Combined MRI-TRUS fusion targeted and systematic biopsy versus systematic biopsy alone for the detection of prostate cancer: protocol for a prospective single-centre trial.

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.

Effect of tumor CD276 expression on infiltrating immune cells and clinicopathological features of prostate cancer.

BACKGROUND: Advanced prostate cancer (PCa) is often resistant to immunotherapy. In this study, we examined the role of CD276 in mediating immunotherapeutic effects through changes in immune cell infiltration. METHODS: Using transcriptomic and proteomic analyses, CD276 was identified as a potential target for immunotherapy. Subsequent in vivo and in vitro experiments confirmed its role as a potential mediator of immunotherapeutic effects. RESULTS: Multi-omic analysis suggested that CD276 was identified as a key molecule regulating the immune microenvironment (IM). In vivo experiments revealed that CD276 knockdown was found to enhance CD8+ T cell infiltration into the IM. Immunohistochemical analysis of PCa samples further confirmed the same findings. CONCLUSION: CD276 was found to inhibit the enrichment of CD8+ T cells in PCa. Thus, CD276 inhibitors may be potential targets for immunotherapy.

Perioperative change of circulating tumor cells in cytoreductive radical prostatectomy for oligometastatic hormone-sensitive prostate cancer: the preliminary safety evidence from long-term oncologic outcomes.

Surgical manipulation has a risk of triggering the shedding of circulating tumor cells (CTCs) in patients with malignancies, However, perioperative change of circulating tumor cells in cytoreductive radical prostatectomy (CRP) for patients with oligometastatic hormone-sensitive prostate cancer (omHSPC) has not yet been well documented. This study aimed to assess whether CRP is a safe procedure for patients with omHSPC by monitoring the perioperative change of CTCs and investigating its impact on long-term oncologic outcomes. We have observed a significant decrease between the median CTC counts before and after surgery (6 vs. 4, p = 0.026). Comparing preoperative and postoperative CTC levels, seven patients increased (CTC increase group), one did not change and nineteen decreased (CTC non-increase group). PSA response rates in CTC increase group were lower than those in CTC non-increase group (73.0% vs 99.8%, p = 0.162), and nadir PSA was higher in CTC increase group (0.043 vs 0.003, p = 0.072). The CTC increase was positively correlated with the nadir PSA (r = 0.386, p = 0.047). The median follow-up period was 71.6 months, we found that there was no significant difference in clinical-pathological, operative variables or long-term oncologic outcomes between perioperative CTC increase and non-increase groups. In the entire cohort, the CTC level significantly decreased after surgery. There was no significant differences in long-term oncologic outcomes between the CTC increase and non-increase groups, implying that CRP potentially represents a safe procedure for the treatment of patients with omHSPC. The results need to be confirmed in a prospective large-scale clinical trial.

Identification of risk factors for urethrovesical anastomotic leakage following laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the risk factors of urethrovesical anastomotic leakage after laparoscopic radical prostatectomy.Methods:The clinical data of 292 patients who underwent laparoscopic radical prostatectomy in the Tenth People's Hospital Affiliated to Tongji University from January to December 2021 were retrospectively analyzed. According to whether there was anastomotic leakage, the patients were divided into leakage group (27 cases) and non-leakage group (265 cases). There were no significant differences in age [(71.5±6.5) years vs. (70.2±6.4) years], body mass index [(24.5±3.6) kg/m 2 vs. (24.2±3.0) kg/m 2], prostate volume[40(27.3, 63.2)ml vs. 38(28.1, 56.2)ml], Gleason score, clinical stage, and risk classification between the leakage group and the non-leakage group ( P>0.05), but the total prostate-specific antigen in the leakage group was significantly higher than that in the non-leakage group[20.0 (9.6, 79.0) ng/ml vs. 13.7 (8.5, 25.0) ng/ml, P=0.049]. Propensity score matching (PSM) was used to match the above indicators between the leakage group and the non-leakage group as 1∶1, so that the baseline of the two groups was balanced. The perioperative indicators of the matched two groups of patients were compared and analyzed. Statistically significant indicators were selected and included in univariate and multivariate logistic regression to analyze the risk factors of anastomotic leakage after radical prostatectomy. Finally, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated. The accuracy of each factor in predicting urine leakage was obtained. Results:After PSM, 24 cases were successfully matched. The leakage group had shorter membranous urethral length (MUL) [(15.5±2.2)mm vs. (17.5±1.5)mm, P<0.001], thinner membranous urethral wall thickness (UWT) [(9.5±1.9)mm vs. (10.6±1.5)mm, P=0.024], longer anastomotic time of urethrovesical neck[(21.6±4.1)min vs. (16.9±2.9)min, P<0.001] and higher failure rate of water injection test [16.7% (4/24) vs. 4.2% (1/24), P=0.045] than the non-leakage group. There was no significant difference in other indicators between the two groups. The results of multivariate logistic regression analysis showed that short MUL ( OR=0.544, 95% CI 0.335-0.884, P=0.014), narrow UWT ( OR=0.538, 95% CI 0.313-0.924, P=0.025) and long anastomotic time of urethrovesical neck ( OR=1.519, 95% CI 1.122-2.110, P=0.009) were independent risk factors for anastomotic urine leakage. ROC curve analysis showed that the AUC of MUL, UWT, and anastomotic time were 0.789 (95% CI 0.651-0.927), 0.715 (95% CI 0.562-0.868), and 0.842 (95% CI 0.731-0.953), respectively. Conclusions:Narrow and short membranous urethra and long anastomosis time in patients with laparoscopic radical prostatectomy may be independent risk factors for postoperative anastomotic leakage, which may predict the occurrence of anastomotic leakage.

