Diagnostic performance of regional systematic biopsy for prostate cancer stratified by PI-RADS and histologic zones.

OBJECTIVES: To explore the diagnostic performance of targeted biopsy (TB) combined with regional systematic biopsy (RSB) in patients with different Prostate Imaging Reporting and Data System (PI-RADS) and histologic zones for prostate lesions. METHODS: This retrospective study included 1301 patients who underwent multiparametric MRI followed by combined MRI/US fusion-guided TB+systematic biopsy (SB) between January 2019 and October 2022. RSB was defined as the four perilesional SB cores adjacent to an MRI-positive lesion. Cancer detection rates were calculated for TB + SB, TB, SB, and TB + RSB, while the McNemar test was utilized for multiple comparisons among them. Subgroup analyses were performed based on different Pl-RADS and histologic zones. RESULTS: Of 1301 included participants (median age, 68 years; interquartile range, 63-74 years), 16,104 total biopsy cores were performed. TB + RSB detected clinically significant prostate cancer in 70.9% (922/1301) of patients, which was significantly higher than TB (67.4%, p < 0.001) or SB (67.5%, p < 0.001) but similar to TB + SB (71.0%, p = 0.50). Compared with TB + SB, TB + RSB required fewer median biopsy cores (6.3 vs. 12.4, p < 0.001) and had a higher proportion of positive cores (56.3% vs. 39.0%, p < 0.001). Subgroup analysis showed that TB had outstanding sensitivity for detecting PI-RADS 5 lesions in the PZ. CONCLUSIONS: Compared with TB + SB, TB + RSB achieved a similar clinically significant prostate cancer detection rate while requiring fewer biopsy cores and exhibiting higher diagnostic efficiency. CRITICAL RELEVANCE STATEMENT: For MRI-positive prostate lesions, targeted biopsy combined with regional systematic biopsy could serve as an alternative diagnostic approach to targeted biopsy combined with systematic biopsy. KEY POINTS: The scheme of prostate biopsy needs to be optimized. Regional systematic biopsy decreases the total number of cores taken. Targeted biopsies combined with regional systematic biopsies improve prostate diagnostic efficiency.

Comparative analysis of salvage partial nephrectomy versus radical nephrectomy after the failure of initial partial nephrectomy.

OBJECTIVES: To compare the oncologic outcomes and renal function discrepancy of salvage partial nephrectomy (sPN) and salvage radical nephrectomy (sRN) after an initial failed PN. MATERIALS AND METHODS: Retrospective data from multiple centers between 2008 and 2022 were analyzed in this study. Patients who received sPN or sRN after an initial failed PN were identified. Comparative analysis and propensity score matching (PSM) was performed and the RENAL score, tumor size, and pathological T stage at salvage surgery were used to match the 2 groups. Local recurrence-free survival (LRFS) and recurrence-free survival (RFS) were assessed using the Cox proportional hazards model and log-rank tests. Renal function after salvage surgery was assessed using the Wilcoxon rank sum test. RESULTS: A total of 140 patients who underwent salvage surgery were evaluated, of whom 60 were considered for PSM analysis after matching. At a median follow-up of 27.0 months, LRFS and RFS showed no significant difference between sPN and sRN, either before (LRFS, HR = 0.673 [95% CI: 0.171-2.644], P = 0.610; RFS, HR = 0.744 [95% CI: 0.271-1.344], P = 0.595) or after matching (LRFS, HR = 1.080 [95% CI: 0.067-17.30], P = 0.957; RFS, HR = 1.199 [95% CI: 0.241-5.983], P = 0.822). During long-term follow-up, sPN preserved renal function (after matching, eGFR, 71.4 vs. 54.0, P < 0.001) and prevented eGFR loss (after matching: 6.6% vs. 25.6%, P < 0.001). CONCLUSION: Salvage partial nephrectomy offers a better alternative than sRN for recurrence after initial PN, as sPN preserves renal function better while maintaining parallel tumor control and acceptable complication rates.

Surgical techniques and oncological outcomes of pure transperitoneal laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma.

