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1.
J Urol ; 211(3): 436-444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38100842

RESUMO

PURPOSE: Flank pain associated with stone disease is typically caused by a stone that obstructs urine flow. However, it is plausible that nonobstructing kidney stones may still cause pain. We performed a multicenter, observational trial to evaluate whether treatment of small nonobstructing calyceal stones improves pain and kidney stone-specific health-related quality of life. MATERIALS AND METHODS: Patients aged 18 years or older with nonobstructing renal stone(s) up to 10 mm in longest diameter and moderate to severe pain were recruited. All participants completed 3 questionnaires: the Brief Pain Inventory (BPI), the Patient-Reported Outcomes Measurement Information System pain interference form 6a, and the Wisconsin Stone Quality of Life questionnaire. Thereafter, all participants underwent ureteroscopy for renal stone treatment. All 3 questionnaires were repeated at 2, 6 to 8, and at 12 weeks postprocedure. The primary outcomes were change in preoperative to 12-week postoperative mean BPI score and worst BPI pain score. RESULTS: A total of 43 patients with nonobstructing kidney stones and associated flank pain were recruited. All stones were removed. Preoperatively, BPI scores for mean pain and worst pain were 5.5 and 7.2, respectively which decreased to 1.8 and 2.8 respectively at 12 weeks postoperatively. Wisconsin Stone Quality of Life questionnaire mean score increased from 70.4 to 115.3 at 12 weeks postoperatively. A total of 86% and 69% of patients had at least a 20% and 50% reduction in their mean pain scores, respectively. CONCLUSIONS: This study determined that patients benefit significantly from the removal of calyceal nonobstructing kidney stones for at least 12 weeks with a reduction in pain and an increase in quality of life. Therefore, surgical removal of these stones in this patient population should be offered as a treatment option.


Assuntos
Dor no Flanco , Cálculos Renais , Humanos , Cálculos Renais/complicações , Cálculos Renais/cirurgia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Ureteroscopia/métodos
2.
BJU Int ; 133(5): 570-578, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38332669

RESUMO

OBJECTIVE: To assess the impact of kidney stone disease (KSD) and its treatment on the health-related quality of life (HRQOL) of high-risk stone formers with hyperparathyroidism, renal tubular acidosis, malabsorptive disease, and medullary sponge kidney. PATIENTS AND METHODS: The Wisconsin Stone Quality of Life questionnaire was used to evaluate HRQOL in 3301 patients with a history of KSD from 16 institutions in North America between 2014 and 2020. Baseline characteristics and medical history were collected from patients, while active KSD was confirmed through radiological imaging. The high-risk group was compared to the remaining patients (control group) using the Wilcoxon rank-sum test. RESULTS: Of 1499 patients with active KSD included in the study, the high-risk group included 120 patients. The high-risk group had significantly lower HRQOL scores compared to the control group (P < 0.01). In the multivariable analyses, medullary sponge kidney disease and renal tubular acidosis were independent predictors of poorer HRQOL, while alkali therapy was an independent predictor of better HRQOL (all P < 0.01). CONCLUSIONS: Among patients with active KSD, high-risk stone formers had impaired HRQOL with medullary sponge kidney disease and renal tubular acidosis being independent predictors of poorer HRQOL. Clinicians should seek to identify these patients earlier as they would benefit from prompt treatment and prevention.


Assuntos
Cálculos Renais , Qualidade de Vida , Humanos , Feminino , Masculino , Cálculos Renais/complicações , Pessoa de Meia-Idade , Adulto , Idoso , Acidose Tubular Renal/complicações , Rim em Esponja Medular/complicações , Inquéritos e Questionários
3.
World J Urol ; 42(1): 383, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904777

