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PURPOSE: AUA guidelines for patients with microhematuria (≥3 red blood cells [RBC]/high-power field [hpf]) include cystoscopy for most over age 40 due to risk of urothelial cancer (UC). Cxbladder Triage (CxbT) is a urinary genomic test with UC negative predictive value of 99%. In this prospective randomized controlled trial, we compared cystoscopy use in a standard of care (SOC) arm vs a marker-based approach. MATERIALS AND METHODS: All patients with hematuria provided urine for a CxbT. Those categorized as lower risk (LR), defined as 3 to 29 RBC/hpf and minimal smoking history (<10 pack-years) were randomized between the test group provided with the CxbT result vs the SOC control group. Negative CxbT patients were offered omission of cystoscopy with surveillance. "Not lower risk" (NLR) patients (>30 RBC/hpf or >10 pack-year smoking history) had a CxbT but otherwise SOC. Patient decision and outcomes were recorded. RESULTS: Of 390 eligible patients, 255 were NLR and 135 were LR randomized to CxbT informed decision or SOC. The median age was 62 years (range 18-94) and 54% were male. Overall, 63% of CxbT tests were negative. For NLR patients, 82% had cystoscopy. In the LR control group, cystoscopy was performed in 67% of SOC and 27% in the test group (relative risk 0.41 [95% CI 0.27-0.61]). Compared to cystoscopy, CxbT had 90% sensitivity, 56% specificity, and 99% negative predictive value for UC. CONCLUSIONS: In this prospective randomized controlled trial, use of CxbT in patients with LR hematuria resulted in 59% reduction of cystoscopy use. This clinical utility of CxbT can reduce the burden of unnecessary cystoscopies.
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Cistoscopia , Hematúria , Triagem , Neoplasias da Bexiga Urinária , Humanos , Cistoscopia/efeitos adversos , Masculino , Hematúria/diagnóstico , Hematúria/etiologia , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Neoplasias da Bexiga Urinária/diagnóstico , Triagem/métodos , Medição de Risco/métodos , Adulto , Doenças AssintomáticasRESUMO
Upper tract urothelial carcinoma (UTUC) is a relatively rare yet aggressive malignancy. While radical nephroureterectomy (RNU) remains the cornerstone treatment, UTUC has high local and metastatic relapse rates, leading to a dismal prognosis. To identify the clinicopathological factors associated with an increased risk of local and metastatic relapse in UTUC, we conducted a retrospective analysis of 133 consecutive UTUC patients who underwent RNU from 1998 to 2018. Patients lost to follow-up or with a history of bladder cancer were excluded from the study. The remaining 87 patients were categorized into two subgroups: those with tumor recurrence/relapse (40 cases) and those without recurrence/relapse (47 cases). Clinical and pathological characteristics were compared across the two groups. Multiple factors are associated with UTUC recurrence/relapse including larger tumor size, histology divergent differentiations/subtypes, high tumor grade, advanced pathologic T stage, positive margin, lymphovascular invasion (LVI), positive lymph node status, and preoperative hydronephrosis. Multivariate Cox regression analysis revealed that squamous differentiation predicted recurrence/relapse (p = 0.012), independent of tumor stage. Moreover, compared to the conventional histology type, UTUC with squamous differentiation had a significantly higher relapse rate (p = 0.0001) and poorer survival (p = 0.0039). This observation was further validated in invasive high-grade UTUC cases. Our findings suggest that many pathological factors contribute to UTUC recurrence/relapse, particularly, squamous differentiation may serve as an independent risk predictor for relapse and a potent prognosticator for adverse cancer-specific survival in UTUC patients. Recognizing and thoroughly assessing the pathological factors is essential for better oncologic management of UTUC.
