Should Patients with Renal Cell Carcinoma and Pathological Nodal Invasion Be Classified As Having Stage IV Disease?

BACKGROUND: Lymph node invasion is associated with poor outcome in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with RCC within a single center from 2001 to 2018 were retrospectively obtained from the Chang Gung Research Database. Patient gender, physical status, Charlson Comorbidity Index, tumor side, histology, age at diagnosis, and body mass index (BMI) were compared. The overall survival (OS) and cancer-specific survival (CSS) of each group were estimated using the Kaplan-Meier method. Log-rank tests were used to compare between the subgroups. RESULTS AND CONCLUSIONS: A total of 335 patients were enrolled, of whom 76 had pT3N0M0, 29 had pT1-3N1M0, 104 had T1-4N0M1, and 126 had T1-4N1M1 disease. Significant OS difference was noted between pT3N0M0 and pT1-3N1M0 groups with 12.08 years [95% confidence interval (CI), 8.33-15.84] versus 2.58 years (95% CI, 1.32-3.85), respectively (P < 0.005). No significant difference was observed in OS between pT1-3N1M0 and T1-4N0M1 groups with 2.58 years (95% CI, 1.32-3.85) versus 2.50 years (95% CI, 1.85-3.15, P = 0.72). The OS of N1M1 group was worse than that of N0M1 group with 1.00 year (95% CI, 0.74-1.26) versus 2.50 years (95% CI, 1.85-3.15, P < 0.05). Similar results were also observed in CSS. In summary, we claim that RCC with lymph node (LN) invasion should be reclassified as stage IV disease in terms of survival outcome.

NASA Satellite Measurements Show Global-Scale Reductions in Free Tropospheric Ozone in 2020 and Again in 2021 During COVID-19.

NASA satellite measurements show that ozone reductions throughout the Northern Hemisphere (NH) free troposphere reported for spring-summer 2020 during the COronaVIrus Disease 2019 pandemic have occurred again in spring-summer 2021. The satellite measurements show that tropospheric column ozone (TCO) (mostly representative of the free troposphere) for 20°N-60°N during spring-summer for both 2020 and 2021 averaged ∼3 Dobson Units (DU) (or ∼7%-8%) below normal. These ozone reductions in 2020 and 2021 were the lowest in the 2005-2021 record. We also include satellite measurements of tropospheric NO2 that exhibit reductions of ∼10%-20% in the NH in early spring-to-summer 2020 and 2021, suggesting that reduced pollution was the main cause for the low anomalies in NH TCO in 2020 and 2021. Reductions of TCO ∼2 DU (7%) are also measured in the Southern Hemisphere in austral summer but are not associated with reduced NO2.

Lesion size may affect diagnostic capabilities of MRI-guided ultrasound fusion biopsy and cognitive targeted biopsy for clinically significant prostate cancer.

MRI-guided targeted biopsy (MRGB) was recommended as part of biopsy paradigm of prostate cancers by current guidelines. This study aimed to analyze the diagnostic efficacy of MRGB and systemic biopsy (SB), and to compare diagnostic capabilities within subgroups of MRGB: MRI-cognitive biopsy (MRCB) and MRI-fusion biopsy (MRFB). We retrospectively enrolled patients who underwent MRGB for suspicious malignant lesion(s) identified on MRI in a single tertiary center, sample size was 74 patients. An mpMRI was performed prior to biopsy and reviewed by an experienced radiologist specialized in prostate cancer. Per-person results of MRGB and each concomitant SB were analyzed as independent biopsies for its positive biopsy rate and positive core percentage. Per-lesion results of MRFB and MRCB were compared for the detection rate. Variables of interest were analyzed with t-test, chi-squared test, and logistic regression analysis. Statistical analyses were performed with IBM Statistical Product and Service Solutions (SPSS), Version 23 (IBM, Armonk, New York). Total of 74 patients fulfilled the inclusion criteria and were enrolled. MRFB had higher PCa detection rate comparing to both MRCB and SB (56.1%, 30.3%, and 33.9% respectively, p value = 0.036); clinically significant prostate cancer (csPCa) detection rate was also significantly higher in MRFB group (43.9%, 24.2%, and 16.9% in each group respectively, p value = 0.011). In per-lesion analysis, MRCB and MRFB had no significant difference in PCa and csPCa detection rate (41.0% vs. 26.2% and 29.5% vs. 16.7% respectively, p value = 0.090 and 0.103). In the lesion ≦ 1.3 cm group, MRFB could achieve higher PCa detection rate, comparing to MRCB (36.4% vs. 14.3%, p value = 0.047); there were also higher positive rates for PCa and csPCa per biopsied cores (22.1% vs. 6.8% and 15.6% vs. 2.7%, p value = 0.029 and 0.028, respectively). Further logistic regression of multi-variate analysis in subgroup of lesion ≦ 1.3 cm revealed that PIRADS score and biopsy method were significant predictors of positive biopsy result for PCa (p value = 0.045 and 0.026, respectively) and for csPCa (p value = 0.043 and 0.025, respectively). In patients receiving trans-perineal prostate biopsy, MRFB had higher cancer detection rate than MRCB and SB. In per lesion comparison, MRFB and MRCB had similar diagnostic accuracy. However, in lesions with diameter less than 1.3 cm, MRFB can provided better diagnose value for PCa and csPCa than MRCB.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

