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1.
J Urol ; : 101097JU0000000000004160, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051515

RESUMO

PURPOSE: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT. MATERIALS AND METHODS: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT. RESULTS: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses. CONCLUSIONS: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

2.
J Urol ; 209(1): 111-120, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250946

RESUMO

PURPOSE: There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy. MATERIALS AND METHODS: Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold. RESULTS: Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (P = .02). BMI was independently associated with developing any complication (OR 1.04 95% CI 1.01, 1.07). Predicted complication risk began to rise consistently above a BMI threshold of 34 kg/m2. Both overweight (OR 2.00 95% CI 1.26-3.17) and obese (OR 1.98 95% CI 1.24-3.18) patients had increased risk of complications compared to normal BMI patients. CONCLUSIONS: Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m2 has been identified, which may inform prehabilitation treatment strategies.


Assuntos
Cistectomia , Obesidade , Humanos , Índice de Massa Corporal , Cistectomia/efeitos adversos , Canadá , Obesidade/complicações , Obesidade/epidemiologia
3.
BJU Int ; 132(4): 452-460, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37409827

RESUMO

OBJECTIVE: To assess if estimated glomerular filtration rate (eGFR) can replace measured GFR (mGFR) in partial nephrectomy (PN) trials, using data from a randomised clinical trial. PATIENTS AND METHODS: We conducted a post hoc analysis of the renal hypothermia trial. Patients underwent mGFR with diethylenetriaminepentaacetic acid (DTPA) plasma clearance preoperatively and 1 year after PN. The eGFR was calculated using the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equations incorporating age and sex, with and without race: 2009 eGFRcr(ASR) and 2009 eGFRcr(AS), and the 2021 equation that only incorporates age and sex: 2021 eGFRcr(AS). Performance was evaluated by determining the median bias, precision (interquartile range [IQR] of median bias), and accuracy (percentage of eGFR within 30% of mGFR). RESULTS: Overall, 183 patients were included. Pre- and postoperative median bias and precision were similar between the 2009 eGFRcr(ASR) (-0.2 mL/min/1.73 m2 , 95% confidence interval [CI] -2.2 to 1.7, IQR 18.8; and -2.9, 95% CI -5.1 to -1.5, IQR 15, respectively) and 2009 eGFRcr(AS) (-0.3 mL/min/1.73 m2 , 95% CI -2.4 to 1.5, IQR 18.8; and -3.0, 95% CI -5.7 to -1.7, IQR 15.0, respectively). Bias and precision were worse for the 2021 eGFRcr(AS) (-8.8 mL/min/1.73 m2 , 95% CI -10.9 to -6.3, IQR 24.7; and -12.0, 95% CI -15.8 to -8.9, IQR 23.5, respectively). Similarly, pre- and postoperative accuracy was >90% for the 2009 eGFRcr(ASR) and 2009 eGFRcr(AS) equations. Accuracy was 78.6% preoperatively and 66.5% postoperatively for 2021 eGFRcr(AS). CONCLUSION: The 2009 eGFRcr(AS) can accurately estimate GFR in PN trials and could be used instead of mGFR to reduce cost and patient burden.


Assuntos
Hipotermia , Insuficiência Renal Crônica , Humanos , Taxa de Filtração Glomerular , Rim , Testes de Função Renal , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/epidemiologia , Creatinina
4.
J Urol ; 208(4): 804-812, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35686812

