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Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC.
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Esclerose Tuberosa , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Esclerose Tuberosa/complicações , Humanos , Consenso , Angiomiolipoma/genética , Angiomiolipoma/etiologia , Guias de Prática Clínica como AssuntoRESUMO
The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD progression through the down-regulation of angiotensinogen (AGT), sodium-glucose cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in RPTCs of T2D.
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We present a case of a patient with recurrent prostate cancer after treatment for favorable intermediate risk cancer. There was an exceptionally steep increase in PSA from <0.5 to 130ng/mL in 27 months accompanied with the development of bone metastasis. The PSA increase was unexpected. We suspect that this unusual development of metastases must have been caused by an impairment of the immune system caused by his IgG4 disease, and this may have allowed residual prostate cancer cells in the prostate to spread quickly. The influence of IgG4 on cancer is debated.
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This is a summary of a research article reporting Part A of the CheckMate 914 study (NCT03138512; EudraCT 2016-004502-34). Following surgery to remove renal cell carcinoma (RCC), people with a high risk of the cancer returning received nivolumab plus ipilimumab (adjuvant therapy) or placebo to see if this risk was reduced. The results of this study showed that the risk of RCC returning or death was not changed with adjuvant nivolumab plus ipilimumab treatment compared with placebo. In addition, people treated with nivolumab plus ipilimumab had more side effects compared with people treated with placebo (89% versus 57%).
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Nefrectomia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgiaRESUMO
INTRODUCTION: In line with Canadian provincial directives due to the COVID-19 pandemic, certain elective urologic surgical cases that are normally performed as inpatient procedures were performed as same-day discharge procedures to reduce hospitalization and the usage of scarce healthcare resources. Since the pandemic, we began performing laser enucleation of the prostate (LEP), robotic-assisted radical prostatectomy (RARP), and percutaneous nephrolithotomy (PCNL ) as outpatient surgeries. This was supported by recent evidence demonstrating the safety and feasibility of performing these minimally invasive surgeries as same-day procedures. As such, we sought to retrospectively evaluate the clinical outcomes and safety during the COVID-19 era at our institution for same-day discharge LEP, RARP, and PCNL procedures. METHODS: All patients operated for LEP, RARP, or PCNL between May 2020 and March 2022 at two academic institutions were included. Surgeries were classified as planned same-day discharge or inpatient surgery. Same-day discharge patients were compared to inpatients for each procedure type. This comparison assessed the occurrence of same-day failure, postoperative complications, and re-admission rates at 30 days. This study was approved by the scientific ethics committee of the Centre de Recherche de l'Université de Montréal (CRCHUM). RESULTS: A total of 413 subjects were included in this study. Among LEP patients (n=169), 104 (62%) were identified as same-day procedures and 65 (38%) were inpatient. Among RARP patients (n=194), 46 (24%) were identified as same-day procedures and 148 (76%) inpatient. Among PCNL patients (n=50), 38 (76%) were identified as same-day procedures and 12 (24%) were inpatient. Of the patients who underwent planned same-day LEP, RARP, and PCNL, 77.9%, 73.9%, and 71.1% were successfully discharged home, respectively. Patients who underwent LEP as inpatients had a higher incidence of overall postoperative complications compared to same-day LEP (23.1% vs. 8.7%, p=0.017). The rates of 30-day emergency department (ED ) visits and hospital re-admission were similar between inpatient and same-day LEP (9.2% vs. 3.8%, p=0.27; and 4.6% vs. 1.0%, p=0.32, respectively). Inpatient RARP, however, was associated with more 30-day ED visits compared to same-day procedures (17.4% vs. 4.1%, p<0.01). No statistically significant differences were found for postoperative complications (15.2% vs. 6.1%, p=0.097) and re-admission rates (1.4% vs. 4.3%, p=0.51). There were no significant differences on overall postoperative complications, 30-day ED visits, and re-admission rates in inpatient vs. same-day PCNL. CONCLUSIONS: Our results suggest that same-day discharge for LEP, RARP, and PCNL is safe and feasible in select patients, with an acceptable complication rate. These results should be validated in a larger, prospective clinical trial comparing same-day and inpatient procedures.
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INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.