RESUMO

PURPOSE: To investigate safety and feasibility of performing water vapor thermal therapy (WVTT; Rezum, Boston Scientific, Marlborough, MA, USA) without postoperative catheterization among men with benign prostatic hyperplasia. METHODS: This is a prospective, single arm, unblinded pilot study of 20 consecutive male patients ages 40-80 who underwent WVTT at a single academic institution. All patients underwent 1 injection per lobe at the point of maximal obstruction based on visualization. Primary outcome was evaluation of voiding parameters, symptom scores, and need for catheterization at 3 day, 1, 3, and 6 month follow up compared to baseline visit 30 days prior to surgery. RESULTS: Mean age was 65 years (range 55-75). Mean prostate volume and PVR were 43 cc (range 30-68) and 89 cc, with 30% (n = 6) having median lobes. Patients received 2-3 treatments based on presence of bilobar versus trilobar hyperplasia. One patient (55 cc prostate, no median lobe) required catheterization for acute urinary retention on postoperative day 2. No patients required antibiotics for urinary tract infection or inpatient readmission within 30 days. Qmax significantly increased from 6 mL/s to 8, 13, 12, and 14 at 3 days, 1, 3, and 6 months (p < 0.05). IPSS decreased from 17 preoperatively to 10, 6, 7, and 8 (p < 0.05). No significant differences were noted in PVR, IIEF, MSHQ-EjD, or SF-12. CONCLUSIONS: In well-selected men, catheter-free WVTT is feasible and improved voiding parameters and symptom scores. No changes in sexual function, infectious complications, or readmission were noted. Only 1 patient (5%) required postoperative catheterization within 30 days.


Assuntos
Estudos de Viabilidade , Hiperplasia Prostática , Vapor , Humanos , Masculino , Hiperplasia Prostática/terapia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Projetos Piloto , Resultado do Tratamento , Idoso de 80 Anos ou mais , Adulto , Hipertermia Induzida/métodos
4.
J Urol ; 205(5): 1379-1386, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33369488

RESUMO

PURPOSE: Postoperative infectious related complications are not uncommon after percutaneous nephrolithotomy. Previously, we noted that 7 days of antibiotics did not decrease sepsis rates compared to just perioperative antibiotics in a low risk percutaneous nephrolithotomy population. This study aimed to compare the same regimens in individuals at moderate to high risk for sepsis undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: Patients were prospectively randomized in this multi-institutional study to either 2 days or 7 days of preoperative antibiotics. Enrolled patients had stones requiring percutaneous nephrolithotomy and had either a positive preoperative urine culture or existing indwelling urinary drainage tube. Primary outcome was difference in sepsis rates between the groups. Secondary outcomes included rate of nonseptic bacteriuria, stone-free rate and length of stay. RESULTS: A total of 123 patients at 7 institutions were analyzed. There was no difference in sepsis rates between groups on univariate analysis. Similarly, there were no differences in nonseptic bacteriuria, stone-free rate and length of stay. On multivariate analysis, 2 days of antibiotics increased the risk of sepsis compared to 7 days of antibiotics (OR 3.1, 95% CI 1.1-8.9, p=0.031). Patients receiving antibiotics for 2 days had higher rates of staghorn calculus than the 7-day group (58% vs 32%, p=0.006) but post hoc subanalysis did not demonstrate increased sepsis in the staghorn only group. CONCLUSIONS: Giving 7 days of preoperative antibiotics vs 2 days decreases the risk of sepsis in moderate to high risk percutaneous nephrolithotomy patients. Future guidelines should consider infectious risk stratification for percutaneous nephrolithotomy antibiotic recommendations.


Assuntos
Antibioticoprofilaxia , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Sepse/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Medição de Risco , Sepse/epidemiologia , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
5.
BJU Int ; 128(1): 88-94, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33205549

RESUMO

OBJECTIVE: To build the Wisconsin Stone Quality of Life Machine-Learning Algorithm (WISQOL-MLA) to predict urolithiasis patients' health-related quality of life (HRQoL) based on demographic, symptomatic and clinical data collected for the validation of the Wisconsin Stone Quality-of-Life (WISQOL) questionnaire, an HRQoL measurement tool designed specifically for patients with kidney stones. MATERIAL AND METHODS: We used data from 3206 stone patients from 16 centres. We used gradient-boosting and deep-learning models to predict HRQoL scores. We also stratified HRQoL scores by quintile. The dataset was split using a standard 70%/10%/20% training/validation/testing ratio. Regression performance was evaluated using Pearson's correlation. Classification was evaluated with an area under the receiver-operating characteristic curve (AUROC). RESULTS: Gradient boosting obtained a test correlation of 0.62. Deep learning obtained a correlation of 0.59. Multivariate regression achieved a correlation of 0.44. Quintile stratification of all patients in the WISQOL dataset obtained an average test AUROC of 0.70 for the five classes. The model performed best in identifying the lowest (0.79) and highest quintiles (0.83) of HRQoL. Feature importance analysis showed that the model weighs in clinically relevant factors to estimate HRQoL, such as symptomatic status, body mass index and age. CONCLUSIONS: Harnessing the power of the WISQOL questionnaire, our initial results indicate that the WISQOL-MLA can adequately predict a stone patient's HRQoL from readily available clinical information. The algorithm adequately relies on relevant clinical factors to make its HRQoL predictions. Future improvements to the model are needed for direct clinical applications.


