RESUMO
To assess the robotic-assisted partial nephrectomy (RAPN) trifecta rate within a fellowship program. Patients undergoing RAPN 01/01/2010-01/07/2023 were enrolled from a prospectively maintained database. All cases were performed jointly with surgical fellows, except when privately insured. Patients were excluded if they were converted to open or radical nephrectomy. The primary outcome was achieving the 'trifecta' of negative surgical margins, no complications < 30 days post-operatively and warm ischaemia time (WIT) < 25 min. The secondary outcomes were factors associated with trifecta success. Ethics approval was obtained. In the enrolment period, 355 patients underwent intended RAPN, of whom seven were excluded due to conversion to conversion to radical nephrectomy (6 patients) or conversion to open (one). Amongst the 348 eligible patients, median age was 60 years, 115 (33%) were female and 19 were private patients. WIT was < 25 min for 324/337 patients (96%), surgical margins were negative in 325 (93%), 294 (84%) were complication-free at 30 days and 301/320 (94%) had a < 30% decline in estimated glomerular filtration rate at 3-6 months postoperatively. Subsequently, trifecta outcomes were achieved in 253/337 (75%) patients. Comparing with patients without those with trifecta success were similar in all thirteen measured patients and tumour factors. In a teaching hospital, with a fellowship training programme, trifecta outcome is achievable for most RAPN patients, and at a rate comparable to international standards. Fellowship centres should monitor their outcomes to ensure high patient outcomes are maintained alongside training requirements.
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Bolsas de Estudo , Neoplasias Renais , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/métodos , Nefrectomia/educação , Procedimentos Cirúrgicos Robóticos/educação , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Masculino , Resultado do Tratamento , Neoplasias Renais/cirurgia , Idoso , Margens de Excisão , Isquemia Quente , Complicações Pós-Operatórias , AdultoRESUMO
BACKGROUND: Non-clear cell renal cell carcinoma (nccRCC) represents a rare form of renal cell carcinoma (RCC) in the clinic. It is now understood that contrast-enhanced ultrasound (CEUS) exhibits diverse manifestations and can be prone to misdiagnosis. Therefore, summarizing the distinctive features of contrast-enhanced ultrasonography is essential for differentiation from ccRCC. OBJECTIVE: This study aims to evaluate the diagnostic efficacy of qualitative and quantitative CEUS in diagnosing nccRCC to enhance our understanding of this condition. METHODS: We conducted a retrospective analysis of 21 patients with confirmed nccRCC following surgery and assessed the characteristic conventional ultrasound and CEUS imaging features. The paired Wilcoxon signed-rank sum test was employed to compare differences in CEUS time-intensity curve (TIC) parameters between the lesions and the normal renal cortex. RESULTS: Routine ultrasound revealed the following primary characteristics in the 21 nccRCC cases: hypoechoic appearance (10/21, 47.6%), absence of liquefaction (18/21, 66.7%), regular shape (19/21, 90.5%), clear boundaries (21/21, 100%), and absence of calcification (17/21, 81%). Color Doppler flow imaging (CDFI) indicated a low blood flow signal (only 1 case of grade III). Qualitative CEUS analysis demonstrated that nccRCC predominantly exhibited slow progression (76.1%), fast washout (57%), uniformity (61.9%), low enhancement (71.5%), and ring enhancement (61.9%). Quantitative CEUS analysis revealed that parameters such as PE, WiAUC, mTTI, WiR, WiPI, WoAUC, WiWoAUC, and WOR in the lesions were significantly lower than those in the normal renal cortex (Z=-3.980, -3.563, -2.427, -3.389, -3.980, -3.493, -3.528, -2.763, P < 0.001, < 0.001, = 0.015, = 0.001, < 0.001, < 0.001, < 0.001, = 0.006). However, there were no significant differences in RT, TTP, FT, or QOF (all P > 0.05). CONCLUSION: nccRCC exhibits distinctive CEUS characteristics, including slow progression, fast washout, low homogeneity enhancement, and ring enhancement, which can aid in distinguishing nccRCC from ccRCC.
