Intraoperative blood loss (IBL) is a critical precipitating factor of intraoperative and postoperative complications. This study aims to identify risk factors and employ machine learning (ML) techniques to develop models for predicting IBL in patients undergo retroperitoneal laparoscopic adrenalectomy (RLA). A retrospective study was performed with data from patients who underwent unilateral RLA at Beijing Anzhen Hospital from 2014 to 2021. The data were randomly divided into training and validation sets. A volume ≥ 100 ml was defined as high IBL. Model training incorporated feature selection with least absolute shrinkage and selection operator (LASSO) and algorithms including logistic regression (LR), random forest (RF), neural network (NN), K-nearest neighbor (KNN), support vector machine (SVM) and AdaBoost. Various indicators were utilized to evaluate model performance. A total of 530 RLA cases were included. LASSO regression identified gender, surgeons’ experience, disease type, lesion diameter and lesion location as predictive factors. Six ML models were derived and evaluated. Among which, LR, RF and NN models exhibited exceptional discriminatory power. The area under the curve (AUC) of the three models were 0.775, 0.769, 0.729 in the validation set, respectively. A nomogram and a online calculator were created. The calibration curve, decision curve analysis and clinical impact curve revealed its excellent clinical utility. This study presented and compared the use of various ML models for predicting IBL in RLA, which could assist in assessing surgical risks and tailored treatments without additional examination, and providing insights for the clinical application of ML.

It is unclear how sex disparities affect surgical outcomes following retroperitoneal laparoscopic adrenalectomy (RLA). Therefore, we studied whether gender could affect RLA outcomes perioperatively. A retrospective study was performed involving consecutive cases underwent unilateral RLA for adrenal disease from January 2012 to December 2021. Coarsened exact matching (CEM) was applied to balance patient groups. Logistic regression analysis was performed to assess the impact of sex on prolonged operative time and increased intraoperative blood loss. A total of 569 patients who underwent RLA were included. After CEM, 112 patients were incorporated in each group. Operative time (male: 129.47 vs. female: 95.53, P < 0.001) and intraoperative blood loss (male: 123.39 vs. female: 101.61, P = 0.009) differed statistically significantly, while equal postoperative length of stay (LOS) (6.7 d vs. 6.8 d, P = 0.686), drainage tube removal time (3.0 d vs. 3.0 d, P = 0.231) and incidence of Clavien-Dindo grade ≥ 2 perioperative complications (8.0

Background:Adrenal vein sampling (AVS) is the gold standard for diagnosing the dominant side in patients with primary aldosteronism (PA). CYP11B2 encodes aldosterone synthase. The aim of this study was to investigate the prognosis of dominant-side adrenalectomy in patients with PA identified by AVS in the context of aldosterone synthase expression in the postoperative pathology of those patients. Methods:This retrospective study included 73 PA patients who underwent AVS followed by unilateral adrenalectomy. Patients were categorized into AVS bilateral success group, AVS unilateral success group, and AVS bilateral failure group based on their AVS status. Immunohistochemistry (IHC) for CYP11B2 was combined with postoperative pathology in these patients, and the clinical and biochemical prognosis of these patients was assessed 6 months after adrenalectomy. Results:Between September 2023 and September 2024, 73 patients underwent unilateral adrenalectomy guided by AVS at our institution, with CYP11B2 IHC successfully performed in 63 cases. Among these, 21 patients (33.33%) achieved bilateral AVS success, 20 (31.75%) demonstrated unilateral AVS success, and 22 (34.92%) exhibited bilateral AVS failure. Pathological analysis of the bilateral AVS success group revealed aldosterone-producing adenoma (APA) in 12 cases, aldosterone-producing micronodule (APM) in 1, multiple-aldosterone-producing micronodules/nodules (MAPM/MAPN) in 2, aldosterone-producing diffuse hyperplasia (APDH) in 1, APA with MAPM in 3, and APA with APDH in 2. In this group, complete and partial clinical success rates were 47.62% (10/21) and 52.38% (11/21), respectively, while biochemical success rates reached 95.24% (20/21) for complete and 4.76% (1/21) for partial success. The unilateral AVS success cohort included APA (n=8), aldosterone-producing nodule (APN) (n=2), MAPM/MAPN (n=3), APA with MAPM (n=4), APA with APDH (n=2), and 1 CYP11B2 IHC-negative lesion, with clinical success rates of 40.00% (8/20) complete and 60.00% (12/20) partial, alongside 90.00% (18/20) complete and 10.00% (2/20) partial biochemical success. The bilateral AVS failure group comprised APA (n=8), MAPM/MAPN (n=1), APA with MAPM (n=5), APA with APDH (n=2), and 6 CYP11B2 IHC-negative lesions, demonstrating 36.36% (8/22) complete, 50.00% (11/22) partial, and 13.64% (3/22) no clinical success, with biochemical outcomes of 72.73% (16/22) complete, 18.18% (4/22) partial, and 9.09% (2/22) no success. Notably, bilateral AVS success correlated with significantly superior biochemical outcomes compared to bilateral failure (P=0.045). Conclusions:Adrenalectomy guided by AVS yields better outcomes in patients with PA when AVS is successful on both sides compared to those with bilateral AVS failure. The source of excess aldosterone secretion on the dominant side identified by AVS is not necessarily an APA/APN. It may also include MAPM/MAPN, diffuse adrenal cortical hyperplasia, and various complex combined conditions. In patients with bilateral AVS failure, adrenal specimens more frequently exhibit negative immunohistochemical staining for CYP11B2.