Assuntos
Cálculos Renais , Aprendizado de Máquina , Qualidade de Vida , Autorrelato , Adulto , Idoso , Feminino , Humanos , Cálculos Renais/diagnóstico , Masculino , Pessoa de Meia-Idade
6.
World J Urol ; 39(6): 2183-2189, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32740804

RESUMO

PURPOSE: Patients presenting with acute renal colic may be at risk of opiate abuse. We sought to analyze prescribing patterns and identify risk factors associated with prolonged opiate use during episodes of acute renal colic. METHODS: Retrospective study of patients presenting with both a stone confirmed on imaging and an acute pain episode from 6/2017-2/2020. Opiate prescription data was obtained from a statewide prescribing database. Primary outcome was an opiate refill or new opiate prescription prior to resolution of the stone episode (either passage or surgery). Univariate and multivariate linear regression analysis was performed. RESULTS: A total of 271 patients met inclusion criteria. Mean age was 52 years and 48% had a history of nephrolithiasis. 180 (66%) patients filled a new opiate prescription during their acute stone episode. Thirty-eight (14%) patients had an existing opiate prescription within 3 months of their stone episode. Seventy-four (27%) patients refilled an opiate prescription prior to stone passage or surgery. Larger stone size, need for surgery, prolonged time to treatment, existing opiate prescription, new opiate prescription at presentation, and greater initial number of pills prescribed were associated with increased risk of requiring a refill prior to stone resolution. CONCLUSIONS: Patients prescribed new opiates for acute nephrolithiasis and those with an existing opioid prescription are likely to require refills before resolution of the stone episode. Larger stones that require surgery (not spontaneous passage) also increase the risk. Timely treatment of these patients and initial treatment with non-narcotics may reduce the risk of prolonged opiate use.


Assuntos
Analgésicos Opioides/uso terapêutico , Alcaloides Opiáceos/uso terapêutico , Cólica Renal/tratamento farmacológico , Adulto , Idoso , Duração da Terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitíase/complicações , Cólica Renal/etiologia , Estudos Retrospectivos , Fatores de Tempo
9.
J Urol ; 202(2): 314-318, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30829131

RESUMO

PURPOSE: Recent studies have demonstrated that quick sequential organ failure assessment criteria may be more accurate than systemic inflammatory response syndrome criteria to predict postoperative sepsis. In this study we evaluated the ability of these 2 criteria to predict septic shock after percutaneous nephrolithotomy. MATERIALS AND METHODS: We performed a retrospective multicenter study in 320 patients who underwent percutaneous nephrolithotomy at a total of 8 institutions. The criteria for quick sequential organ failure assessment and systemic inflammatory response syndrome were collected 24 hours postoperatively. The study primary outcome was postoperative septic shock. Secondary outcomes included 30 and 90-day emergency department visits, and the hospital readmission rate. RESULTS: Three of the 320 patients (0.9%) met the criteria for postoperative septic shock. These 3 patients had positive criteria for quick sequential organ failure assessment and systemic inflammatory response syndrome. Of the entire cohort 23 patients (7%) met quick sequential organ failure assessment criteria and 103 (32%) met systemic inflammatory response syndrome criteria. Specificity for postoperative sepsis was significantly higher for quick sequential organ failure assessment than for systemic inflammatory response syndrome (93.3% vs 68.4%, McNemar test p <0.001). The positive predictive value was 13% for quick sequential organ failure assessment criteria and 2.9% for systemic inflammatory response syndrome criteria. On multivariate logistic regression systemic inflammatory response syndrome criteria significantly predicted an increased probability of the patient receiving a transfusion (ß = 1.234, p <0.001). Positive quick sequential organ failure assessment criteria significantly predicted an increased probability of an emergency department visit within 30 days (ß = 1.495, p <0.05), operative complications (ß = 1.811, p <0.001) and transfusions (p <0.001). The main limitation of the study is that it was retrospective. CONCLUSIONS: Quick sequential organ failure assessment criteria were superior to systemic inflammatory response syndrome criteria to predict infectious complications after percutaneous nephrolithotomy.


