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Introduction: Patient education is an essential element of the treatment pathway. Augmented reality (AR), with disease simulations and three-dimensional visuals, offers a developing approach to patient education. We aim to determine whether this tool can increase patient understanding of their disease and post-visit satisfaction in comparison to current standard of care (SOC) educational practices in a randomized control study. Methods: Our single-site study consisted of 100 patients with initial diagnoses of kidney masses or stones randomly enrolled in the AR or SOC arm. In the AR arm, a physician used AR software on a tablet to educate the patient. SOC patients were educated through traditional discussion, imaging, and hand-drawn illustrations. Participants completed pre- and post-physician encounter surveys adapted from the Press Ganey® patient questionnaire to assess understanding and satisfaction. Their responses were evaluated in the Readability Studio® and analyzed to quantify rates of improvement in self-reported understanding and satisfaction scores. Results: There was no significant difference in participant education level (P = 0.828) or visit length (27.6 vs. 25.0 min, P = 0.065) between cohorts. Our data indicate that the rate of change in pre- to post-visit self-reported understanding was similar in each arm (P ≥ 0.106 for all responses). The AR arm, however, had significantly higher patient satisfaction scores concerning the educational effectiveness and understanding of images used during the consultation (P < 0.05). Conclusions: While AR did not significantly increase self-reported patient understanding of their disease compared to SOC, this study suggests AR as a potential avenue to increase patient satisfaction with educational tools used during consultations.
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PURPOSE: To prevent avoidable treatment and make more informed care decisions about small renal masses, the use of renal mass biopsies has increased since the early 2000s. In April 2017, Atrium Health Carolinas Medical Center began requiring biopsies before all percutaneous thermal ablation procedures for renal masses. We aim to determine the effect of this preablation biopsy mandate on small renal mass treatment decisions. MATERIALS AND METHODS: Our study is a retrospective analysis of a prospectively managed database designed to track patients with small renal masses presented at the Kidney Tumor Program from 2000-2020. We separated patients into 2 cohorts (pre- and postmandate) based on the initial encounter date, excluding those from April 2017-April 2018 to allow for implementation of the mandate. We also excluded patients with masses >4 cm. RESULTS: Overall, we found no significant difference between the pre- and postmandate cohorts, with race as an exception. Implementation of the mandate coincided with an increase in biopsies for both ablation and nonablation treatment pathways (P < .001, P = .01). Renal mass biopsy rates increased in all socioeconomic groups except the lowest quartile. Additionally, Black/Hispanic patients had the highest biopsy rate. We found significant changes in treatment decisions between our cohorts: surgery decreased 24% (P < .001), active surveillance increased 28% (P < .001), and patients with no follow-up decreased 8% (P = .03). CONCLUSIONS: Our data indicate that a preablation renal mass biopsy mandate is associated with the wider use of biopsies for all small renal mass patients, fewer surgical interventions, and an increase in active surveillance.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Rim/cirurgia , BiópsiaRESUMO
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
Introduction: The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs. Methods: This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS. Results: A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age (P = 0.01), better kidney function (P = 0.01), and higher tumor growth rates (GRs) (P = 0.02). Higher eGFR was associated with better survival (P = 0.03), while higher tumor GRs (P = 0.014), greater Charlson Comorbidity Index (P = 0.01), and larger tumors (P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS (P = 0.01). Conclusions: Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs.
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OBJECTIVE: To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma. METHODS: In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis. RESULTS: Median follow-up was 40 months (interquartile range 24-56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non-clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence-free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non-clear cell renal cell carcinoma. CONCLUSION: GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non-clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence-free survival and should remain the standard approach to risk stratify patients during follow-up when all data are available.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/epidemiologia , Nefrectomia/métodos , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions. MATERIALS AND METHODS: In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned 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: AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency. CONCLUSION: AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.
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Continuidade da Assistência ao Paciente , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Tomada de Decisão Clínica , Humanos , Medição de Risco , Conduta ExpectanteRESUMO
PURPOSE: This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions. MATERIALS/METHODS: The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. 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: Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article. CONCLUSION: Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.
