Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

The role of sentinel lymph node status performed in melanoma patients with local recurrence or in transit metastasis

BackgroundSentinel Node Biopsy (SNB) is routinely performed for primary melanoma, but its role in the treatment of Local Recurrence (LR) and In-Transit metastasis (IT) is controversial. This study aims to assess the role of SNB in melanoma patients who developed first loco-regional recurrence.MethodsA series of consecutive melanoma patients who received SNB for a first IT or LR at the National Cancer Institute of Milan, Italy, from 2000 to 2015 were selected from a prospective database. Clinicopathological characteristics were analyzed.ResultsSeventy-two patients met selection criteria. Forty-three patients (59.7%) received SNB for LR and 29 (40.3%) for IT. The average interval between treatment of primitive melanoma and first recurrence diagnosis was 19 months (interquartile range: 6.9–49.0). SN identification rate was 97.2%. SN positivity was detected in 26 (37.1%) patients. The SN-positive ratein melanoma patients who had LR or IT was significantly higher than reported for primary tumours. Of patients with nodal involvement 17 had LR and 9 IT lesions. Disease Free Survival (DFS) was slightly higher in SN negative patients, in the absence of statistically significant differences. Overall Survival (OS) analysis showed similar values in the two groups.ConclusionSince DFS and OS do not show significant differences between SN negative and positive patients, our data do not give clear indications about performing SNB in case of first LR or IT. However, we suggest submitting patients with LR to this procedure to obtain a more accurate staging and eventually candidate these patients to adjuvant treatment.     

柴胡皂苷D通过诱导自噬抑制人结直肠癌细胞SW480增殖的实验

目的:研究柴胡皂苷D（saikosaponin-D，SSD）对人结直肠癌细胞SW480自噬的影响，并探讨诱导的自噬对细胞增殖的影响。方法:Western-blot检测SSD对自噬相关蛋白LC3A/B和p62表达的影响，LC3翻转实验和GFP-RFP-LC3荧光实验验证自噬流的发生。Western-blot检测3-MA对SSD所诱导自噬的抑制作用，MTT和细胞计数实验研究3-MA抑制自噬后SSD对SW480细胞增殖的影响。结果:SSD能够诱导SW480细胞发生自噬，表现在LC3A/B II及LC3A/B II/I比值的增高、自噬经典底物蛋白p62的减少、LC3翻转试验阳性以及LC3荧光实验中黄色和红色荧光颗粒的增多（P＜0.05）。自噬抑制剂3-MA能够抑制SSD所诱导自噬的发生（P＜0.05），且3-MA抑制自噬后，SSD对SW480的增殖抑制效应减弱（P＜0.05），提示SSD诱导的自噬对细胞的增殖起抑制作用。结论:SSD通过诱导自噬抑制人结直肠癌细胞SW480的增殖。     

Prognostic value of circulating tumor cells and immune-inflammatory cells in patients with renal cell carcinoma

PurposeThe relationships among circulating tumor cells (CTCs), inflammatory cells, and platelets in patients with renal cell carcinoma (RCC) are not transparent. We evaluated the correlations among CTCs, blood inflammatory cells, and platelets in patients with RCC and their prognostic value for metastasis-free survival.MethodsCTC and typical tumor cell chip data were collected and analyzed by the GEO database. The baseline data, survival data, CTCs data, and blood test results were statistically analyzed.ResultsBioinformatics analysis showed that the function of the differentially expressed genes between CTCs and normal tumor cells mainly involved platelets and immune inflammation. A total of 82 patients whose follow-up time was 3 to 68 months were included in the analysis. Clinical data of the patients confirmed that there is a correlation between platelets and mesenchymal CTCs. Simultaneously, there was a correlation between immune inflammatory cells and platelets. The univariate Cox proportional hazards model indicated that staging, mesenchymal CTCs, and the monocyte-to-neutrophil ratio (MNR) had prognostic value. The multivariate Cox proportional hazards model indicated that staging and the MNR had prognostic value and high accuracy.ConclusionsBioinformatics analysis showed that CTCs were related to platelets and immune-inflammatory cells. Furthermore, the clinical data confirmed that platelets were correlated with mesenchymal CTCs and immune-inflammatory cells in the blood. By using mesenchymal CTCs, the MNR, or staging respectively, it is possible to predict the risk of postoperative metastasis in RCC patients. As a compound prognostic factor, staging, and the MNR can provide more convenient and accurate condition monitoring.     

