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1.
World J Mens Health ; 40(2): 257-263, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35021307

RESUMEN

PURPOSE: Selective serotonin re-uptake inhibitors (SSRIs) are frequently used to treat premature ejaculation (PE) in men. We performed a Cochrane review to assess the efficacy of SSRI treatment for PE. MATERIALS AND METHODS: We extensively searched a range of databases up to May 2020 and only included randomized controlled trials. RESULTS: A total of 31 studies with 8,254 men were included in this analysis. We found that SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better'; risk ratio [RR], 1.92; 95% confidence interval [CI], 1.66-2.23; moderate-certainty evidence) and satisfaction with intercourse (defined as a rating of 'good' or 'very good'; RR, 1.63; 95% CI, 1.42-1.87; moderate-certainty evidence) compared to placebo. Furthermore, SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good'; RR, 2.29; 95% CI, 1.72-3.05; moderate-certainty evidence) and probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR, 1.54; 95% CI, 1.26-1.88; moderate-certainty evidence). SSRI treatment may increase IELT compared to placebo (mean difference, 3.09 minutes higher; 95% CI, 1.94 higher to 4.25 higher; low-certainty evidence). However, SSRIs may increase treatment cessations due to adverse events compared to placebo (RR, 3.80; 95% CI, 2.61-5.51; low-certainty evidence). CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo.

2.
J Urol ; 207(1): 181-182, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34607448
3.
Sex Med Rev ; 10(3): 460-467, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34896063

RESUMEN

INTRODUCTION: Men with normal penis size sometimes mistakenly believe they have below average penile dimensions and often seek out treatment. Many men suffer from significant anxiety regarding this perceived defect. In this review, we evaluate the current literature of psychological, medical, and surgical treatment options for men with a complaint of a small penis. OBJECTIVE: To review the current practice for treatment of men presenting for penile augmentation surgery. METHODS: A literature review was conducted, using PubMed to identify current studies regarding penile enhancement. Search terms included "penile enhancement," "small penis anxiety," "small penis syndrome," "body dysmorphic disorder," and "penile augmentation." RESULTS: The literature consistently reveals that men who seek out penile augmentation surgery usually have normal penile dimensions. There are limited published data on the practice of penile lengthening surgery or procedures to increase penile girth. New techniques have expanded on suspensory ligament release, such as tissue grafting and flaps. Structured psychological counseling continues to be the recommended initial standard of care for these men. CONCLUSION: Many social forces have increased the perception among men that their penis size is inadequate. This increases anxiety and can lead to psychological disorders such as Penile Dysmorphic Disorder and Small Penis Syndrome. Men who undergo penile enhancement are often not satisfied with the results and may develop complications. Soubra A, Natale C, Brimley S, et al. Revelations on Men Who Seek Penile Augmentation Surgery: A Review. Sex Med Rev 2022;10:453-460.


Asunto(s)
Enfermedades del Pene , Procedimientos de Cirugía Plástica , Consejo , Genitales , Humanos , Masculino , Enfermedades del Pene/cirugía , Pene/cirugía , Procedimientos de Cirugía Plástica/métodos
4.
Urology ; 153: 320-326, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33901530

RESUMEN

OBJECTIVE: To determine whether ejaculatory dysfunction (EjD) and post-void dribbling (PVD) after urethroplasty are associated, providing evidence for a common etiology. METHODS: We reviewed a prospectively maintained database for first-time, anterior urethroplasties. One item from the Male Sexual Health Questionnaire (MSHQ) assessed EjD: "How would you rate the strength or force of your ejaculation". One item from the Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) assessed PVD: "How often have you had slight wetting of your pants after you had finished urinating?". The frequency of symptoms was compared after penile vs. bulbar repairs, and anastomotic versus augmentation bulbar repairs. Associations were assessed with chi-square. RESULTS: A total of 728 men were included. Overall, postoperative EjD and PVD were common; 67% and 66%, respectively. There was a significant association between EjD and PVD for the whole cohort (p<0.0001); this association remained significant after penile repairs (p=0.01), bulbar repairs (p<0.0007), and bulbar anastomotic repairs (p=0.002), but not after bulbar augmentation repairs (p=0.052). EjD and PVD occurred at similar rates after penile and bulbar urethroplasty. The rate of EjD was similar after bulbar augmentation and bulbar anastomotic urethroplasties, but PVD was more common after bulbar augmentation (70% vs. 52%) (p = 0.0001). CONCLUSION: EjD and PVD after anterior urethroplasty are significantly associated with one another, supporting the theory of a common etiology. High rates after penile repairs argue against a bulbospongiosus muscle damage etiology, and high rates after anastomotic repairs argue against graft sacculation. More work is needed to better understand and prevent symptoms.