Recognition of Postoperative Cystography Features by Artificial Intelligence to Predict Recovery from Postprostatectomy Urinary Incontinence: A Rapid and Easy Way to Predict Functional Outcome.

Purpose: Post-operative cystography has been used to predict the recovery of postprostatectomy urinary incontinence (PPI) in patients with localized prostate cancer. This study aimed to validate the predictive value of cystography for PPI and utilize a deep learning model to identify favorable and unfavorable features. Methods: Medical records and cystography images of patients who underwent robotic-assisted radical prostatectomy for localized prostate cancer were retrospectively reviewed. Specific cystography features, including anastomosis leakage, a downward bladder neck (BN), and the bladder neck angle, were analyzed for the prediction of PPI recovery. Favorable and unfavorable patterns were categorized based on the three cystography features. The deep learning model used for transfer learning was ResNet 50 and weights were trained on ImageNet. We used 5-fold cross-validation to reduce bias. After each fold, we used a test set to confirm the model's performance. Result: A total of 170 consecutive patients were included; 31.2% experienced immediate urinary continence after surgery, while 93.5% achieved a pad-free status and 6.5% were still incontinent in the 24 weeks after surgery. We divided patients into a fast recovery group (≤4 weeks) and a slow recovery group (>4 weeks). Compared with the slow recovery group, the fast recovery group had a significantly lower anastomosis leakage rate, less of a downward bladder neck, and a larger bladder neck angle. Test data used to evaluate the model's performance demonstrated an average 5-fold accuracy, sensitivity, and specificity of 93.75%, 87.5%, and 100%, respectively. Conclusions: Postoperative cystography features can predict PPI recovery in patients with localized prostate cancer. A deep-learning model can facilitate the identification process. Further validation and exploration are required for the future development of artificial intelligence (AI) in this field.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Introduction: Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Methods: Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. Results: A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Discussion: Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. METHODS: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). RESULTS: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. CONCLUSIONS: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.

Clinical predictors for biochemical failure in patients with positive surgical margin after robotic-assisted radical prostatectomy.

OBJECTIVE: Patients with positive surgical margins (PSMs) after radical prostatectomy for localized prostate cancer have a higher risk of biochemical failure (BCF). We investigated the risk factors of BCF in patients with PSMs after robotic-assisted radical prostatectomy (RARP). METHODS: We evaluated 462 patients who underwent RARP in a single medical center from 2006 through 2013. Of them, 61 with PSMs did not receive any treatment before BCF. Kaplan-Meier curve and Cox regression analysis were used to compare patients with (n = 19) and without (n = 41) BCF. RESULTS: Overall, 13.2% of patients had PSMs, and of those, 31.7% experienced BCF during follow-up. The mean follow-up duration was 43.7 months (42.4 [non-BCF] vs 46.35 (BCF], p = 0.51). In univariant analyses, the platelet to lymphocyte ratio (6.26 [non-BCF] vs 8.02 [BCF], p = 0.04) differed statistically. When patients were grouped by pathologic grade ≦2 or ≧3 (p = 0.004), the BCF-free survival rates differed significantly. Seminal vesicle invasion also differed significantly (5 [non-BCF] vs 7 [BCF], p = 0.005). Patients with undetectable nadir prostate-specific antigen (PSA) after RARP (BCF rate 4/34) differed statistically from those with detectable PSA after RARP (BCF rate 15/26) (p < 0.001). In the multivariate analysis, the platelet/lymphocyte (P/L) ratio, pathologic grade, and undetectable nadir PSA remained statistically significant. CONCLUSIONS: In patients who undergo RARP and have PSMs, P/L ratio >9 preoperatively, pathologic grade ⩾3, and detectable nadir PSA after RARP should be considered adverse features. Early intervention such as salvage radiation therapy or androgen deprivation therapy should be offered to these patients.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer.

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. MATERIALS AND METHODS: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. RESULTS: The patients' median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). CONCLUSIONS: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Instillation Strategies for Non-Muscle-Invasive Bladder Cancer in the Bacillus Calmette-Guerin Shortage Era: A Simple Solution for BCG Discontinuation.