Background: Open radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for upper urinary tract urothelial carcinoma (UTUC). Traditional laparoscopic radical nephroureterectomy (LSRNU) is not minimally invasive enough due to the complex surgical procedure. This study aims to discuss the clinical feasibility and oncological outcomes of pure transperitoneal LSRNU for UTUC. Methods: Between July 2010 and December 2020, 115 patients were admitted to the hospital with the diagnosis of UTUC treated with pure LSRNU by one surgeon. A special laparoscopic bulldog clamp was placed at the bladder cuff before cutting and suturing. The clinical and follow-up data were preoperatively collected and analyzed. Overall survival (OS) and cancer-specific survival (CSS) were estimated by the Kaplan-Meier method. Results: All surgeries were completed uneventfully in this cohort. The mean operative time was 145.69 minutes. The mean estimated blood loss was 56.61 mL. The mean removal time of the drain was 3.46 days. The mean time of having liquid diet was 1.32 days, and the ambulation time was 1.50 days. All surgeries were effectively completed, and no case required open conversion. According to the Clavien-Dindo classification system, postoperative complications occurred in two patients (II, III). The mean length of postoperative hospital stay was 5.78 days. The mean follow-up duration was 54.50 months. Recurrence in the bladder was 16.0% (15/94), compared with 4.6% (4/87) in the contralateral upper tract. The 5-year OS and CSS rates were 78.9% and 81.4%, respectively. Conclusions: Pure transperitoneal LSRNU is a safe and effective minimally invasive technology for the treatment of UTUC.

Integrated analysis to identify the prognostic and immunotherapeutic roles of coagulation-associated gene signature in clear cell renal cell carcinoma.

The coagulation system is closely related to the physiological status and immune response of the body. Recent years, studies focusing on the association between coagulation system abnormalities and tumor progression have been widely reported. In clear cell renal cell carcinoma (ccRCC), poor prognosis often occurs in patients with venous tumor thrombosis and coagulation system abnormalities, and there is a lack of research in related fields. Significant differences in coagulation function were also demonstrated in our clinical sample of patients with high ccRCC stage or grade. Therefore, in this study, we analyzed the biological functions of coagulation-related genes (CRGs) in ccRCC patients using single-cell sequencing and TCGA data to establish the 5-CRGs based diagnostic signature and predictive signature for ccRCC. Univariate and multivariate Cox analyses suggested that prognostic signature could be an independent risk factor. Meanwhile, we applied CRGs for consistent clustering of ccRCC patients, and the two classes showed significant survival and genotype differences. The differences in individualized treatment between the two different subtypes were revealed by pathway enrichment analysis and immune cell infiltration analysis. In summary, we present the first systematic analysis of the significance of CRGs in the diagnosis, prognosis, and individualized treatment of ccRCC patients.

Special issue "The advance of solid tumor research in China": Presurgical therapy in the management of local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy.

Local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) is rare in patients with renal cell carcinoma (RCC); however, it is associated with poor prognosis and lacks standard treatment. Our study aimed to assess oncological outcomes and prognostic factors of patients that underwent targeted therapy for RPR after RN, and to evaluate the role of presurgical targeted therapy in this context. This was a retrospective multicenter study of 85 patients with RPR treated with targeted therapy for RPR after RN (July 2008-October 2020). Clinical and pathological characteristics were reported using descriptive statistics. Cancer-specific survival (CSS) was examined using the Cox proportional hazards model. The median follow-up time was 50 months (95% confidence interval [CI]: 33.3-66.7) after the RPR diagnosis. The median CSS was 96 months in the presurgical targeted therapy followed by surgical resection group and 42 months (95% CI: 28.8-55.2) in the targeted therapy alone group (P = .0011). In multivariate analysis, International Metastatic RCC Database Consortium classification intermediate/poor risk, number of recurrence lesions and surgical resection were independent predictors of CSS. Presurgical targeted therapy may increase the feasibility of tumor resection for RPR after RN. Patients who underwent surgical resection following presurgical targeted therapy had better CSS than those treated with targeted therapy alone.