Asunto(s)
Eyaculación , Complicaciones Posoperatorias/etiología , Disfunciones Sexuales Fisiológicas/etiología , Uretra/cirugía , Incontinencia Urinaria de Urgencia/etiología , Adulto , Anastomosis Quirúrgica , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Disfunciones Sexuales Fisiológicas/complicaciones , Incontinencia Urinaria de Urgencia/complicaciones , Micción , Procedimientos Quirúrgicos Urológicos Masculinos/métodos
5.
Cochrane Database Syst Rev ; 3: CD012799, 2021 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-33745183

RESUMEN

BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition. OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE  were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE. MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs.  SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs.  Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs.  SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs.  SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs.  SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence). AUTHORS' CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.


Asunto(s)
Eyaculación Prematura/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adolescente , Adulto , Coito/psicología , Intervalos de Confianza , Eyaculación/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Satisfacción del Paciente/estadística & datos numéricos , Placebos/uso terapéutico , Eyaculación Prematura/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Adulto Joven
7.
Urology ; 148: 32-36, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33285214

RESUMEN

OBJECTIVE: To create and validate a grading scale that facilitates communication between providers managing gross hematuria (GH). METHODS: A blood simulant was used to create a spectrum of GH in 5 foley catheter tubes which were shown to a group of experienced urologists. The urologists were asked how they would adjust the continuous bladder irrigation rate if the samples represented the urine of hypothetical patients, and a 5-point scale was created by group consensus with pictures of the representative tubes printed onto a visual aid. Another cohort were then shown the 5 tubes at random and asked to describe the GH. Raters were then shown the visual aid and asked to assign a grade to the same samples. Fleiss' kappa analysis was used to measure inter-rater agreement, and therefore fidelity of the scale. RESULTS: Fourteen urologists were surveyed to determine the samples used to create the 5-point scale. After the scale was created, 43 raters (22 nurses, 16 urologists, and 5 advanced practice providers) attempted match the tubes to their corresponding images on the printout. When asked to describe the degree of GH for the samples as they would in clinical practice, 28 different descriptors were used (mean 8.6 per sample). When using the 5-point GH scale, however, raters exhibited near perfect agreement in matching each sample to its corresponding severity on the scale (κ = 0.93, P < .001). CONCLUSION: We created a clinically useful GH scale that improves communication and reduces ambiguous language among providers of varying levels of experience.


Asunto(s)
Comunicación , Hematuria/clasificación , Catéteres Urinarios , Urólogos , Escala Visual Analógica , Adulto , Anciano , Color , Femenino , Hematuria/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros , Índice de Severidad de la Enfermedad , Irrigación Terapéutica , Adulto Joven
8.
Urol Oncol ; 37(5): 299.e1-299.e6, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30797649

RESUMEN

OBJECTIVE: A number of studies have described the overall institutional learning curve for magnetic resonance imaging-guided biopsy but none have evaluated differences and interactions between clinicians. Therefore, we aim to measure and compare the cancer detection rates between individual radiologists and urologists at a single academic institution. METHODS: A consecutive sample of patients undergoing magnetic resonance imaging-guided biopsy at a single institution were included for analysis. The detection of any and clinically significant (Gleason score ≥3+4) prostate cancer was compared between radiologists and urologists after adjusting for relevant demographic and clinical characteristics. Analysis was conducted on a perlesion basis and only the results of the targeted cores were considered in the primary analysis. RESULTS: Two hundred eighty-one patients with 418 lesions were included in the study. Prostate cancer of any grade was detected in 43.7% (183/418) of targeted lesions. There was no difference in the distribution of Prostate Imaging Reporting and Data System (PIRADS) scores attributed by each radiologist (p = 0.43). The individual radiologist cancer detection rate for both overall and clinically significant cancer was similar across each PIRADS score except for the detection of any cancer in PIRADS 3 lesions (p = 0.03). There was no difference in the detection rates of any grade or clinically significant cancer between urologists. CONCLUSION: This single institutional analysis found that the performance of radiologists and urologists was largely comparable. Theonly variation observed was among radiologists for PIRADS 3 lesions.