To study the prognostic difference of unilateral adrenalectomy in patients with Primary Aldosteronism (PA) with different renin levels. The clinical data of 159 patients with PA who underwent unilateral adrenalectomy at Beijing Anzhen Hospital of Capital Medical University from August 2022 to January 2025 were retrospectively analyzed. The mean age of the 159 patients was 51.98 ± 10.61 years old, the body mass index was 26.10 ± 3.94 kg/m2, and the preoperative glomerular filtration rate was 88.53 ± 20.30 ml/(min*1.73m2), preoperative serum creatinine 81.83 ± 27.66 µmol/L. The expression of aldosterone synthase in adrenal specimens was detected postoperatively and staged according to the 2022 World Health Organization Consensus on Histopathology of PA. The 159 patients with PA were divided into low and high renin groups according to the lower limit of the reference range of renin level of 4.4 µIU/ml in our institution, respectively. Both clinical success and biochemical success including complete, partial and no success were assessed with reference to the 2016 Consensus on Prognostic Evaluation of PA Surgery Comparison. The prognosis of different aldosterone level groups was compared using non-parametric tests. There were 121 cases in the low renin group, of which 87 cases (71.90

Primary aldosteronism (PA) is a leading cause of secondary hypertension, but the lack of representative preclinical models hampers translational research and imaging evaluation. We aimed to establish a patient-derived organoids-based xenograft (PDOX) model of PA and to assess its imaging characteristics using [18F]AlF-NOTA-pentixather PET/CT, with validation in clinical patients. Adrenal tissues from patients with PA were used to generate adrenal organoids in vitro. After serial passaging, these organoids were implanted subcutaneously into immunodeficient mice to establish PA PDOX models. The xenografted mice were subjected to [18F]AlF-NOTA-pentixather PET/CT to evaluate tracer uptake and lesion detectability. In parallel, clinical PA patients underwent [18F]AlF-NOTA-pentixather PET/CT to assess the imaging performance in a clinical setting. The PDOX models successfully engrafted and proliferated in vivo, maintaining key pathological features of PA. [18F]AlF-NOTA-pentixather PET/CT imaging in the PDOX models demonstrated high and specific tracer uptake in xenografted lesions, with strong concordance to histopathological findings. In clinical PA patients, [18F]AlF-NOTA-pentixather PET/CT also showed excellent performance in localizing PA lesions and provided valuable diagnostic information. We established a novel PDOX model of PA and demonstrated the effectiveness of [18F]AlF-NOTA-pentixather PET/CT in both preclinical and clinical applications. This approach provides a robust translational platform for mechanistic studies and for advancing precision imaging and therapy in PA.