Surgical Management and Oncologic Outcomes for Local Retroperitoneal Recurrence of Renal Cell Carcinoma After Radical Nephrectomy.

INTRODUCTION: Local retroperitoneal recurrence (RPR) after racial nephrectomy (RN) of renal cell carcinoma (RCC) remains a therapeutic challenge and has a poor prognosis. We aimed to compare the oncological outcomes of patients with RPR treated with RPR surgery or targeted therapy alone and assess the prognostic factors of these patients. PATIENTS AND METHODS: This is a retrospective multi-center study of patients with RPR after prior RN treated with or without surgical treatment from 2008 to 2020. RPR of RCC is defined as an ipsilateral recurrence confined to the renal fossa, adrenal gland or retroperitoneal lymph nodes after prior nephrectomy, which was diagnosed by cross-sectional imaging. Clinical and pathological features, perioperative complications were reported using descriptive statistics. Cancer-specific survival (CSS) was evaluated by Kaplan-Meier method and studied using Cox proportional hazards model. RESULTS: Median follow-up period was 35 months (IQR 20-61) for the RPR surgery group and 23 months (IQR 9-40.5) for the targeted therapy group. No patients had distant metastatic disease at the time of RPR diagnosis. Treatment with RPR surgery resulted in significantly longer CSS than targeted therapy alone (P < .001). In multivariable analysis, high Fuhrman grade, size of RPR tumor, mixed type of RPR, multiple recurrence lesions and the absence of RPR surgery were associated with a significantly increased risk of death from RCC. CONCLUSION: Aggressive surgical resection of RPR after RN represents a potentially curative treatment for selected RCC patients without synchronous metastases, resulting in significantly longer CSS than targeted therapy alone.

Robot-assisted Partial Nephrectomy with the Newly Developed KangDuo Surgical Robot Versus the da Vinci Si Surgical System: A Double-center Prospective Randomized Controlled Noninferiority Trial.

BACKGROUND: The KangDuo surgical robot (KD-SR) was recently developed in China. OBJECTIVE: To compare the safety and efficacy of the KD-SR versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted partial nephrectomy (RAPN). DESIGN, SETTING, AND PARTICIPANTS: A double-center prospective randomized controlled noninferiority trial of patients aged 18-75 yr with a suspicion of T1a N0M0 renal cancer (RENAL nephrometry score ≤9) was conducted. INTERVENTION: RAPN with the KD-SR versus the DV-SS-Si. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the success rate of operation. The operation was successful if (1) there was no open or laparoscopic conversion, (2) the warm ischemia time was <30 min for RENAL nephrometry scores of 4-6 or 40 min for RENAL nephrometry scores of 7-9, and (3) the pathological margin was negative. The secondary endpoint was the estimated glomerular filtration rate (eGFR). A threshold of 10% was set to demonstrate noninferiority. RESULTS AND LIMITATIONS: From September 2020 to March 2021, 100 participants were enrolled, of whom 99 (49 in the KD-SR group and 50 in the DV-SS-Si group) were finally included in the full analysis set and 98 (49 in the KD-SR group and -49 in the DV-SS-Si group) in the per-protocol set. Baseline demographic and clinical characteristics were similar between the two groups. All surgeries were completed successfully. The eGFR at postoperative weeks 4-12 and adverse events were similar between the two groups. The docking time and suture time per stitch were longer in the KD-SR group. The main limitation was that a negative margin was considered as the primary outcome rather than survival. CONCLUSIONS: The KD-SR achieved noninferior outcomes as compared with the DV-SS-Si regarding safety and efficacy for T1a tumors. PATIENT SUMMARY: The first trial comparing the KangDuo surgical robot (KD-SR) versus the da Vinci Si Surgical System for robot-assisted partial nephrectomy showed that the KD-SR is a viable option for minimally invasive treatment of T1a renal tumors.

Identification of a claudin-low subtype in clear cell renal cell carcinoma with implications for the evaluation of clinical outcomes and treatment efficacy.