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PURPOSE: Microhematuria is a highly prevalent condition with a low associated risk of urothelial and upper tract malignancy. The AUA Guidelines recently changed recommendations for imaging favoring renal ultrasound for low- and intermediate-risk patients with microhematuria. We summarize the diagnostic test characteristics of computed tomography urography, renal ultrasound, and magnetic resonance urography in comparison with surgical pathology for the diagnosis of upper urinary tract cancer in microhematuria and gross hematuria patients. MATERIALS AND METHODS: This study is a systematic review and meta-analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from evidence collected for the 2020 AUA Microhematuria Guidelines report, including studies assessing imaging following diagnosis of hematuria published from January 2010 through December 2019. RESULTS: The search identified 20 studies which reported the prevalence of malignant and benign diagnoses in relation to imaging modality, of which 6 were included in the quantitative analysis. For the detection of renal cell carcinoma and upper urinary tract carcinoma in patients with microhematuria and gross hematuria, computed tomography urography had a sensitivity of 94% (95% CI, 84%-98%) and a specificity of 99% (95%CI, 97%-100%) with a certainty of evidence rating of very low and low, respectively when 4 studies were pooled. In comparison, ultrasound demonstrated a sensitivity ranging from 14%-96% (low certainty of evidence) and a specificity of 99%-100% in 2 studies (moderate certainty of evidence), while magnetic resonance urography demonstrated a sensitivity of 83% and specificity of 86% in 1 study with a low certainty of evidence. CONCLUSIONS: In a limited data set for each individual imaging modality, computed tomography urography appears the most sensitive imaging modality for the diagnostic evaluation of microhematuria. Future studies will be needed to evaluate the clinical and health system financial impacts of the change in guideline recommendations from computed tomography urography to renal ultrasound in evaluating low- and intermediate-risk patients with microhematuria.
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Neoplasias Renais , Neoplasias Urológicas , Humanos , Tomografia Computadorizada por Raios X/métodos , Hematúria/diagnóstico por imagem , Hematúria/etiologia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/diagnóstico por imagem , Ultrassonografia , Urografia/métodosRESUMO
PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.
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Carcinoma in Situ , Carcinoma de Células de Transição , Telomerase , Neoplasias da Bexiga Urinária , Humanos , Adolescente , Adulto , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urina , Hematúria/etiologia , Hematúria/genética , Estudos Prospectivos , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Cistoscopia , Medição de Risco , Mutação , Sensibilidade e Especificidade , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Telomerase/genéticaRESUMO
PURPOSE: The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC). MATERIALS/METHODS: The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy. CONCLUSION: This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.
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Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/terapia , Revisões Sistemáticas como Assunto , Rim , Oregon , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/terapiaRESUMO
PURPOSE: Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging. MATERIALS AND METHODS: This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy. RESULTS: Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy. CONCLUSIONS: Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/patologia , Excisão de Linfonodo/métodos , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.
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Neoplasias Renais , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Nomogramas , Neoplasias Renais/patologia , Estudos Retrospectivos , Insuficiência Renal Crônica/cirurgia , Nefrectomia/métodos , Taxa de Filtração GlomerularRESUMO
PURPOSE: Daily aspirin use following cardiovascular intervention is commonplace and creates concern regarding bleeding risk in patients undergoing surgery. Despite its cardio-protective role, aspirin is often discontinued 5-7 days prior to major surgery due to bleeding concerns. Single institution studies have investigated perioperative outcomes of aspirin use in robotic partial nephrectomy (RPN). We sought to evaluate the outcomes of perioperative aspirin (pASA) use during RPN in a multicenter setting. MATERIALS AND METHODS: We performed a retrospective evaluation of patients undergoing RPN at 5 high volume RPN institutions. We compared perioperative outcomes of patients taking pASA (81 mg) to those not on aspirin. We analyzed the association between pASA use and perioperative transfusion. RESULTS: Of 1,565 patients undergoing RPN, 228 (14.5%) patients continued pASA and were older (62.8 vs 56.8 years, p <0.001) with higher Charlson scores (mean 3 vs 2, p <0.001). pASA was associated with increased perioperative blood transfusions (11% vs 4%, p <0.001) and major complications (10% vs 3%, p <0.001). On multivariable analysis, pASA was associated with increased transfusion risk (OR 1.94, 1.10-3.45, 95% CI). CONCLUSIONS: In experienced hands, perioperative aspirin 81 mg use during RPN is reasonable and safe; however, there is a higher risk of blood transfusions and major complications. Future studies are needed to clarify the role of antiplatelet therapy in RPN patients requiring pASA for primary or secondary prevention of cardiovascular events.
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Perda Sanguínea Cirúrgica/estatística & dados numéricos , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Aspirina/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Nefrectomia/estatística & dados numéricos , Assistência Perioperatória/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Resultado do TratamentoRESUMO
PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.
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Antibióticos Antineoplásicos/uso terapêutico , Hidrogéis/uso terapêutico , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Técnicas de Ablação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Feminino , Humanos , Hidrogéis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Gradação de Tumores , Invasividade Neoplásica , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.