Background: There is inconsistent evidence regarding obesity's effect on surgical outcomes following retroperitoneal laparoscopic adrenalectomy (RLA). This study aimed to investigate the influence of obesity on surgical outcomes in patients undergoing RLA, with an emphasis on operative time, drainage tube removal time, postoperative hospital stays and perioperative complications. Methods: In this retrospective, single-center, observational study, all consecutive cases of unilateral RLA for adrenal disease from January 2012 to December 2021 were incorporated. The patients were divided into two groups based on their body mass index (BMI) of 28 kg/m 2 . To mitigate selection bias, propensity score matching (PSM) was conducted, using logistic regression to calculate propensity scores for balancing baseline characteristics. A multivariate logistic regression analysis was performed to assess how obesity affects operative time and intraoperative blood loss as well. The linear correlation between BMI and surgical outcomes, including prolonged operative time and increased intraoperative blood loss, was also examined using restricted cubic spline (RCS) analysis. Results: A total of 569 patients who underwent RLA were included. After PSM, 122 patients were apportioned to each group. Statistically significant differences were observed between the obese and nonobese group in operative time (97.5 vs. 115 min, P<0.001). There were no statistically significant differences between the two groups regarding hospital stay (6.7 vs. 6.8 days, P=0.58), drainage tube removal time (3.0 vs. 3.0 days, P=0.19), nor postoperative complications (9.0% vs. 12.3%, P=0.41). Furthermore, univariate logistic regression analysis revealed that, obese patients undergoing RLA were linked to prolonged operative time and increased intraoperative blood loss. After adjusting for potential confounders, the obese group showed a 67% increased risk of prolonged operative time and a 69% increased intraoperative blood loss. The RCS analysis revealed that BMI had a linear relationship with operative time (P for nonlinearity =0.47) and blood loss during surgery (P for linearity =0.89). Conclusions: In patients undergoing RLA, obesity exerts a significant influence on surgical outcomes, particularly with regard to operative time and intraoperative blood loss, as shown in multivariable logistic regression analysis and PSM to balance baseline characteristics.

BACKGROUND:Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA).METHODS:In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital.RESULTS:We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort.CONCLUSIONS:Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.

Background Ferroptosis and disulfidptosis are regulatory forms of cell death that play an important role in tumorigenesis and progression. However, few biomarkers about disulfidptosis and ferroptosis related genes (DFRGs) have been developed to predict the prognosis of bladder cancer (BC). Methods We conducted a bioinformatics analysis using public BC datasets to examine the prognostic significance of differentially expressed DFRGs. A Lasso regression was employed to create a prognostic prediction model from these DFRGs. Hub DFRGs that play a role in immunotherapy response and immunoregulation were pinpointed. Immunohistochemistry (IHC) experiment was performed to assess NUBPL and c-MYC expression in BC patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy at Peking University Cancer Hospital. Results We constructed a valid model to predict the prognosis of BC based on DFRGs and performed relevant validation, the results demonstrated that the model was an independent prognostic factor for BC. Further analysis indicated that the model score, combined with the expression of various immune factors and tumor mutation burden (TMB), could predict the prognosis for BC. In addition, we also found that NUBPL was strongly associated with prognosis and response to ICI treatment, and NUBPL may influence BC malignant progression through the c-MYC pathway. Conclusions Our research findings highlight the satisfactory predictive value of DFRGs in the immune microenvironment and suggest that NUBPL may be a highly promising biomarker for predicting the prognosis and efficacy of ICI treatment in BC patients.

Background Lateral retroperitoneal laparoscopic adrenalectomy (LRLA) is widely performed for the resection of adrenal disorders, but when larger and more malignant lesions are involved, the difficulty of LRLA increases. We aimed to develop and evaluate a predictive model for the surgical difficulty of LRLA. Methods A retrospective, observational, single-center study was performed involving all consecutive cases of unilateral RLA for adrenal disease from 2012.01 to 2021.12. Cases were randomly divided into training and validation cohorts (split ratio =7:3), then the least absolute shrinkage and selection operator (LASSO) regression was applied to reduce data dimension and select predictors. Multivariate logistic regression followed to develop the prediction nomogram for the surgical difficulty of LRLA. Finally, receiver operating characteristic (ROC) curve, calibration curve plot and decision curve analysis (DCA) were used to evaluate the nomogram’s discrimination, calibration, and clinical usefulness, respectively. Results A total of 621 cases were enrolled with a median age of 53 years and a median tumor diameter of 1.7 cm. After LASSO regression analysis, surgeon’s experience, tumor diameter, resection procedure, histological type, patient’s sex and body mass index (BMI) were identified to establish the nomogram. The model displayed good discrimination with area under the curve (AUC) in both the training cohort (0.754, 95% CI: 0.701–0.806) and validation cohort (0.742, 95% CI: 0.646–0.838). Additionally, excellent calibration curves were revealed for surgical difficulty evaluation in both the training cohort (P=0.999) and validation cohort (P=0.444). DCA results indicated the prediction model was clinically useful. Conclusions Our novel and effective predictive model can be used to assess the individual surgical difficulty of LRLA. By stratifying patients at risk of having a difficult LRLA for adrenal disease, the model could contribute to improvements in perioperative strategy and therapy.

