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PURPOSE: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease. METHODS: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements. RESULTS: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including non-invasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB. CONCLUSION: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences.
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Bexiga Urinária Hiperativa , Urologia , Humanos , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Urologia/normas , Tomada de Decisão Compartilhada , Sociedades Médicas/normasRESUMO
PURPOSE: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease. METHODS: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements. RESULTS: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including Noninvasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB. CONCLUSION: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences.
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PURPOSE: The symptoms of urethral stricture are non-specific and may overlap with other common conditions that can confound diagnosis. Urologists play a key role in the initial evaluation of urethral stricture, currently provide all accepted treatments, and must be familiar with the evaluation, diagnostic tests, and surgical treatments for urethral stricture. MATERIALS AND METHODS: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates January 1, 1990 to January 12, 2015) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of urethral stricture in men. The review yielded an evidence base of 250 articles after application of inclusion/exclusion criteria. The search for the 2023 Amendment was modified to included females and males (search dates December 2015-October 2022 for males; January 1990-October 2022 for females) and a new Key Question on sexual dysfunction was added (search dates: January 1990-10/2022). After inclusion and exclusion criteria were applied, 81 studies were added to the existing evidence base. RESULTS: Once a urethral stricture is diagnosed, clinicians should determine the length and location of the stricture in order to inform treatment. After a period of urethral rest, patients with short (<2cm) bulbar urethral stricture may be treated endoscopically. Urethroplasty may be performed by an experienced surgeon in patients with first time or recurrent anterior and posterior urethral strictures. The best treatment option for urethral stricture in female patients is urethroplasty using oral mucosa grafts or vaginal flaps rather than endoscopic treatment. CONCLUSION: This guideline provides evidence-based guidance to clinicians and patients regarding how to recognize symptoms and signs of a urethral stricture/stenosis, carry out appropriate testing to determine the location and severity of the stricture, and recommend the best options for treatment. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient's history, values, and goals for treatment.
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Estreitamento Uretral , Masculino , Humanos , Feminino , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/cirurgia , Constrição Patológica/cirurgia , Resultado do Tratamento , Uretra/cirurgia , Retalhos Cirúrgicos , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
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: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part II of a two-part series focusing on initial and repeat biopsies, and biopsy technique. Please refer to Part I for discussion of initial prostate cancer screening recommendations. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsies, and biopsy technique. CONCLUSIONS: The evaluation of prostate cancer risk should be focused on the detection of clinically significant prostate cancer (Grade Group 2 or higher [GG2+]). The use of laboratory biomarkers, prostate MRI, and biopsy techniques described herein may improve detection and safety when a prostate biopsy is deemed necessary following prostate cancer screening.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Detecção Precoce de Câncer , Antígeno Prostático Específico , Revisões Sistemáticas como Assunto , Biópsia , Imageamento por Ressonância Magnética , Biópsia Guiada por Imagem/métodosRESUMO
PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique. CONCLUSIONS: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Detecção Precoce de Câncer/métodos , Revisões Sistemáticas como Assunto , Biópsia , Programas de Rastreamento/métodosRESUMO
PURPOSE: The authors of this guideline reviewed the urologic trauma literature to guide clinicians in the appropriate methods of evaluation and management of genitourinary injuries. MATERIALS AND METHODS: The Panel amended the Guideline in 2020 to reflect additional literature published through February 2020. When sufficient evidence existed, the Panel assigned the body of evidence 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, the Panel provided additional information as Clinical Principles and Expert Opinions (See table 1[Table: see text]). RESULTS: The Panel updated a total of six existing statements on renal, ureteral, bladder, urethra, and genital trauma. Additionally, four new statements were added based on literature released since the 2017 amendment. Statement 5b was added based on new evidence for treatment of hemodynamically unstable patients with renal trauma. Statement 20b was added based on new literature for percutaneous or open suprapubic tube placement following pelvic fracture urethral injury. Statements 30a and 30b were also added to provide guidance on ultrasonography for blunt scrotal injuries suggestive of testicular rupture and for performing surgical exploration with repair or orchiectomy for penetrating scrotal injuries respectively. CONCLUSIONS: These evidence-based updates to the AUA Guidelines further inform the treatment of urotrauma.