Assuntos
Nefrolitotomia Percutânea , Escores de Disfunção Orgânica , Complicações Pós-Operatórias , Choque Séptico , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Nefrolitotomia Percutânea/efeitos adversos , Admissão do Paciente , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Choque Séptico/etiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia
10.
J Pathol ; 243(4): 457-467, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28940538

RESUMO

Benign prostatic hyperplasia is the most common proliferative abnormality of the prostate. All men experience some prostatic growth as they age, but the rate of growth varies among individuals. Steroid 5α-reductase 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Previous work indicates that one-third of adult prostatic samples do not express SRD5A2, secondary to epigenetic modifications. Here we show that the level of oestradiol is dramatically elevated, concomitant with significant upregulation of oestrogen response genes, in prostatic samples with methylation at the SRD5A2 promoter. The phosphorylation of oestrogen receptor-α in prostatic stroma is upregulated when SRD5A2 expression is absent. We show that tumour necrosis factor (TNF)-α suppresses SRD5A2 mRNA and protein expression, and simultaneously promotes expression of aromatase, the enzyme responsible for conversion of testosterone to oestradiol. Concomitant suppression of SRD5A2 and treatment with TNF-α synergistically upregulate the aromatase levels. The data suggest that, in the absence of prostatic SRD5A2, there is an androgenic to oestrogenic switch. These findings have broad implications for choosing appropriate classes of medications for the management of benign and malignant prostatic diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Metilação de DNA , Epigênese Genética , Estradiol/metabolismo , Proteínas de Membrana/genética , Próstata/enzimologia , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/genética , Testosterona/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Aromatase/genética , Aromatase/metabolismo , Boston , Células Cultivadas , Di-Hidrotestosterona/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/patologia , Interferência de RNA , Transdução de Sinais , Células Estromais/metabolismo , Texas , Transfecção , Fator de Necrose Tumoral alfa/farmacologia
11.
Am J Pathol ; 185(3): 870-82, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25700986

RESUMO

5-α Reductase type 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Inhibition of SRD5A2 by finasteride is used commonly for the management of urinary obstruction caused by benign prostatic hyperplasia. Contrary to common belief, we have found that expression of SRD5A2 is variable and absent in one third of benign adult prostates. In human samples, absent SRD5A2 expression is associated with hypermethylation of the SRD5A2 promoter, and in vitro SRD5A2 promoter activity is suppressed by methylation. We show that methylation of SRD5A2 is regulated by DNA methyltransferase 1, and inflammatory mediators such as tumor necrosis factor α, NF-κB, and IL-6 regulate DNA methyltransferase 1 expression and thereby affect SRD5A2 promoter methylation and gene expression. Furthermore, we show that increasing age in mice and humans is associated with increased methylation of the SRD5A2 promoter and concomitantly decreased protein expression. Artificial induction of inflammation in prostate primary epithelial cells leads to hypermethylation of the SRD5A2 promoter and silencing of SRD5A2, whereas inhibition with tumor necrosis factor α inhibitor reactivates SRD5A2 expression. Therefore, expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues. Methylation and expression of SRD5A2 may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Envelhecimento/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas de Membrana/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Animais , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Próstata/patologia , Hiperplasia Prostática/patologia
12.
Semin Neurol ; 36(1): 34-40, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26866494

RESUMO

Voiding dysfunction is a common and debilitating consequence of multiple sclerosis (MS). The prevalence and severity of voiding dysfunction increases with the increasing severity of MS, but even the mildest forms of the disease are associated with urinary symptoms in 30% of patients. Every component of the central nervous system is involved in regulating voiding; as a result, MS can lead to a wide variety of urinary symptoms and urologic complications. The effect of MS on voiding can be classified according to the resulting function of the bladder and the urethral sphincter during storage and emptying of urine. Therapy is targeted to the specific bladder and sphincter abnormalities that occur. The primary goals of therapy are prevention of injury to the upper urinary tract (kidneys), reduction in urinary tract infections, and maintenance of urinary continence. These goals can be achieved by interventions ranging from behavioral modification to major reconstructive surgery.