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PURPOSE: To compare characteristics and outcomes of patients included versus those not in adjuvant therapy trials post complete resection of renal cell carcinoma (RCC). METHODS: Adult patients following complete resection for clear cell RCC between January 1, 2011, and March 31, 2021, were included. Patients had intermediate high, high risk nonmetastatic disease (modified UCLA Integrated Staging System) or fully resected metastatic (M1) disease as per the inclusion criteria of adjuvant studies. Demographic, clinical, and outcomes between trial and nontrial patients were compared. RESULTS: Of 1,459 eligible patients, 63 (4.3%) participated in an adjuvant trial. Disease characteristics were similar between groups. Trial patients were younger (mean age 58.1 vs. 63.6 years; P < 0.0001) and had lower Charlson Comorbidity Index scores (mean 4.2 vs. 4.9; Pâ¯=â¯0.009). Unadjusted disease-free survival (DFS) at 5 years for trial patients was 48.6% and 39.2% for nontrial patients (HR 0.71, 0.48-1.05, Pâ¯=â¯0.08). Median DFS was higher for trial patients in comparison to nontrial patients (4.4 years, IQR 1.7- not reached; vs. 3.0 years, IQR 0.8-8.6; Pâ¯=â¯0.08). Cancer specific survival (CSS) at 5 years for trial patients was 85.2% in comparison to 78.6% for nontrial patients (HR 0.45, 0.22-0.92, Pâ¯=â¯0.03). Unadjusted estimated overall survival (OS) at 5 years was 80.8% for trial patients and 74.8% (HR 0.42, 0.18-0.94; Pâ¯=â¯0.04) for nontrial patients. CONCLUSIONS: Patients in adjuvant trials were younger and healthier with longer CSS and OS in comparison to those not included in adjuvant trials. These findings may have implications when we generalize trial results to real world patients.
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Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias Renais/cirurgia , Neoplasias Renais/tratamento farmacológico , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Effective adjuvant therapy for patients with resected localised renal cell carcinoma represents an unmet need, with surveillance being the standard of care. We report results from part A of a phase 3, randomised trial that aimed to assess the efficacy and safety of adjuvant nivolumab plus ipilimumab versus placebo. METHODS: The double-blind, randomised, phase 3 CheckMate 914 trial enrolled patients with localised clear cell renal cell carcinoma who were at high risk of relapse after radical or partial nephrectomy between 4-12 weeks before random assignment. Part A, reported herein, was done in 145 hospitals and cancer centres across 20 countries. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks for 12 doses plus ipilimumab (1 mg/kg) intravenously every 6 weeks for four doses, or matching placebo, via an interactive response technology system. The expected treatment period was 24 weeks, and treatment could be continued until week 36, allowing for treatment delays. Randomisation was stratified by TNM stage and nephrectomy (partial vs radical). The primary endpoint was disease-free survival according to masked independent central review; safety was a secondary endpoint. Disease-free survival was analysed in all randomly assigned patients (intention-to-treat population); exposure, safety, and tolerability were analysed in all patients who received at least one dose of study drug (all-treated population). This study is registered with ClinicalTrials.gov, NCT03138512. FINDINGS: Between Aug 28, 2017, and March 16, 2021, 816 patients were randomly assigned to receive either adjuvant nivolumab plus ipilimumab (405 patients) or placebo (411 patients). 580 (71%) of 816 patients were male and 236 (29%) patients were female. With a median follow-up of 37·0 months (IQR 31·3-43·7), median disease-free survival was not reached in the nivolumab plus ipilimumab group and was 50·7 months (95% CI 48·1 to not estimable) in the placebo group (hazard ratio 0·92, 95% CI 0·71-1·19; p=0·53). The number of events required for the planned overall survival interim analysis was not reached at the time of the data cutoff, and only 61 events occurred (33 in the nivolumab plus ipilimumab group and 28 in the placebo group). 155 (38%) of 404 patients who received nivolumab plus ipilimumab and 42 (10%) of 407 patients who received placebo had grade 3-5 adverse events. All-cause adverse events of any grade led to discontinuation of nivolumab plus ipilimumab in 129 (32%) of 404 treated patients and of placebo in nine (2%) of 407 treated patients. Four deaths were attributed to treatment with nivolumab plus ipilimumab and no deaths were attributed to treatment with placebo. INTERPRETATION: Adjuvant therapy with nivolumab plus ipilimumab did not improve disease-free survival versus placebo in patients with localised renal cell carcinoma at high risk of recurrence after nephrectomy. Our study results do not support this regimen for the adjuvant treatment of renal cell carcinoma. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Feminino , Nivolumabe , Ipilimumab , Carcinoma de Células Renais/tratamento farmacológico , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Adjuvantes Imunológicos , Método Duplo-Cego , Neoplasias Renais/patologia , NefrectomiaRESUMO
