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BACKGROUND: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. METHODS: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). RESULTS: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. CONCLUSIONS: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.
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PURPOSE: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients. MATERIALS AND METHODS: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score. RESULTS: A total of 51 and 55 patients underwent focal and extended irreversible electroporation, respectively. The median follow-up time was 30 months. Rates of erectile dysfunction and rates of adverse events were similar between the 2 groups at 3 months. The focal ablation group seemed to have better International Index of Erectile Function scores at 3 months; it also had a better Expanded Prostate Cancer Index Composite-sexual function score than the extended ablation group across time that was close to statistical significance (mean difference 1.4; 95% CI -0.13 to 2.9, P = .073). There were no significant differences between the 2 groups in other quality-of-life measures. Upon prostate biopsy at 6 months, the rate of residual clinically significant prostate cancer (Gleason ≥3 + 4) was 18.8% and 13.2% in the focal and extended irreversible electroporation groups, respectively, without significant differences. CONCLUSIONS: Focal and extended irreversible electroporation ablation had similar safety profile, urinary function, and oncologic outcomes in men with localized low-intermediate risk prostate cancer. In addition, focal ablation demonstrated superior erectile function outcome over extended irreversible electroporation in the first 3-6 months.
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Disfunción Eréctil , Neoplasias de la Próstata , Masculino , Humanos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Calidad de Vida , Método Simple Ciego , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Electroporación , Resultado del TratamientoRESUMEN
PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Próstata/patología , Antígeno Prostático Específico/análisis , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
BACKGROUND AND AIMS: EUS-guided gallbladder drainage (EUS-GBD) is a safe alternative to percutaneous cholecystostomy (PT-GBD) for acute cholecystitis. How the procedure compares with laparoscopic cholecystectomy (LC) is uncertain. The aim of the current study is to compare the outcomes of EUS-GBD with LC for acute cholecystitis. METHODS: This was propensity score analysis of all patients admitted for acute cholecystitis between 2012 and 2018. Consecutive patients who received EUS-GBD or LC were included. Patients were matched for age, sex, and age-adjusted Charlson score. Outcome measurements included 30-day adverse events, mortality, recurrent cholecystitis, recurrent biliary events, reinterventions, and readmissions. RESULTS: During the study period, 60 patients were selected (30 EUS-GBD vs 30 LC) after propensity score matching. Technical success rates (100% vs 100%), clinical success rates (93.3% vs 100%, P = 1), lengths of hospital stay (6.8 [8.1] vs 5.5 [2.7], P = 1), 30-day adverse events (4 [13.3%] vs 4 [13.3%], P = 1), and mortality rates (2 [6.7%] vs 0 [0%], P = .492) were similar. The rates of recurrent biliary events (3 [10%] vs 3 [10%], P = .784), reinterventions (4 [13.3%] vs 3 [10%], P = 1), and unplanned readmissions (3 [10%] vs 3 [10%], P = .784) in 1 year were also similar. CONCLUSIONS: The outcomes of EUS-GBD for acute cholecystitis were comparable with LC with acceptable rates of recurrent acute cholecystitis. These results support the role of EUS-GBD as an alternative to LC in patients who may or may not be surgically fit to undergo definitive cholecystectomy.
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Colecistectomía Laparoscópica , Colecistitis Aguda , Colecistitis Aguda/cirugía , Drenaje , Estudios de Seguimiento , Vesícula Biliar/cirugía , Humanos , Puntaje de Propensión , Resultado del TratamientoRESUMEN
OBJECTIVE: The optimal management of acute cholecystitis in patients at very high risk for cholecystectomy is uncertain. The aim of the current study was to compare endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) to percutaneous cholecystostomy (PT-GBD) as a definitive treatment in these patients under a randomised controlled trial. DESIGN: Consecutive patients suffering from acute calculous cholecystitis but were at very high-risk for cholecystectomy were recruited. The primary outcome was the 1-year adverse events rate. Secondary outcomes include technical and clinical success, 30-day adverse events, pain scores, unplanned readmissions, re-interventions and mortalities. RESULTS: Between August 2014 to February 2018, 80 patients were recruited. EUS-GBD significantly reduced 1 year adverse events (10 (25.6%) vs 31 (77.5%), p<0.001), 30-day adverse events (5 (12.8%) vs 19 (47.5%), p=0.010), re-interventions after 30 days (1/39 (2.6%) vs 12/40 (30%), p=0.001), number of unplanned readmissions (6/39 (15.4%) vs 20/40 (50%), p=0.002) and recurrent cholecystitis (1/39 (2.6%) vs 8/40 (20%), p=0.029). Postprocedural pain scores and analgesic requirements were also less (p=0.034). The technical success (97.4% vs 100%, p=0.494), clinical success (92.3% vs 92.5%, p=1) and 30-day mortality (7.7% vs 10%, p=1) were statistically similar. The predictor to recurrent acute cholecystitis was the performance of PT-GBD (OR (95% CI)=5.63 (1.20-53.90), p=0.027). CONCLUSION: EUS-GBD improved outcomes as compared to PT-GBD in those patients that not candidates for cholecystectomy. EUS-GBD should be the procedure of choice provided that the expertise is available after a multi-disciplinary meeting. Further studies are required to determine the long-term efficacy. TRIAL REGISTRATION NUMBER: NCT02212717.