Assuntos
Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Transtornos Urinários/complicações , Transtornos Urinários/terapia , Humanos , Esclerose Múltipla/epidemiologia , Prevalência , Transtornos Urinários/epidemiologia
13.
Cancer Cell ; 13(2): 141-52, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18242514

RESUMO

How breast cancers are able to disseminate and metastasize is poorly understood. Using a hyperplasia transplant system, we show that tumor dissemination and metastasis occur in discrete steps during tumor progression. Bioinformatic analysis revealed that loss of the transcription factor GATA-3 marked progression from adenoma to early carcinoma and onset of tumor dissemination. Restoration of GATA-3 in late carcinomas induced tumor differentiation and suppressed tumor dissemination. Targeted deletion of GATA-3 in early tumors led to apoptosis of differentiated cells, indicating that its loss is not sufficient for malignant conversion. Rather, malignant progression occurred with an expanding GATA-3-negative tumor cell population. These data indicate that GATA-3 regulates tumor differentiation and suppresses tumor dissemination in breast cancer.


Assuntos
Neoplasias da Mama/patologia , Diferenciação Celular , Fator de Transcrição GATA3/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Células Epiteliais/patologia , Feminino , Fator de Transcrição GATA3/deficiência , Deleção de Genes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Hiperplasia , Imuno-Histoquímica , Glândulas Mamárias Animais , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia
14.
J Urol ; 194(4): 1031-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25916673

RESUMO

PURPOSE: In men with symptomatic benign prostatic hyperplasia 5α-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5α-reductase inhibitors. We have found that a third of adult prostate samples do not express 5α-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5α-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5α-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen. MATERIALS AND METHODS: Prostate samples from men undergoing transurethral prostate resection were used. We determined 5α-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, hypertension, hyperlipidemia, diabetes, prostate specific antigen and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: Body mass index and age significantly correlated with methylation of the 5α-reductase type 2 gene promoter (p <0.05) whereas prostate volume, prostate specific antigen or benign prostatic hyperplasia medication did not correlate. Methylation highly correlated with 5α-reductase protein expression (p <0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p <0.01). CONCLUSIONS: Increasing age and body mass index correlate with increased 5α-reductase type 2 gene promoter methylation and decreased protein expression in men with symptomatic benign prostatic hyperplasia. These results highlight the interplay among age, obesity and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic benign prostatic hyperplasia, which may be important to choose appropriate personalized treatment options.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Obesidade/metabolismo , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Obesidade/complicações , Psicoterapia Centrada na Pessoa , Hiperplasia Prostática/complicações
15.
Curr Opin Cell Biol ; 20(2): 164-70, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18358709

RESUMO

The GATA family of transcription factors plays essential roles in the specification and maintenance of differentiated cell types. GATA-3 was identified in a microarray screen of the mouse mammary gland as the most highly expressed transcription factor in the mammary epithelium and is expressed exclusively in the luminal epithelial cell population. Targeted deletion of GATA-3 in mammary glands leads to profound defects in mammary development and inability to specify and maintain the luminal cell fate in the adult mouse. In breast cancer, GATA-3 has emerged as a strong predictor of tumor differentiation, estrogen-receptor status, and clinical outcome. GATA-3 maintains tumor differentiation and suppresses tumor dissemination in a mouse model of breast cancer. This review explores our current understanding of GATA-3 signaling in luminal cell differentiation, both in mammary development and breast cancer.


Assuntos
Linhagem da Célula , Fator de Transcrição GATA3/metabolismo , Glândulas Mamárias Humanas/citologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos
16.
J Urol ; 192(1): 16-23, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24582540