Background: Studies have shown that the circulating tumor cells (CTCs) play a key role for invasion and formation of distant metastases in prostate cancer (PCa). However, few CTCs-related genes (CRGs) have been developed for biochemical recurrence (BCR) prediction and clinical applications of PCa patients. Materials and methods: Bioinformatics analysis with public PCa datasets were used to investigate the relationship between the differentially expressed CRGs and BCR. Lasso-COX regression analysis was used to constructed and validated a CRGs-based BCR prediction signature for PCa. Single-cell data were used to validate the expression levels of signature genes in different cell types and then explored the cell-cell communication relationships. Finally, the expression levels of signature genes were verified and the CRGs involved in immunotherapy response were further identified. Results: Thirteen CRGs were differentially expressed and closely associated with BCR in PCa. Then we constructed and validated a BCR prediction signature for PCa patients based on 3 differentially expressed CRGs (EMID1, SPP1 and UBE2C), and the signature was an independent factor to predict BCR for PCa. Single-cell data showed the specific expression patterns of the signature genes, while the SPP1 pathway plays an important role in cell-cell communication. Further analyses suggested UBE2C was highly expressed in BCR group and high expression of UBE2C had a better response for patients who received immunotherapy. Moreover, the expression levels of UBE2C in CTCs were higher than other cells and tissues, indicated that UBE2C may affect the BCR event of PCa patients through CTCs. Conclusion: Our findings demonstrated that CRGs were significantly associated with BCR and immunotherapy efficacy in PCa and CRGs may influence the BCR event through CTCs.

Objective:To explore the risk factors of prolonged operation time and higher intraoperative blood loss of retroperitoneal laparoscopic radical nephrectomy (LRN).Methods:The data of patients who underwent retroperitoneal LRN from August 2010 to December 2021 were analyzed retrospectively. Demographic and hospital admission data were collected from these patients with complete medical records. Furthermore, univariate and multivariate logistic analysis were performed to determine the risk factor related to prolonged operation time and increased blood lose following LRN. Receiver operating characteristic (ROC) curve was used to assess the value of risk factors for predicting prolonged operation time and high intraoperative blood loss.Results:A total of 22 patients (24.4%) had prolonged operation time, and 14 patients (15.6%) had high intraoperative blood loss. The risk factor associated with prolonged operation time in a multivariate analysis was surgical experience (OR=0.13, P<0.001). The area under the ROC curve was 0.759 (95% confidence interval: 0.638-0.880) in the multivariate logistic regression model for predict prolonged operation time. Those associated with high intraoperative blood loss were surgical experience (OR=0.25, P=0.032) and tumor T stage (OR=3.18, P=0.007). The area under the ROC curve was 0.769 (95% confidence interval: 0.627-0.910) in the multivariate logistic regression model for predict high intraoperative blood loss.Conclusions:Surgical experience and tumor T stage were associated with the risk of prolonged operation time and high intraoperative blood loss.