RESUMO

PURPOSE: Percutaneous ablation therapy (AT) and partial nephrectomy (PN) are successful management strategies for T1a renal cancer. Our objective was to compare AT to PN with respect to recurrence-free survival (RFS) and overall survival (OS). MATERIALS AND METHODS: Patients post-PN or -AT for cT1aN0M0 renal cancer from 2011 to 2021 were identified from the national Canadian Kidney Cancer information system. Inverse probability of treatment weighting (IPTW) using propensity score (PS) was used. The primary outcomes, RFS and OS, were compared using Kaplan-Meier log-rank test analyses and Cox proportional hazard regression models. RESULTS: A total of 275 patients underwent AT and 2,001 underwent PN, with a median followup of 2.0 years (IQR 0.6-4.1). Covariates were well balanced between the AT and PN cohorts following PS matching. Two-year RFS following IPTW PS analysis for patients undergoing AT and PN was 88.1% and 97.4% (p <0.0001), respectively, while 2-year OS was 97.4% and 99.0% (p=0.7), respectively. Five-year RFS following IPTW PS analysis for patients undergoing AT and PN was 86.0% and 95.1%, respectively (p=0.003), while 5-year OS was 94.2% and 95.1%, respectively (p=0.9). Following IPTW PS analysis, treatment modality (PN vs AT) was a predictor of disease recurrence (HR 0.36, p=0.003) but not for OS (HR 0.96, p=0.9). CONCLUSIONS: With short followup, PN offers better RFS than AT, although no significant difference in OS was detected following PS adjustments. Both modalities can be offered to appropriately selected patients while we await prospective randomized data.


Assuntos
Carcinoma de Células Renais , Ablação por Cateter , Neoplasias Renais , Canadá , Carcinoma de Células Renais/patologia , Humanos , Sistemas de Informação , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Nefrectomia/métodos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
5.
Ann Surg Oncol ; 29(8): 5333-5337, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35381936

RESUMO

PURPOSE: The aim of this study is to examine the rates of clinical actions (CAs) as a result of serial creatinine (SCr) values and to examine postoperative SCr trends to assess the utility of SCr measurements in radical cystectomy (RC) patients. METHODS: We performed a retrospective chart review using our institution's database on all patients who underwent radical cystectomy for urothelial carcinoma (UC) from 2009 to 2019. Preoperative and all postoperative inpatient creatinine values were recorded. Minor CAs included fluid boluses, fluid rate changes, and medication changes. Major CAs included OR take-backs for stent repositioning, nephrostomy tube placement, nephrology consultation, and hemodialysis. RESULTS: A total of 238 RCs were performed with a resultant 2952 SCr measurements. The median number of SCr measurements per patient was 9 (interquartile range, IQR 7) with median length of hospital stay of 10 days (IQR 9 days). There were 92 minor and 12 major CAs as a result of 3% and 0.44% of SCr measurements, respectively. All major CAs were seen in patients experiencing complicated postoperative course. The median postoperative day with the highest creatinine was day 2. Predictors of postoperative CAs included preoperative renal dysfunction and obesity. CONCLUSION: SCr measurements remain a clinically valuable tool in postoperative management. Nonetheless, this present study suggests that prolonged SCr monitoring is of limited clinical utility. As such, discontinuing SCr checks after postoperative day 3 in patients experiencing uncomplicated postoperative course is safe and may lead to both cost savings and decreased patient discomfort.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/cirurgia , Creatinina , Cistectomia/efeitos adversos , Humanos , Rim/patologia , Rim/fisiologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
6.
J Urol ; 205(1): 78-85, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32614274

RESUMO

PURPOSE: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. MATERIALS AND METHODS: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. RESULTS: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. CONCLUSIONS: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Nefrectomia/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Canadá/epidemiologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Nefrectomia/normas , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Radiografia/estatística & dados numéricos , Fatores de Tempo , Tempo para o Tratamento/normas , Triagem/normas , Triagem/estatística & dados numéricos
7.
J Urol ; 205(5): 1303-1309, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33347776

RESUMO

PURPOSE: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. MATERIALS AND METHODS: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at 6 academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m2 at a 5% significance level. RESULTS: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/minute/1.73 m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1 year after surgery. The change in mGFR 1 year after surgery was -6.6 ml/minute/1.73 m2 in the hypothermia group and -7.8 ml/minute/1.73 m2 in the control group (mean difference 1.2 ml/minute/1.73 m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 ml/minute/1.73 m2; mean difference 0.5 ml/minute/1.73 m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. CONCLUSIONS: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.


