Far from the truth: Real-world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification.

OBJECTIVES: Real-world uptake of treatment intensification (TI) with novel hormonal agents (NHA) or chemotherapy as treatment of metastatic prostate cancer remains low outside of trial settings. We aim to report the prescription patterns and treatment outcomes of de novo metastatic hormone-sensitive prostate cancer (mHSPC) in a tertiary institution. METHODS: This is a retrospective cohort study using real-world data from a prospectively maintained prostate cancer registry. We selected patients newly diagnosed with mHSPC from January 2016 to December 2020. Clinicopathological parameters were recorded to determine their impact on prescription patterns. RESULTS: In total, 585 patients with metastatic prostate cancer were identified. Prescription of NHA increased from 10.5% (2016) to 50.4% (2020), but that of chemotherapy declined. Factors associated with TI were (1) baseline health status: Charlson Comorbidity Index 0-2, ECOG 0-1, age ≤ 65, (2) disease burden: PSA (>400, CHAARTED high volume disease, p = 0.004), development of systemic complications and (3) physician factor: primary physician being uro-oncologist and medical oncologist versus general urologist. Patients with TI had a longer mean time to castration-resistant prostate cancer (45.0 vs. 32.5 months, HR 0.567, 95% CI: 0.441-0.730, p < 0.001) and overall survival (55.3 vs. 46.8 months, HR 0.612, 95% CI, 0.447-0.837, p = 0.001). CONCLUSION: This study demonstrated the trend of treatment prescription of mHSPC and factors contributing to the use of TI. TI improved mean time to CRPC and OS.

Intravesical Bacillus Calmette-Guerin and its complications: 12 years of learning experience in a single local institution.

INTRODUCTION: Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population. METHODS: This retrospective study was conducted using a large, prospectively maintained bladder cancer database. 336 patients received intravesical BCG therapy for bladder cancer in our institution between 2004 and 2016, with an average follow-up duration of 63 months. RESULTS: The study included 258 (76.8%) male and 78 (23.2%) female patients. The median age of the patients at diagnosis of bladder cancer was 69 (range 17-94) years, and the median number of BCG instillations was 6 (range 1-27). 52 (15.5%) patients received maintenance therapy. The most common complications included urinary tract infection with/without sepsis (n = 18, 5.4%), haematuria (n = 9, 2.7%) and acute urinary retention (n = 4, 1.2%). 93.3% of the patients with complications presented early, within one month of completion of therapy. 22 out of 30 complications were Clavien-Dindo grade ≤ 2. 10 (33.3%) patients were admitted to hospital because of BCG-related adverse effects. The most common reasons for termination were urosepsis (2/30, 6.7%) and acute urinary retention (2/30, 6.7%). Patients aged ≥ 80 years at diagnosis were at higher risk of developing BCG-related complications (19.0% vs. 7.5%, p = 0.01). CONCLUSION: This retrospective cohort and subgroup study showed that intravesical BCG therapy is well tolerated and has a low incidence of complications even in the elderly and patients with multiple comorbidities.

Clinicopathological features of non-conventional renal cell carcinoma histological subtypes: Learning points from a large contemporary series spanning over three decades.

PURPOSE: To perform a retrospective review of the clinicopathological features of patients with conventional and non-conventional renal cell carcinoma (cRCC and ncRCC). MATERIALS AND METHODS: A large prospectively maintained uro-oncological registry was accessed to extract clinicopathological data of patients diagnosed with renal tumors who subsequently underwent nephrectomy from 1990-2019. Demographics and operative parameters were extracted. Analyses of overall survival (OS) and cancer-specific survival (CSS) were performed using the Kaplan-Meier method. Cox proportional-hazards analysis was used to identify risk factors which influenced survival. RESULTS: There were a total of 1,686 consecutive nephrectomies which was retrieved, with 1,286 cRCC and 400 ncRCC. The commonest ncRCC subtypes were papillary (n=198, 11.7%), clear cell papillary (n=50, 3.0%) and chromophobe (n=49, 2.9%) RCC. Kaplan-Meier estimates of OS were higher in cRCC (0.74; 95% confidence interval [CI], 0.71-0.78) than ncRCC (hazard ratio, 1.47; 95% CI, 1.16-1.87). Among individual subtypes, chromophobe RCC had the highest 5-year OS (0.90; 95% CI, 0.79-1.0). Among ncRCC subtypes, acquired cystic RCC demonstrated the highest association with end-stage renal failure and hypertension, with the highest CSS. MiT family translocation RCC had the youngest mean age at presentation (45.6±12.8 y) and excellent CSS. Factors associated with increased OS in the entire cohort included shorter operative time, partial nephrectomy and lower tumor stages. CONCLUSIONS: This study provides a comprehensive contemporary overview of ncRCCs which are yet poorly characterized, in comparison to cRCCs. Data from this study would contribute towards tailored patient counseling and healthcare resource planning.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