The androgen inactivating UGT2B28 pathway emerges as a predictor of progression in prostate cancer (PCa). However, the clinical significance of UGT2B28 tumoral expression and its contribution to PCa progression remain unclear. Using the Canadian Prostate Cancer Biomarker Network biobank (CPCBN; n = 1512), we analyzed UGT2B28 tumor expression in relation to clinical outcomes in men with localized PCa. UGT2B28 was overexpressed in tumors compared to paired normal adjacent prostatic tissue and was associated with inferior outcomes. Functional analyses indicated that UGT2B28 promoted cell proliferation, and its expression was regulated by the androgen receptor (AR)/ARv7. Mechanistically, UGT2B28 was shown to be a protein partner of the endocytic adaptor protein huntingtin-interacting protein 1 (HIP1), increasing its stability and priming AR/epidermal growth factor receptor (EGFR) pathways, leading to ERK1/2 activation triggering cell proliferation and epithelial-to-mesenchymal transition (EMT). HIP1 knockdown in UGT2B28 positive cells, and dual pharmacological targeting of AR and EGFR pathways, abolished cell proliferative advantages conferred by UGT2B28. In conclusion, UGT2B28 is a prognosticator of progression in localized PCa, regulates both AR and EGFR oncogenic signaling pathways via HIP1, and therefore can be therapeutically targeted by using combination of existing AR/EGFR inhibitors.
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Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Próstata/patologia , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Canadá , Neoplasias da Próstata/patologia , Proteínas de Ligação a DNA/genéticaRESUMO
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.
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Cistectomia , Obesidade , Humanos , Índice de Massa Corporal , Cistectomia/efeitos adversos , Canadá , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
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.
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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 TratamentoRESUMO
Milk fat globule-epidermal growth factor-8 (MFG-E8) is a glycoprotein secreted by different cell types, including apoptotic cells and activated macrophages. MFG-E8 is highly expressed in a variety of cancers and is classically associated with tumor growth and poor patient prognosis through reprogramming of macrophages into the pro-tumoral/pro-angiogenic M2 phenotype. To date, correlations between levels of MFG-E8 and patient survival in prostate and renal cancers remain unclear. Here, we quantified MFG-E8 and CD68/CD206 expression by immunofluorescence staining in tissue microarrays constructed from renal (n = 190) and prostate (n = 274) cancer patient specimens. Percentages of MFG-E8-positive surface area were assessed in each patient core and Kaplan-Meier analyses were performed accordingly. We found that MFG-E8 was expressed more abundantly in malignant regions of prostate tissue and papillary renal cell carcinoma but was also increased in the normal adjacent regions in clear cell renal carcinoma. In addition, M2 tumor-associated macrophage staining was increased in the normal adjacent tissues compared to the malignant areas in renal cancer patients. Overall, high tissue expression of MFG-E8 was associated with less disease progression and better survival in prostate and renal cancer patients. Our observations provide new insights into tumoral MFG-E8 content and macrophage reprogramming in cancer.
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INTRODUCTION: We aimed to investigate several clinical and biochemical parameters, including palliative external beam radiation therapy (EBRT) to predict survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). METHODS: We tested known and possible prognostic parameters, including palliative EBRT, both prior and concurrent to 223Ra. Logrank test (Kaplan-Meier method) and Cox regression analysis were used to predict overall survival (OS). RESULTS: A total of 133 patients were treated with 223Ra; median age was 72 years. Median OS was 9.0 (95% confidence interval [CI] 7.4-10.6) months. By univariate analysis (log-rank test), baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (p=0.001), ≥5 cycles of 223Ra (p<0.001), baseline hemoglobin (Hb) ≥120 g/L (p <0.001), baseline total alkaline phosphatase (tALP) <110 U/L (p=0.001), and any prostate-specific antigen (PSA) decline at week 12 (p=0.013) were associated with increased OS. EBRT prior and/or concurrent to 223Ra showed a trend (p=0.051) towards inferior OS by univariate analysis only. By multivariate analysis, significant factors were PS 0-1 (hazard ratio [HR] 1.94, 95% CI 1.3-2.9, p=0.001), Hb ≥120 g/L (HR 0.5, 95% CI 0.3-0.9, p=0.011), and absence of docetaxel use prior to 223Ra (HR 1.86, 95% CI 1.08-3.22, p=0.026). With baseline Hb, tALP, and ECOG PS, we were able to divide patients into three groups with different median OS (months): 23.0 (95% CI 12.8-33.2), 8.0 (95% CI 6.7-9.3), and 5.0 (95% CI 3.1-6.9) for low-, intermediate-, and high-risk, respectively (p<0.001). CONCLUSIONS: We found that 223Ra therapy can result in an OS of close to two years in carefully selected patients. Earlier administration of 223Ra therapy to fitter patients with mCRPC should be tested.