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Colecistitis Aguda/cirugía , Colecistostomía/métodos , Drenaje/métodos , Vesícula Biliar/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Vesícula Biliar/diagnóstico por imagen , Humanos , Masculino , Resultado del Tratamiento , Ultrasonografía IntervencionalAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Máscaras , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Opinión Pública , COVID-19 , Infecciones por Coronavirus/epidemiología , Conductas Relacionadas con la Salud , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2RESUMEN
Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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BACKGROUND AND OBJECTIVE: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). The objective of this study is to investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. METHODS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤ 3cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. KEY FINDINGS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1- yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with NMIBC of ≤ 3cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR. The study results support ERBT as the first-line surgical treatment for patients with bladder tumours of≤ 3cm.
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Cistectomía , Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Anciano , Cistectomía/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Uretra/cirugía , Factores de TiempoRESUMEN
OBJECTIVE: This population-based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)-related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). METHODS: Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa-related mortality. RESULTS: Altogether, 4126 patients (median follow-up 3.1[interquartile range 1.4-6.0] years) were included. A J-shaped association was observed between baseline UA level and PCa-related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above-mean baseline UA levels (hazard ratio (HR) per standard deviation-increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below-mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. CONCLUSIONS: A J-shaped relationship between baseline UA level and PCa-related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.
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Neoplasias de la Próstata , Masculino , Adulto , Humanos , Ácido Úrico , Antagonistas de Andrógenos/efectos adversos , Andrógenos , Estudios de CohortesRESUMEN
PURPOSE: 5-alpha reductase inhibitor (5ARI) reduces prostate-specific antigen (PSA) by half but its effect on prostate health index (phi) is unknown. This study aims to investigate this effect and to enable accurate interpretation of phi in men with elevated PSA and on 5ARI. METHODS: This is a prospective study evaluating the effect of finasteride on PSA, free PSA (fPSA), [ - 2]proPSA (p2PSA) and phi at 6 and 12 moths in men with PSA 4-20 ng/mL, no prior 5ARI use, and one negative prostate biopsy within 6 months before recruitment. The 5ARI Finasteride (5 mg/day) for 1 year was offered if International Prostatic Symptom Score (IPSS) was ≥ 8 at baseline. 5ARI group included patients taking finasteride, while control group included patients not on finasteride. The blood results were compared with t-test between baseline and different time points in each group and between groups at 1 year. RESULTS: 164 men fit the inclusion criteria and 150 were analyzed. In 5ARI group (n = 100) at 1 year, mean PSA reduced by 51.4% from 8.9(± SD 3.7) to 4.4(± SD 2.8)ng/mL (paired t-test, p < 0.001), fPSA reduced by 52.4% from 1.6(± 0.6) to 0.8(± 0.4)ng/mL (p < 0.001), p2PSA reduced by 55.3% from 18.4(± 8.8) to 8.3(± 5.6)pg/mL (p < 0.001), and phi reduced by 34.2% from 33.7(± 11.9) to 22.4(± 12.5) (p < 0.001). PSA and phi values in the control group remained static over 1 year and significantly higher than those in 5ARI group. CONCLUSION: This study demonstrated p2PSA and phi are reduced by about 55% and 34% in men on 5ARI. A conversion factor of division by 0.66 is needed for phi in men on finasteride to allow the interpretation and use of phi in men on 5ARI.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Finasterida/farmacología , Finasterida/uso terapéutico , Neoplasias de la Próstata/patología , Próstata/patología , Estudios ProspectivosRESUMEN
BACKGROUND: While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients. METHODS: Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups. RESULTS: In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3-21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59-0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42-0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33-0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59-0.85], p < 0.001). CONCLUSION: Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.