[Effects of Butylphthalide on the expressions of HMGB1 and RAGE in frontal lobe of rats after chronic sleep deprivation].

OBJECTIVE: To investigate the effects of Butylphthalide on the expressions of HMGB1 and RAGE in frontal lobe of rats after chronic sleep deprivation. METHODS: Chronic sleep deprivation and butylphthalide treatment was performed in Sprague Dawley(SD)rats and the rats were divided into three groups (n＝6): platform control group, chronic sleep deprivation group and chronic sleep deprivation + butylphthalide intervention group. Rats suffering chronic sleep deprivation were put in multiple platforms box for 18 h per day and sleep deprivation lasted for 28 days. Rats in butylphthalide intervention group were intraperitoneally injected with butylphthalide 100 mg/(kg·d) for 14 days after sleep deprivation. After collecting brains, high-mobility group box (HMGB1) and nuclear transcription factor kappB (NF-κB)p65 were detected by immunohistochemistry. The expression of HMGB1, silent information regulator of transcription 1 (SIRT1), receptor for advanced glycation end-products (RAGE) and NF-κB in frontal lobe were determinated by Western blot. RESULTS: Compared with platform control group, the expression levels of HMGB1, RAGE and nuclear NF-κB p65 were increased significantly, while the expression of SIRT1 was decreased siginificantly in frontal lobe of chronic sleep deprivation group (all P＜0.05). Compared with chronic sleep deprivation group, the expression levels of of HMGB1, RAGE and nuclear NF-κB p65 were decreased significantly, while the expression of SIRT1 was increased significantly in chronic sleep deprivation + butylphthalide intervention group (all P＜0.05). CONCLUSION: Butylphthalide can inhibit HMGB1/RAGE/NF-κB pathway in frontal lobe of rats after chronic sleep deprivation by changing the expression of HMGB1 and RAGE, and reducing the nuclear translocation of NF-κBp65.

Predictive value of neutrophil-to-lymphocyte ratio in diagnosis of early prostate cancer among men who underwent robotic transperineal prostate biopsy.

ABSTRACT: To evaluate the predicted value of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of early prostate cancer by using standardized Full blood count (FBC) performed within 4 weeks before biopsy and histology results from transperineal prostate biopsy (RTPB).Patients who underwent RTPB under general anesthesia (GA), at Urology Department, Singapore General Hospital between September 2006 and Febuary 2016 were retrospectively reviewed.NLR was calculated using full blood count (FBC) that was done as a pre-admission test before GA within 4 weeks before the biopsy. Statistical analyses were done to establish the correlation of NLR and different clinical parameters such as biopsy histology, pre-biopsy PSA, and prostate volume.A total of 652 patients who underwent RTPB for diagnostic purposes with a valid PSA level were included in this study. There was total of 409 (62.7%) benign histology and 243 (37.3%) prostate cancer. There was no significant difference in median NLR between the benign and prostate cancer group (2.00 vs 1.99; P = .29).In the subgroups analysis, there was also no significant difference of median NLR value in clinical significant cancer (defined as Gleason 3 + 4 and above) and benign histology group (NLR 2.00 vs 2.01, P = .41), as well as prostate cancer and benign group according to different pre-biopsy PSA levels: PSA (ug/l) < 4, 4 to 10, 10 to 20, and >20, respectively. (Median NLR 1.34 vs 1.76; 1.97 vs 1.97; 1.97 vs 2.18; 2.18 vs 1.98, P > .05). NLR is neither associated with prostate cancer using logestic regression model nor a strong predictor of the Gleason grade group and D'Amico risk stratification group using ordinal regression model. (P > .05)There was no statistically significant difference of NLR between the benign and prostate cancer group as a whole or in the subgroup analyses for patients who underwent robotic transperineal prostate biopsy. NLR may have a limited role in predicting early-stage prostate cancer.