Objective: Among intravesical instillation protocol in patients with non-muscle-invasive bladder cancer (NMIBC), chemotherapy agents have been widely used during the bacillus Calmette-Guérin (BCG) shortage era since the patient might under the risk of BCG discontinuation. This study evaluates the efficacy of incomplete BCG instillation compared with pure chemotherapy instillation protocol. Materials and Methods: Patients newly diagnosed with intermediate- and high-risk NMIBC who received incomplete BCG intravesical instillation or chemotherapy instillation were retrospectively included. Patients were divided into three groups according to different intravesical instillation schedules: [BCG only], [BCG + Chemo], and [Chemo only]. Comparisons between these three groups were performed. Bladder recurrence-free survival (RFS) was analyzed as the primary endpoint. Results: A total of 475 patients who received intravesical instillations were enrolled. Compared to the [Chemo only] group, the [BCG + Chemo] group had significantly better bladder RFS (p = 0.027). Multivariate analysis of recurrence revealed the [BCG + Chemo] regimen has a hazard ratio 0.381 (95% CI 0.154-0.941, p = 0.037). The total instillation number >12 was associated with better RFS (p = 0.001) compared with other instillation numbers. Conclusion: For NMIBC patients facing the risk of unexpected BCG instillation interruption, instead of starting instillation with chemotherapy agents, receiving BCG first till stoppage then shifting to chemotherapy agents is recommended.

Clinical Outcome of Immediate Transurethral Surgery for Benign Prostate Obstruction Patients with Acute Urinary Retention: More Radical Resection Resulted in Better Voiding Function.

INTRODUCTION: Transurethral surgery of the prostate is currently the gold standard treatment modality for patients with benign prostatic hyperplasia (BPH) with recurrent acute urinary retention. This study aimed to evaluate the outcome and predictors of patients receiving immediate surgery after acute urinary retention (AUR) episodes. MATERIALS AND METHODS: From January 2016 to January 2017, we retrospectively included 714 patients who received transurethral surgery of prostate due to BPH. Among them, 158 patients received surgeries immediately after an AUR episode. General characteristics data including age, Body mass index (BMI), International prostate symptom score (IPSS score), prostate volume and Prostate-specific antigen (PSA) were reviewed. We also collected surgery-related parameters including surgical types, operation time, and specimen weight. Resection ratio was defined as (resected specimen weight)/(Transurethral ultrasound (TRUS) volume). The catheterization status on discharge, post-operative medication for BPH, and AUR within 3 months after operation were evaluated. Statistical analysis was performed with Statistical product and service solutions (SPSS). RESULTS: The mean age of the patients was 73.5 years, with a BMI of 24 kg/m2. IPSS total score was 25 with a Voiding symptom/Storage symptom score (V/S score) of 14.6 and 10.4, respectively. A total of 74 (46.8%) patients still took medication for BPH for over 1 month after the surgeries, 28 (17.7%) patients were not catheter-free at the time of discharge, and 14 (8.9%) patients had AUR within 3 months after the surgeries. Surgical type did not impact the outcome of surgeries. In patients who received Transurethral resection of the prostate (TURP), the resection ratio is the only predictor for the catheterization status on discharge and post-operative medication for BPH within 3 months after operation. CONCLUSIONS: In patients with BPH-related AUR followed by immediate transurethral surgeries, more radical resection is significantly correlated with short-term medication-free and catheter-free status.

Earth Observations from DSCOVR/EPIC Instrument.

The NOAA Deep Space Climate Observatory (DSCOVR) spacecraft was launched on February 11, 2015, and in June 2015 achieved its orbit at the first Lagrange point or L1, 1.5 million km from Earth towards the Sun. There are two NASA Earth observing instruments onboard: the Earth Polychromatic Imaging Camera (EPIC) and the National Institute of Standards and Technology Advanced Radiometer (NISTAR). The purpose of this paper is to describe various capabilities of the DSCOVR/EPIC instrument. EPIC views the entire sunlit Earth from sunrise to sunset at the backscattering direction (scattering angles between 168.5° and 175.5°) with 10 narrowband filters: 317, 325, 340, 388, 443, 552, 680, 688, 764 and 779 nm. We discuss a number of pre-processingsteps necessary for EPIC calibration including the geolocation algorithm and the radiometric calibration for each wavelength channel in terms of EPIC counts/second for conversion to reflectance units. The principal EPIC products are total ozone O3amount, scene reflectivity, erythemal irradiance, UV aerosol properties, sulfur dioxide SO2 for volcanic eruptions, surface spectral reflectance, vegetation properties, and cloud products including cloud height. Finally, we describe the observation of horizontally oriented ice crystals in clouds and the unexpected use of the O2 B-band absorption for vegetation properties.