Background: In bladder and breast cancer, the claudin-low subtype is widely identified, revealing a distinct tumor microenvironment (TME) and immunological feature. Although we have previously identified individual claudin members as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC), the existence of an intrinsic claudin-low subtype and its interplay with TME and clinical outcomes remains unclear. Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA)- kidney clear cell carcinoma (KIRC) cohort and E-MTAB-1980 were derived as the training and validation cohorts, respectively. In addition, GSE40435, GSE53757, International Cancer Genome Consortium (ICGC) datasets, and RNA-sequencing data from local ccRCC patients were utilized as validation cohorts for claudin clustering based on silhouette scores. Using weighted correlation network analysis (WGCNA) and multiple machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), CoxBoost, and random forest, we constructed a claudin-TME related (CTR) risk signature. Furthermore, the CTR associated genomic characteristics, immunity, and treatment sensitivity were evaluated. Results: A claudin-low phenotype was identified and associated with an inferior survival and distinct TME and cancer immunity characteristics. Based on its interaction with TME, a risk signature was developed with robust prognostic prediction accuracy. Moreover, we found its association with a claudin-low, stem-like phenotype and advanced clinicopathological features. Intriguingly, it was also effective in kidney chromophobe and renal papillary cell carcinoma. The high CTR group exhibited genomic characteristics similar to those of claudin-low phenotype, including increased chromosomal instability (such as deletions at 9p) and risk genomic alterations (especially BAP1 and SETD2). In addition, a higher abundance of CD8 T cells and overexpression of immune checkpoints, such as LAG3, CTLA4 and PDCD1, were identified in the high CTR group. Notably, ccRCC patients with high CTR were potentially more sensitive to immune checkpoint inhibitors; their counterparts could have more clinical benefits when treated with antiangiogenic drugs, mTOR, or HIF inhibitors. Conclusion: We comprehensively evaluated the expression features of claudin genes and identified a claudin-low phenotype in ccRCC. In addition, its related signature could robustly predict the prognosis and provide guide for personalizing management strategies.

Construction and validation of a ferroptosis-related long noncoding RNA signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear. METHODS: After sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients. RESULTS: The prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients. CONCLUSIONS: Our study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database. Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses. Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system. Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.

The Evolution of Clinicopathological Diagnostic Features of Upper Tract Urothelial Carcinoma in China: A Summary of 2561 Cases in the Last 20 Years.

Objectives: To summarize the clinicopathological diagnostic features and evolutionary trends of upper tract urothelial carcinoma (UTUC) in China over the past 20 years. Methods: All patients diagnosed with upper tract urothelial carcinoma in the Peking University First Hospital from 2001 to 2020 were retrospectively collected. Data were divided into two groups (2001-2010 and 2011-2020) according to the date of diagnosis. Statistical analysis was done with the SPSS V22.0. Chi-square analysis and t-test were adopted to analyze depending on the data type. Subgroup analysis based on 5 years was used for visualization to present trends. Both Kaplan-Meier curve and Cox regression were used for univariate and multivariate survival analysis. Results: The study included 2561 cases diagnosed with upper tract urothelial carcinoma in total. Compared with the first decade (2001-2010), patients of the second decades (2011-2020) had elder mean age (66.65 versus 67.59, years, p=0.025), higher male proportion (43.5% versus 49.0%, p=0.034), lower incidence of renal pelvic tumors (53.4% versus 45.8%, p<0.001) and multifocality (18.6% versus 12.0%, p<0.001), higher incidence of ureteral tumors (52.2% versus 60.9%, p<0.001).In recent ten years, the incidence of muscle-invasive urothelial carcinoma (pT2+) decreased significantly (64.4% versus 54.9%, p<0.001),and the mean size of renal pelvic tumors increased(3.46 versus 3.73, cm, p=0.043). The size of the ureteral tumor, the histopathologic grade showed no significant change. The prognostic analysis based on 709 patients regularly followed at our center revealed that the male gender and G3 histopathological grade were independent risk factors for poorer prognosis in patients with UTUC. Conclusion: In the past 20 years, the clinicopathological diagnostic features of upper tract urothelial carcinoma in the Chinese population has changed significantly, suggesting an increased risk of a poorer prognosis for UTUC. This trend may be related to updating diagnostic techniques and self-monitoring awareness. However, we need more high-grade, multicenter trials to verify it in the future.