Assuntos
Hipotermia Induzida , Neoplasias Renais/cirurgia , Nefrectomia , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Resultado do Tratamento
8.
World J Urol ; 39(5): 1569-1575, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32656670

RESUMO

INTRODUCTION: The "trifecta" is a summary measure of outcome after partial nephrectomy (PN) that encompasses three parameters: negative surgical margin, ≤ 10% decrease in post-operative estimated glomerular filtration rate (eGFR) and absence of urological complications. We assessed trifecta rates in patients undergoing open (OPN), laparoscopic (LPN), and robotic PN (RPN) for a clinical T1 renal mass (≤ 7 cm). METHODS: Clinical and pathologic parameters were extracted from the prospectively maintained Canadian Kidney Cancer Information System for patients treated between January 2011 and October 2018. Comparisons between groups were made using Kruskal-Wallis test for continuous variables and Chi-squared independence test for categorical variables. Multivariable analysis was performed to identify predictors of each component of the trifecta and the trifecta itself. RESULTS: Of 1708 total patients, 746 underwent OPN, 678 LPN, and 284 RPN for a T1 renal mass. A 'trifecta' was achieved in 53% OPN, 52% LPN and 47% RPN (p = 0.194). On multivariable analysis, OPN and LPN were associated with less frequent post-operative decline in eGFR and more frequent trifecta when compared to RPN, but there was no difference between OPN and LPN. OPN also predicted a higher rate of negative margins compared to RPN but not LPN. CONCLUSION: After correction for confounding variables, OPN and LPN were more likely than RPN to achieve the trifecta, which appeared to be due primarily to loss of renal function. No difference was observed between OPN and LPN. Analyses were limited by the lack of nephrometry score.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento
9.
J Urol ; 202(1): 57-61, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30932757

RESUMO

PURPOSE: We report the natural history of small renal masses in patients undergoing active surveillance with extended followup. MATERIALS AND METHODS: We performed a prospective cohort study in patients undergoing active surveillance of small renal masses diagnosed between 2001 and 2011 at a single institution. All patients underwent active surveillance of small renal masses presumed to be renal cell carcinoma based on diagnostic imaging. Reported patient outcomes included progression to treatment, metastatic disease and/or death. Linear and volumetric tumor growth rates were evaluated. RESULTS: Included in study were 103 patients with a total of 107 small renal masses. Median followup was 55.5 months in patients who continued on active surveillance. Median maximum diameter and volume at diagnosis were 2.1 cm (IQR 1.5-2.7) and 4.8 cm3 (IQR 1.7-11.9), respectively. At last followup 53 patients (51.5%) were alive without metastatic disease, 48 (45.6%) had died of another cause and metastatic disease had developed in 2 (1.9%), including 1 (1.0%) who ultimately died of metastatic renal cell carcinoma. The mean ± SEM linear and volumetric growth rates of all small renal masses were 0.21 ± 0.03 cm per year and 6.15 ± 2.15 cm3, respectively. Study limitations include nonstandardized followup and a lack of biopsy data on most patients. CONCLUSIONS: During extended followup the majority of small renal masses in patients on active surveillance display indolent behavior. The risk of progression to metastatic disease remains low.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Conduta Expectante/métodos , Idoso , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/patologia , Masculino , Estudos Prospectivos , Fatores de Tempo , Carga Tumoral , Conduta Expectante/estatística & dados numéricos
10.
J Urol ; 202(5): 1001-1007, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31099720

RESUMO

PURPOSE: The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid. RESULTS: Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria. CONCLUSIONS: We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.


Assuntos
Cistectomia/psicologia , Tomada de Decisão Compartilhada , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/psicologia , Cistectomia/métodos , Feminino , Humanos , Masculino , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/psicologia , Derivação Urinária/métodos
11.
BJU Int ; 119(4): 543-549, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27528446