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Carcinoma de Células Renais , Meios de Contraste , Neoplasias Renais , Ultrassonografia , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Ultrassonografia/métodos , AdultoRESUMO
INTRODUCTION: Cabozantinib is one of the preferred treatment options in the latest metastatic renal cell carcinoma (mRCC) guidelines. Cabozantinib is also associated with high drug expenses irrespective of the used dose, because a flat-prizing model has been implemented. In addition, concomitant intake with a high-fat meal increases its bioavailability on average by 57%. Combined with the long terminal half-life of cabozantinib (99 h), this creates possibilities to extend the dosing interval to reduce drug expenses whilst maintaining equivalent exposure. OBJECTIVES: The primary objective was to evaluate the population pharmacokinetic (POPPK) model of cabozantinib developed for its registration using real-world patients' therapeutic drug monitoring (TDM) data. The secondary objective was to design, simulate, and evaluate alternative dose regimens with the aim to reduce drug expenses whilst maintaining comparable exposure. METHODS: Retrospective TDM data from mRCC patients treated with cabozantinib were obtained. The data were evaluated using the published Food and Drug Administration (FDA) cabozantinib POPPK model, a two-compartment disposition model with a dual (fast and slow) lagged first-order absorption process derived from FDA registration documents, as a basis. Subsequently, simulations of alternative drug expenses saving regimens were evaluated. RESULTS: Twenty-seven mRCC patients with 75 pharmacokinetic observations were included. Patients were treated for a median of 75 days with a median dose of 40 mg. Model evaluation results showed that the cabozantinib TDM concentrations were adequately predicted by the published FDA cabozantinib POPPK model, except for a slightly higher clearance (CL) of 3.11 L/h compared to the reported value (2.23 L/h). The simulation study indicated that an alternative dose regimen that consists of taking 60 mg of cabozantinib for 2 days and then skipping 1 day results in comparable average exposure when compared with a 40 mg daily dose, both without food interaction, while saving 33.3% of the total drug expenses per month. The food effect of a high-fat meal was also taken into account when simulating other alternative dose regimens; 40 mg every 72 h combined with a high-fat meal resulted in comparable exposure when compared with a 20 mg daily dose fasted, while saving 66.7% in drug expenses. CONCLUSIONS: In this study, the optimized cabozantinib POPPK model resulted in adequate prediction of real-world cabozantinib pharmacokinetic data. Alternative dosing regimens with and without using known food interactions were proposed that resulted in potential strategies to significantly reduce cabozantinib drug expenses.
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Anilidas , Carcinoma de Células Renais , Neoplasias Renais , Piridinas , Humanos , Piridinas/farmacocinética , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/economia , Anilidas/farmacocinética , Anilidas/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Modelos Biológicos , Monitoramento de Medicamentos/métodos , Adulto , Antineoplásicos/farmacocinética , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Custos de Medicamentos , Idoso de 80 Anos ou maisRESUMO
Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8-3.6), 1.4 (1.2-1.6), and 37.2 (32.0-42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75-79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5-19 age and males aged 5-14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region.
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Neoplasias Renais , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Masculino , Feminino , África do Norte/epidemiologia , Oriente Médio/epidemiologia , Pessoa de Meia-Idade , Idoso , Adulto , Incidência , Adulto Jovem , Adolescente , Criança , Pré-Escolar , Idoso de 80 Anos ou mais , Carga Global da Doença/tendências , Anos de Vida Ajustados por Deficiência , LactenteRESUMO
INTRODUCTION: Surgical video review is an emerging tool for assessing patient outcomes, especially in complex surgeries such as robot-assisted partial nephrectomy (RAPN). Assessing and measuring warm ischaemia time (WIT) during RAPN by dividing it into the time used for tumour excision time (ExcT), time used for kidney reconstruction time (RecT) and intermediate time (IntT) has not been performed before. This study aimed to analyse the factors that can influence all surgical times and assess their impact on positive surgical margins (PSMs) and complication rates. METHODS: We evaluated 32 surgical video recordings from patients undergoing RAPN and measured WIT, ExcT, RecT and IntT with a stopwatch. Factors such as tumour characteristics and surgeon experience were also recorded. SPSS software was used to identify the predictors for all surgical times and to correlate ExcT with PSM and RecT with complication rate. RESULTS: We recorded a median WIT of 1,048 s (17 min and 28 s). The median of ExcT, RecT and IntT was 398 s (37.1% of WIT), 518 s (46.7% of WIT) and 180 s (16.2% of WIT), respectively. We found a significant correlation (P < 0.001) between R.E.N.A.L. score and all surgical times. No correlation was found between ExcT and PSM (P = 0.488) and between RecT and the probability of developing complications (P = 0.544). CONCLUSION: Tumour morphology influences all surgical times, and surgeon experience influences only ExcT. We observed a short RecT during RAPN though at the cost of increased ExcT, and we believe that improving surgical experience, especially for the excision of more complex tumours, can reduce WIT during RAPN.