Feasibility and utility of facemask sampling in the detection of SARS-CoV-2 during an ongoing pandemic.

Easy access to screening for timely identification and isolation of infectious COVID-19 patients remains crucial in sustaining the international efforts to control COVID-19 spread. A major barrier limiting broad-based screening is the lack of a simple, rapid, and cost-effective COVID-19 testing method. We evaluated the feasibility and utility of facemask sampling in a cohort of 42 COVID-19-positive and 36 COVID-19-negative patients. We used a prototype of Steri-Strips™ (3 M) applied to the inner surface of looped surgical facemasks (Assure), which was worn by patients for a minimum wear time of 3 h, then removed and sent for SARS-CoV-2 PCR testing. Baseline demographics and symptomatology were also collected. Facemask sampling positivity was highest within the first 5 days of symptomatic presentation. Patients with nasopharyngeal and/or oropharyngeal swab SARS-CoV-2 PCR Ct values < 25.09 had SARS-CoV-2 detected on facemask sampling, while patients with Ct values ≥ 25.2 had no SARS-CoV-2 detected on facemask sampling. Facemask sampling can identify patients with COVID-19 during the early symptomatic phase or those with high viral loads, hence allowing timely identification and isolation of those with the highest transmission risk. Given the widespread use of facemasks, this method can potentially be easily applied to achieve broad-based, or even continuous, population screening.

Serum testosterone levels and testosterone 'bounce' phenomenon predict response to novel anti-androgen therapies in castration-resistant prostate cancer.

BACKGROUND: The relevance of continuous testosterone (TT) monitoring in castration-resistant prostate cancer (CRPC) remains in question. OBJECTIVE: To determine if TT levels before and during novel anti-androgen therapies (NAAT), and the TT 'bounce' phenomenon may predict treatment response in CRPC. MATERIALS AND METHODS: From 2014 through 2018, we identified 92 CRPC patients treated with either Abiraterone or Enzalutamide from a prospectively maintained cancer registry. The TT levels measured before and during NAAT were correlated with the oncological outcomes, determined by PSA response (% change), PSA progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: At CRPC, 58 (63.0%) and 34 (37.0%) patients opted for Abiraterone and Enzalutamide respectively. Median TT levels at CRPC status before and during NAAT were 10.37 ng/dl and 20.46 ng/dl respectively. PSA response was superior in patients with a higher TT before NAAT (P:0.048, median difference: 18.22%, 95% CI 0.70 - 40.37) and longer time to CRPC (P: 0.041, median difference: 15.31%, 95% CI 1.84 -34.84), with a trend towards lower TT during NAAT (P: 0.062). Over a follow up of 33.0 months, 65 patients (70.7%) developed PSA progression. PSA PFS was longer in patients with higher TT before NAAT (16.3 vs. 10.8 months; P: 0.023), lower TT during NAAT (17.0 vs. 9.1 months; P: 0.001), and longer time to CRPC (13.4 vs. 8.0 months; P: 0.032). Importantly, better OS was observed in lower TT during NAAT (45.0 vs. 33.0 months; P:0.029) and longer time to CRPC (43.0 vs. 31.0 months; P: 0.025). The TT 'bounce' phenomenon was observed in 28 patients (33.3%), and was associated with a poorer PSA response (P: 0.029, median difference: 18.90%, 95% CI 3.83 - 41.45), shorter PSA PFS (8.6 vs 15.2 months, P: 0.002) and shorter OS (29.0 vs. 45.0 months, P: 0.012). CONCLUSION: In CRPC patients, TT behaviors before and during NAAT, and the 'bounce' phenomenon continue to predict treatment response and could guide clinical decisions.

Limitations of overlapping cores in systematic and MRI-US fusion biopsy.