RESUMO

OBJECTIVE: To validate, in a multi-institution review, the safety, accuracy and reliability of renal tumour biopsy (RTB) and its role in decreasing unnecessary treatment. MATERIALS AND METHODS: We conducted a multi-institution retrospective study of patients who underwent RTB to characterize a small renal mass (SRM) between 2011 and May 2015. Patients were identified using the prospectively maintained Canadian Kidney Cancer information system. Diagnostic and concordance rates were presented using proportions, whereas factors associated with a diagnostic RTB were identified using a logistic regression model. RESULTS: Of the 373 biopsied SRMs, the initial biopsy was diagnostic in 87% of cases. Of the 47 non-diagnostic biopsies, 15 had a repeat biopsy of which, 80% were diagnostic. When both were combined, therefore, a diagnosis was obtained in 91% of SRMs. Of these, 18% were benign. Size was the only factor found to be associated with achieving a diagnostic biopsy. RTB histology and nuclear grade (high or low) were found to be highly concordant with surgical pathology (86 and 81%, respectively). Of the discordant tumours (n = 16), all were upgraded from low to high grade on surgical pathology. Adverse events were rare (<1% of cases). CONCLUSION: The present multi-institution study confirms that RTB of SRMs is safe, accurate and reliable across institutions, while decreasing unnecessary treatment. Given our findings, RTBs may be a helpful tool with which to triage SRMs and guide appropriate management.


Assuntos
Biópsia por Agulha Fina/efeitos adversos , Biópsia por Agulha Fina/normas , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/normas , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Sistema de Registros , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Procedimentos Desnecessários/estatística & dados numéricos
13.
Prostate ; 75(15): 1726-36, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26202060

RESUMO

BACKGROUND: Carboxypeptidase-D (CPD) cleaves C-terminal arginine for conversion to nitric oxide (NO) by nitric oxide synthase (NOS). Prolactin (PRL) and androgens stimulate CPD gene transcription and expression, which increases intracellular production of NO to promote viability of prostate cancer (PCa) cells in vitro. The current study evaluated whether hormonal upregulation of CPD and NO promote PCa cell viabilty in vivo, by correlating changes in expression of CPD and nitrotyrosine residues (products of NO action) with proliferation marker Ki67 and associated proteins during PCa development and progression. METHODS: Fresh prostate tissues, obtained from 40 men with benign prostatic hyperplasia (BPH) or PCa, were flash-frozen at the time of surgery and used for RT-qPCR analysis of CPD, androgen receptor (AR), PRL receptor (PRLR), eNOS, and Ki67 levels. Archival paraffin-embedded tissues from 113 men with BPH or PCa were used for immunohistochemical (IHC) analysis of CPD, nitrotyrosines, phospho-Stat5 (for activated PRLR), AR, eNOS/iNOS, and Ki67. RESULTS: RT-qPCR and IHC analyses showed strong AR and PRLR expression in benign and malignant prostates. CPD mRNA levels increased ∼threefold in PCa compared to BPH, which corresponded to a twofold increase in Ki67 mRNA levels. IHC analysis showed a progressive increase in CPD from 11.4 ± 2.1% in benign to 21.8 ± 3.2% in low-grade (P = 0.007), 40.7 ± 4.0% in high-grade (P < 0.0001) and 50.0 ± 9.5% in castration-recurrent PCa (P < 0.0001). Immunostaining for nitrotyrosines and Ki67 mirrored these increases during PCa progression. CPD, nitrotyrosines, and Ki67 tended to co-localize, as did phospho-Stat5. CONCLUSIONS: CPD, nitrotyrosine, and Ki67 levels were higher in PCa than in benign and tended to co-localize, along with phospho-Stat5. The strong correlation in expression of these proteins in benign and malignant prostate tissues, combined with abundant AR and PRLR, supports in vitro evidence that the CPD-Arg-NO pathway is involved in the regulation of PCa cell proliferation. It further highlights a role for PRL in the development and progression of PCa.