Down-Regulation of lncRNA MBNL1-AS1 Promotes Tumor Stem Cell-like Characteristics and Prostate Cancer Progression through miR-221-3p/CDKN1B/C-myc Axis.

The recurrence, progression, and drug resistance of prostate cancer (PC) is closely related to the cancer stem cells (CSCs). Therefore, it is necessary to find the key regulators of prostate cancer stem cells (PCSCs). Here, we analyzed the results of a single-class logistic regression machine learning algorithm (OCLR) to identify the PCSC-associated lncRNA MBNL1-AS1. The effects of MBNL1-AS1 on the stemness of CSCs was assessed using qPCR, western blot and sphere-forming assays. The role of MBNL1-AS1 in mediating the proliferation and invasion of the PC cell lines was examined using Transwell, wounding-healing, CCK-8, EdU and animal assays. Dual-luciferase and ChIRP assays were used to examine the molecular mechanism of MBNL1-AS1 in PCSCs. MBNL1-AS1 was shown to be negatively correlated with stemness index (mRNAsi), and even prognosis, tumor progression, recurrence, and drug resistance in PC patients. The knockdown of MBNL1-AS1 significantly affected the stemness of the PC cells, and subsequently their invasive and proliferative abilities. Molecular mechanism studies suggested that MBNL1-AS1 regulates CDKN1B through competitive binding to miR-221-3p, which led to the inhibition of the Wnt signaling pathway to affect PCSCs. In conclusion, our study identified MBNL1-AS1 as a key regulator of PCSCs and examined its mechanism of action in the malignant progression of PC.

Development of nomograms related to inflammatory biomarkers to estimate the prognosis of bladder cancer after radical cystectomy.

BACKGROUND: Bladder cancer is one of the most common carcinomas and it brings about huge social economic burden. There is not a reliable way to predict the prognosis of bladder patients. We develop the nomogram to predict the prognosis of bladder cancer patients. METHODS: A total of 127 bladder cancer patients after radical cystectomy were studied retrospectively. Their clinicopathological data were collected for statistical analysis. RESULTS: The level of albumin/globulin ratio (AGR), C-reactive protein/albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) associated with pathological and hematological parameters like T stage and hemoglobin. Furthermore, the AGR was associated with overall survival (OS) and CAR, NLR, and PLR were associated with both OS and progression-free survival (PFS) (P<0.05). The multivariate analysis revealed that tobacco smoking, tumor T stage, M stage, NLR, CAR, and AGR were all independent predictors for OS of patients and tobacco smoking, tumor T stage, NLR, CAR, and AGR were independent predictors for PFS of patients. In addition, AGR, CAR, and NLR, as well as, the clinicopathological parameters in the development of nomograms with a C index of 0.901 (95% CI: 0.505-1.269) for OS, and 0.807 (95% CI: 0.755-0.858) for PFS. The nomograms were able to provide a prognosis of the OS with the area under the curve (AUC) =0.86. Further, tests assessed the PFS with the AUC =0.84. CONCLUSIONS: This study demonstrates that the nomograms of the inflammatory biomarkers were able to predict prognosis of bladder cancer patients after radical cystectomy.

The Innovative Use of Ureter Catheter in the Surgery of Obstructive Uropathy.