Background: While laparoscopic adrenalectomy (LA) represents a gold standard for treating most adrenal lesions, no effective visual model for the prediction of perioperative complications of retroperitoneal laparoscopic adrenalectomy (RLA) exists.Methods: A retrospectively study was conducted involving all consecutive patients underwent unilateral RLA for adrenal disease from January 2012 to December 2021. The entire cohort was randomly divided into 2 subsets (70% of the data for training, 30% for validation). Subsequently, a Least Absolute Shrinkage Selection Operator (LASSO) regression was performed to select the predictor variables, which were further consolidated via random forest (RF) and Boruta algorithm. Then the nomogram was established using the bivariate logistic regression analysis. Eventually, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate discrimination, calibration and clinical usefulness of the model, respectively.Results: A total of 610 patients underwent unilateral RLA for adrenal diseases were enrolled. After machine learning analyses, a weighted nomogram was established with 7 factors associated with complications including operative time, lesion laterality, intraoperative blood loss, pheochromocytoma, body mass index (BMI) and 2 preoperative comorbidities (respiratory diseases, cardiovascular diseases (CVD)). The model displayed a fine calibration curve for perioperative complications evaluation in both the training dataset (P=0.847) and validation dataset (P=0.248). ROC with AUC revealed an excellent discrimination in the training dataset (0.817, 95% CI: 0.758-0.875) and validation dataset (0.794, 95% CI: 0.686-0.901). DCA curves showed that using this nomogram provided a more net benefit where threshold probabilities lay in the range of 0.1 to 0.9.Conclusions: An effective nomogram that incorporating 7 predictors was established in this study to identify patients at high risk of perioperative complications for RLA. It would contribute to the improvement of perioperative strategy due to its accuracy and convenience.

The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.

Objective:To investigate the experience, safety and feasibility of robot assisted simple prostatectomy for large volume benign prostatic hyperplasia (BPH).Methods:The clinical data of 21 patients who underwent robot assisted simple prostatectomy in our hospital from Jan. 2017 to Jan. 2021 were retrospectively analyzed, and the surgical procedures, intraoperative and postoperative problems were summarized.Results:All cases were operated successfully without conversion to open surgery. The average operation time was (135.7±23.2) min. The average blood loss was (168.4±21.5) ml without blood transfusion in all cases. Bladder irrigation time was within 24 h after operation. The average suprapubic catheter time was 2 days. The average drain time was 3 days, and the mean catheter time was (12.5±2.4) days. Post-void residual, international prostate symptom score (IPSS) and maximum urine flow were improved significantly 3 months after operation (P<0.01).Conclusions:Transperitoneal robot assisted simple prostatectomy is a safe and effective minimally invasive method for large volume benign prostatic hyperplasia, which may become an alternative treatment.

Objective:To analyze the side effects and complications in prostate cancer patients treated with brachytherapy.Methods:A total of 120 prostate cancer patients with average age of (73±5) years were recruited. All the patients were diagnosed as prostate cancer and accepted prostate brachytherapy from 2011 to 2019 under the guidance of transrectal ultrasound. The adverse reactions of urinary tract and their complications after prostate cancer 125I seed implantation were analyzed retrospectively.Results:A total of 120 patients with prostate cancer were collected and the clinical average Gleason score was (8.4±1.1). The IPSS scores of the patients were (13.1±3.6), (21.6±4.6), (19.2±4.4), (15.9±3.9), (13.9±3.1) and (13.5±2.7) before operation, 1 month after operation, 3 months after operation, half a year after operation, 1 year after operation and 2 years after operation, respectively. The incidence of grade I and grade II complications was 14.2% and 5.8% respectively within 1 month after operation, and 5.0% and 2.5% respectively within 3 months after operation. There were no grade III or IV complications.Conclusions:Prostate brachytherapy is a minimally invasive treatment for prostate cancer. Although the implantation of particles has a certain impact on the urination of patients, but the degree is relatively light, with a certain degree of self-limiting. Intraoperative accurate localization and making accurate implantation plan are factors to the prevention of serious complications.

Background Recently, there are growing evidence indicated that pyroptosis play a critical role in the incidence of many diseases. Here, we aimed to identify the specific function and prognosis predictive of pyroptosis-related genes (PRGs) in bladder cancer (BLCA) patients. Methods The gene expression and corresponding clinical data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA), and the expression level of PRGs was identified between normal and tumor tissues. Furthermore, univariate Cox regression was conducted to filter the PRGs related to overall survival, and LASSO Cox regression was subsequently conducted to establish the PRGs risk model. Besides, the correlation of risk score with patients’ clinical features, tumor mutational burden (TMB) as well as tumor microenvironment (TME) was also investigated. Results A total of 6 PRGs was used to establish the risk prognostic model. According the median value of risk score, the patients were classified into low- and high-risk subgroup. Kaplan-Meier survival analysis revealed that the BLCA patients in low-risk group exhibited a better survival prognosis compared with high-risk group. More important, after adjusting for age, gender, tumor grade, and clinical stage, the risk score resulted as an independent factor affecting the clinical prognosis of BLCA patients. In addition, the PRGs risk signature was also correlated with immune cell infiltration, TMB and TME. Conclusions The present study offered a novel PRGs risk model to access the clinical prognosis of BLCA and provided new insight for future study to improve overall survival and responses to cancer therapy targeting pyroptosis.