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Antibióticos Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Mitomicina/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Carcinoma/patologia , Feminino , Humanos , Hidrogéis , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Gradação de Tumores , Neoplasias da Bexiga Urinária/patologia , Urotélio/efeitos dos fármacosRESUMO
PURPOSE: Cxbladder (Cxb) tests combine genomic biomarkers in urine with phenotypic and clinical data to classify hematuria patients into those at low/high probability of urothelial carcinoma (UC). Cxbladder Resolve (CxbR) is designed for use after Cxb Triage (CxbT) and Detect (CxbD), where CxbT-positive tests reflex to CxbD and CxbD-positive to CxbR to identify patients at high probability of high-impact tumors (HIT; high grade Ta, Tis or T1-T3). This study validated the diagnostic performance of CxbR in identifying HIT, and validated the algorithm of Cxb tests to segregate high-impact from low-impact tumors. MATERIALS AND METHODS: CxbR was developed in 863 hematuria patients in 3 studies in United States, Australia and New Zealand. CxbR, separately and combined with other Cxb tests, was validated in a prospective, observational U.S. study in 548 hematuria patients. All UC diagnoses were confirmed by histopathology. RESULTS: In the development data set, CxbR sensitivity was 92.4% (95% CI 83.3-96.7) and specificity 93.8% (95% CI 86.8-97.2) for identifying HIT within the high priority category. During external validation, sequential Cxb tests correctly ruled out 87.6% of patients from further workup (negative predictive value 99.4%); 100% of HIT were correctly identified (specificity 96.3%), and 3 low-grade tumors were missed. In both studies, all patients with HIT were correctly assigned to prioritized evaluation. CONCLUSIONS: CxbR has high sensitivity and specificity, correctly identifying all HIT. Sequential Cxb tests accurately segregate patients with a low vs high probability of HIT, focusing resources on those patients, with a diagnostic yield 4.8-fold higher than American Urological Association guideline stratification.
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Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Urinálise/métodos , Adulto JovemRESUMO
PURPOSE: Imaging characteristics in bladder cancer (BC), such as hydronephrosis, are predictive of ≥ pT3 disease at time of radical cystectomy (RC). The predictive capacity of other findings, such as perivesical stranding (PS), remains unclear. We investigated whether PS was associated with ≥ pT3 BC in patients who did not receive neoadjuvant chemotherapy (NAC). METHODS: We identified 433 patients with BC who underwent RC from 2003 to 2018 of which 128 did not receive NAC. Evidence of PS on pre-TURBT imaging was determined by radiologist review and a stranding grading system was created. Factors associated with PS and hydronephrosis were identified. Multivariable logistic regressions evaluated PS and hydronephrosis as predictors for ≥ pT3 BC. RESULTS: Of the 128 patients who did not receive NAC, 48 (38%) had pT3 and 12 (9%) had pT4 BC. 125 (98%) patients had CT and three (2%) had MRI. PS and hydronephrosis on imaging were identified in 19 (15%) and 45 (35%) patients. PS was not associated with imaging type (p = 0.38), BMI (p = 0.18), or pathologic T stage (p = 0.24). Hydronephrosis was more frequently associated with higher pathologic T stage (p = 0.034). Multivariable analysis demonstrated that PS was not predictive of ≥ pT3 BC (p = 0.457), while hydronephrosis was positively associated (p = 0.003). Stratification by grade of stranding did not improve the predictive capacity of PS (p = 0.667). CONCLUSION: While hydronephrosis is an indicator of higher stage BC, PS failed to be a reliable predictor of ≥ pT3 stage. These observations should give pause in using PS on imaging to guide decisions until further investigations can be explored.
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Cistectomia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Idoso , Humanos , Hidronefrose/diagnóstico por imagem , Hidronefrose/etiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
PURPOSE: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC. METHODS: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity. RESULTS: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients. CONCLUSION: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.