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BACKGROUND: Treatment options for metastatic renal cell carcinoma (mRCC) include cytoreductive nephrectomy (CN) and systemic therapy (ST). Results from the CARMENA and SURTIME trials suggest that CN before ST may not be the optimal treatment strategy for mRCC. OBJECTIVE: To use real-world data to evaluate and compare outcomes for patients with mRCC who underwent CN before, after, or without ST to those patients who only received ST. DESIGN, SETTING, AND PARTICIPANTS: The Canadian Kidney Cancer information system (CKCis) database was used to identify patients diagnosed with mRCC between January 2011 and April 2020. Only patients with synchronous disease, treated within 12 mo from their initial RCC diagnosis, with International Metastatic Renal Cell Carcinoma Database Consortium intermediate/high risk, and confirmed RCC histology were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were classified into four groups according to the initial treatment received for mRCC. Inverse probability of treatment weighting using propensity scores was used to balance the treatment groups. Cox proportional hazards models were used to assess the impact of CN after adjusting for potential confounding variables in the weighted cohorts. RESULTS AND LIMITATIONS: A total of 788 patients were included in the study cohort. Of these 383 patients underwent CN before ST, 73 underwent CN after ST, 80 underwent CN only, and 252 patients received ST only. The median patient age was 63 yr and 73% of the cohort were men. In weighted analysis, the groups undergoing CN before ST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52-0.82) and CN after ST (HR 0.41, 95% CI 0.28-0.60) both had better survival compared to the ST only group. No survival benefit was observed for CN only compared to ST only, or for CN before ST compared to CN after ST. CONCLUSIONS: We evaluated the association between different sequences of treatment with CN and survival in patients with mRCC using CKCis real world data. The results demonstrate that the selected patients who undergo CN, whether performed before or after ST, have an associated improvement in survival. PATIENT SUMMARY: Two of the treatment options for metastatic kidney cancer are surgery and systemic therapy (chemotherapy or immunotherapy). We used data from the Canadian Kidney Cancer information system to determine whether there are differences in survival according to the sequencing of these treatments. Patients who had both surgery and systemic therapy, regardless of which treatment was first, had better survival than patients who only received systemic therapy.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Canadá/epidemiologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos de Citorredução , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.
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Angiomiolipoma , Epilepsia Resistente a Medicamentos , Epilepsia , Hamartoma , Neoplasias Renais , Esclerose Tuberosa , Angiomiolipoma/epidemiologia , Canadá/epidemiologia , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Esclerose Tuberosa/diagnósticoRESUMO
OBJECTIVE: To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm. PATIENTS AND METHODS: A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention-to-treat population of the immediate and deferred arm. Descriptive methods and 95% confidence-intervals (CI) were used. RESULTS: In the deferred arm, 97.7% (95% CI 89.3-99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9-88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm. CONCLUSIONS: In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Sunitinibe/uso terapêuticoRESUMO
INTRODUCTION: In the past year, due to the COVID-19 pandemic, in-person clinical activities have been drastically restricted, driving the already growing interest in the use of telemedicine in the urban setting to reduce unnecessary commute. Therefore, there has been a rapid shift to telephone and video consultations in outpatient practice. We sought to conduct a pilot trial to establish feasibility and acceptability of video consultations as an alternative to telephone consultations in urology patients to inform the design of a future randomized controlled trial. METHODS: We conducted a single-center, prospective, non-randomized pilot trial comparing telephone consultations (TC) vs. video consultations (VC) for urology outpatient visits. Two patient questionnaires were used to collect demographic information, as well as data about acceptability, feasibility, satisfaction, cost, and issues with telemedicine. Questions were identical for both VC and TC except for certain questions inquiring about issues specific to each technology. RESULTS: Forty-eight TC and 66 VC urology patients were included in this study. Patients believed that telemedicine visits did not significantly hinder their ability to communicate with their urologists and that these visits would be associated with cost savings. There was 1/48 (2.1%) failed TC and 16/66 (24.2%) failed VC. VC failures were concentrated at the beginning of the trial prior to giving feedback to the VC platform creators, with only one failure occurring thereafter. When comparing TC to VC, differences between the two patient groups were small but tended to be in favor of VC. Patients' satisfaction was greater with VC compared to TC. Both modalities were associated with many cost benefits for patients. CONCLUSIONS: Despite more technical issues with VC, this modality is feasible and acceptable to patients, likely due to improved shared decision-making with VC. Future considerations for trials comparing VC and TC should include adequate Wi-Fi infrastructure and choice of platform. For the VC, continuous knowledge transfer between investigators and platform engineers plays an important role in limiting failed encounters.