Asunto(s)
Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Neoplasias de la Próstata/patología , Radiología , Urología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Retrospectivos
9.
Clin Genitourin Cancer ; 16(5): 360-364, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30001845

RESUMEN

PURPOSE: To determine the accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET/CT) scans in assessing the response to neoadjuvant chemotherapy (NAC) in patients with bladder cancer scheduled to undergo radical cystectomy (RC). PATIENTS AND METHODS: All patients treated at our center for muscle-invasive bladder cancer (MIBC) were counseled and offered NAC before RC. FDG-PET/CT scans were performed before the initiation of chemotherapy and after completion of the regimen. Patients with disease with complete response to NAC were those who had (pT0) or residual carcinoma-in-situ (pTis) on final pathology. Those who were downstaged from MIBC to non-MIBC were considered to have a chemosensitive tumor. We used percentage reduction in standardized maximum uptake value (SUVmax) from PET/CT scans as our measure to correlate with the final pathology after cystectomy. RESULTS: Thirty-seven patients with MIBC who underwent NAC followed by RC were included in the final analysis. FDG-PET/CT had 75% sensitivity (89.66% specificity) in identifying those with complete pathologic response with a 100% change in SUVmax, and 83% sensitivity (94% specificity) for the detection of chemosensitive tumors. CONCLUSION: FDG-PET/CT can help determine the response of primary tumor to NAC in patients with MIBC and thus can more accurately predict the prognosis of the patients, or potentially the appropriate time for cystectomy.


Asunto(s)
Quimioterapia Adyuvante/métodos , Fluorodesoxiglucosa F18/administración & dosificación , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Sensibilidad y Especificidad , Resultado del Tratamiento
10.
Prostate Cancer Prostatic Dis ; 21(4): 573-578, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30038389

RESUMEN

INTRODUCTION: Magnetic resonance imaging is being widely adopted in the clinical management of prostate cancer. The correlation of the Prostate Imaging Reporting and Data System (PIRADS) to the presence of cancer has been established but studies have primarily evaluated this in a single clinical setting. This study aims to characterize the correlation of PIRADS score to the diagnosis of cancer on fusion biopsy among men who are undergoing primary biopsy, those who have had a previous negative biopsy or men on active surveillance. MATERIALS & METHODS: A consecutive sample of men undergoing US-MR biopsy at a single academic institution from 2014 to 2017 were included in this retrospective study. Men were stratified into groups according to their clinical history: biopsy-naïve, previous negative transrectal ultrasound (TRUS) biopsy or on active surveillance. The correlation of PIRADS score to the diagnosis of any and clinically significant cancer (Gleason score ≥ 3 + 4) was determined. RESULTS: A total of 255 patients with 365 discrete lesions were analyzed. PIRADS score 1-2, 3, 4 and 5 yielded any prostate cancer in 7.7, 29.7, 42.3 and 82.4% of the cases, respectively, across all indications while clinically significant cancer was found in 0, 8.9, 21.4 and 62.7%, respectively. The area under the receiver operative curves for the diagnosis of any and significant cancer was 0.69 (95%CI: 0.64-0.74) and 0.74 (95%CI: 0.69-0.79) respectively. Men who have had a previous negative biopsy had lower detection rates for any prostate cancer for PIRADS 3 and 4 lesions compared to those that were biopsy-naïve or on active surveillance. CONCLUSION: Cancer detection rates are significantly associated with PIRADS score. Biopsy yields differ across biopsy indications which should be considered when selecting a PIRADS score threshold for biopsy. Biopsy of PIRADS 3 lesions could potentially be avoided in men who have previously undergone a negative TRUS biopsy.