RESUMO

PURPOSE: Benign prostatic hyperplasia affects more than 50% of men by age 60 years, and is the cause of millions of dollars in health care expenditure for the treatment of lower urinary tract symptoms and urinary obstruction. Despite the widespread use of medical therapy, there is no universal therapy that treats all men with symptomatic benign prostatic hyperplasia. At least 30% of patients do not respond to medical management and a subset require surgery. Significant advances have been made in understanding the natural history and development of the prostate, such as elucidating the role of the enzyme 5α-reductase type 2, and advances in genomics and biomarker discovery offer the potential for a more targeted approach to therapy. We review the current understanding of benign prostatic hyperplasia progression as well as the key genes and signaling pathways implicated in the process such as 5α-reductase. We also explore the potential of biomarker screening and gene specific therapies as tools to risk stratify patients with benign prostatic hyperplasia and identify those with symptomatic or medically resistant forms. MATERIALS AND METHODS: A PubMed® literature search of current and past peer reviewed literature on prostate development, lower urinary tract symptoms, benign prostatic hyperplasia pathogenesis, targeted therapy, biomarkers, epigenetics, 5α-reductase type 2 and personalized medicine was performed. An additional Google Scholar™ search was conducted to broaden the scope of the review. Relevant reviews and original research articles were examined, as were their cited references, and a synopsis of original data was generated with the goal of informing the practicing urologist of these advances and their implications. RESULTS: Benign prostatic hyperplasia is associated with a state of hyperplasia of the stromal and epithelial compartments, with 5α-reductase type 2 and androgen signaling having key roles in the development and maintenance of the prostate. Chronic inflammation, multiple growth factor and hormonal signaling pathways, and medical comorbidities have complex roles in prostate tissue homeostasis as well as its evolution into the clinical state of benign prostatic hyperplasia. Resistance to medical therapy with finasteride may occur through silencing of the 5α-reductase type 2 gene by DNA methylation, leading to a state in which 30% of adult prostates do not express 5α-reductase type 2. Novel biomarkers such as single nucleotide polymorphisms may be used to risk stratify patients with symptomatic benign prostatic hyperplasia and identify those at risk for progression or failure of medical therapy. Several inhibitors of the androgen receptor and other signaling pathways have recently been identified which appear to attenuate benign prostatic hyperplasia progression and may offer alternative targets for medical therapy. CONCLUSIONS: Progressive worsening of lower urinary tract symptoms and bladder outlet obstruction secondary to benign prostatic hyperplasia is the result of multiple pathways including androgen receptor signaling, proinflammatory cytokines and growth factor signals. New techniques in genomics, proteomics and epigenetics have led to the discovery of aberrant signaling pathways, novel biomarkers, DNA methylation signatures and potential gene specific targets. As personalized medicine continues to develop, the ability to risk stratify patients with symptomatic benign prostatic hyperplasia, identify those at higher risk for progression, and seek alternative therapies for those in whom conventional options are likely to fail will become the standard of targeted therapy.


Assuntos
Medicina de Precisão , Hiperplasia Prostática/terapia , Biomarcadores , Humanos , Masculino , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/etiologia
17.
J Endourol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38874261

RESUMO

Introduction: Next-generation sequencing (NGS) is a new molecular technique for identifying microorganisms. Treating bacteriuria in patients undergoing stone removal procedures is important for preventing postoperative urinary tract infection (UTI). The objective of this study is to assess the usefulness of preoperative urine NGS testing by comparing NGS with standard urine culture in predicting postoperative UTI after ureteroscopic lithotripsy (URSL) and percutaneous nephrolithotomy (PCNL). Materials and Methods: This prospective study was conducted from February 16, 2022, to January 11, 2024. Sixty subjects who underwent URSL or PCNL were included. Preoperative voided urine samples were collected for urine culture and tested by MicroGenDX for urine polymerase chain reaction (PCR) and urine NGS. Stone specimens obtained intraoperatively were also sent for stone culture and MicrogenDx. Patients were monitored for 4 weeks post-operation for recording clinical outcomes related to infections and complications. Results: Twenty-six (43.3%) male and 34 (56.7%) female participants were included. Twenty-six (43.3%) patients underwent PCNL (15 standard PCNL and 11 mini PCNL), and 34 (56.7%) underwent URSL. Standard urine culture identified positive results in 26 cases (43.3%), PCR for 17 cases (28.3%), and NGS for 31 cases (51.7%). The overall postoperative UTI rate was 6 (10%). Standard urine culture demonstrated a sensitivity of 50%, specificity of 57.4%, and accuracy of 56.7%. Positive predictive value (PPV) was notably poor at 11.5%. Urine NGS showed a higher sensitivity of 83.3%, specificity of 53.7%, accuracy of 55%, and PPV of 16.7%. Conclusion: Urine NGS significantly improves the sensitivity of detecting microorganisms in preoperative urine compared with standard urine culture. Despite its high sensitivity and capability to identify nonculturable bacteria, using NGS alongside standard urine culture is recommended. This parallel approach harnesses the strengths of both methods. Integrating NGS into standard practice could elevate the quality of care, especially for patients at high risk of UTIs, such as those undergoing invasive stone removal procedures.

