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1.
World J Urol ; 38(6): 1525-1533, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31520111

RESUMO

BACKGROUND: Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized. PATIENTS AND METHODS: RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival. RESULTS: Hypertension was associated with less advanced T stages (p = 0.025), a lower risk of lymph-node (p = 0.026) and distant metastases (p = 0.001), and improved cancer specific survival in univariable analysis (HR 0.81 95% CI 0.69-0.96, p = 0.013). However, hypertension was not an independent prognostic factor after adjustment for TNM stages, grading, and ECOG performance status (HR 0.95, 95% CI 0.80-1.12; p = 0.530). A correlation between the use of concomitant anti-hypertensive medications and improved survival outcome was not identified. All other investigated co-morbidities did not show significant associations with clinicopathological features or cancer-specific survival. CONCLUSION: Although the investigated co-morbidities are capable or inducing pathophysiological changes that are predisposing factors for tumor progression, none is an independent prognostic factor in patients with RCC.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Idoso , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
2.
Cancer Immunol Immunother ; 68(5): 743-751, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30790015

RESUMO

BACKGROUND: Melanoma-associated antigen-A (MAGE-A) and programmed-death ligand 1 (PD-L1) are present in urothelial carcinoma (UC). We assessed survival outcomes in patients with MAGE-A and PD-L1 expression. METHODS: MAGE-A and PD-L1 expression on neoplastic cells was analyzed using tissue microarrays from patients with UC. We compared differential expression between disease stage and grade. MAGE-A and PD-L1 co-expression was subcategorized. Fisher's exact test was done for categorical variables followed by univariable and multivariable analysis of recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Co-expression of MAGE+/PD-L1+ was higher in advanced disease; however, only MAGE+/PD-L1- was associated with shorter RFS [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.19-2.99; p = .006]. MAGE+/PD-L1+ was associated with the worst PFS (HR 17.1; 95% CI 5.96-49.4; p ≤ .001). MAGE-A expression was more prevalent with high-grade (p = .015), and higher-stage ≥ pT2 (p = .001) disease. The 5-year RFS was 44% for MAGE+ versus 58% for MAGE- patients. On multivariable analysis, MAGE+ was also associated with shorter RFS (HR 1.55; 95% CI 1.05-2.30; p = .03). Similarly, MAGE+ was associated with shorter PFS (HR 3.12; 95% CI 1.12-8.68; p = .03). CONCLUSION: MAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+ provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais/metabolismo , Antígenos Específicos de Melanoma/metabolismo , Melanoma/metabolismo , Neoplasias Urológicas/metabolismo , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/genética , Melanoma/mortalidade , Antígenos Específicos de Melanoma/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Neoplasias Urológicas/genética
3.
Proc Natl Acad Sci U S A ; 113(8): 2170-5, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26864202

RESUMO

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Mutação , Idoso , Carcinoma de Células Renais/classificação , Desdiferenciação Celular/genética , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA , Exoma , Feminino , Genes p53 , Humanos , Neoplasias Renais/classificação , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Oncogenes , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
4.
World J Urol ; 32(3): 597-605, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24700308

RESUMO

INTRODUCTION: Currently, most of renal tumors are small, low grade, with a slow growth rate, a low metastatic potential, and with up to 30 % of these tumors being benign on the final pathology. Moreover, they are often diagnosed in elderly patients with preexisting medical comorbidities in whom the underlying medical conditions may pose a greater risk of death than the small renal mass. Concerns regarding overdiagnosis and overtreatment of patients with indolent small renal tumors have led to an increasing interest in minimally invasive, ablative as an alternative to extirpative interventions for selected patients. OBJECTIVE: To provide an overview about the state of the art in radiofrequency ablation (RFA), high-intensity focused ultrasound, and cryoablation in the clinical management of renal cell carcinoma. METHODS: A PubMed wide the literature search of was conducted. RESULTS: International consensus panels recommend ablative techniques in patients who are unfit for surgery, who are not considered candidates for or elect against elective surveillance, and who have small renal masses. The most often used techniques are cryoablation and RFA. These ablative techniques offer potentially curative outcomes while conferring several advantages over extirpative surgery, including improved patient procedural tolerance, faster recovery, preservation of renal function, and reduction in the risk of intraoperative and postsurgical complications. While it is likely that outcomes associated with ablative modalities will improve with further advances in technology, their application will expand to more elective indications as longer-term efficacy data become available. CONCLUSION: Ablative techniques pose a valid treatment option in selected patients.


Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Gerenciamento Clínico , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Neoplasias Renais/cirurgia , Humanos
5.
Cancer ; 119(8): 1547-54, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23335244

RESUMO

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α (HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/-14q (VHL-WT plus HIF2α [WT/H2]), -3p/+14q (HIF1α and HIF2α [H1H2]), and -3p/-14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with -3p/-14q (H2) alterations were larger (P = .002), had higher grade (P = .002) and stage (P = .001), and more often were metastatic (P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with -3p/-14q (H2) had worse cancer-specific survival (P = .014), and patients who had localized disease (P = .012) and primary T1 (pT1) tumors (P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Deleção Cromossômica , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 3 , Neoplasias Renais/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Carcinoma de Células Renais/patologia , Análise Citogenética , Intervalo Livre de Doença , Genes Supressores de Tumor , Humanos , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Análise de Sobrevida
6.
J Urol ; 190(6): 1999-2004, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23831313

RESUMO

PURPOSE: The preoperative neutrophil-to-lymphocyte ratio was proposed as a prognostic factor for localized clear cell renal cell carcinoma. We evaluated its role in nonclear cell renal cell carcinoma. MATERIALS AND METHODS: We queried 2 prospective kidney cancer databases. Patients who underwent full resection of localized (T1-3 N0/+ M0) nonclear cell renal cell carcinoma by radical or partial nephrectomy were included in analysis. Associations of the continuously coded neutrophil-to-lymphocyte ratio with disease-free survival were assessed with univariable and multivariable Cox regression models. Prognostic accuracy was evaluated with the Harrell concordance index. RESULTS: Our final cohort included 281 patients. The 5-year disease-free survival rate was 88.1%. The neutrophil-to-lymphocyte ratio was significantly associated with disease-free survival. With each 1.0 increase in the ratio the risk of recurrence increased by 15% (HR 1.15, p=0.028). On multivariable analysis TNM group (HR 2.84, p=0.025), Fuhrman grade (HR 3.40, p<0.001) and the neutrophil-to-lymphocyte ratio (HR 1.17, p=0.022) were independently associated with disease-free survival. Adding the neutrophil-to-lymphocyte ratio improved the accuracy of a base model to predict disease-free survival from 78.8% to 80.8%. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is an independent prognostic factor for disease-free survival after surgery with curative intent for localized nonclear cell renal cell carcinoma. It significantly increases the accuracy of established prognostic factors. The neutrophil-to-lymphocyte ratio may provide a meaningful adjunct for patient counseling and clinical trial design.


Assuntos
Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Linfócitos , Neutrófilos , Idoso , Carcinoma de Células Renais/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Estudos Prospectivos
7.
Cancer ; 118(7): 1795-802, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21997347

RESUMO

BACKGROUND: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. METHODS: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. RESULTS: Smokers presented more commonly with pulmonary comorbidities (P < .0001) and cardiac comorbidities (P = .014) and with a worse performance status (P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = .022), higher pathologic tumor classification (P = .037), an increased risk of bulky lymph node metastases (P = .031), and the presence of distant metastases (P < .0001), especially lung metastases (P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = .012). CONCLUSIONS: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
8.
Cancer ; 118(23): 5777-82, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22605478

RESUMO

BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015). CONCLUSIONS: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway.


Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 8 , Neoplasias Renais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Feminino , Genes myc , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas
9.
J Urol ; 187(2): 418-23, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22177164

RESUMO

PURPOSE: While microvascular invasion is an accepted risk factor in various cancers, its prognostic role in renal cell carcinoma is still unclear. Therefore, a large multicenter study examining the experience of 5 international institutions was performed to evaluate the prognostic value of microvascular invasion in the occurrence of metastases and cancer specific survival. MATERIALS AND METHODS: A total of 2,596 patients (475 with microvascular invasion and 2,121 without microvascular invasion) having up to 212 (median 22.4) months of followup were compared for differences in clinicopathological features, occurrence of metastases and cancer specific survival. RESULTS: Patients with microvascular invasion presented with higher age (p = 0.001) and a worse Eastern Cooperative Oncology Group performance status (p <0.0001). Microvascular invasion was associated with larger tumor diameter (p <0.0001), higher Fuhrman grade (p <0.0001), more advanced pT stage (p <0.0001), and the presence of lymph node and distant metastases (p <0.0001). In particular, in nonmetastatic cases worse survival was associated with microvascular invasion (p <0.0001, HR 2.38). Univariate analysis demonstrated a strong correlation between microvascular invasion and cancer specific survival (p <0.0001). However, after controlling for gender, Eastern Cooperative Oncology Group performance status, Fuhrman grade and TNM stage statistical significance was lost. Of interest, low stage tumors with microvascular invasion were strongly correlated with the occurrence of metastases (p <0.0001). CONCLUSIONS: Microvascular invasion occurs in nearly 1 of 5 patients with renal cell carcinoma, is tightly correlated with adverse clinicopathological features and is an independent predictor of metastatic spread including in those presenting with low stage tumors.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Vasculares/mortalidade , Neoplasias Vasculares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/secundário , Feminino , Humanos , Masculino , Microvasos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
10.
BJU Int ; 109(11): 1600-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22221668

RESUMO

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sarcomatoid renal cell carcinoma can occur in the setting of all histological subtypes of kidney cancer. These tumours are very aggressive and many patients present with disseminated disease. Long-term survival is poor and the durable responses to systemic therapy are infrequent. Our large cohort analyses the influence of pathological tumour characteristics in determining prognosis for patients with sarcomatoid renal cell carcinoma undergoing surgical resection. This series helps define the prognostic influence of histological subtype, type of sarcomatoid morphology, the percentage necrosis and sarcomatoid features, and the presence of microvascular invasion. OBJECTIVES: To examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design. Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy. PATIENTS AND METHODS: A single-centre database was reviewed to identify all patients with sRCC. Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome. RESULTS: Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5-30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation. The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis. A total of 85 patients (81.7%) died during the follow-up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7-8.9). In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome. A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool. CONCLUSIONS: Both patients with localized and metastatic sRCC have very poor survival outcomes. Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis. A prognostic model, if validated, could aid in patient counselling and/or clinical trial design.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/terapia , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Taxa de Sobrevida
11.
Oncologist ; 16 Suppl 2: 4-13, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21346035

RESUMO

In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biomarcadores , Carcinoma de Células Renais/patologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Renais/patologia , Prognóstico , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Risco , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Radiology ; 261(3): 854-62, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22025734