Assuntos
Carboxipeptidases/metabolismo , Antígeno Ki-67/metabolismo , Prolactina/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Testosterona/farmacologia , Tirosina/análogos & derivados , Humanos , Masculino , Gradação de Tumores , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptores da Prolactina/metabolismo , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tirosina/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
BJU Int ; 116(1): 72-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24825476

RESUMO

OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Idoso , Quimioterapia Adjuvante/métodos , Quimioterapia Combinada/métodos , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/cirurgia , Urotélio/patologia , Urotélio/cirurgia
15.
Prostate ; 74(7): 732-42, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24615730

RESUMO

BACKGROUND: Carboxypeptidase-D (CPD) cleaves C-terminal arginine for nitric oxide (NO) production. CPD and NO levels are upregulated by testosterone (T) and prolactin (PRL) to promote survival of prostate cancer (pCa) cells. This study evaluated CPD immunostaining and T/PRL regulation of CPD and NO levels in benign and malignant prostate tissues/cells to determine the role of CPD in pCa. METHODS: Immunohistochemistry (IHC) and tissue microarrays (TMA) were used to determine CPD immunostaining in prostate specimens. QPCR and immunoblotting were used to quantify CPD mRNA/protein expression in prostate cells. NO production was measured using 4,5-diaminofluorescein diacetate assay. RESULTS: CPD staining increased from 8.9 ± 3.8% (Mean ± SEM, n = 15) of benign epithelial cell area to 30.9 ± 2.9% (n = 30) of tumor cell area in one set of TMAs (P = 0.0008) and from 5.9 ± 0.9% (n = 45) of benign epithelial cell area to 18.8 ± 1.9% (n = 55) of tumor area in another (P < 0.0001). IHC of prostate tissues (≥50 mm(2)) confirmed increased CPD staining, from 13.1 ± 2.9% in benign (n = 16) to 29.5 ± 4.4% in pCa (n = 31, P = 0.0095). T and/or PRL increased CPD expression in several pCa but not benign cell lines. T and PRL acted synergistically to increase NO production, which was abolished only when receptor antagonists flutamide and Δ1-9-G129R-hPRL were used together. CONCLUSIONS: CPD immunostaining and T/PRL-stimulated CPD expression were higher in pCa than benign tissues/cells. Elevated CPD increased NO production, which was abolished when both AR and PRLR were inhibited. Our study implicates a critical role for the T/PRL-stimulated CPD-Arg-NO pathway in pCa progression, and suggests that AR+PRLR inhibition is a more effective treatment for pCa.


Assuntos
Apoptose/fisiologia , Carboxipeptidases/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Receptores da Prolactina/metabolismo , Antagonistas de Androgênios/farmacologia , Androgênios/farmacologia , Apoptose/efeitos dos fármacos , Carboxipeptidases/genética , Linhagem Celular Tumoral , Flutamida/farmacologia , Humanos , Masculino , Óxido Nítrico/biossíntese , Prolactina/farmacologia , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Receptores da Prolactina/genética , Transdução de Sinais/efeitos dos fármacos , Testosterona/farmacologia , Regulação para Cima/efeitos dos fármacos
16.
World J Urol ; 32(5): 1295-301, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24213922

RESUMO

PURPOSE: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. METHODS: We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. RESULTS: In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. CONCLUSION: These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.


Assuntos
Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve , Estudos Retrospectivos , Resultado do Tratamento
17.
Can J Urol ; 21(4): 7379-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25171283

RESUMO

INTRODUCTION: To develop a classification tree for the preoperative prediction of benign versus malignant disease in patients with small renal masses. MATERIALS AND METHODS: This is a retrospective study including 395 consecutive patients who underwent surgical treatment for a renal mass < 5 cm in maximum diameter between July 1st 2001 and June 30th 2010. A classification tree to predict the risk of having a benign renal mass preoperatively was developed using recursive partitioning analysis for repeated measures outcomes. Age, sex, volume on preoperative imaging, tumor location (central/peripheral), degree of endophytic component (1%-100%), and tumor axis position were used as potential predictors to develop the model. RESULTS: Forty-five patients (11.4%) were found to have a benign mass postoperatively. A classification tree has been developed which can predict the risk of benign disease with an accuracy of 88.9% (95% CI: 85.3 to 91.8). The significant prognostic factors in the classification tree are tumor volume, degree of endophytic component and symptoms at diagnosis. As an example of its utilization, a renal mass with a volume of < 5.67 cm3 that is < 45% endophytic has a 52.6% chance of having benign pathology. Conversely, a renal mass with a volume ≥ 5.67 cm3 that is ≥ 35% endophytic has only a 5.3% possibility of being benign. CONCLUSIONS: A classification tree to predict the risk of benign disease in small renal masses has been developed to aid the clinician when deciding on treatment strategies for small renal masses.