18.
Urology ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38677371

RESUMO

OBJECTIVE: To identify predictors of retreatment for symptomatic recurrence among men who undergo water vapor thermal therapy (WVTT; Rezum, Boston Scientific, Marlborough, MA), a minimally invasive surgical treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. METHODS: We retrospectively reviewed patients treated with WVTT at a single institution from August 2017 to February 2022. Patients who underwent a second benign prostatic hyperplasia procedure for persistent or recurrent lower urinary tract symptoms within 2years of original treatment were compared to the remaining cohort who did not undergo retreatment. Multivariate analysis was used to assess for predictors of retreatment. RESULTS: Data were obtained from 192 patients. 10 (5%) patients were retreated. The retreatment cohort had smaller prostate volumes (50.4±18.2 cc vs 48.5±35.7 cc; P = .003) and received a greater number of water vapor injections (4.4±1.8 vs 5.2±3.9; P < .001). At 6month follow-up, total International Prostate Symptom Score (IPSS; 10.13 ± 7.40 vs 18.5 ± 11.55, P = .044) and voiding subscores (4.59 ± 4.39 vs 9.5 ± 7.84, P = .006) were significantly worse in the retreatment group. On multivariate analysis, >1 treatment per lobe was independently associated with increased risk of retreatment (hazard ratio 8.509, 95% CI [1.109-65.293]; P = .039). CONCLUSION: WVTT has a low retreatment rate. Men who required retreatment received more injections and showed worsened voiding symptom scores 6months postoperatively. Decreasing the number of injections may help reduce treatment failure rates.

19.
J Endourol ; 37(1): 85-92, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36106604

RESUMO

Purpose: To evaluate whether computer program-estimated urolith stone volume (SV) was a better predictor of spontaneous passage (SP) compared with program-estimated stone diameter (PD) or manually measured stone diameter (MD), and whether utilizing SV and MD together provided additional value in SP prediction compared with MD alone. Materials and Methods: Retrospective analysis of patients with acute renal colic and single renal/ureteral stone on CT from July 2017 to April 2020. Diameter obtained from radiology reports or manually measured when report not available. Semiautomated stone analysis software (qSAS) was used to estimate SV and PD. ROC analysis was performed to compare accuracy of SV vs MD vs PD in predicting SP by 2, 4, and 6 weeks. Subgroup analysis was performed by stone size (

Assuntos
Cálculos Renais , Cálculos Ureterais , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Remissão Espontânea , Cálculos Ureterais/diagnóstico por imagem , Software
20.
J Endourol ; 37(11): 1174-1178, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37675902

RESUMO

Introduction: The American Urological Association guidelines state that continuing anticoagulant (AC) and antiplatelet (AP) agents during ureteroscopy (URS) is safe. Through a multi-institutional retrospective study, we sought to determine whether pre-stenting in patients on AP or AC was associated with fewer URS bleeding-related complications. Methods: A series of 8614 URS procedures performed across three institutions (April 2010 to September 2017) was electronically reviewed for AC/AP use at time of URS. Records indicating AC or AP use at time of URS were then manually reviewed to characterize intraoperative and 30-day postoperative (intraoperative bleeding, postoperative hematuria, emergency department visits, hospital readmission, unplanned reoperation, phone calls, and other minor 30-day complications). Results: A total of 293 identified URS procedures were completed on patients on AC/AP therapy-112 cases were on AC only (38 were pre-stented), 158 on AP only (51 pre-stented), and 23 on both AP and AC (8 pre-stented). Patient characteristics and comorbidities were similar between the pre-stented and non-pre-stented groups. For AC and AP subjects, pre-stenting did not decrease the composite risk of bleeding complications (10.3% pre-stent vs 12.2% non-prestent, p = 0.6). Pre-stented patients did have a significantly lower likelihood of requiring an unplanned reoperation (1.0% vs 5.6%, p = 0.04). In the subgroup of patients on AP alone, pre-stented patients had significantly fewer episodes of intraoperative bleeding (0% vs 9%, p = 0.04), unplanned reoperations (0% vs 6.5%, p = 0.02), and 30-day complications (14% vs 27%, p = 0.05). In the subgroup of patients on AC alone, there were no significant differences in outcomes based on stent status. Conclusions: In this multi-institutional study, we found that pre-stenting before URS was not associated with fewer bleeding complications. However, pre-stenting appeared to be associated with improved outcomes for those patients on AP therapy. These results suggest a need for prospective studies to clarify the role of pre-stenting for URS.


Assuntos
Cálculos Ureterais , Ureteroscopia , Humanos , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Cálculos Ureterais/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Anticoagulantes/efeitos adversos , Hemorragia/etiologia , Stents/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia
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