Asunto(s)
Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Curva ROC , Estudios Retrospectivos , Ultrasonografía
11.
Urology ; 116: 120-124, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29551621

RESUMEN

OBJECTIVE: To determine the preoperative incidence of subclinical lower-extremity deep vein thrombosis (DVT), as well as to evaluate the utility of preoperative DVT screening in patients with bladder cancer before undergoing radical cystectomy. MATERIALS AND METHODS: Beginning in 2014, we prospectively instituted a policy of obtaining a screening lower-extremity duplex ultrasound on all patients within 7 days before undergoing radical cystectomy. We reviewed the electronic medical records of all patients at our institution who underwent radical cystectomy for bladder cancer from January 2012 through December 2015. The screened group (n = 65) underwent preoperative screening; the historical control group (n = 78) did not. Primary outcome was a lower-extremity duplex ultrasound positive screening. Secondary outcome measures included the development of symptomatic venous thromboembolism (VTE) postoperatively, and the rate and severity of complications. RESULTS: DVT was identified in 13.9% of patients before undergoing cystectomy. Univariate analysis demonstrated an increased risk of subclinical DVT in patients who were exposed to neoadjuvant chemotherapy (35.3% vs 5.1%, P = .008). Postoperatively, there was a nonsignificant trend of lower DVT rate in the screened group compared to historical control. Overall complication rate and severity were similar between the groups. CONCLUSION: Subclinical DVT is present in a significant number of pre-cystectomy patients, especially those exposed to neoadjuvant chemotherapy. Ultrasound screening in patients before undergoing radical cystectomy may identify opportunities for early intervention to reduce morbidity and mortality associated with perioperative DVT or venous thromboembolism in the cystectomy population.


Asunto(s)
Cistectomía/efectos adversos , Extremidad Inferior/irrigación sanguínea , Complicaciones Posoperatorias/epidemiología , Neoplasias de la Vejiga Urinaria/cirugía , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler Dúplex , Vejiga Urinaria/patología , Vejiga Urinaria/cirugía , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/diagnóstico por imagen
12.
Urol Oncol ; 36(2): 77.e9-77.e13, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29097086

RESUMEN

PURPOSE: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism, is a common cause of morbidity and mortality after radical cystectomy. The purpose of our study was to evaluate the utility of extended outpatient chemoprophylaxis against VTE after radical cystectomy-with a focus on any reduction in the incidence of VTE, including DVT and pulmonary embolism. MATERIALS AND METHODS: Beginning in April 2013, we prospectively instituted a policy of extending inpatient VTE prophylaxis with subcutaneous heparin/enoxaparin for 30 days postoperatively. For this study, we reviewed the electronic medical records of all patients who underwent radical cystectomy at our institution from January 2012 through December 2015. The experimental group (n = 79) received extended outpatient chemoprophylaxis against VTE; the control group (n = 51) received no chemoprophylaxis after discharge. The primary outcome was the 90-day incidence of VTE. The secondary outcomes included the overall complication rate, the hemorrhagic complication rate, as well as the rate of readmission within 30 days of hospital discharge. RESULTS: The experimental group experienced a significantly lower rate of DVT (5.06%), assessed as of 90 days postoperatively, than the control group (17.6%): a relative risk reduction of 71.3% (P = 0.021). We found no significant differences in secondary outcomes between the 2 groups, including the overall complication rate (54.4% vs. 68.6%), the hemorrhagic complication rate (3.7% vs. 2.0%), and the readmission rate (21.5% vs. 29.4%). CONCLUSION: Extended outpatient chemoprophylaxis significantly reduced the incidence of VTE.


Asunto(s)
Quimioprevención/métodos , Cistectomía/métodos , Enoxaparina/uso terapéutico , Tromboembolia Venosa/prevención & control , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Cistectomía/efectos adversos , Enoxaparina/administración & dosificación , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Tromboembolia Venosa/etiología
13.
Prostate ; 77(6): 584-596, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28144973

RESUMEN

BACKGROUND: With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. METHODS: Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. RESULTS: Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal studies further confirmed that Minnelide was more efficacious than the standard of care therapies, Docetaxel and Enzalutamide. CONCLUSION: Our study indicates that Minnelide is very effective as a therapeutic option against CRPC at a dose that is currently tolerated by patients in the ongoing clinical trials. Prostate 77: 584-596, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Organofosfatos/farmacología , Fenantrenos/farmacología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Isoformas de Proteínas/biosíntesis , Receptores Androgénicos/biosíntesis , Animales , Línea Celular Tumoral , Diterpenos , Relación Dosis-Respuesta a Droga , Compuestos Epoxi , Humanos , Masculino , Ratones , Ratones Desnudos , Organofosfatos/uso terapéutico , Fenantrenos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Distribución Aleatoria , Receptores Androgénicos/genética , Carga Tumoral/efectos de los fármacos , Carga Tumoral/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
J Urol ; 197(3 Pt 1): 596-601, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27664580

RESUMEN

PURPOSE: Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events. RESULTS: A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride. CONCLUSIONS: In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride.