RESUMO

PURPOSE: To determine whether imaging characteristics at multiphasic multidetector computed tomography (CT) correlate with common karyotypic abnormalities in patients with clear cell renal cell carcinomas (ccRCCs). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. From January 2000 through September 2007, the prenephrectomy multiphasic (corticomedullary, nephrographic, and excretory phases), multidetector helical CT images of 58 histologically proved and karyotyped ccRCCs were reviewed by two readers with experience in abdominal imaging. Imaging features assessed included degree of attenuation, contour, and presence of calcifications and neovascularity. These features were independently correlated with specific karyotypic abnormalities on the resected specimens. Degree of attenuation data were analyzed with logistic regression for significance (P < .05), and morphologic characteristics were analyzed with odds ratios for assessing their diagnostic power. RESULTS: On unenhanced scans, 7% (two of 28) of ccRCCs with the loss of chromosome 3p were calcified, whereas 37% (11 of 30) of lesions without this anomaly were calcified (odds ratio, 0.13). During the corticomedullary phase, ccRCCs with the loss of chromosome Y enhanced more than those without this anomaly (130.0 vs 102.5 HU, P = .04), and ccRCCs with trisomy 7 enhanced less than those without this anomaly (105.8 vs 139.3 HU, P = .04). During the excretory phase, ccRCCs with trisomy 5 enhanced more than those without this anomaly (115.5 vs 83.4 HU, P = .03). CONCLUSION: The genetic makeup of ccRCCs affects their imaging features at multidetector CT examinations. Multidetector CT imaging characteristics may help suggest differences at the cytogenetic level among ccRCCs.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Tomografia Computadorizada Multidetectores/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Meios de Contraste , Feminino , Humanos , Iohexol , Cariótipo , Neoplasias Renais/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Trissomia
13.
J Urol ; 186(6): 2168-74, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22014797

RESUMO

PURPOSE: The prognostic usefulness of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma due to its frequent nuclear and nucleolar pleomorphism. Chromophobe tumor grade, a novel 3-tier tumor grading system based on geographic nuclear crowding and anaplasia, was recently reported to be superior to the Fuhrman system. We compared the 2 scoring systems in a large sporadic chromophobe renal cell carcinoma cohort to determine which grading scheme provides the most predictive assessment of clinical risk. MATERIALS AND METHODS: We identified a total of 84 cases of sporadic chromophobe renal cell carcinoma in 82 patients from a total of 2,634 cases (3.2%) spanning 1989 to 2010. A subset of 11 tumors had secondary areas of sarcomatoid transformation. All cases were reviewed for Fuhrman nuclear grade and chromophobe tumor grade according to published parameters by an expert genitourinary pathologist blinded to clinicopathological information. RESULTS: The distribution of Fuhrman nuclear grades 1 to 4 was 0%, 52.4%, 32.9% and 14.7% of cases, and the distribution of chromophobe tumor grades 1 to 3 was 48.8%, 36.5% and 14.7%, respectively. Metastasis developed in 20 patients (24.4%). Survival analysis revealed statistically significant differences in recurrence-free survival when adjusted for chromophobe tumor grade and Fuhrman nuclear grade. Chromophobe tumor grade showed a slightly higher AUC for recurrence-free survival and overall survival than the Fuhrman nuclear grading system. Neither chromophobe tumor grade nor Fuhrman nuclear grade was retained as an independent predictor of outcome in multivariate modeling when patients with sarcomatoid lesions were excluded. CONCLUSIONS: Chromophobe tumor grade effectively stratifies patients with chromophobe renal cell carcinoma across all grading levels. Since it does not rely on nuclear features, it avoids the hazard of overestimating the malignant potential of chromophobe renal cell carcinoma. Overall chromophobe tumor grade has higher predictive accuracy than the Fuhrman nuclear grading system.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Valor Preditivo dos Testes , Medição de Risco
14.
J Urol ; 185(1): 30-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21074210

RESUMO

PURPOSE: Papillary renal cell carcinoma is characterized histologically by tumors with cells arranged in a papillary pattern. Typically the cells have a chromophilic appearance but areas may show cells with clear cytoplasm, similar to those in clear cell renal cell carcinoma. MATERIALS AND METHODS: We re-reviewed the histological slides of 148 patients with papillary renal cell carcinoma who underwent nephrectomy for the presence of clear cells. Results were correlated with other pathological features, immunohistochemical expression of 22 protein markers, cytogenetic analysis and overall survival. RESULTS: Papillary renal cell carcinoma with clear cells was identified in 57 patients (39%). Clear cells were associated with higher T classification and grade, vascular invasion and type 2 papillary renal cell carcinoma. On immunohistochemistry these tumors revealed higher expression of epithelial vascular endothelial growth factor receptor-2 than papillary renal cell carcinoma without clear cells. All papillary renal cell carcinomas with clear cells expressed α-methylacyl-coenzyme A racemase and 76% expressed cytokeratin 7. Six of 8 tumors (75%) with chromosome 3p loss had clear cell features. The presence of clear cells was retained as an independent prognostic factor on multivariate analysis. In cases of papillary renal cell carcinoma with clear cells the loss of 3p material and absent cytokeratin 7 expression were associated with a worse outcome. CONCLUSIONS: Papillary renal cell carcinoma with clear cells is a novel entity with a unique clinical, immunohistochemical and cytogenetic phenotype. The presence of clear cells is associated with aggressive pathological characteristics and poorer prognosis.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
BJU Int ; 108(3): 343-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21087450