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Neoplasias Renais , Nefrectomia , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos , Isquemia Quente , Humanos , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Gravação em Vídeo , Rim/cirurgia , Margens de Excisão , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Procedimentos de Cirurgia Plástica/métodosRESUMO
INTRODUCTION: Previous literature suggests socioeconomic status and racial disparities impact management decisions for patients with small renal masses. We aim to build upon these findings and examine how these modalities impact patient adherence to their management plan. METHODS: This retrospective study analyzed our Kidney Tumor Program database (n = 1476) containing patients from 2000 to 2020. Socioeconomic status was estimated using 2 modalities: Area Deprivation Index and household income. Patients were then evaluated for differences in adherence, nonadherence, and loss to follow-up. Adherent patients completed all recommended appointments within 6 months of their initial follow-up. Nonadherent patients did not complete all recommended appointments within 6 months of their originally scheduled follow-up but eventually did. Patients lost to follow-up were recommended to follow up but never did. RESULTS: Patient adherence was not significantly different across sex or primary treatment method but differed with respect to race/ethnicity. Black patients were significantly more likely to be nonadherent (P = .021) and lost to follow-up (P = .008). After adjusting for race/ethnicity, Area Deprivation Index and income bracket were significantly associated with adherence and loss to follow-up. Patients with a high socioeconomic status had significantly higher rates of adherence (ADI, quartile [Q] 1 vs Q4, P = .038; income, >$120,000 vs $30,000-$59,999, P < .003) and decreased loss to follow-up (ADI, Q1 vs Q4, P = .03; income, >$120,000 vs $30,000-$59,999, P = .002). CONCLUSIONS: Our results demonstrate that Black race and low socioeconomic status are associated with decreased adherence and increased loss to follow-up. Possible strategies to target these disparities include financial assistance programming, social determinants of health screening, and nurse navigator programs.
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Neoplasias Renais , Cooperação do Paciente , Classe Social , Humanos , Masculino , Estudos Retrospectivos , Neoplasias Renais/terapia , Neoplasias Renais/economia , Neoplasias Renais/etnologia , Feminino , Cooperação do Paciente/estatística & dados numéricos , Cooperação do Paciente/etnologia , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: To assess the outcomes, total healthcare utilization, and cost savings for same-day discharge (SDD) vs inpatient robotic-assisted partial nephrectomy (RAPN) and robotic-assisted radical nephrectomy (RARN). METHODS: We compared 146 RAPNs and 65 RARNs consecutively performed as SDD (RAPN=21, RARN=9) vs inpatient (RAPN=125, RARN=56) from April 2015 to May 2023 at two academic medical centers. We collected baseline demographics, perioperative characteristics, and 30-day complications. We applied the Time-Driven Activity-Based Costing analysis to compare total costs of RAPN and PARN throughout the cycle of care, including inpatient vs SDD. RESULTS: Baseline demographics and comorbidities were similar between patients undergoing inpatient vs SDD RAPN and RARN. One Clavien-Dindo grade II complication (3.3%) requiring readmission due to wound infection for antibiotics occurred after SDD RAPN; no complications occurred after SDD RARN. Two unscheduled office or emergency department visits (6.7%) occurred after SDD RAPN for surgical-site infection and urinary retention. SDD vs inpatient RAPN and RARN demonstrated a $3091 (18%) and $4003 (25%) overall cost reduction, respectively. CONCLUSION: SDD RAPN and RARN result in cost savings of 18%-25% without a difference in complications, and thereby improves value-based care for appropriately selected patients.