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Asiático , Índice de Massa Corporal , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Nefroureterectomia , Obesidade/complicações , Neoplasias Ureterais/complicações , Neoplasias Ureterais/cirurgia , População Branca , Idoso , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Ureterais/mortalidadeRESUMO
To investigate the association of adherent perinephric fat (APF) with perioperative outcomes, we conducted a systematic review and meta-analysis of the literature to clarify the impact of APF in patients undergoing partial nephrectomy. A systematic literature search using the Medline, Scopus, and Cochrane databases was performed in April 2019 and updated in November 2019 to identify studies investigating the effect of APF on perioperative outcomes in patients treated with partial nephrectomy with the aim of evaluating its impact on intraoperative, postoperative and oncological outcomes. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. A total of 1534 patients in nine nonrandomized, observational studies met our inclusion criteria. Patients with APF were significantly older (p = 0.0001), had a higher BMI (p = 0.0001) and were predominately male (p = 0.003). APF was associated with a higher operative time (p = 0.001) and higher blood loss (p = 0.002). No significant impact of APF was found in terms of postoperative complications, positive margins or length of stay. APF was also found to be associated with malignant renal histology of RCC on final pathology (p = 0.005). APF was associated with some adverse perioperative outcomes, especially a prolonged operating time and higher blood loss. In addition, APF was also associated with underlying renal malignancy, but the precise causal mechanism requires further exploration.
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Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Tecido Adiposo , Índice de Massa Corporal , Humanos , Rim , Neoplasias Renais/cirurgia , Masculino , Nefrectomia , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
INTRODUCTION: To assess whether patients with a large renal mass, treated by radical nephrectomy (RN), could have benefited from preoperative renal mass biopsy (RMB). The decision to perform partial nephrectomy (PN) for an organ-confined > 4 cm renal mass can be complex. Albeit often feasible, oncologic safety of PN in this cohort is debated. Yet, a significant portion of large renal masses that undergo RN prove benign or indolent, indicating a potential role for RMB to guide nephron preservation. MATERIALS AND METHODS: We queried prospectively maintained databases from three institutions to identify patients who underwent RN for localized > 4 cm renal mass. We excluded patients with nodal or distant metastases. Multivariable analysis assessed how clinicopathologic variables, mass anatomic complexity, and patient comorbidities related to the likelihood of harboring an indolent neoplasm. RESULTS: A total of 702 patients underwent RN for localized > 4 cm renal mass (median tumor size 7.0 cm (IQR 5.5-9.2); 12.8% (n = 90) of patients were diagnosed with oncocytoma/oncocytic neoplasm (n = 27, 3.8%) or chromophobe RCC (n = 63, 9.0%). When stratified by tumor size, indolent tumors comprised 10.1% of 4-7 cm masses, 15.6% of ≥ 7-10 cm masses, and 17.3% of ≥ 10 cm tumors. Upon multivariate analysis, younger age was associated with indolent tumors (p = 0.04, OR 0.97, 95% CI 0.94-0.99). CONCLUSIONS: Approximately 1 in 8 patients with a renal mass > 4 cm harbored benign or low risk indolent potential lesions and were associated with younger age. As such, patients with large renal masses for whom risk trade-offs between PN and RN are unclear, present a unique opportunity for greater utilization of RMB.
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Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Rim/patologia , Nefrectomia/métodos , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Carga TumoralRESUMO
BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. FUNDING: UroGen Pharma.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Portadores de Fármacos , Neoplasias Renais/tratamento farmacológico , Mitomicina/administração & dosagem , Urotélio/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Carcinoma/patologia , Composição de Medicamentos , Feminino , Humanos , Hidrogéis , Israel , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Gradação de Tumores , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Urotélio/patologiaRESUMO
Bladder cancer is an increasingly common malignancy, and muscle invasive bladder cancer is associated with particularly high rates of morbidity and mortality. The morphologic and molecular diversity of bladder cancer poses significant challenges in elucidating the invasion mechanisms responsible for disease progression. Furthermore, conventional invasion assays do not provide a physiological context for studying bladder cancer invasion within 3D microenvironments and have limited ability to capture the contribution of cellular phenotypic heterogeneity to disease progression. Here, we describe the development of a 3D microtumor invasion model suitable for the analysis of cellular phenotypic heterogeneity in cell lines and primary tumor cells from bladder cancer patients. This model incorporates a self-assembly approach for recapitulating features of bladder cancer invasion in 3D microenvironments and probing the invasive cell subpopulations. The gene expression profiles of invading microtumors were analyzed by incorporating a gold nanorod-locked nucleic acid biosensor. The incorporation of the single cell biosensor and transient gene knockdown into the system revealed the formation of invasive leader cells with upregulated Delta-like ligand 4 (DLL4) expression as well as the role of NOTCH1-DLL4 signaling in collective bladder cancer invasion. The involvement of DLL4 expressing cells in bladder cancer invasion was also observed in patient samples obtained from transurethral resection. Collectively, our study demonstrates a 3D microtumor invasion model for investigating intracellular heterogeneity of bladder cancer invasion and analyzing patient derived samples toward personalized medicine applications.