Objective:To explore the risk factors associated with postoperative complications and prolonged length of stay (LOS) following retroperitoneal laparoscopic radical nephrectomy (LRN).Methods:A retrospective data gathering from 103 patients in Beijing Anzhen hospital who underwent retroperitoneal LRN from Aug. 2010 to Aug. 2021 was conducted. The demographic and clinical data of the patients, including age, gender, Body Mass Index (BMI), comorbidities, American Society of Anesthesiologists (ASA) score, previous abdominal surgery, tumor size, T stage, intraoperative blood loss, intraoperative blood transfusions, postoperative complications and postoperative length of stay, were retrospectively collected. We examined the overall postoperative complications, which were categorized using the Dindo-Clavien classification system. A prolonged LOS was quantified in terms of postoperative hospital stay >10 days, which was defined as LOS >75th percentile of the dataset. Furthermore, univariate and multivariate logistic analysis were performed to identify the risk factor related to postoperative Clavien-Dindo complications and prolonged LOS.Results:Overall, 103 participants participated in the study. A total of 16 cases (15.5%) suffered postoperative complications of Clavien-Dindo classification grade of 2 or more, and 17 cases (16.5%) had prolonged LOS. The risk factors associated with an increased prevalence of postoperative complications in a multivariate analysis were: operation time ≥240 minutes (OR: 5.17, P=0.024) and intraoperative blood loss >300 ml (OR: 22.89, P=0.001). Those associated with an increased prevalence of prolonged LOS was intraoperative blood transfusion (OR: 9.94, P=0.023).Conclusions:Postoperative complications and prolonged LOS following LRN were related to intraoperative blood loss, operative time, and intraoperative blood transfusion.

Among many factors of causing castration-resistant prostate cancer (CRPC) progression, a growing number of evidences have shown androgen receptors play a critical role. Therefore, blocking androgen receptor remains a therapeutic goal of CRPC. However, resistance to androgen receptor inhibitors, for example, enzalutamide, limits therapeutic efficacy for many patients. In this study, to develop an enzalutamide-resistant cell model for molecular mechanism investigation of enzalutamide-resistance, we continuously treated C4-2B cells with multiplied concentrations of enzalutamide. The IC50 of resistant cells was identified as 14.7705 µM, and the resistance index was calculated as 12.4. In addition, we verified the resistance of resistant cells through experiments in vivo and found the genes in androgen receptor signaling pathway (androgen receptor, Jagged1, Notch1) and those in androgen receptor alternative signaling pathways behaved the opposite. For some of the former, their mRNA and protein expression reduced markedly while for the latter, for example, CXCR7, AKT, STAT3, FOXP3, they rose dramatically in the expression level of protein and mRNA. More importantly, the tumor volume, tumor wet weight, PSA and VEGF secretion level, positive staining rate of Ki67 nuclei in resistant strain heterogeneous tumor treated with enzalutamide were significantly higher than those of maternal cell heterogeneous tumor treated with enzalutamide, whereas no obvious difference was detected between resistant strain heterogeneous tumor treated with enzalutamide and those of the resistant strain treated with reference drug. Finally, we identified 654 differentially expression genes and 2 compounds (atracurium besilate, methotrexates) associated with the amelioration of enzalutamide-resistance. Overall, we successfully established an enzalutamide-resistance cell model and screened out some resistance genes and candidate small molecule drugs.