Definición de continencia y factores pronósticos para la recuperación temprana de la continencia urinaria en la prostatectomía radical robótica con reconstrucción posterior del rabdoesfínter. Análisis post hoc de un ensayo clínico aleatorizado

IntroductionUrinary incontinence after radical prostatectomy (RP) is an adverse event with high impact on patient's quality of life. Nowadays there is no standardized method for urinary continence measurement. Posterior rhabdosphincter reconstruction (PRR) is a surgical step that can improve early urinary continence after RP. Our objective was to analyse different continence definitions and predictors of urinary continence recovery after robot-assisted RP (RARP).Materials and methodsWe conducted a double-blind, randomised controlled trial (NCT03302169) including 152 consecutive patients with localized prostate cancer subjected to RARP. Patients were randomised to single urethrovesical anastomosis (control arm) or PRR before urethrovesical anastomosis (PRR arm). Urinary continence was measured with the EPIC-26 and ICIQ-SF validated questionnaires, and pad use (0-1 pads and no pads), at 7, 15, 30, 90, 180 and 365 days after catheter removal. Prognostic factors for early urinary continence recovery were analysed.Results72 patients were included in the control arm and 80 in the PRR arm. Baseline characteristics were similar between arms, except body mass index, which was higher in PRR arm. “No pad” was the only definition assessing the benefit of PRR at 30 days, 33.8% in PRR arm and 18.1% in control arm, p = 0.022; and at 90 days, 58.8 and 43.1% respectively, p = 0.038. Questionnaires did not detect differences in terms of continence recovery. PRR was the only predictor for early continence recovery, p = 0.03.ConclusionsPRR increased early urinary continence recovery after RARP. Continence definition was critical to assess benefit. The only predictive factor for early continence recovery was PRR.     

Removal of Numerous Vesical Magnetic Beads with a Self-Made Magnetic Sheath

IntroductionSexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies.AimThe aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made “magnetic sheath.”MethodsA 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way.Main Outcome MeasureThe feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration.ResultsUnder direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath.ConclusionsThe self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation. Zeng S-X, Li H-Z, Zhang Z-S, Lu X, Yu X-W, Yang Q-S, Ma C, Xu C-L, and Sun Y-H. Removal of numerous vesical magnetic beads with a self-made magnetic sheath. J Sex Med 2015;12:567–571.     

The Prevalence and the Risk Factors of Testosterone Deficiency in Newly Diagnosed and Previously Known Type 2 Diabetic Men

IntroductionWhile the epidemiology of testosterone deficiency has been well described in men with previously known type 2 diabetes mellitus (T2DM), it was less reported in those with untreated, newly diagnosed T2DM.AimThe aim of this study was to investigate the prevalence and the risk factors of testosterone deficiency of men with newly diagnosed T2DM.MethodsThe cross-sectional study included 105 men (mean age: 61.2 ± 6.8 years) with previously known T2DM and another 81 (57.8 ± 8.8 years) with newly diagnosed T2DM. All received health checkup and sex hormone measurement at our institute in 2009.Main Outcome MeasuresWe calculated the prevalence and explored the risk factors of low total (<300 ng/dL) and free (<6 ng/dL) testosterone in men with newly diagnosed and previously known T2DM.ResultsMen with previously known T2DM were older and had higher diastolic pressure and greater fasting glucose. There was no significant difference in total (358.0 [155.0] ng/dL vs. 363.0 [154.0] ng/dL, P = 0.68) and free (7.2 [2.5] ng/dL vs. 7.4 [2.4] ng/dL, P = 0.84) testosterone and sex-hormone binding globulin (SHBG) (27.3 [22.3] nmol/L vs. 28.7 [14.9] nmol/L, P = 0.46). The prevalence of low total and free testosterone was 28.4% and 21.0%, respectively, in men with newly diagnosed T2DM, and was 26.7% and 19.0% in those with previously known T2DM. In men with previously known T2DM, better glycemic control (HbA1c <7%) was associated with a higher level of total testosterone and a lower risk of low total testosterone. Men with newly diagnosed and previously known T2DM shared similar risk factors of low total testosterone, including high HbA1c (≥7%), low SHBG (<20 nmol/L), obesity, hyperuricemia, hypertriglycemia, and metabolic syndrome. Elevated prostate-specific antigen was a protective factor of low total testosterone. However, none of these factors was associated with low free testosterone.ConclusionsThe prevalence and the risk factors of testosterone deficiency are similar between newly diagnosed and previously known type 2 diabetic men. Ho C-H, Jaw F-S, Wu C-C, Chen K-C, Wang C-Y, Hsieh J-T, Yu H-J, and Liu S-P. The prevalence and the risk factors of testosterone deficiency in newly diagnosed and previously known type 2 diabetic men. J Sex Med 2015;12:389–397.