PURPOSE: Relieving obstruction and protecting renal function are the main therapeutic purposes of obstructive uropathy which often involve surgical treatment, and the ureter catheter is one of the surgical instruments commonly used in surgery. We aimed to explore the innovative use of a ureter catheter in the surgery of obstructive uropathy. METHODS: We used a ureteral catheter to innovate the surgical procedure of the most common causes of obstructive uropathy: ureteral calculi and stricture, establishing an internal circulation system (ICS), proposing a three-step dilatation method, and reviewing their effects on patients. Furthermore, we introduced a simple real-time intrapelvic pressure measurement device to monitor intrarenal pressure during operation. RESULTS: Postoperative laboratory examination showed that blood CRP, leukocyte neutrophil level, changes in the hemoglobin, urine occult blood, and positive rate of urine culture in the ICS group are significantly lower than those in the control group, corresponding to a lower incidence of bleeding and infection-related complications clinically. A three-month follow-up revealed 1/3 rate of ureteral stricture in the ICS group comparing to the control. We applied the three-step dilatation in patients with severe stenosis in which the balloon could not pass; the overall effective rate was 90.9%. The pressure of the renal pelvis was displayed on the monitor in real time. The surgeon could estimate the degree of filling of the renal pelvis and adjust the intake volume through the data. CONCLUSION: The innovative application of ureteral catheters in the operation of obstructive uropathy can realize the real-time monitor of intraoperative renal pelvis pressure, reduce the incidence of lithotripsy postoperative complications, and expand the indications of balloon dilatation in ureteral stricture, which has certain clinical significance.

O-GlcNAcylation Enhances NUSAP1 Stability and Promotes Bladder Cancer Aggressiveness.

OBJECTIVE: NUSAPl and O-GlcNAcylation were reported to be hyper-activated in many kinds of cancers and involved in the advanced progression of cancers. In bladder cancer, O-GlcNAc transferase (OGT) expresses in patients' urine samples, with no expression in healthy individuals, indicating O-GlcNAcylation might involve in the occurrence and development of bladder cancer. Therefore, the present study aims to investigate the effects of O-GlcNAcylation in bladder cancer and if it can regulate NUSAP1 protein. MATERIALS AND METHODS: Western blot, immunohistochemistry, and PCR were used to evaluate the protein expression and mRNA level of NUSAP1; CCK-8 and flow cytometry used to evaluate the proliferation and inhibited the apoptosis of bladder cancer. RESULTS: The results showed that NUSAP1 was highly expressed in bladder cancer cells and tissue samples. NUSAP1 up-regulation significantly promoted the proliferation and inhibited the apoptosis of bladder cancer HT-1376 and T24 cells. Besides, the expression of O-GlcNAc was elevated in bladder cancer tissues and cells, and up-regulation of O-GlcNAc with GlcNAc and PuGNAc obviously increased NUSAP1 protein expression and stability. Moreover, knockdown OGT significantly inhibited the proliferation and tumorigenesis and promoted the apoptosis of bladder cancer cells, confirmed by CCK-8, in vivo xenotransplantation, and flow cytometry, whereas these roles were impaired when NUSAP1 was up-regulated. CONCLUSION: Overall, our study makes clear that hyper-O-GlcNAcylation accelerates bladder cancer progression through promotion of NUSAP1 expression and its stability.

Effects of Radiotherapy or Radical Prostatectomy on the Risk of Long-Term Heart-Specific Death in Patients With Prostate Cancer.

Objective: The prognosis of patients with prostate cancer (PCa) has improved in recent years, but treatment-related cardiotoxicity remains unclear. This study investigated the heart-specific mortality and prognostic factors of patients with PCa after radiotherapy (RT) or radical prostatectomy (RP), and compared their long-term heart-specific mortality with that of the general male population. Materials and Methods: Data were taken from the Surveillance, Epidemiology, and End Result (SEER) database. Patients with PCa were included who underwent RT or RP from 2000 to 2012, and were followed through 2015. A cumulative mortality curve and a competitive risk regression model were applied to assess the prognostic factors of heart-specific mortality. Standardized mortality rates (SMRs) were calculated. Results: Of 389,962 men, 49.7% and 50.3% received RP and RT, respectively. The median follow-up was 8.3 years. For patients given RT, in about 9 years postdiagnosis, the cumulative mortality due to heart-specific disease exceeded that due to PCa. In patients who underwent RP, cumulative mortality from heart-specific disease or PCa was comparable. Relative to the general male population, overall, the heart-specific mortality of patients with PCa receiving RT or RP was not higher, but in patients aged 70 to 79 years, those given RT experienced slightly higher heart-specific mortality than the age-matched general population. Conclusions: Patients with PCa treated with RT or RP overall do not incur risk of heart-specific mortality higher than that of the general male population, except for patients aged 70-74 years receiving RT.

Downregulation of Long Noncoding RNA LUCAT1 Suppresses the Migration and Invasion of Bladder Cancer by Targeting miR-181c-5p.