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BACKGROUND: To investigate the value of machine learning(ML) in enhancing prostate cancer(PCa) diagnosis. METHODS: Consecutive systematic prostate biopsies performed from Jan 2003-June 2017 were used as the training cohort, and prospective biopsies performed from July 2017-November 2019 were used as validation cohort. Men were included if PSA was 0.4-50 ng/mL, and information of digital rectal examination (DRE), Transrectal ultrasound(TRUS) prostate volume, TRUS abnormality were known. Clinically significant PCa(csPCa) was defined as Gleason 3 + 4 or above cancers. Area-under-curve (AUC) of receiver-operating characteristics (ROC) was compared between PSA, PSA density, European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (ERSPC-RC), and various ML techniques using PSA, DRE and TRUS information. ML techniques used included XGBoost, LightGBM, Catboost, Support vector machine (SVM), Logistic regression (LR), and Random Forest (RF), where cost sensitive learning was applied. RESULTS: Training and validation cohorts included 3881 and 778 consecutive men, respectively. RF model performed better than other ML techniques and PSA, PSA density and ERSPC-RC for prediction of PCa or csPCa in the validation cohort. In csPCa prediction, AUC of PSA, PSA density, ERSPC-RC and RF was 0.71, 0.80, 0.83 and 0.88 respectively. At 90-95% sensitivity for csPCa, RF model achieved a negative predictive value (NPV) of 97.5-98.0% and avoided 38.3-52.2% unnecessary biopsies. Decision curve analyses (DCA) showed RF model provided net clinical benefit over PSA, PSA density and ERSPC-RC. CONCLUSION: By using the same clinical parameters, ML techniques performed better than ERSPC-RC or PSA density in csPCa predictions, and could avoid up to 50% unnecessary biopsies.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Estudios Prospectivos , Medición de Riesgo/métodos , Biopsia/métodos , Aprendizaje Automático , AlgoritmosRESUMEN
BACKGROUND: Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. This study aims to investigate the role of initial phi and phi density in predicting future PCa risk in men with initial negative biopsy. METHODS: Five hundred sixty nine men with PSA 4-10 ng/mL were recruited between 2008 and 2015 for prostate biopsy with prior phi. Electronic clinical record of men with initial negative biopsy was reviewed. Patients and follow-up doctors were blinded to phi. Kaplan-Meier curves were used to analyze the PCa-free survival in different baseline phi and phi density groups. RESULTS: Four hundred sixty-one men with complete follow-up data were included. Median follow-up is 77 months. PCa and HGPCa was diagnosed in 8.2% (38/461) and 4.8% (22/461) of cohort respectively. A higher baseline phi value was associated with PCa (p = 0.003) and HGPCa (p < 0.001). HGPCa was diagnosed in 0.6% (1/163) of phi < 25, 4.6% (9/195) of phi 25-34.9, and 11.7% (12/103) of phi ≥ 35 (p < 0.001). HGPCa was diagnosed in 0% (0/109) and 21.0% (13/62) with phi density of <0.4 and ≥1.2, respectively, (p < 0.001). Kaplan-Meier curves showed phi and phi density predicted PCa and HGPCa diagnoses (log-rank test, all p ≤ 0.002). CONCLUSIONS: Initial phi or phi density predicted 6-year risk of PCa in men with initial negative prostate biopsy. Men with higher phi (≥35) or phi density (≥1.2) need closer follow-up and repeated investigation, while men with lower phi (<25) or phi density (<0.4) could have less frequent follow-up.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Estudios de Seguimiento , BiopsiaRESUMEN
BACKGROUND: Patients with metastatic HER2/neu-positive (HER2/neu +) breast cancer (BC) often experience treatment resistance, disease recurrences and metastases. Thus, new approaches for improving the treatment of HER2/neu + BC to prevent metastatic dissemination are urgently needed. Our previous studies have shown that losartan, an angiotensin receptor blocker, increases tumor perfusion and decreases hypoxia in a number of tumor models. Hypoxia reduces the efficacy of radiation and increases metastases. We therefore hypothesized that by modifying tumor stroma and increasing oxygenation, losartan will improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2/neu + murine BC model. METHODS: We established a metastatic HER2/neu + murine BC line (MCa-M3C) and used it to generate mammary fat pad isografts in syngeneic female FVB/N mice. Starting on day 3 after orthotopic tumor implantation, we administered a 7-day losartan treatment (40 mg/kg BW, gavage daily); or a 7-day losartan treatment followed by 20 Gy single dose local irradiation (S-IR) on day 10 (tumor size ~ 100 mm3), or 20 Gy local fractionated (5 × 4 Gy daily) irradiation (F-IR) on days 10-14. We analyzed tumor-growth delay (TGD), development of spontaneous lung metastases, animal survival, tumor vascular density, and tumor hypoxia. RESULTS: Treatments with S-IR, F-IR, Losartan + S-IR, or Losartan + F-IR resulted in a significantly increased TGD (8-16 days) in MCa-M3C tumors versus controls. However, the combination of Losartan + S-IR and Losartan + F-IR further enhanced tumor response to radiation alone by increasing TGD an additional 5 to 8 days for both single and fractionated dose irradiation (P < 0.01), decreasing lung metastasis (Losartan + IR vs. Control, P < 0.025), and increasing animal survival (Losartan + IR vs. Control, P = 0.0303). In addition, losartan treatment significantly increased tumor vascularity (P = 0.0314) and decreased pimonidazole positive (hypoxic) area (P = 0.0002). CONCLUSIONS: Combining losartan with local irradiation significantly enhanced tumor response, at least in part via reduced tumor hypoxia presumably due to increased tumor perfusion. Our findings suggest that combining losartan with radiotherapy is a potential new treatment strategy for local control and inhibiting metastasis in HER2 + BC.