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Neoplasias Renais , Nefrectomia , Alta do Paciente , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/economia , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/cirurgia , Neoplasias Renais/economia , Alta do Paciente/estatística & dados numéricos , Idoso , Estudos Retrospectivos , Redução de Custos/estatística & dados numéricos , Fatores de Tempo , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Pacientes Internados/estatística & dados numéricosRESUMO
BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.
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Neoplasias Renais , Tumor de Wilms , Humanos , Tumor de Wilms/mortalidade , Tumor de Wilms/terapia , Tumor de Wilms/economia , África Subsaariana/epidemiologia , Feminino , Masculino , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Neoplasias Renais/economia , Pré-Escolar , Taxa de Sobrevida , Criança , Lactente , Adolescente , Prognóstico , Seguimentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economiaRESUMO
The kidney cancer (KC) burden measures have changed dramatically in recent years due to changes in exposure to the determinants over time. We aimed to decompose the difference in the KC burden measures between 1990 and 2019. This ecological study included data on the KC burden measures as well as socio-demographic index (SDI), behavioral, dietary, and metabolic risk factors from the global burden of disease study. Non-linear multivariate decomposition analysis was applied to decompose the difference in the burden of KC. Globally, ASIR, ASMR, and ASDR of KC increased from 2.88 to 4.37, from 1.70 to 2.16, and from 46.13 to 54.96 per 100,000 people between 1990 and 2019, respectively. The global burden of KC was more concentrated in developed countries. From 1990 to 2019, the burden of KC has increased the most in Eastern European countries. More than 70% of the difference in the KC burden measures between 1990 and 2019 was due to changes in exposure to the risk factors over time. The SDI, high body mass index (BMI), and alcohol use had the greatest contribution to the difference in the KC burden measures. Changes in characteristics over time, including SDI, high BMI, and alcohol consumption, appear to be important in the evolving landscape of KC worldwide. This finding may help policymakers design policies and implement prevention programs to control and manage KC.
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Carga Global da Doença , Neoplasias Renais , Humanos , Neoplasias Renais/epidemiologia , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Índice de Massa Corporal , Saúde Global , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologiaRESUMO
Background Accurate characterization of suspicious small renal masses is crucial for optimized management. Deep learning (DL) algorithms may assist with this effort. Purpose To develop and validate a DL algorithm for identifying benign small renal masses at contrast-enhanced multiphase CT. Materials and Methods Surgically resected renal masses measuring 3 cm or less in diameter at contrast-enhanced CT were included. The DL algorithm was developed by using retrospective data from one hospital between 2009 and 2021, with patients randomly allocated in a training and internal test set ratio of 8:2. Between 2013 and 2021, external testing was performed on data from five independent hospitals. A prospective test set was obtained between 2021 and 2022 from one hospital. Algorithm performance was evaluated by using the area under the receiver operating characteristic curve (AUC) and compared with the results of seven clinicians using the DeLong test. Results A total of 1703 patients (mean age, 56 years ± 12 [SD]; 619 female) with a single renal mass per patient were evaluated. The retrospective data set included 1063 lesions (874 in training set, 189 internal test set); the multicenter external test set included 537 lesions (12.3%, 66 benign) with 89 subcentimeter (≤1 cm) lesions (16.6%); and the prospective test set included 103 lesions (13.6%, 14 benign) with 20 (19.4%) subcentimeter lesions. The DL algorithm performance was comparable with that of urological radiologists: for the external test set, AUC was 0.80 (95% CI: 0.75, 0.85) versus 0.84 (95% CI: 0.78, 0.88) (P = .61); for the prospective test set, AUC was 0.87 (95% CI: 0.79, 0.93) versus 0.92 (95% CI: 0.86, 0.96) (P = .70). For subcentimeter lesions in the external test set, the algorithm and urological radiologists had similar AUC of 0.74 (95% CI: 0.63, 0.83) and 0.81 (95% CI: 0.68, 0.92) (P = .78), respectively. Conclusion The multiphase CT-based DL algorithm showed comparable performance with that of radiologists for identifying benign small renal masses, including lesions of 1 cm or less. Published under a CC BY 4.0 license. Supplemental material is available for this article.