PURPOSE: The long noncoding RNA LUCAT1 (lung cancer-associated transcript 1) has been reported to be highly expressed in bladder cancer samples, but its role and molecular mechanisms need to be elucidated. METHODS: Bioinformatics methods show that miR-181c-5p is a target of LUCAT1. Here, we aimed to reveal whether LUCAT1 participates in the development of bladder cancer via targeting miR-181c-5p. The expression levels of LUCAT1 and miR-181c-5p were detected by RT-PCR technology in bladder cells and tissues. The effects of the LUCAT1/miR-181c-5p axis on cell proliferation, migration, invasion, and apoptosis were tested by CCK-8, wound healing, Transwell chambers, and flow cytometry assays. The expressions of apoptosis/migration-related proteins were detected by western blotting assays. RESULTS: The results demonstrated that LUCAT1 was overexpressed in bladder cancer tissue and cells, while miR-181c-5p showed a low expression pattern as compared to normal bladder cells and tissues. Cell proliferation, migration, and invasion capacities were significantly impaired, and cell apoptosis was enhanced when LUCAT1 was silenced in UM-UC-3 and T24 cell lines, but this effect was abolished by miR-181c-5p downregulation. In addition, miR-181c-5p downregulation impaired LUCAT1 downregulation which mediated the decreased expressions of Bcl2 and N-cadherin and the increased expressions of Bax and E-cadherin. Moreover, we found that KRAS was a direct target of miR-181c-5p and was under the positive regulation of LUCAT1. CONCLUSION: Collectively, this study reveals that knockdown of LUCAT1 inhibits the migration and invasion of bladder cancer cells in a miR-181c-5p-dependent manner, which may be related to KRAS downregulation.

MicroRNA-769-5p suppresses cell growth and migration via targeting NUSAP1 in bladder cancer.

BACKGROUND: Nucleolar and spindle-associated protein 1 (NUSAP1) has been identified to be strongly implicated in the carcinogenesis of cervical carcinoma, breast cancer, and liver cancer, and shows a high expression level in bladder cancer, indicating that NUSAP1 might be a potent target for cancer treatment. Using bioinformatics methods, we found that NUSAP1 was a putative target of miR-769-5p. Here, we aimed to explore whether miR-769-5p is involved in bladder cancer progression via targeting NUSAP1. METHODS: MiR-769-5p expression patterns in bladder cancer tissues and cells were detected by RT-PCR. Kaplan-Meier was used to determine the clinical effects of miR-769-5p expression levels on the overall survival of bladder cancer patients. Bioinformatics methods were used to predict the binding sites between miR-769-5p and NUSAP1, which was verified by the luciferase gene reporter assay. CCK-8, flow cytometry, wound healing and transwell chamber experiments were performed to test cell growth, apoptosis, migration and invasion capacities. RESULTS: miR-769-5p was lowly expressed in bladder cancer tissues and cells, which was closely associated with poor prognosis. Overexpression of miR-769-5p induced significant repressions in cell growth, migration, and invasion and caused an obvious increase in cell apoptosis, whereas these tendencies were reversed when NUSAP1 was upregulated. CONCLUSION: This study demonstrates that miR-769-5p functions as a tumor suppressor in bladder cancer via targeting NUSAP1.

Impact of peri-prostatic fat measurements using MRI on the prediction of prostate cancer with transrectal ultrasound-guided biopsy.

OBJECTIVES: To estimate the impact of peri-prostatic fat (PPF) measurements using preoperative magnetic resonance imaging on the prediction of prostate cancer (PCa) with transrectal ultrasound-guided biopsy. PATIENTS AND METHODS: We performed a retrospective 2-center study on 660 consecutive patients receiving transrectal ultrasound-guided biopsy-biopsy from June 2016 to October 2018. Pathologic and immunohistochemical characteristics were collected. PPF measurements including PPF area (PPFA) and PPFA to prostate area (PA) ratio (PPFA/PA) were assessed by preoperative staging magnetic resonance imaging. Clinical variables were correlated with Gleason score by using Spearman (ρ) correlation coefficients. Multivariable analysis was performed to identify independent predictors of PCa. The diagnostic performance was estimated using ROC curves. RESULTS: The Gleason score was significantly correlated with age (ρ = 0.114, P = 0.035), prostate-specific antigen (PSA) (ρ = 0.482, P < 0.001), PIRADS scoring (ρ = 0.403, P < 0.001) and PPFA/PA (ρ = 0.238, P < 0.001). Multivariate analysis revealed that PPFA/PA, age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring were independently predictive of PCa. The ROC AUC to detect PCa or clinically significant PCa (CS-PCa; Gleason Score 3 + 4 or greater) improved with the addition of PPFA/PA (PCa: 0.93 vs. 0.89; CS-PCa: 0.92 vs. 0.90). CONCLUSION: PPFA/PA is an independent predictor for PCa along with age, digital rectal examination, family history of PCa, PSA, and PIRADS scoring. PPF measurements especially PPFA/PA may help detect PCa or CS-PCa, thus helping improve PCa risk stratification and screening to avoid unnecessary biopsies.