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Medicina Baseada em Evidências/normas , Sistema Urogenital/lesões , Urologia/normas , Ferimentos e Lesões/terapia , Medicina Baseada em Evidências/métodos , Humanos , Sociedades Médicas/normas , Estados Unidos/epidemiologia , Urologia/métodos , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologiaRESUMO
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: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. CONCLUSIONS: NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.
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Assistência ao Convalescente/normas , Sintomas do Trato Urinário Inferior/terapia , Bexiga Urinaria Neurogênica/terapia , Urologia/normas , Antagonistas Adrenérgicos alfa/uso terapêutico , Adulto , Assistência ao Convalescente/métodos , Terapia Combinada/métodos , Terapia Combinada/normas , Tomada de Decisão Compartilhada , Terapia por Exercício/métodos , Terapia por Exercício/normas , Humanos , Cateterismo Uretral Intermitente/métodos , Cateterismo Uretral Intermitente/normas , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Medição de Risco/métodos , Medição de Risco/normas , Sociedades Médicas/normas , Estados Unidos , Bexiga Urinaria Neurogênica/complicações , Bexiga Urinaria Neurogênica/diagnóstico , Urodinâmica , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/normas , Urologia/métodosRESUMO
PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed. CONCLUSIONS: NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.
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Sintomas do Trato Urinário Inferior/diagnóstico , Bexiga Urinaria Neurogênica/diagnóstico , Urologia/normas , Adulto , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sociedades Médicas/normas , Estados Unidos , Bexiga Urinaria Neurogênica/complicações , Urodinâmica , Urologia/métodosRESUMO
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.
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Hematúria/diagnóstico , Algoritmos , Hematúria/etiologia , Humanos , Medição de RiscoRESUMO
PURPOSE: The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder (OAB). MATERIALS & METHODS: The primary source of evidence for the original version of this guideline was the systematic review and data extraction conducted as part of the Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment Number 187 titled Treatment of Overactive Bladder in Women (2009). That report was supplemented with additional searches capturing literature published through December 2011. Following initial publication, this guideline underwent amendment in 2014 and 2018. The current document reflects relevant literature published through October 2018. RESULTS: When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low). Such statements are provided as Standards, Recommendations, or Options. In instances of insufficient evidence, additional guidance information is provided as Clinical Principles and Expert Opinions. CONCLUSIONS: The evidence-based statements are provided for diagnosis and overall management of OAB, as well as for the various treatments. Diagnosis and treatment methodologies can be expected to change as the evidence base grows and as new treatment strategies become obtainable.
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Procedimentos Clínicos/normas , Sociedades Médicas/normas , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Medicina Baseada em Evidências/normas , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normas , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos , Urologia/normasRESUMO
BACKGROUND: TBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition. METHODS: The relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells. RESULTS: TBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness. CONCLUSIONS: Overall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions.
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Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Regulação Neoplásica da Expressão Gênica , Hiperplasia/patologia , Proteínas com Domínio T/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Colágeno , Progressão da Doença , Combinação de Medicamentos , Transição Epitelial-Mesenquimal , Feminino , Humanos , Hiperplasia/genética , Hiperplasia/metabolismo , Laminina , Invasividade Neoplásica , Isoformas de Proteínas , Proteoglicanas , RNA Interferente Pequeno/genética , Proteínas com Domínio T/antagonistas & inibidores , Proteínas com Domínio T/genética , Células Tumorais CultivadasRESUMO
AIM: To investigate the role of family history, race/ethnicity, and genetics in prostate cancer (PCa) screening. METHODS: We conducted a systematic review of articles from January 2013 through September 2023 that focused on the association of race/ethnicity and genetic factors on PCa detection. Of 10,815 studies, we identified 43 that fulfilled our pre-determined PICO (Patient, Intervention, Comparison and Outcome) criteria. RESULTS: Men with ≥1 first-degree relative(s) with PCa are at increased risk of PCa, even with negative imaging and/or benign prostate biopsy. Black men have higher PCa risk, while Asian men have lower risk. Most of the differences in risks are attributable to environmental and socioeconomic factors; however, genetic differences may play a role. Among numerous pathogenic variants that increase PCa risk, BRCA2, MSH2, and HOXB13 mutations confer the highest risk of PCa. Polygenic risk score (PRS) models identify men at higher PCa risk for a given age and PSA; these models improve when considering other clinical factors and when the model population matches the study population's ancestry. CONCLUSIONS: Family history of PCa, race/ethnicity, pathogenic variants (particularly BRCA2, MSH2, and HOXB13), and PRS are associated with increased PCa risk and should be considered in shared decision-making to determine PCa screening regimens.