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Meios de Contraste , Aprendizado Profundo , Neoplasias Renais , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Algoritmos , Rim/diagnóstico por imagem , AdultoRESUMO
BACKGROUND AND OBJECTIVES: Despite significant progress in biomedical research, the rate of success in oncology drug development remains inferior to that of other therapeutic fields. Mechanistic models provide comprehensive understanding of the therapeutic effects of drugs, which is crucial for designing effective clinical trials. This study was performed to acquire a better understanding of PI3K-AKT-TOR pathway modulation and preclinical to clinical translational bridging for a specific compound, apitolisib (PI3K/mTOR inhibitor), by developing integrated mechanistic models. METHODS: Integrated pharmacokinetic (PK)-pharmacodynamic (PD)-efficacy models were developed for xenografts bearing human renal cell adenocarcinoma and for patients with solid tumors (phase 1 studies) to characterize relationships between exposure of apitolisib, modulation of the phosphorylated Akt (pAkt) biomarker triggered by inhibition of the PI3K-AKT-mTOR pathway, and tumor response. RESULTS: Both clinical and preclinical integrated models show a steep sigmoid curve linking pAkt inhibition to tumor growth inhibition and quantified that a minimum of 35-45% pAkt modulation is required for tumor shrinkage in patients, based on platelet-rich plasma surrogate matrix and in xenografts based on tumor tissue matrix. Based on this relationship between targeted pAkt modulation and tumor shrinkage rate, it appeared that a constant pAkt inhibition of 61% and 65%, respectively, would be necessary to achieve tumor stasis in xenografts and patients. CONCLUSIONS: These results help when it comes to evaluating the translatability of the preclinical analysis to the clinical target, and provide information that will enhance the value of future preclinical translational dose-finding and dose-optimization studies to accelerate clinical drug development. TRIAL REGISTRY: ClinicalTrials.gov NCT00854152 and NCT00854126.
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Carcinoma de Células Renais , Neoplasias Renais , Inibidores de MTOR , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias Renais/tratamento farmacológico , Inibidores de MTOR/uso terapêutico , Inibidores de MTOR/farmacologia , Inibidores de MTOR/farmacocinética , Neoplasias/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Estudos Retrospectivos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We introduce a Bayesian approach for biclustering that accounts for the prior functional dependence between genes using hidden Markov models (HMMs). We utilize biological knowledge gathered from gene ontologies and the hidden Markov structure to capture the potential coexpression of neighboring genes. Our interpretable model-based clustering characterized each cluster of samples by three groups of features: overexpressed, underexpressed, and irrelevant features. The proposed methods have been implemented in an R package and are used to analyze both the simulated data and The Cancer Genome Atlas kidney cancer data.
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Teorema de Bayes , Neoplasias Renais , Cadeias de Markov , Neoplasias Renais/genética , Humanos , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Biometria/métodosRESUMO
ChatGPT-4V model with image interpretation tested for distinguishing kidney & prostate tumors from normal tissue.
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Neoplasias Renais , Neoplasias Urológicas , Masculino , Humanos , Leitura , Neoplasias Urológicas/diagnóstico , Neoplasias Renais/diagnóstico por imagem , Pelve , PróstataRESUMO
Importance: Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. Objective: To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Exposures: Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). Main Outcomes and Measures: The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. Results: The sample included 15â¯407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12â¯966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. Conclusions and Relevance: In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.
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Carcinoma de Células Renais , Disparidades em Assistência à Saúde , Neoplasias Renais , Medicare , Humanos , Masculino , Feminino , Idoso , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/etnologia , Estados Unidos , Estudos Retrospectivos , Medicare/estatística & dados numéricos , Neoplasias Renais/terapia , Neoplasias Renais/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Idoso de 80 Anos ou mais , Vulnerabilidade Social , Populações Vulneráveis/estatística & dados numéricos , Fatores SocioeconômicosRESUMO
BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.