RESUMO

OBJECTIVE: • To evaluate whether current nephrectomy pathology reports are sufficient to allow clinicians to use prognostic nomograms, tailor surveillance, enroll patients into adjuvant trials and select systemic therapy for renal cell carcinoma (RCC). PATIENTS AND METHODS: • Nephrectomy pathology reports were obtained from the LA County Tumor Registry. Key reporting elements identified by the College of American Pathology (CAP) and utilized in RCC prognostic models were abstracted. Hospital type was coded as community, teaching or cancer centre. • Reporting quality was assessed across hospital type and year. RESULTS: • A total of 317 of 344 sampled reports (92.2%) met the inclusion criteria. Tumour size and margin status were commonly reported. Some 90.2% and 84.2% of reports provided data on histology and Fuhrman grade. Tumour classification was omitted in 27.8%. • Microvascular invasion and necrosis were infrequently reported (44.5% and 25.6%, respectively). Only 59.9% of reports met CAP guidelines for tumour classification, margin, size, histology and grade. • Two prognostic nomograms (Stage, Size, Grade and Necrosis system and Kattan) could rarely be utilized (15.8% and 12.3%, respectively), whereas the UCLA Integrated Staging System could be used frequently (65.6%). There were discrepancies satisfying CAP guidelines between community, teaching and cancer centre hospitals, with 54.7%, 70.5% and 75% of reports meeting CAP criteria (P= 0.0102). CONCLUSIONS: • Current RCC pathology reporting fails to satisfy CAP guidelines, does not permit the use of prognostic systems, and may hinder enrollment into adjuvant trials and the selection of systemic therapy. Important reporting discrepancies exist between hospital types, with cancer centres performing best. • Quality improvement initiatives to encourage consistent, comprehensive and clinically relevant pathology reports would improve the quality of RCC patient care.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Carcinoma de Células Renais/cirurgia , Métodos Epidemiológicos , Humanos , Neoplasias Renais/cirurgia , Prontuários Médicos/normas , Nefrectomia/normas , Patologia Clínica/normas , Prognóstico , Melhoria de Qualidade , Projetos de Pesquisa
16.
BJU Int ; 107(5): 724-728, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20626391

RESUMO

OBJECTIVE: • To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP). PATIENTS AND METHODS: • A multi-institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings. • Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded. • Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed. • A Cox regression model determined predictors of perioperative/in-hospital mortality. RESULTS: • In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%. • There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA. • Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P = 0.006). • The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance (P = 0.357). • On multivariate analysis, age of > 60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5-31.1, P = 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036-0.51, P = 0.003) were independent predictors of perioperative mortality. CONCLUSIONS: • Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality. • The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality. • Further prospective studies should be performed to confirm the benefit of DHCA.


