) in patients with prostate cancer stratified by established preoperative risk factors (such as prostate-specific antigen (PSA) level, Gleason score, and tumour stage), as increasing age has been associated with more indolent behaviour in some cancers. PATIENTS AND METHODS: A retrospective analysis of men treated with RP from 1988 to 2008 was conducted. Patients were divided into two groups by age at the time of RP, and RFS rates were analysed using Kaplan-Meier survival curves. The subgroups were stratified by preoperative PSA level, biopsy Gleason score, and clinical stage; multivariate analyses with Cox proportional hazards models were used to identify independent predictors of recurrence. Recurrence was defined as a single PSA level of > or =0.2 ng/mL at least 28 days after RP. RESULTS: In all, 1984 patients met inclusion criteria and were divided into groups 1 (1325 men aged 40-64 years) and 2 (659 men aged > or =65 years). The 5-year RFS rates were 80.6% (confidence interval, CI 78.0-82.9%) and 75.6% (CI 71.5-79.1%) for groups 1 and 2, respectively. In the univariate model, advanced age was significantly associated with an increased overall risk of recurrence (hazard ratio, HR 1.30, P = 0.012). However, in multivariate analyses accounting for PSA level, Gleason score, and clinical stage, age was not an independent predictor of recurrence (HR 1.04, P = 0.76). CONCLUSION: Older patients who undergo RP appear to have an increased risk of recurrence. However, age is not an independent predictor of recurrence when accounting for PSA level, grade, and stage.


Assuntos
Recidiva Local de Neoplasia/patologia , Próstata/patologia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Adulto , Fatores Etários , Idoso , Métodos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estadiamento de Neoplasias , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Falha de Tratamento
15.
BJU Int ; 104(8): 1098-102, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19389012

RESUMO

OBJECTIVE: To analyse the durability of response for patients with non-muscle-invasive bladder cancer (NMIBC) refractory to bacille Calmette-Guérin (BCG) therapy and treated with intravesical docetaxel in a combined induction and maintenance regimen. PATIENTS AND METHODS: A previous phase I trial showed docetaxel to be safe for intravesical therapy, with no systemic absorption and minimal toxicity after six weekly instillations for patients with BCG-refractory NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12 weeks, but the durability was only 22%. Thus a second group of patients was treated with a 6-week induction and then given monthly maintenance therapy with intravesical docetaxel. Thirteen patients with BCG-refractory Ta, T1, or Tis transitional cell carcinoma were treated. Induction therapy was administered as six weekly intravesical instillations of 75 mg followed by single-dose monthly maintenance therapy for nine additional instillations in patients who had a CR. The initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy, and urine cytology. The follow-up consisted of quarterly cystoscopy with biopsy and cytology, and periodic imaging. RESULTS: The median follow-up was 13 months; 10 of 13 patients had a CR after induction, and six have remained disease-free during the follow-up. Of those in who the treatment failed, six had transurethral resection of the tumour and one a cystectomy. All 10 initial responders completed at least three instillations of maintenance therapy to date (median nine instillations), of whom six have remained recurrence-free. CONCLUSION: Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a selected group of patients with BCG-refractory NMIBC, and might decrease the overall risk of recurrence in high-risk NMIBC.


Assuntos
Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
16.
World J Urol ; 27(3): 331-5, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19214528

RESUMO

OBJECTIVES: Since the success of our Phase I trial of intravesical docetaxel for treatment-refractory non-muscle invasive bladder cancer (NMIBC), we have found this agent to be a favorable alternative for BCG-refractory patients unable or unwilling to undergo cystectomy. This study analyzes the safety and efficacy of intravesical docetaxel in a larger patient population with extended follow-up. METHODS: A retrospective analysis of all patients who received salvage intravesical docetaxel at our institution was conducted, including 18 patients treated during the Phase I trial and 15 patients treated after the trial's completion. Toxicity, efficacy and recurrence-free survival were analyzed. RESULTS: Thirty-three patients with refractory NMIBC received salvage intravesical docetaxel therapy between 2003 and 2008 at a single institution. Twenty of thirty-three (61%) patients had a complete response (CR) after six weekly induction treatments. Ten patients with CRs were given maintenance docetaxel therapy, and one patient received maintenance BCG and interferon. With a median follow-up of 29 months, 1 and 2-year recurrence-free survival rates were and 45 and 32%, respectively. Twelve of thirty-three patients (36%) had Grade 1 or 2 local toxicities. No patients experienced Grade 3 or 4 toxicities. CONCLUSIONS: Docetaxel is a promising intravesical agent with minimal toxicity and significant efficacy and durability for the management of BCG-refractory NMIBC.