Assuntos
Neoplasias Renais , Nefrectomia , Tumor de Wilms , Humanos , Tumor de Wilms/terapia , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Tumor de Wilms/cirurgia , Gana/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pré-Escolar , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Carga Tumoral , Lactente , Criança , Intervalo Livre de Doença , Determinantes Sociais da Saúde , Terapia Neoadjuvante/estatística & dados numéricosRESUMO
INTRODUCTION: Delayed bleeding is a potentially serious complication after partial nephrectomy (PN), with reported rates of 1%-2%. Patients with multiple renal tumors, including those with hereditary forms of kidney cancer, are often managed with resection of multiple tumors in a single kidney which may increase the risk of delayed bleeding, though outcomes have not previously been reported specifically in this population. The objective of this study was to evaluate the incidence and timing of delayed bleeding as well as the impact of intervention on renal functional outcomes in a cohort primarily made up of patients at risk for bilateral, multifocal renal tumors. METHODS: A retrospective review of a prospectively maintained database of patients with known or suspected predisposition to bilateral, multifocal renal tumors who underwent PN from 2003 to 2023 was conducted. Patients who presented with delayed bleeding were identified. Patients with delayed bleeding were compared to those without. Comparative statistics and univariate logistic regression were used to determine potential risk factors for delayed bleeding. RESULTS: A total of 1256 PN were performed during the study period. Angiographic evidence of pseudoaneurysm, AV fistula and/or extravasation occurred in 24 cases (1.9%). Of these, 21 were symptomatic presenting with gross hematuria in 13 (54.2%), decreasing hemoglobin in 4(16.7%), flank pain in 2(8.3%), and mental status change in 2 (8.3%), while 3 patients were asymptomatic. Median number of resected tumors was 5 (IQR 2-8). All patients underwent angiogram with super-selective embolization. Median time to bleed event was 13.5 days (IQR 7-22). Factors associated with delayed bleeding included open approach (OR 2.2, IQR(1.06-5.46), Pâ¯=â¯0.04 and left-sided surgery (OR 4.93, IQR(1.67-14.5), Pâ¯=â¯0.004. Selective embolization had little impact on ultimate renal functional outcomes, with a median change of 11% from the baseline eGFR after partial nephrectomy and embolization. One patient required total nephrectomy for refractory bleeding after embolization. CONCLUSIONS: Delayed bleeding after PN in a cohort of patients with multifocal tumors is an infrequent event, with similar rates to single tumor series. Patients should be counseled regarding timing and symptoms of delayed bleeding and multidisciplinary management with interventional radiology is critical for timely diagnosis and treatment.
Assuntos
Neoplasias Renais , Nefrectomia , Hemorragia Pós-Operatória , Humanos , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Neoplasias Renais/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Incidência , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Idoso , Fatores de Tempo , Fatores de Risco , Recidiva Local de Neoplasia/cirurgiaRESUMO
OBJECTIVE: To examine the cost-effectiveness of the clear cell likelihood score compared to renal mass biopsy (RMB) alone. METHODS: The clear cell likelihood score, a new grading system based on multiparametric magnetic resonance imaging, has been proposed as a possible alternative to percutaneous RMB for identifying clear cell renal carcinoma in small renal masses and expediting treatment of high-risk patients. A decision analysis model was developed to compare a RMB strategy where all patients undergo biopsy and a clear cell likelihood score strategy where only patients that received an indeterminant score of 3 undergo biopsy. Effectiveness was assigned 1 for correct diagnoses and 0 for incorrect or indeterminant diagnoses. Costs were obtained from institutional fees and Medicare reimbursement rates. Probabilities were derived from literature estimates from radiologists trained in the clear cell likelihood score. RESULTS: In the base case model, the clear cell likelihood score was both more effective (0.77 vs 0.70) and less expensive than RMB ($1629 vs $1966). Sensitivity analysis found that the nondiagnostic rate of RMB and the sensitivity of the clear cell likelihood score had the greatest impact on the model. In threshold analyses, the clear cell likelihood score was the preferred strategy when its sensitivity was greater than 62.7% and when an MRI cost less than $5332. CONCLUSION: The clear cell likelihood score is a more cost-effective option than RMB alone for evaluating small renal masses for clear cell renal carcinoma.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Biópsia/economia , Biópsia/métodos , Carcinoma de Células Renais/economia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/diagnóstico , Análise de Custo-Efetividade , Técnicas de Apoio para a Decisão , Rim/patologia , Rim/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/economia , Neoplasias Renais/diagnóstico , Imageamento por Ressonância Magnética Multiparamétrica/economia , Gradação de TumoresRESUMO