Assuntos
Classificação/métodos , Nefropatias/classificação , Nefropatias/epidemiologia , Neoplasias Renais/classificação , Neoplasias Renais/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Carga Tumoral
18.
Can Urol Assoc J ; 18(8): 245-250, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38587976

RESUMO

INTRODUCTION: In 2019, our center attempted to transition all partial nephrectomies (PNs) to robotic-assisted laparoscopic PN (RALPN). The purpose of this study was to compare RALPN outcomes to laparoscopic PN (LPN) and open PN (OPN) at our institution, as there is limited literature from Canadian centers. METHODS: In this single-center, two-surgeon, retrospective cohort study, we compared RALPN outcomes during the early phase of our robotics program to OPN and LPN performed just before the introduction of RALPN. RESULTS: A total of 106 patients underwent OPN, 83 LPN, and 82 RALPN during the study period. Median RALPN REN AL score was 7 vs. 6 for LPN (p<0.05) and 8 for OPN (p=0.10). Median RALPN length of stay (LOS) was two days vs. three and four days for LPN and OPN (p<0.05), respectively. OPN median procedure time was 104 minutes vs. 94 and 82 minutes for LPN and RALPN (p<0.05), respectively. Median OPN operating room (OR) time was 160 minutes vs. 150 and 146 minutes for LPN and RALPN (p<0.05), respectively. There were no significant differences in intraoperative (p=0.92) or postoperative complication rates (p=0.47). RALPN warm ischemia time (WIT) was 17 minutes vs. 14.5 and 15 minutes for OPN and LPN (p<0.05), respectively. Median RALPN estimated blood loss (EBL) was 165 ml vs. 250 ml for OPN (p<0.05) and 125 ml for LPN (p=0.15). CONCLUSIONS: Although patients who underwent RALPN had longer WIT, they had similar rates of complications, required less total OR time, and had shorter procedure times and LOS compared with OPN and LPN despite similar REN AL scores compared to OPN and greater scores than LPN.

19.
Can Urol Assoc J ; 18(6): 185-189, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381923

RESUMO

INTRODUCTION: Patients undergoing radical nephrectomy (RN) are often admitted with protocolized bloodwork for several days following their operation, yet the clinical value of serial hemoglobin (Hgb) measurements has not been established. This can lead to unnecessary costs and can prolong patient stay, despite the absence of an intervention based on these lab values. This study sought to examine perioperative Hgb values and identify those patients at high risk of bleeding requiring intervention, as well as those patients who are unlikely to require further monitoring. METHODS: Patient and perioperative factors were retrospectively examined for a cohort of 259 radical nephrectomy patients from 2015-2021 in Atlantic Canada. Postoperative Hgb values and transfusion rates were recorded. A multivariate logistic regression analysis was performed to identify variables associated with requiring a blood transfusion. RESULTS: Overall, 31 (12%) patients required a blood transfusion in the postoperative period. Median estimated blood loss (EBL) was 150 (interquartile range [IQR] 100-300) ml, with a median Hgb change of 15 (IQR 9-22) g/L from preoperative to postoperative day 1 (POD1). In patients with a Hgb loss of ≤15 g/L (n=131), transfusion was only required in four patients (3.1%). Among those with a POD1 Hgb >100 g/L (n=199), only four (2%) required transfusion. These patients were identified as having complications based on hemodynamic instability. On multivariate regression analysis, factors found to be associated with higher transfusion risk were age and intraoperative EBL, while higher preoperative Hgb was found to be associated with a lower transfusion risk. CONCLUSIONS: In patients who have a reassuring POD1 Hgb value, with a drop of <15 g/L or an absolute value of >100 g/L, consideration can be made towards discontinuing routine Hgb testing in the absence of a clinical indication. Age, blood loss, and preoperative Hgb are factors that may affect a patient's overall risk of transfusion.

20.
Can Urol Assoc J ; 18(6): 180-184, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381924

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There was a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

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