OBJECTIVES: To evaluate the clinically-significant prostate cancer (csCaP) detection rate of systematic (SBx) vs. targeted biopsy (TBx), after accounting for the overlapping systematic cores within the MRI regions of interest. MATERIALS AND METHODS: We identified 398 consecutive men who underwent both transperineal systematic and targeted biopsy between January 2015 to January 2019. We reclassified overlapping systematic cores in the MRI regions of interest as target cores. The detection rates of SBx and TBx were compared using McNemar's test. RESULTS: Detection rate of csCaP (grade group ≥2) was 42% (168/398). Median number of systematic and targeted cores were 23 (IQR 19-29) and 9 (IQR 6-12) respectively. A median of 3 (IQR 2-4) overlapping systematic cores were reclassified as targeted cores. After accounting for overlap, csPC detection rate on SBx decreased from 37% and 21% while the csCaP detection rate of TBx increased from 34% to 39% (both P < 0.001), with TBx having a better detection rate (39% vs. 21%, P < 0.001). A previous negative biopsy was associated with a lower risk of having csCaP on non-targeted SBx (OR 0.27, 95% CI: 0.12 - 0.58, P = 0.001). Only 5% (13/243) of those who had no cancer detected on TBx had csCaP on non-targeted SBx compared to 45% (70/155) of those who had csCaP on TBx (P< 0.001). CONCLUSIONS: The utility of SBx in detecting csCaP decreases after accounting for overlap into the MRI region of interest, especially in men with a prior negative biopsy. Overlapping systematic cores improve the csCaP detection rate on TBx.

External validation and comparison of magnetic resonance imaging-based predictive models for clinically significant prostate cancer.

PURPOSE: Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population. PATIENTS AND METHODS: A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses. RESULTS: A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%. CONCLUSIONS: The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies.

Prostatic ductal adenocarcinoma variant predicts worse pathological and oncological outcomes: Insight from over 1000 consecutive patients from a large prospective uro-oncology registry.

OBJECTIVE: To evaluate if prostatic ductal adenocarcinoma (PDA) independently predicts poorer pathological and oncological outcomes after radical prostatectomy (RP). METHODS AND MATERIALS: Utilizing a large prospective uro-oncology registry, clinicopathological parameters of 1027 consecutive patients who underwent RP (2008-2017) were recorded. Oncological outcomes were determined by failure to achieve unrecordable PSA postoperatively and biochemical failure (BCF). RESULTS: PDA was present in 79 (7.7%) patients, whereas 948 (92.3%) patients had conventional prostatic acinar adenocarcinoma (PAA). Patients with PDA were older (mean 64.4 vs. 62.8-years old; p = .045), had higher PSA at diagnosis (mean 12.53 vs. 10.80 ng/ml; p = .034), and a higher percentage of positive biopsy cores (mean 39.34 vs. 30.53%; p = .006). Compared to PAA, PDA exhibited a more aggressive tumor biology: (1) Grade groups 4 or 5 (26.6 vs. 9.4%, p < .001), (2) tumor multifocality (89.9 vs. 83.6%; p = .049), and (3) tumor size (mean 2.97 vs. 2.00 cm; p < .001). On multivariate analysis, PDA was independently associated with locally advanced disease (p = .002, hazard ratio [HR]: 2.786, 95% confidence interval [CI]: 1.473-5.263), with a trend towards positive surgical margins (p = .055) and nodal involvement (p = .061). Translating the poorer pathological features to oncological outcomes, presence of PDA independently predicted less likelihood of achieving unrecordable PSA (p = .019, HR: 2.368, 95% CI: 1.152-4.868, and higher BCF (p = .028, HR: 1.918, 95% CI: 1.074-3.423). Subgroup analysis demonstrated that a higher ductal component greater than 15% proportionally predicted worse oncological outcomes, with a shorter time to BCF of 14.3 months compared to 19.8 months in patients with ductal component lesser than 15% (p = .040, HR: 2.660, 95% CI: 1.046-6.757). CONCLUSION: PDA is independently associated with adverse pathological and oncological outcomes after RP. A higher proportion of PDA supports a higher BCF rate with a shorter time interval. An aggressive extirpative approach with close monitoring of postoperative serum PSA levels is warranted for these patients.

[Effects of butylphthalide on microglia activation in frontal lobe of rats after chronic sleep deprivation].