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Losartán/uso terapéutico , Neoplasias Pulmonares/prevención & control , Neoplasias Mamarias Experimentales/terapia , Animales , Quimioradioterapia , Femenino , Neoplasias Pulmonares/secundario , Neoplasias Mamarias Experimentales/patología , Ratones , Dosificación Radioterapéutica , Receptor ErbB-2/genética , Tasa de Supervivencia , Resultado del Tratamiento , Células Tumorales Cultivadas , Hipoxia Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: To investigate the role of urine spermine and Spermine Risk Score in prediction of high-grade prostate cancer (HGPCa, ISUP grade group ≥2). METHODS: Nine hundred and five consecutive men with elevated PSA were prospectively recruited from two hospitals. Core analyses focused on consecutive men with PSA 4-20 ng/mL (n = 600). Pre-biopsy urine without prior prostatic massage was analyzed for spermine level with ultra-high performance liquid chromatography with triple quadrupole mass spectrometer (UPLC-MS/MS). The proportions of PCa and HGPCa were compared across different spermine ranges. Logistic regressions were used to form different models, and their performances were compared using area under curve (AUC) and decision curve analysis (DCA). RESULTS: PCa and HGPCa were diagnosed in 30.8% (185/600) and 17.2% (103/600) men, respectively, and were significantly associated with lower urine spermine levels. Between the lowest and highest quartiles of spermine results, a threefold increase in PCa risk (49.3% vs. 16.7%) and 3.5-fold increase in ISUP grade group ≥2 PCa risk (31.3% vs. 8.7%) were observed. Multivariate analysis showed PSA, prostate volume (PV), digital rectal examination (DRE), and spermine, which were independent predictors for PCa and HGPCa, and a Spermine Risk Score with these factors achieved the highest AUC of 0.78 for PCa and 0.82 for HGPCa. At 90% sensitivity for HGPCa, 36.7% biopsies and 24.4% ISUP grade group 1 diagnoses could have been avoided, with a negative predictive value of 95.4%. DCA revealed net clinical benefit of the Spermine Risk Score. Internal validation with bootstrapping showed good discrimination and calibration. CONCLUSION: Urine spermine and Spermine Risk Score identified men at higher risk of HGPCa and reduced unnecessary biopsies.
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Biomarcadores de Tumor/orina , Neoplasias de la Próstata/patología , Medición de Riesgo/métodos , Espermina/orina , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estudios Prospectivos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/orina , Curva ROC , Factores de RiesgoRESUMEN
BACKGROUND: To investigate the feasibility of a freehand transperineal (TP) systematic prostate biopsy protocol under local anaesthesia (LA) and the value of different sectors in diagnosing prostate cancer (PCa). METHODS: A total of 611 consecutive freehand TP biopsies under LA in 2 hospitals were prospectively evaluated. Cancer detection rate in each of the four different sectors (anterior, mid, posterior, basal) was recorded to evaluate the value of each sector. Procedure tolerability was assessed by pain score and complications were documented. RESULTS: Systematic biopsies were performed in 556 out of 611 men with a median of 20 (IQR 12-24) biopsy cores taken. The median PSA was 9.9 (Inter-quartile range[IQR] 6.4-16.2) ng/mL, and 89.0% were first biopsies. All PCa and ISUP grade group (GG) ≥ 2 PCa (HGPCa) were diagnosed in 41.4% (230/556) and 28.2% (157/556) biopsies respectively. 77.0% HGPCa was diagnosed in ≥2 sectors. Single-sector HGPCa was predominantly found in anterior or posterior sector. Omitting base sector would have missed 1.5% (1/65) HGPCa out of the 219 cases with ≥24-core biopsies performed. Further omission of mid sector would have missed 3.1% (2/65) HGPCa and 7.4% (7/94) ISUP GG1 PCa (in which 3/7 involved 2 sectors). LA TP biopsy was well tolerated and the mean pain scores of the different steps of the procedure were between 1.9-3.1 (out of 10). Post-biopsy fever occurred in 0.3% of patients (2/611) and no sepsis was reported. The risk of urinary retention in men with ≥20 cores in ≥60 ml prostate was 7.8% (14/179), compared with 1.7% (7/423) in other groups (p < 0.001). CONCLUSIONS: TP sectoral prostate biopsy under LA was well tolerated with minimal sepsis risk. Basal sector biopsies had minimal additional value to HGPCa detection and its omission can be considered.