Assuntos
Antineoplásicos/administração & dosagem , Taxoides/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/uso terapêutico , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Falha de Tratamento , Neoplasias da Bexiga Urinária/patologia
17.
Urology ; 111: 122-128, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28888753

RESUMO

OBJECTIVE: To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis. MATERIALS AND METHODS: We performed a prospective case-control pilot study evaluating the gut microbiome of 20 men with either benign prostatic conditions (n = 8) or intermediate or high risk clinically localized prostate cancer (Gleason ≥4 + 3 cN0M0) (n = 12) undergoing care at tertiary referral center from September 1, 2015 to March 1, 2016. Key exclusion criteria included recent antibiotic use, significant gastrointestinal disorders, hormonal or systemic therapy for prostate cancer. Computational genomics analysis was performed on collected stool samples using MetaPhlAn2 and HUMAnN2 platforms. Linear discriminant analysis effect size method was used to support high-dimensional class comparisons to find biologically relevant features. Kruskal-Wallis sum-rank test was used to detect features with significant differential abundance with respect to class, with biological consistency investigated using a set of pairwise tests among subclasses using the Wilcoxon rank-sum test, both to an α ≤0.05. RESULTS: Higher relative abundance of Bacteriodes massiliensis was seen in prostate cancer cases compared to controls. Faecalibacterium prausnitzii and Eubacterium rectalie had higher relative abundance among controls. Biologically significant differences were also found in relative gene, pathway, and enzyme abundance. CONCLUSION: Biologically significant differences exist in the gut microbial composition of men with prostate cancer compared to benign controls. These differences may play a role in the pathobiology of prostate cancer, and warrant further exploration.


Assuntos
Microbioma Gastrointestinal , Neoplasias da Próstata/microbiologia , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
18.
Urology ; 162: 31, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35469611
20.
Urology ; 86(6): 1104-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26408500

RESUMO

OBJECTIVE: To evaluate whether there is a correlation between publicized health ranking systems and surgical outcomes after radical cystectomy (RC) in New York State (NYS). MATERIALS AND METHODS: Using the Statewide Planning and Research Cooperative System, data were collected in an aggregated fashion per hospital for the 20 hospitals with the highest RC volume in NYS from 2009 to 2012. Hospital characteristics were obtained from the publicly available sources such as the Centers for Medicare and Medicaid Services. Publicized ranking systems evaluated included the US News & World Health Report for Urology ranking (USHR), Healthgrades (HG) score, and Consumer Reports (CR) safety ranking. Outcomes measured included mortality, readmissions, and causes of readmissions. RESULTS: CR safety scores were inversely associated with overall death at 90 days after surgery (R = -0.527, P = .030), number of readmissions (R = -0.608, P = .030), and readmissions because of surgical complications (R = -0.523, P = .031) on a Pearson correlation test. On Kendall rank tau test, USHR and HG were not associated with any outcome of interest, although the scores correlated with increasing RC volume. CONCLUSION: In our analysis of 20 hospitals with the highest RC volume in NYS, USHR and HG scores were not strongly associated with any clinical outcome after RC. CR performed well in comparison with USHR and HG. Nevertheless, better metrics are needed to compare hospitals and to incorporate curative rates for morbid surgeries.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/efeitos adversos , Hospitais com Alto Volume de Atendimentos/normas , Meios de Comunicação de Massa , Garantia da Qualidade dos Cuidados de Saúde , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cistectomia/mortalidade , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde
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