Objective: To evaluate the effects of butylphthalide on microglia activation and inflammatory factors in frontal lobe of rats after chronic sleep deprivation. Methods: Rats were divided into four groups(n＝8): control group, platform group, chronic sleep deprivation group and butylphthalide intervention group. Chronic sleep deprivation was performed in rats of chronic sleep deprivation group and butylphthalide intervention group for 18 h per day using the multiple platforms method, and sleep deprivation lasted for 28 days. At the same time, rats in platform group were put in platform, while rats in control group were in normal sleep. After 28 days of sleep deprivation, rats in butylphthalide intervention group were intraperitoneally injected with butylphthalide 100 mg/kg for 14 days, meanwhile rats in other groups were intraperitoneally injected with saline. Then brains were collected and ionized calcium binding adaptor molecule-1 (Iba-1) positive cells in cortex in frontal lobe were studied and counted. The expressions of inducible nitric oxide synthase (iNOS) and arginase1 (Arg1) in frontal lobe were detected by Western blot, and the mRNA levels of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α) were determined by real-time PCR. Results: Compared with control or platform group, the Iba-1 positive cells in chronic sleep deprivation group were large with long process, and increased cell counts were also found in the chronic sleep deprivation group (all P＜0. 05). Moreover, the mRNA expression levels of iNOS, IL-1, IL-6, TNF-α were increased, while the expression of Arg1 was decreased in frontal lobe in rats of the chronic sleep deprivation group compared with the control or platform group (all P＜0. 05). The Iba-1 positive cells in butylphthalide intervention group were reduced compared with chronic sleep deprivation group (P＜0. 05). And the mRNA expression levels of iNOS, IL-1, IL-6 and TNF-α were decreased, while the expression of Arg1 did not chang in rats of the butylphthalide intervention group compared with the chronic sleep deprivation group (all P＜0. 05). Conclusion: Butylphthalide might inhibit the activation and decrease the inflammatory factors in frontal lobe of rats after chronic sleep deprivation.

Benefits of robotic cystectomy compared with open cystectomy in an Enhanced Recovery After Surgery program: A propensity-matched analysis.

OBJECTIVES: To compare the perioperative and oncological outcomes between robot-assisted radical cystectomy with intracorporeal urinary diversion versus open cystectomy for bladder cancer in a contemporary Enhanced Recovery After Surgery cohort. METHODS: All consecutive patients who underwent radical cystectomy and managed under an Enhanced Recovery After Surgery protocol, from December 2013 to October 2018, were reviewed. Propensity score adjustment was carried out to reduce biases attributable to covariate imbalances. RESULTS: There were 19 robot-assisted radical cystectomy with intracorporeal urinary diversion and 21 open cystectomy patients. The robot-assisted radical cystectomy with intracorporeal urinary diversion cohort was associated with lower estimated blood loss (397 vs 787 mL, P = 0.05), with a trend toward shorter duration of ileus and postoperative opioid administration. These benefits were apparent, despite a longer operative time (581 vs 446 mins, P = 0.03), a higher proportion of orthotopic bladder reconstruction (26.3 vs 9.5%, P = 0.08), a more prevalent use of neoadjuvant chemotherapy and a higher number of salvage cystectomies for the robot-assisted radical cystectomy with intracorporeal urinary diversion group. Comparable perioperative complications and length of hospital stay were observed. The pathological and intermediate oncological outcomes were similar in both groups (locally advanced disease: 52.6 vs 47.6%, P = 0.85; lymph node yield: 29 vs 34, P = 0.23). The mean recurrence-free survival and overall survival in the robot-assisted radical cystectomy with intracorporeal urinary diversion group was 37.5 and 43.0 months, respectively, compared with 21.4 (P = 0.09) and 35.5 (P = 0.14) months, respectively, in open cystectomy. CONCLUSION: Robot-assisted radical cystectomy with intracorporeal urinary diversion has perioperative benefits of lower estimated blood loss, with a trend toward faster bowel recovery and a shorter duration of opioid analgesia when compared with open cystectomy. Robot-assisted radical cystectomy with intracorporeal urinary diversion also achieves similar intermediate-term oncological and survival outcomes.

[The effects of prenatal radiation of mobile phones on white matter in cerebellum of rat offspring].

OBJECTIVE: To evaluate the effects of prenatal radiation of 850～1 900 MHz mobile phone on white matter in cerebellum of adult rat offspring. METHODS: Pregnant rats were randomly divided into short term maternal radiation group, long term maternal radiation group and control group. Rats in short term and long term maternal radiation group were exposed to 6 h/d and 24 h/d mobile phone radiation during 1-17 days of pregnancy, respectively. The cerebellums of offspring rats at the age of 3 month(n＝8)were taken. Cell morphology in cerebellum was studied by hematoxylin-eosin (HE) staining. The expressions of myelin basic protein (MBP), neurofilament-L (NF-L) and glial fibrillary acidic protein (GFAP) in cerebellum of rat offspring were detected by immunohistochemistry and Western blot. RESULTS: Compared to control group, the morphological changes of purkinje cells in cerebellum were obvious in rat offspring of short term and long term maternal radiation group. Compared to control group, decreased MBP and NF-L expressions and increased GFAP expression were observed in long term maternal radiation group(all P＜0.05). Compared to short term radiation group, the expressions of MBP and NF-L were down-regulated (all P＜0.05) and the expression of GFAP was up- regulated(P＜0.05) in long term radiation group. CONCLUSION: Prenatal mobile phone radiation might lead to the damage of myelin and axon with activity of astrocytes in cerebellum of male rat offspring, which is related to the extent of radiation.