Asunto(s)
Anestesia Local/métodos , Biopsia con Aguja/instrumentación , Perineo/patología , Próstata/patología , Neoplasias de la Próstata/patología , Anciano , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Biopsia Guiada por Imagen , Masculino , Persona de Mediana Edad , Perineo/cirugía , Pronóstico , Estudios Prospectivos , Próstata/cirugía , Neoplasias de la Próstata/cirugíaRESUMEN
BACKGROUND: Little is known about the key composition of a successful tweet in urology. OBJECTIVE: To investigate for predictors of engagement with urology content on Twitter. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study based on 2-wk Twitter data surrounding a major international urology conference. INTERVENTION: We examined the engagement for all original tweets containing the hashtags for the European Association of Urology conference ("#EAU19" and/or "#EAU2019"). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Study outcomes included engagement with tweets, as measured by the number of "likes" and "retweets." Tweet- and Twitter user-related parameters of each individual tweet were recorded. Multiple linear regression analyses were performed to investigate for predictors of likes and retweets. RESULTS AND LIMITATIONS: From March 9 to 22, 2019, there were a total of 37 222 tweets. Among them, 3534 were "original tweets" that had 31 889 likes and 10 031 retweets. On multivariable analysis, the word count, number of mentions, and presence of a photo were predictors of likes and retweets. An increasing number of hashtags were associated with fewer likes. The number of "followings" and "followers" of the contributor, and their time since joining Twitter did not have any associations with the number of likes or retweets. The major limitation of the study is the lack of assessment about the quality of the tweet content. CONCLUSIONS: Based on the Twitter data from a urology conference, we concluded that the word count, number of mentions, and presence of a photo within the tweet were associated with audience engagement. PATIENT SUMMARY: We could engage the audience more successfully by increasing the number of words and mentions, and including a photo within a tweet. The results formulated the basic principles in creating successful tweets for sharing urological knowledge.
Asunto(s)
Medios de Comunicación Sociales/estadística & datos numéricos , Urología , Congresos como Asunto , Estudios TransversalesRESUMEN
BACKGROUND: Prostate-specific antigen (PSA) and prostate health index (PHI) have been used as biomarkers for prostate cancer detection. In this study, we aimed to evaluate the cost-effectiveness of PHI for prostate cancer detection in Chinese men. METHOD: We developed a Markov model for Chinese male patient aged 50-75 years old. The PSA strategy was to offer TRUS-PB for all patients with elevated PSA of 4-10 ng/mL. The PHI strategy was to offer PHI for patients with elevated PSA of 4-10 ng/mL. TRUS-PB would only be offered for patients with PHI >35.0. Model inputs were extracted from local data when available. The cost per quality-adjusted life years gained for both strategies were calculated. The incremental cost-effectiveness ratios in relation to the willingness-to-pay (WTP) threshold were compared. One-way sensitivity analysis and probabilistic sensitivity analysis were performed. Cost-effectiveness acceptability curves were also constructed. RESULTS: With a Markov model of 25 screening cycles from age 50 to 75 years, the mean total costs per man were estimated to be USD 27,439 in the PSA strategy and USD 22,877 in the PHI strategy. The estimated effects were estimated to be 15.70 in the PSA strategy and 16.05 in the PHI strategy. The PHI strategy was associated with an expected decrease in cost of USD 4562 and an expected gain of 0.35 QALY, resulting in an ICER of USD -13056.56. The results were shown to be robust upon one-way sensitivity analysis. Upon Monte Carlo simulation, the PHI strategy was more cost-effective for 100% of the iterations. The PHI strategy demonstrated dominance over the PSA strategy regardless of what WTP threshold we use. CONCLUSIONS: A PHI-based screening strategy may be more cost-effective than a PSA-based strategy for prostate cancer detection in Chinese men. These results support consideration of a PHI-based approach for prostate cancer in Hong Kong.