Asunto(s)
Ácido Aminolevulínico/análogos & derivados , Carcinoma/diagnóstico , Carcinoma/cirugía , Cistoscopía/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes , Estudios Retrospectivos , Urotelio
15.
World J Urol ; 34(9): 1229-37, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26847182

RESUMEN

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET-CT) to predict nodal metastases in patients with bladder cancer (BC) scheduled to undergo radical cystectomy (RC). METHODS: We retrospectively reviewed records of patients diagnosed with BC and scheduled to undergo RC at our center from January 2011 through February 2015, who also underwent FDG-PET-CT at the time of diagnosis. All patients underwent RC and an extended pelvic lymph node dissection as the reference standard. The primary endpoints were the sensitivity, specificity and overall accuracy of FDG-PET-CT in detecting lymph node metastasis. We also examined its accuracy in identifying distant metastasis. In addition, we conducted a protocol-driven systematic review and meta-analysis of accuracy of FDG-PET-CT for preoperative staging of BC, as compared to CT alone, as reported in individual studies. To assess the methodological quality of eligible studies, we used the QUADAS-2 tool (a revised tool for the Quality Assessment of Diagnostic Accuracy Studies) and pooled diagnostic accuracy measures using Meta-DiSc statistical software. RESULTS: For detecting nodal metastases in 78 patients, the sensitivity of FDG-PET-CT was 0.56 (95 % CI 0.29-0.80) and the specificity, 0.98 (95 % CI 0.91-1.00). Pooled sensitivity and specificity for detecting lymph node metastasis were 0.57 and 0.95, respectively. Positive likelihood ratio was 9.02. All lesions that were suspicious for distant metastasis were found to be positive on biopsy. CONCLUSION: FDG-PET-CT was more accurate than CT alone in staging BC in patients undergoing surgery. Standardization of FDG-PET-CT protocol and cost-effectiveness analysis are required before widespread implementation of this technology.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Estudios Retrospectivos
16.
Clin Genitourin Cancer ; 14(1): 38-47.e1, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26525859

RESUMEN

UNLABELLED: The precise utility of positron emission tomography (PET) scanning for urologic cancers is not well defined. We examined the trends of usage in a population-based data set. PET scans were performed in 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with renal cell carcinoma. This selective usage might be driven by reimbursement constraints or identification of appropriate medical indications. INTRODUCTION: Positron emission tomography (PET) scanning is increasingly being used for imaging a variety of cancers, including urologic cancers. The precise utility of PET scanning for bladder cancer, prostate cancer, and renal cell carcinoma (RCC) is not yet well known. We examined the trends in PET scan usage for 3 cancers using a large population-based data set. MATERIALS AND METHODS: We analyzed all individuals identified with a diagnosis of nonmetastatic bladder cancer, prostate cancer, and RCC from the Surveillance, Epidemiology, and End Results-Medicare data set for 2004 to 2009 with follow-up data available to 2010. Logistic regression analysis and χ(2) and trend tests were performed to determine the predictors of performing PET scanning. Separate models were run for each of the cancer diagnoses. All analyses were performed using SAS, version 9.3, and P < .05 was considered significant. RESULTS: We identified 20,865, 70,414, and 7007 patients with a diagnosis of bladder cancer, prostate cancer, and RCC, respectively, from 2004 to 2009. PET scans had been performed for 3.60% of patients with bladder cancer, 1.09% of those with prostate cancer, and 5.32% of those with RCC. On regression analysis, a more recent year of diagnosis, younger age, and high stage or grade were predictors of PET scan usage for patients with bladder cancer and RCC. A higher Gleason score and higher D'Amico risk group predicted imaging with prostate cancer. CONCLUSION: The usage of PET scanning for bladder cancer, prostate cancer, and RCC is increasing but still very selective. The selective use might be driven by a combination of reimbursement constraints and careful identification of the appropriate medical indication.