Comparative study of surgical orchidectomy and medical castration in treatment efficacy, adverse effects and cost based on a large prospective metastatic prostate cancer registry.

INTRODUCTION: Androgen deprivation therapy (ADT) remains the mainstay of treatment for metastatic prostate cancer (mPCa) but is associated with significant morbidities. Comparisons of medical castration (MC) and surgical orchidectomy (SO) have yielded varied results. We aimed to evaluate the oncological outcomes, adverse effect (AE) profiles and costs of MC and SO in patients with mPCa. METHODS AND MATERIALS: We reviewed 523 patients who presented with de novo mPCa from a prospectively maintained prostate cancer database over 15 years (2001-2015). All patients received ADT (either MC or SO) within 3 months of diagnosis. The data were analyzed with chi-square, binary and logistics regression models. RESULTS: One hundred and fifty one (28.9%) patients received SO while 372 (71.1%) patients had MC. The median age of presentation was 73 [67 -79] years old. The median prostate-specific antigen (PSA) was 280ng/ml [82.4-958]. Three hundred and thirty one patients (66.3%) had high volume bone metastasis and 57 patients (10.9%) had visceral metastasis. Clinical demographics and clinicopathological were similar across both groups. Similar oncological outcomes were observed in both groups. The proportion of PSA response (PSA <1ng/ml) was 65.6% for SO and 67.2% for MC (P = 0.212). Both therapies achieve >95% of effective androgen suppression (testosterone <50ng/dL). Time to castrate-resistance was similar (18 vs 16 months, P = 0.097), with comparative overall survival (42 vs. 38.5 months, P = 0.058) and prostate cancer mortality (80.1 vs. 75.9%, P = 0.328). Similarly, no difference was observed for the 4 AE profiles between SO and MC respectively; change in Haemoglobin (-0.75 vs. -1.0g/dL, P = 0.302), newly diagnosed Diabetes mellitus (4.6 vs. 2.9%, P = 0.281), control measured by HbA1c (0.2 vs. 0.25%, P = 0.769), coronary artery disease events (9.9 vs. 12.9%, P = 0.376) and skeletal-related fractures (9.3 vs. 7.3%, P = 0.476). After adjusting for varying governmental subsidies and inflation rates, the median cost of SO was $5275, compared to MC of $9185.80. CONCLUSION: Both SO and MC have similar oncological outcomes and AE profiles. However, SO remains a much more cost-effective form of ADT for the long-term treatment of mPCa patients.

Survival outcomes of Asian younger men (< 55 years) undergoing radical prostatectomy: a review of prostate cancer database in a tertiary hospital in Singapore.

PURPOSE: Prostate cancer largely affects older men. This study aims to investigate prostate cancer in younger men (< 55 years) to shed light on the survival outcomes of this unique subset of patients in Asian context. METHODS: Data were obtained from the Singapore General Hospital Prostate Cancer Registry. Data on all men with clinically organ confined prostate cancer who underwent radical prostatectomy between 1998 and 2016 were obtained from the registry. Tumor characteristics, follow-up data, and cause of death were acquired. RESULTS: A total of 1120 men underwent radical prostatectomy between 1998 and 2016. Of these, 12 were aged ≤ 44 years, 106 were aged 45-54 years, 596 were aged 55-64, 397 were aged 65-74 and 9 were aged ≥ 75. There was no difference across age groups when comparing Gleason ≤ 7 vs Gleason ≥ 8 disease, T1/2 vs T3/4 disease and the median PSA values were similar. No difference was observed in overall survival or prostate cancer specific survival among 4 age groups (≤ 44, 45-54, 55-64, 65-74) (p = 0.156 and p = 0.227 respectively). Although there was a trend of increasing rate of biochemical recurrence for older patients, it's not statistically significant (p = 0.157). Time to biochemical recurrence was similar as well (p = 0.257). CONCLUSION: This large cohort of Asian patients who underwent radical prostatectomy did not show significant age-related differences in important parameters and outcomes.