Assuntos
Carcinoma de Células Renais/cirurgia , Parada Circulatória Induzida por Hipotermia Profunda , Neoplasias Renais/cirurgia , Nefrectomia/mortalidade , Assistência Perioperatória/mortalidade , Trombectomia/mortalidade , Trombose/cirurgia , Idoso , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/mortalidade , Ponte Cardiopulmonar , Métodos Epidemiológicos , Feminino , Mortalidade Hospitalar , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Trombectomia/métodos , Trombose/complicações , Trombose/mortalidade
17.
Curr Urol Rep ; 12(3): 209-15, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21394596

RESUMO

Potentially curative salvage options for radio-recurrent prostate cancer include prostatectomy, brachytherapy, high-intensity focused ultrasound, and cryotherapy. Salvage cryoablation technology, surgical technique, oncologic outcomes, and complication rates have improved dramatically over the past few decades, shifting this treatment modality from investigational status to an established therapeutic option. In this review, we focus on the most up-to-date oncologic and functional outcomes, as well as complications of salvage cryotherapy for radiation-recurrent prostate cancer.


Assuntos
Braquiterapia/efeitos adversos , Criocirurgia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Terapia de Salvação/métodos , Braquiterapia/métodos , Criocirurgia/efeitos adversos , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/fisiopatologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
18.
Int J Urol ; 18(2): 94-101, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21073543

RESUMO

At present, immunotherapy in urological malignancy is experiencing a renaissance, particularly with the emergence of a host of innovative cancer vaccines. Herein, we will review promising immunotherapeutic approaches and evaluate the data supporting their inclusion in novel combination strategies.


Assuntos
Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/terapia , Vacinas Anticâncer , Humanos
19.
J Urol ; 184(3): 833-41; quiz 1235, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20643450

RESUMO

PURPOSE: Renal cell carcinoma with intravenous tumor thrombus remains one of the most intriguing and challenging topics in urological oncology. With better understanding of the biology of intravascular tumor invasion and improvements in overall survival, the surgical and medical treatment of these patients is being completely redefined. MATERIALS AND METHODS: We performed a MEDLINE(R) search for relevant articles on renal cell carcinoma with intravenous tumor thrombus. RESULTS: We describe the staging systems, prognostic factors and surgical techniques involved in the management of renal cell carcinoma with intravenous tumor thrombus. We also review long-term survival of local, advanced and metastatic renal cell carcinoma with tumor thrombus invasion. Finally, we propose a clinical algorithm for the treatment of patients with renal cell carcinoma invading the venous system. CONCLUSIONS: Management of a kidney cancer tumor invading the venous system should now consider the primary biology and natural behavior of a given tumor in that specific patient rather than only focusing on the level and extent of venous invasion. Treatment must be individualized for every patient based on performance status, tumor biology and risk of surgery.


Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Células Neoplásicas Circulantes , Algoritmos , Humanos , Estadiamento de Neoplasias , Prognóstico , Veias Renais , Veia Cava Inferior
20.
J Urol ; 183(6): 2143-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20399450

RESUMO

PURPOSE: Recent evidence suggests that nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. We tested this hypothesis in an independent large series from a single institution. MATERIALS AND METHODS: One dedicated uropathologist regraded 158 cases of papillary renal cell carcinoma by nucleolar and Fuhrman grades. The prognostic value and predictive accuracy of these grading systems to predict disease specific survival were analyzed by Cox proportional hazards models and the concordance index. RESULTS: There were 39 papillary renal cell carcinoma related deaths (25%) at a mean followup of 50 months. On univariate analysis nucleolar grade predicted disease specific survival with a concordance index of 67.8% but the survival difference between grades 1 and 2 did not attain statistical significance (p = 0.1441). Fuhrman grade predicted disease specific survival significantly better (concordance index 74.7%, p <0.001). Comparison of survival estimates between the grades revealed statistical significance across each grade category (each p <0.05). Fuhrman but not nucleolar grade was retained as an independent prognostic factor on multivariate analysis (p = 0.027 and 0.128, respectively). CONCLUSIONS: Each grading system performs well but the predictive accuracy of Fuhrman grade is statistically superior to that of nucleolar grade and only Fuhrman grade provides independent prognostic information on patients with papillary renal cell carcinoma. Thus, Fuhrman grade should be the standard grading system for papillary renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Nucléolo Celular/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
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