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Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Técnicas de Ablação , Antineoplásicos/uso terapêutico , Aconselhamento , Medicina Baseada em Evidências , Humanos , Neoplasias Renais/patologia , NefrectomiaRESUMO
PURPOSE: Contemporary trends and racial disparities in prostate cancer screening and referral to urology for prostate cancer risk are not well characterized, despite consensus that Black men are at higher risk for poor prostate cancer outcomes. The objective of this study was to characterize current racial disparities in prostate cancer screening and referral from primary care to urology for prostate cancer concern within our large, integrated health care system. MATERIALS AND METHODS: This retrospective cohort study used data from Atrium Health's enterprise data warehouse, which includes patient information from more than 900 care locations across North Carolina, South Carolina and Georgia. We included all men seen in the ambulatory or outpatient setting between 2014 and 2019 who were ≥40 years old. Clinical and demographic data were collected for all men, including age and race. Racial outcomes were reported for all groups with >2% representation in the population. Between-group comparisons were determined using chi-squared analysis, Wilcoxon rank sum testing and multivariable logistic regression, with significance defined as p <0.05. RESULTS: We observed a significant decrease in prostate specific antigen testing across all age and racial groups in a cohort of 606,985 men at Atrium Health, including 87,189 Black men, with an overall relative decline of 56%. As compared to White men, Black men were more likely to undergo prostate specific antigen testing (adjusted OR 1.24, 95% CI 1.22-1.26) and be referred to urology for prostate cancer (adjusted OR 1.94, 95% CI 1.75-2.16). CONCLUSIONS: There was a continued significant decline in prostate cancer screening between 2014 and 2019. Despite having modestly elevated odds of being screened for prostate cancer compared to White men, Black men are relatively underscreened when considering that those who undergo prostate specific antigen screening are more likely to be referred by primary care to urology for additional prostate cancer diagnostic evaluation.
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Negro ou Afro-Americano/estatística & dados numéricos , Detecção Precoce de Câncer , Disparidades em Assistência à Saúde , Antígeno Prostático Específico/análise , Encaminhamento e Consulta/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Prestação Integrada de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
PURPOSE: We aim to assess the safety of decreasing ureteral stenting duration following Radical Cystectomy with Urinary Diversion (RCUD). MATERIALS AND METHODS: We analyzed a prospectively and retrospectively collected dataset for cystectomy patients at our tertiary center. Adult patient who underwent RCUD for malignancy from January 2013 to February 2018 were included. Patients with a history of abdominal/pelvic radiation and continent diversions were excluded. The patient population was divided to late stent removal group (LSR-POD 14) and early stent removal group (ESR-POD5). Our endpoints were total stent duration, 90-day readmission, 90-day total-UTI, 90-day urinary-readmissions, complications and Ureteroenteric Stricture (UES) rates. Statistical methods included t test, Chi-squared test and multivariate logistic regression. RESULTS: One hundred and seventy-eight patients were included in the final analysis after inclusion/exclusion criteria were applied. The LSR (n = 74) and ESR (n = 104) groups were similar in preoperative characteristics except higher intracorporeal ileal conduit formation in ESR. The duration of stenting decreased significantly from approximately 15.5-5 days (P < 0.001). The LSR had higher 90-day overall readmission rates (OR = 2.57, 95% CI 1.19-5.53, P = 0.016) and total-UTIs (OR = 2.36, 95%CI 1.11-5.04, P = 0.026). With a median follow-up of 9.8 months, UES was similar between the two groups. CONCLUSION: Shorter ureteral stent duration is a safe and non-inferior option following RCUD. It allows for stent removal prior to discharge and less outpatient visits. In addition, decreasing stent duration was linked decreased readmissions and total-UTIs without increased risk of UES. However, future studies are needed to establish causality and promote stent duration change.