Multiparametric MRI-ultrasonography software fusion prostate biopsy: initial results using a stereotactic robotic-assisted transperineal prostate biopsy platform comparing systematic vs targeted biopsy.

OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.

Are small renal masses all the same?

OBJECTIVES: To evaluate variables that can predict synchronous metastasis in patients presenting with small renal masses. METHODS: We reviewed our institution's prospectively maintained database of 565 patients diagnosed with small renal masses (≤4 cm) over a 16-year period. Variables associated with synchronous metastasis and subsequent relapse were analyzed using χ2 and logistic regression models. RESULTS: A total of 16 patients (2.7%) presented with synchronous metastasis. Just three patients with tumor size <3 cm had metastatic disease at presentation. On multivariate analyses, tumor size >3 cm, symptomatic cancer, age >65 years and ipsilateral synchronous tumors were independent predictors of M1 renal cell carcinoma. A weighted predictive model (concordance index 0.786) showed that a score ≥2 significantly increases the risk of synchronous metastasis (7.9% vs <1% for score <2, P < 0.01, hazard ratio 12.56, 95% confidence interval 5.52-22.85). A total of 498 (90.7%) patients underwent nephrectomies, 27 (4.9%) had ablative therapies and 24 (4.4%) continued on active surveillance/watchful waiting. Over a median follow-up period of 62.8 months, 30 patients (6.1%) had disease recurrence. On multivariate analyses, higher Fuhrman grade and lymphovascular invasion were independent predictors of recurrence. A separate predictive model (concordance index 0.723) showed that either pathological outcome increases recurrence risk up to 15% (P < 0.01, hazard ratio 11.83, 95% confidence interval 5.82-18.76). CONCLUSIONS: Several clinical variables can better identify the metastatic potential of small renal masses. The two proposed predictive models can be valuable tools in future clinical practice.

Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry.

OBJECTIVE: To evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore. DESIGN: Retrospective analysis of a large prospective Uro-oncology registry of mPCa. SETTING: This study is carried out in a tertiary hospital in Singapore. PARTICIPANTS: We reviewed our institution's prospectively maintained database of 685 patients with mPCa over a 20-year period (1995-2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years. RESULTS: 237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7-27). The median overall survival was 45 months (IQR 20-63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995-1999) to 47.8 months (2010-2014) (p<0.01). CONCLUSION: Morbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

Prognostic Significance of Inflammation-associated Blood Cell Markers in Nonmetastatic Clear Cell Renal Cell Carcinoma.

OBJECTIVES: Our objective was to evaluate the effect of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and red blood cell distribution width (RDW) on the survival outcomes of nonmetastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We accessed our single-center, urologic-oncologic registry to extract the data for patients who had undergone nephrectomy for nonmetastatic ccRCC. The optimal cutoff for these markers was determined using X-tile software, and survival analyses using Cox regression were performed. RESULTS: A total of 687 patients had undergone nephrectomy. The optimal cutoffs for NLR, PLR, LMR, and RDW were 3.3, 210, 2.4, and 14.3%, respectively. The NLR, PLR, LMR, and RDW were significantly associated with a larger pathologic tumor size, and stage, more aggressive Fuhrman grade, and the presence of tumor necrosis. After adjusting for age, baseline Eastern Cooperative Oncology Group, pathologic tumor and nodal stage, and Fuhrman grade, only PLR remained an independent prognostic marker for both cancer-specific survival (hazard ratio, 2.69; 95% confidence interval, 1.36-5.33; P = .004) and overall survival (hazard ratio, 2.19; 95% confidence interval, 1.36-3.50; P = .001). When the PLR was included with the Leibovich score and University of California, Los Angeles, integrated staging system, the Harrell's c-index increased from 0.854 to 0.876 and 0.751 to 0.810, respectively, for cancer-specific survival at 5 years after nephrectomy. When risk stratified by the Leibovich risk group and UCLA integrated staging system, PLR was a significant prognostic factor only within the intermediate- to high-risk groups. CONCLUSIONS: PLR is a robust prognostic marker in nonmetastatic ccRCC that clearly outperforms other inflammatory indexes in those who had undergone nephrectomy. However, its prognostic effect was limited in the low-risk category of ccRCC.