Assuntos
Técnicas Biossensoriais/métodos , Neoplasias da Bexiga Urinária/patologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Ouro/química , Humanos , Imageamento Tridimensional , Modelos Biológicos , Nanotubos/química , Invasividade Neoplásica , Oligonucleotídeos/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Microambiente Tumoral , Regulação para Cima , Neoplasias da Bexiga Urinária/metabolismoRESUMO
PURPOSE: Robot-assisted radical prostatectomy has become the predominant surgical modality to manage localized prostate cancer in the U.S. However, there are few studies focusing on the associations between hospital volume and outcomes of robot-assisted radical prostatectomy. MATERIALS AND METHODS: We identified robot-assisted radical prostatectomies for clinically localized (cT1-2N0M0) prostate cancer diagnosed between 2010 and 2014 in the National Cancer Database. We categorized annual average hospital robot-assisted radical prostatectomy volume into very low, low, medium, high and very high by most closely sorting the final included patients into 5 equal-sized groups (quintiles). Outcomes included 30-day mortality, 90-day mortality, conversion (to open), prolonged length of stay (more than 2 days), 30-day (unplanned) readmission, positive surgical margin and lymph node dissection rates. RESULTS: A total of 114,957 patients were included in the study, and hospital volume was categorized into very low (3 to 45 cases per year), low (46 to 72), medium (73 to 113), high (114 to 218) and very high (219 or more). Overall 30-day mortality (0.12%), 90-day mortality (0.16%) and conversion rates (0.65%) were low. Multivariable logistic regressions showed that compared with the very low volume group, higher hospital volume was associated with lower odds of conversion to open surgery (OR 0.23, p <0.001 for very high), prolonged length of stay (OR 0.25, p <0.001 for very high), 30-day readmission (OR 0.53, p <0.001 for very high) and positive surgical margins (OR 0.61, p <0.001 for very high). Higher hospital volume was also associated with higher odds of lymph node dissection in the intermediate/high risk cohort (OR 3.23, p <0.001 for very high). CONCLUSIONS: Patients undergoing robot-assisted radical prostatectomy at higher volume hospitals are likely to have improved perioperative and superior oncologic outcomes compared to lower volume hospitals.
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Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Seguimentos , Humanos , Incidência , Tempo de Internação/tendências , Masculino , Readmissão do Paciente/tendências , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
PURPOSE: A minimum number of index procedures is required for graduation. Without thresholds for surgical technique, it is unclear if robotic and open learning is balanced. We assessed the distribution of robotic and open surgeries performed by residents upon graduation. MATERIALS AND METHODS: Voluntary Accreditation Council for Graduate Medical Education resident case logs from 11 institutions were de-identified and trends in robotic and open major surgeries were compared using Wilcoxon rank sum and 2-sample t-tests. RESULTS: A total of 89,199 major cases were recorded by 209 graduates from 2011 to 2017. The median proportion of robotic cases increased from 2011 to 2017 in reconstruction (4.7% to 15.2%), oncology (27.5% to 54.2%) and pediatrics (0% to 10.9%) (all values p <0.001). Robotic and open cases remained most divergent in reconstruction, with a median of 12 robotic (IQR 9-19) to 70 open cases (IQR 55-106) being performed by residents in 2017. Similar observations occurred in pediatrics. In oncology the number of robotic procedures superseded that of open in 2016 and rose to a median of 148 robotic (IQR 108-214) to 121 open cases (IQR 90-169) in 2017, with the driver being robotic prostatectomy. Substantial differences in surgical technique were observed between institutions and among graduates from the same institution. CONCLUSIONS: Although robotic volume is increasing, the balance of surgical technique and the pace of change differ in reconstruction, oncology and pediatrics, as well as among individual institutions and graduates themselves. This raises questions about whether more specific guidelines are needed to ensure equity and standardization in training.
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Competência Clínica/normas , Educação de Pós-Graduação em Medicina/métodos , Internato e Residência/métodos , Procedimentos Cirúrgicos Robóticos/educação , Procedimentos Cirúrgicos Urológicos/educação , Urologia/educação , Acreditação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Estados Unidos , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricosRESUMO
PURPOSE: Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy. MATERIALS AND METHODS: The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens. RESULTS: Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation. CONCLUSIONS: Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.