OBJECTIVE: To analyze temporal trends and costs associated with the use of minimally invasive surgery (MIS) for kidney cancer in the US over the past decade. To examine the impact of social determinants of health (SDOH) on perioperative outcomes. METHODS: The PearlDiver Mariner, a national database of insurance billing records, was queried for this retrospective observational cohort analysis. The MIS population was identified and stratified according to treatment modality, using International Classification of Diseases and current procedural terminology codes. SDOH were assessed using International Classification of Diseases codes. Negative binomial regression was used to evaluate the overall number of renal MIS and Cochran-Armitage tests to compare the utilization of different treatment modalities, over the study period. Multivariable logistic regression analysis identified predictors of perioperative complications. RESULTS: A total of 80,821 MIS for kidney cancer were included. Minimally invasive partial nephrectomy adoption as a fraction of total MIS increased significantly (slope of regression line, reg. = 0.026, P <.001). Minimally invasive radical nephrectomy ($26.9k ± 40.9k) and renal ablation ($18.9k ± 31.6k) were the most expensive and cheapest procedures, respectively. No statistically significant difference was observed in terms of number of complications (P = .06) and presence of SDOH (P = .07) among the treatment groups. At multivariable analysis, patients with SDOH undergoing minimally invasive radical nephrectomy had higher odds of perioperative complications, while renal ablation had a significantly lower probability of perioperative complications. CONCLUSION: This study describes the current management of kidney cancer in the US, offering a socioeconomic perspective on the impact of this disease in everyday clinical practice.
Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Minimamente Invasivos , Nefrectomia , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/economia , Estados Unidos , Estudos Retrospectivos , Feminino , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Pessoa de Meia-Idade , Nefrectomia/economia , Nefrectomia/métodos , Nefrectomia/tendências , IdosoRESUMO
BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.
Assuntos
Neoplasias Renais , Neoplasias da Próstata , Masculino , Humanos , Fatores Socioeconômicos , Carga Global da Doença , Bexiga Urinária , Efeitos Psicossociais da Doença , Neoplasias Renais/epidemiologia , Rim , Neoplasias da Próstata/epidemiologiaRESUMO
OBJECTIVE: This retrospective study aimed to construct and validate a nomogram for personalized prognostic assessment of favorable histology Wilms tumor (FHWT) based on clinical and pathological variables. METHODS AND MATERIALS: This was a retrospective study collected data from patients who underwent surgery for FHWT between March 2007 and November 2022 at Beijing Children's Hospital. Univariate and multivariate Cox proportional hazards regression analyses were conducted to determine the significance variables and constructed the nomogram in predicting event-free survival (EFS) in FHWT patients. RESULTS: A total of 401 FHWT patients were included in the study, with the median age of the patients was 3.4 years. The overall 1-, 3-, and 5-year OS rates were 98.2%, 96.3%, and 93.9%. The 1-, 3-, and 5-year EFS rates were 91.2%, 88.2%, and 86.6%. Subgroup analysis revealed age greater than 2 years was associated with a worse prognosis than age less than or equal to 2 years (P < 0.001), and patients with high-risk Wilms tumors were associated with a higher rate of recurrence and death (P < 0.001). Multivariate analysis showed that age (HR: 2.449, 95%CI: 1.004-5.973), stage (HR: 1.970, 95% CI:1.408-2.756), and histological risk (HR:9.414, 95% CI: 4.318-20.525) were identified as independent predictors of EFS (P < 0.05) and used to construct the nomogram. The prognostic nomogram demonstrated good calibration, great clinical utility, and the time-dependent receiver operating curve analysis showed that the nomogram had precise predictability, with area under the curve values of 0.85(95CI:0.796-0.913), 0.85(95CI:0.80-0.91), and 0.88(95CI:0.839-0.937) for 1-,3-year and 5-year EFS. CONCLUSION: This study provides valuable insights into the clinical characteristics and outcomes of FHWT patients. Accurate staging and histological risk assessment are important in predicting outcomes, and the prognostic nomogram we developed can be a useful tool for clinicians to assess patient prognosis and make informed treatment decisions.