Purpose To identify the differences in oncological outcomes for patients with different pT3a renal tumor invasion patterns and pathological features. Methods The protocol of this study was registered on PROSPERO (CRD42021234475). Relevant studies were identified by searching the PubMed, Cochrane library, Embase, and Web of Science databases. Cancer-specific survival (CSS) was selected as the endpoint. Pooled hazard ratio (HR) and 95% confidence interval (CI) extracted from multivariate Cox models were evaluated to identify the hazard association. Results A total of 22 studies, which enrolled 12384 patients were included for quantitative synthesis. Sinus fat invasion (SFI) + perinephric fat invasion (PFI) was associated with inferior CSS compared to SFI only (p = 0.02). Comparable CSS was observed between SFI and PFI (p = 0.57). SFI +/- PFI showed inferior CSS compared to PFI only (p = 0.0002). The presence of pelvicalyceal system invasion significantly increased the risk of cancer-specific mortality (p = 0.0005). Renal vein invasion (RVI) indicated poor oncological outcomes in terms of CSS (p = 0.002). The concomitant RVI and fat invasion (FI) significantly increased the risk of deterioration of CSS compared to RVI or FI (p < 0.0001). Multiple invasion patterns translated into a significantly decreased CSS (p < 0.0001). Aggressive tumor behavior, including lymph node involvement (p = 0.006), distant metastases (p < 0.00001), sarcomatoid differentiation (p < 0.0001), necrosis (p < 0.0001), Fuhrman grade III or IV (p < 0.0001), positive margin (p < 0.0001), and tumor size >7cm (p < 0.0001) were the predictors of inferior CSS. The lymphovascular invasion (p = 0.67) was indolent in terms of CSS. Conclusion This study confirmed the heterogenicity of pT3a renal tumors. Multiple invasion patterns could translate into a significantly decreased CSS, and SFI should not be merged in the SFI + PFI group. The presence of PSI or RVI could significantly increase the risk of cancer-specific mortality. Lymph node involvement, distant metastases, sarcomatoid differentiation, necrosis, high Fuhrman grade, positive margin, and size >7cm were the predictors of inferior CSS. A precise-risk grade of CSS for different invasion patterns including comprehensive combinations may be useful for the further refinements of the TNM system. Systematic Review Registration The current study was registered on PROSPERO, and the registration numbers is CRD42021234475.

背景与目的 去势抵抗性前列腺癌阶段的恩杂鲁胺耐药问题是临床上亟待解决的难题.本研究旨在建立一种可用于体外研究的人前列腺癌(prostate cancer,PCa)恩杂鲁胺(enzalutamide Enza)耐药细胞模型并筛选相关耐药基因.方法 采用MTT法检测雄激素非依赖的人PCa细胞株C4-2B的IC50值,确定Enza的初始处理浓度.然后,成倍增加Enza的初始浓度作用于C4-2B细胞,诱导建立PCa的Enza耐药细胞株(命名为C4-2B-ENZ).应用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)、MTT法评估C4-2B-ENZ细胞株的耐药情况.采用聚合酶链式反应(polymerase chain reaction,PCR)及蛋白质免疫印迹检测耐药细胞株mRNA和蛋白质的表达情况.在此基础上,通过裸鼠体内成瘤实验,ELISA法检测人前列腺特异性抗原(prostate specific antigen,PSA)和人血管内皮生长因子(vascular endothelial growth factor,VEGF)水平,免疫组化检测Ki67水平,进一步验证C4-2B-ENZ细胞的耐药性.最后,应用高通量芯片技术进一步筛选C4-2B与C4-2B-ENZ细胞差异表达的基因.结果 C4-2B细胞的IC50值为1.2μmol/L,C4-2B-ENZ细胞的IC50为14.77μmol/L,其耐药指数为12.4,属于中度耐药.蛋白质免疫印迹和PCR结果显示,与C4-2B细胞相比,C4-2B-ENZ细胞中Enza耐药基因CXCR7、AKT、STAT3、FOXP3的mRNA及蛋白质高表达,而AR、Jagged1、Notch1低表达.与C4-2B细胞异质瘤相比,耐药细胞C4-2B-ENZ异质瘤Enza处理后,瘤体生长曲线(P=0.0296)、瘤体质量(P<0.0001)、VEGF水平(P=0.0003)、PSA水平(P<0.0001)、Ki67胞核染色阳性率(P=0.0007)均显著升高.芯片筛选结果显示,与C4-2B细胞相比,C4-2B-ENZ细胞中有653个基因表达显著差异,其中211个基因表达上调,443个基因表达下调.结论 本研究建立了Enza耐药细胞模型并筛选出一些潜在的Enza耐药基因,为研究去势抵抗型前列腺癌耐药机制及药物靶点提供了研究线索.