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Cistectomia , Complicações Pós-Operatórias/prevenção & controle , Stents , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , Idoso , Cistectomia/métodos , Duração da Terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Stents/efeitos adversos , Stents/estatística & dados numéricosRESUMO
BACKGROUND: Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cells in vitro. However, the status of NFIB in prostate cancer was unknown. METHODS: We immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation. We interrogated publically available data sets in cBioPortal to correlate NFIB expression and AR and neuroendocrine prostate cancer (NEPCa) activity scores. We analyzed prostate cancer cell lines for NFIB expression via Western blot analysis and used nuclear and cytoplasmic fractionation to assess where NFIB is localized. We performed co-immunoprecipitation studies to determine if NFIB and AR interact. RESULTS: NFIB increased in the nucleus and cytoplasm of prostate cancer samples versus matched normal controls, independent of Gleason score. Similarly, cytoplasmic AR and synaptophysin increased in primary prostate cancer. We observed strong NFIB staining in primary small cell prostate cancer. The ratio of cytoplasmic-to-nuclear NFIB staining was predictive of earlier biochemical recurrence in prostate cancer, once adjusted for tumor margin status. Cytoplasmic AR was an independent predictor of biochemical recurrence. There was no statistically significant difference between NFIB and synaptophysin expression in primary and castration-resistant prostate cancer, but cytoplasmic AR expression was increased in castration-resistant samples. In primary prostate cancer, nuclear NFIB expression correlated with cytoplasmic NFIB and nuclear AR, while cytoplasmic NFIB correlated with synaptophysin, and nuclear and cytoplasmic AR. In castration-resistant prostate cancer samples, NFIB expression correlated positively with an AR activity score, and negatively with the NEPCa score. In prostate cancer cell lines, NFIB exists in several isoforms. We observed NFIB predominantly in the nuclear fraction of prostate cancer cells with increased cytoplasmic expression seen in castration-resistant cell lines. We observed an interaction between AR and NFIB through co-immunoprecipitation experiments. CONCLUSION: We have described the expression pattern of NFIB in primary and castration-resistant prostate cancer and its positive correlation with AR. We have also demonstrated AR interacts with NFIB.
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Fatores de Transcrição NFI/biossíntese , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/biossíntese , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Fatores de Transcrição NFI/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/genética , Análise Serial de Tecidos , TranscriptomaRESUMO
Hemorrhagic cystitis (HC) is a common and important complication of allogeneic hematopoietic cell transplantation (HCT). Reactivation of BK virus is its most common cause. The more intense immunosuppressive regimens administered to recipients of grafts from alternative donors have been reported to account for the increased susceptibility to HC in this population. This study compares patients undergoing HCT with either a haploidentical donor or a matched related donor, all of whom received identical immunosuppression with a post-transplantation cyclophosphamide-based regimen. The incidence of HC was significantly higher in the patients receiving a haploidentical graft (Pâ¯=â¯.01). The higher incidence of HC in haploidentical graft recipients is therefore directly related to the inherent immune deficiency that follows HLA-mismatched transplantation, independent of the intensity of pharmacologic immunosuppression. This finding carries significant clinical impact for the prevention and treatment of HC in haploidentical graft recipients.
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Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Transplante Haploidêntico/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adulto JovemRESUMO
PURPOSE: We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy. MATERIALS AND METHODS: A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm/m in males and less than 39 cm/m in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality. RESULTS: The oral nutrition supplement group lost less weight (-5 vs -6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement group but increased 20% in the multivitamin multimineral supplement group (p = 0.01). Mean length of stay and 30-day hospital free days were similar in the groups. The oral nutrition supplement group had a lower rate of overall and major (Clavien grade 3 or greater) complications (48% vs 67% and 19% vs 25%, respectively) and a lower readmission rate (7% vs 17%) but the differences did not reach statistical significance. CONCLUSIONS: Patients who undergo radical cystectomy after consuming an oral nutrition supplement perioperatively have a reduced prevalence of sarcopenia and may also experience fewer and less severe complications and readmissions. A larger blinded, randomized, controlled trial is necessary to determine whether oral nutrition supplement interventions can improve outcomes following radical cystectomy.
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Cistectomia , Suplementos Nutricionais , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Sarcopenia/epidemiologia , Sarcopenia/prevenção & controle , Administração Oral , Idoso , Cistectomia/métodos , Feminino , Humanos , Masculino , Projetos Piloto , Prevalência , Estudos ProspectivosRESUMO
PURPOSE: To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. METHODS: A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. RESULTS: BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. CONCLUSIONS: A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.
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Carcinoma de Células de Transição/epidemiologia , Cistoscopia , Dinâmica Populacional , Abandono do Hábito de Fumar , Fumar Tabaco/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Algoritmos , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/prevenção & controle , Detecção Precoce de Câncer , Humanos , Incidência , Imageamento por Ressonância Magnética , Imagem de Banda Estreita , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Prevalência , Fatores de Risco , Sociedades Médicas , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/prevenção & controle , UrologiaRESUMO
BACKGROUND: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. METHODS: Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology. RESULTS: MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, -0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880-0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%). CONCLUSIONS: These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post-operative surveillance intervals.