Asunto(s)
Neoplasias Renales/diagnóstico por imagen , Tomografía de Emisión de Positrones/tendencias , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Análisis Multivariante , Tomografía de Emisión de Positrones/estadística & datos numéricos , Programa de VERF
17.
Indian J Urol ; 31(4): 283-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26604438

RESUMEN

INTRODUCTION: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. METHODS: Articles were identified through a literature review of articles obtained through PubMed searches including the terms "bladder cancer" and various diagnostic techniques described in the article. RESULTS: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. CONCLUSIONS: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC.

19.
Clin Genitourin Cancer ; 13(3): e173-81, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25600760

RESUMEN

INTRODUCTION: Patients who undergo surgical treatment for malignancy often receive perioperative blood transfusion (PBT). We examined the association between PBT and mortality in patients who received surgical treatment of prostate, bladder, and kidney cancer. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare data set from 1992-2009, we identified 28,854 men with prostate cancer, 5462 patients with bladder cancer, and 14,379 patients with renal cell carcinoma who underwent radical prostatectomy (RP), radical cystectomy (RC), or radical (RN) or partial nephrectomy (PN) as primary therapy. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: The rate of PBT in bladder and kidney cancer have been increasing over time, and PBT in prostate cancer steadily increased and peaked in 2002 and declined afterward. The median follow-up for the RP, RC, and RN/PN cohorts were 70 months, 21 months, and 39 months, respectively. In the RP cohort, PBT was associated with greater CSM (hazard ratio [HR], 1.609; 95% confidence interval [CI], 1.235-2.097; P = .0004) and ACM (HR, 1.121; 95% CI, 1.006-1.251; P = .0394). In the RC cohort, PBT was not associated with greater CSM (HR, 1.047; 95% CI, 0.917-1.195; P = .4962) or ACM (HR, 1.095; 95% CI, 0.998-1.200; P = .0547). In the nephrectomy cohort, PBT was associated with greater CSM (HR, 1.365; 95% CI, 1.167-1.597; P = .0001) and ACM (HR, 1.402; 1.273-1.544; P < .0001). CONCLUSION: PBT was associated with increased CSM and ACM for prostate and kidney cancer in a multivariate model. Although these data do not identify a causative relationship between PBT and mortality, efforts made to limit PBT in patients who undergo urologic cancer surgery can yield long-term survival benefits.


Asunto(s)
Transfusión Sanguínea/mortalidad , Neoplasias Renales/cirugía , Neoplasias de la Próstata/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Humanos , Neoplasias Renales/sangre , Neoplasias Renales/mortalidad , Masculino , Atención Perioperativa , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Factores de Riesgo , Programa de VERF , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/mortalidad
20.
Nat Rev Clin Oncol ; 11(6): 354-64, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24821211

RESUMEN

The incidence of prostate cancer increases with age. Current evidence suggests that prostate cancer is under treated in patients aged ≥70 years, despite evidence of efficacy and acceptable toxicity. Radical cystectomy and definitive radiotherapy are often denied owing to fears of post-operative complications and radiotherapy-associated gastrointestinal and genitourinary toxicity. However, modern radical prostatectomy techniques provide excellent clinical outcomes with low perioperative morbidity. Moreover, volume-restricted intensity-modulated radiation therapy is a significant improvement over previous 2D conformal radiotherapy with similar efficacy and lower toxicity. Androgen-deprivation therapy is also under-prescribed among the elderly, owing to concerns of increases in cardiac deaths and osteoporosis acceleration. However, prospective trials have not identified any increase in cardiovascular mortality among elderly men receiving androgen-deprivation therapy compared to age-matched controls. Most patients on androgen deprivation eventually progress to a castration-resistant state. At this stage, the disease still responds to newer agents that target the androgen pathway and to chemotherapy. Among the elderly, chemotherapy is under-prescribed even though it has been demonstrated to be palliative and improve survival. We describe the trends in prostate cancer management in the elderly and the importance of assessing comorbidity status, tumour characteristics, and health status, including a complete geriatric evaluation, before making treatment recommendations.


Asunto(s)
Neoplasias de la Próstata/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Incidencia , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Factores de Riesgo
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