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CONTEXT.: Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice. OBJECTIVE.: To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer. DESIGN.: The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. RESULTS.: Six recommendation statements were developed. CONCLUSIONS.: This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and TMB testing in the clinical setting.
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Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Mutação , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , ImunoterapiaRESUMO
CONTEXT.: The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status. OBJECTIVE.: To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy. DESIGN.: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope. RESULTS.: Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract. CONCLUSIONS.: An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories.
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Neoplasias Colorretais , Instabilidade de Microssatélites , Feminino , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Inibidores de Checkpoint Imunológico , Patologistas , Patologia Molecular/métodos , Revisões Sistemáticas como AssuntoRESUMO
CONTEXT.: The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used. OBJECTIVE.: To develop an evidence-based guideline for the initial laboratory detection of M proteins. DESIGN.: To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.: Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies. CONCLUSIONS.: This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein.
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Paraproteinemias , Humanos , Laboratórios , Paraproteinemias/diagnóstico , Revisões Sistemáticas como AssuntoRESUMO
CONTEXT.: The diagnosis and clinical management of patients with diffuse gliomas (DGs) have evolved rapidly over the past decade with the emergence of molecular biomarkers that are used to classify, stratify risk, and predict treatment response for optimal clinical care. OBJECTIVE.: To develop evidence-based recommendations for informing molecular biomarker testing for pediatric and adult patients with DGs and provide guidance for appropriate laboratory test and biomarker selection for optimal diagnosis, risk stratification, and prediction. DESIGN.: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. A systematic review of literature was conducted to address the overarching question, "What ancillary tests are needed to classify DGs and sufficiently inform the clinical management of patients?" Recommendations were derived from quality of evidence, open comment feedback, and expert panel consensus. RESULTS.: Thirteen recommendations and 3 good practice statements were established to guide pathologists and treating physicians on the most appropriate methods and molecular biomarkers to include in laboratory testing to inform clinical management of patients with DGs. CONCLUSIONS.: Evidence-based incorporation of laboratory results from molecular biomarker testing into integrated diagnoses of DGs provides reproducible and clinically meaningful information for patient management.
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Glioma , Patologistas , Adulto , Criança , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glioma/diagnóstico , Glioma/genética , Técnicas de Diagnóstico Molecular , Receptor ErbB-2/genética , Revisões Sistemáticas como AssuntoRESUMO
INTRODUCTION: The 2020 AUA microhematuria (MH) guideline stratifies patients into low, intermediate and high-risk for urologic malignancy based on established risk-factors for urothelial carcinoma. Notably, urine-based tumor markers (UBTMs) were not included in the risk classification. We evaluated the impact of incorporating UBTMs (cytology and multiple commercially available UBTMs) into this risk stratification. METHODS: We performed a systematic review of performance characteristics of UBTMs for the detection of bladder cancer during hematuria evaluation, pooled the reported sensitivity and specificity, and calculated positive and negative likelihood ratios (LR). These were then applied to the estimated pre-test probability for the diagnosis for each AUA risk strata: low-risk 0.5%, intermediate-risk 1.0%, and high-risk (2%-3%) in order to calculate a post-test probability of bladder cancer in the event of a positive or negative test. RESULTS: The pooled sensitivity for urinary cytology and commercially available UBTMs was 68% and 58%-95%, respectively while the specificity was estimated at 91% and 34%-90%, respectively. The positive LRs of UBTMs ranged from 2.1-7.67 and negative LRs ranged from 0.07-0.48. A negative UBTM was associated with a post-test probability of cancer for low, intermediate, and high-risk patients of 0-0.2%, 0.2%-0.5%, and 0.4%-1.1%, respectively. In the setting of a positive UBTM, the post-test probability of cancer for low, intermediate, and high-risk patients was 1.1%-3.7%, 2.1%-7.8%, 4.2%-19.2%, respectively. CONCLUSION: Pending prospective validation, UBTMs may be able to enhance risk stratification and inform shared decision-making over clinical factors alone and allow for re-classification of patients into higher or lower risk categories.