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Adenocarcinoma/genética , Proteínas de Transporte/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Progressão da Doença , Expressão Gênica , Guanilato Quinases , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapiaRESUMO
The TGF-ß and Wnt/ß-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-ß has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-ß signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-ß type 2 receptor specifically in this epithelial segment. Compared with littermate controls, mice lacking the proximal tubular TGF-ß receptor had significantly increased tubular injury and tubulointerstitial fibrosis in two different models of CKD. RNA sequencing indicated that deleting the TGF-ß receptor in proximal tubule cells modulated many growth factor pathways, but Wnt/ß-catenin signaling was the pathway most affected. We validated that deleting the proximal tubular TGF-ß receptor impaired ß-catenin activity in vitro and in vivo Genetically restoring ß-catenin activity in proximal tubules lacking the TGF-ß receptor dramatically improved the tubular response to CKD in mice. Deleting the TGF-ß receptor alters many growth factors, and therefore, this ameliorated response may be a direct effect of ß-catenin activity or an indirect effect of ß-catenin interacting with other growth factors. In conclusion, blocking TGF-ß and ß-catenin crosstalk in proximal tubules exacerbates tubular injury in two models of CKD.
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Falência Renal Crônica/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo , Animais , Ácidos Aristolóquicos/química , Núcleo Celular/metabolismo , Colágeno/química , Cruzamentos Genéticos , Epitélio/metabolismo , Feminino , Deleção de Genes , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Receptor do Fator de Crescimento Transformador beta Tipo II , Transdução de Sinais , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inibidoresAssuntos
Carcinoma de Células de Transição , Mycobacterium bovis , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , GencitabinaRESUMO
PURPOSE: Fine needle aspiration with and without concurrent core needle biopsy is a minimally invasive method to diagnose and assist in management of renal masses. We assessed the pathological accuracy of fine needle aspiration compared to and associated with core needle biopsy and the impact on management. MATERIALS AND METHODS: We performed a single institution, retrospective study of 342 cases from 2001 to 2015 with small and large renal masses (4 or less and greater than 4 cm, respectively). Diagnostic and concordance rates, and the impact on management were analyzed. RESULTS: Adequacy rates for fine needle aspiration only, core needle biopsy only and fine needle aspiration plus core needle biopsy were 21%, 12% and 8% (aspiration vs aspiration plus biopsy p <0.026). In the aspiration plus biopsy group adding aspiration to biopsy and biopsy to aspiration reduced the inadequacy rate from 23% to 8% and from 27% to 8% for a total reduction rate of 15% and 19%, respectively, corresponding to 32 cases (9.3%). Rapid on-site examination contributed to a 22.5% improvement in fine needle aspiration adequacy rates. In this cohort 30% of aspiration only, 5% of biopsy only and 12% of aspiration plus biopsy could not be subtyped (aspiration vs biopsy p <0.0001, aspiration vs aspiration plus biopsy p <0.0127 and biopsy vs aspiration plus biopsy p = 0.06). The diagnostic concordance rate with surgical resection was 99%. Conversion of an inadequate specimen to an adequate one by a concurrent procedure impacted treatment in at least 29 of 32 patients. Limitations include the retrospective design and accuracy measurement based on surgical intervention. CONCLUSIONS: Fine needle aspiration plus core needle biopsy vs at least fine needle aspiration alone may improve diagnostic yield when sampling renal masses but it has subtyping potential similar to that of core needle biopsy only.
Assuntos
Biópsia por Agulha Fina , Biópsia com Agulha de Grande Calibre , Neoplasias Renais/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions. MATERIALS AND METHODS: Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions. RESULTS: Great progress has been made since the previous guidelines on management of localized renal masses were released (2009). The current guidelines provide updated, evidence-based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well-defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision-making about active surveillance are explicitly defined. CONCLUSIONS: Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.
Assuntos
Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Técnicas de Ablação , Humanos , Nefrectomia , Seleção de Pacientes , Estados Unidos , Conduta ExpectanteRESUMO
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.