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PURPOSE: The prognostic significance of level of venous tumor thrombus (VTT) extension in patients with non-metastatic renal cell carcinoma (RCC) has been controversial. The aim of this study was to examine the prognostic significance of VTT extent in patients who underwent surgery for non-metastatic RCC. MATERIALS AND METHODS: The Canadian Kidney Cancer information system database was used to identify patients who underwent surgery for non-metastatic RCC and VTT from January 2011 to December 2019. Association between VTT level and recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) was examined. Univariable and multivariable analyses were performed to estimate predictors of survival. RESULTS: Out of 6,340 patients during the study period, 228 patients (3.6%) had VTT. VTT was level 0 in 84 (37%), level I to II in 112 (49%), and level III to IV in 33 (14%) patients as per the Mayo Clinic classification. Median age was 65.4 years (interquartile range [IQR] 57.6-72.2) and 169 (74.1%) were male. After a median follow-up of 21.2 months, VTT level did not significantly impact the RFS, CSS, or OS. For VTT level 0, I to II, and III to IV, there was no significant difference in estimated 5-year RFS (31%, 23%, and 30.5%; P > 0.05), CSS (70%, 69%, and 55%; P > 0.05) and OS (64%, 66%, and 50%; P > 0.05). Adjusting for known prognostic factors, thrombus level was not associated with risk of recurrence or death. CONCLUSION: In a large, multi-institutional cohort of patients undergoing surgery for non-metastatic RCC with tumor thrombus, thrombus extent was not independently associated with recurrence or death.
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Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Trombose Venosa/etiologia , Canadá , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Trombose Venosa/patologiaRESUMO
INTRODUCTION: Prostate cancer (PC) is the most common cancer in North American men. Advanced PC is incurable. The androgen receptor antagonist enzalutamide is used to manage advanced PC, often over a period of months or years; it is therefore important to evaluate the safety profile of enzalutamide. AREAS COVERED: This literature review presents safety data from pivotal trials and real-world data studies of enzalutamide in patients with advanced PC, including metastatic hormone-sensitive prostate cancer (mHSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). A large body of evidence supports the maintenance or improvement in the health-related quality of life (HRQoL) afforded by enzalutamide treatment in patients with mHSPC, nmCRPC, or chemotherapy-naïve mCRPC, as well as improvement in the HRQoL in patients with later-stage symptomatic mCRPC. Efficacy data from clinical trials are also briefly discussed. EXPERT OPINION: We aim to provide clinicians with a better understanding of how to properly interpret enzalutamide clinical trial safety data. This knowledge may help clinicians guide their patients with PC to achieve optimal clinical benefit from enzalutamide therapy, and to properly manage their patients to mitigate any potential risk.
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Antineoplásicos/administração & dosagem , Benzamidas/administração & dosagem , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Receptores de Andrógenos/administração & dosagem , Antagonistas de Receptores de Andrógenos/efeitos adversos , Antineoplásicos/efeitos adversos , Benzamidas/efeitos adversos , Humanos , Masculino , Nitrilas/efeitos adversos , Feniltioidantoína/efeitos adversos , Neoplasias da Próstata/patologia , Qualidade de VidaRESUMO
OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.