MiR-182-5p inhibits the tumorigenesis of clear cell renal cell carcinoma by repressing UBE2T.

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. However, the role of UBE2T in clear cell renal cell carcinoma (ccRCC) has not been clarified. MicroRNAs (miRNAs) participate in tumorigenesis by binding to genes and proteins that regulate cell proliferation or cell apoptosis. The aim of this study was to determine the role of UBE2T and the relationship between miR-182-5p and UBE2T in ccRCC. In the present study, UBE2T expression levels in ccRCC tissues and cells were assessed using real-time quantitative PCR (RT-qPCR) and western blotting. UBE2T protein expression was assessed in a total of 93 ccRCC patients from Peking University First Hospital (PKU) via immunohistochemistry (IHC). The effects of UBE2T knockdown on ccRCC cells were assessed with MTS assays, wound healing assays, Transwell invasion assays and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. The relationship between miR-182-5p and UBE2T was verified with a dual-luciferase reporter gene assay. We found that UBE2T was highly expressed in ccRCC cells and tissues. High UBE2T expression was positively correlated with advanced pathological stage, histological grade, maximum tumor diameter and distant metastasis. Multivariate analysis revealed that UBE2T expression was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in patients with ccRCC. Knockdown of UBE2T significantly suppressed RCC cell proliferation, migration and invasion. Flow cytometry analysis showed that UBE2T knockdown promoted RCC cell cycle arrest at G2/M phase and increased cell apoptosis. The xenograft model confirmed that suppression of UBE2T significantly delayed tumor formation and growth in vivo. In addition, miR-182-5p inhibited UBE2T protein expression by targeting UBE2T mRNA and then inhibited the proliferation, migration and invasion of ccRCC cell. Our research reveals that UBE2T likely plays a critical role in ccRCC progression and may be a potential therapeutic target for ccRCC.

NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer.

The high incidence and vulnerability to recurrence of bladder cancer (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in BLCA has not been elucidated. In this study, NFE2L3 expression was significantly increased in BLCA samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival and metastasis-free survival in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited BLCA cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition in BLCA cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

Natural history of Von Hippel-Lindau disease-associated and sporadic clear cell renal cell carcinoma: a comparative study.

PURPOSE: To compare the tumor growth kinetics between sporadic clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau disease-associated renal cell carcinoma (VHL-associated RCC). To analyze predictive markers for the growth rate of these two types of RCC. METHODS: The clinical data of patients with renal tumors who received active surveillance were collected retrospectively. Immunohistochemical staining was utilized to analyze the expression levels of VHL, PBRM1, H3K36me3, and BAP1 in the postoperative specimens. RESULTS: The age of the VHL group was significantly younger than that of the sporadic group (P < 0.0001). The mean linear growth rate (LGR) was significantly faster in the sporadic group (P = 0.0004). The tumors of those in the sporadic group tended to have a higher histologic grade (P = 0.0011). In the sporadic group, tumor histologic grade was an independent predictor for rapid mean LGR (P = 0.0022). In the VHL group, initial maximal tumor diameter (MTD) was the only independent predictor for rapid mean LGR (P < 0.0001). Tumors with low VHL expression and negative PBRM1 expression showed a faster growth rate in the sporadic group (P = 0.001 and P = 0.008, respectively). The expression levels of the four biomarkers showed no impact on the tumor growth rate in the VHL group. CONCLUSION: Sporadic ccRCC grew faster than VHL-associated RCC. High histologic grade, low VHL expression and negative PBRM1 expression were predictors of faster growth in sporadic ccRCC. A large initial MTD was a predictor of faster growth for VHL-associated RCC.

Partial nephrectomy through retroperitoneal approach with a new surgical robot system, KD-SR-01.

BACKGROUND: To present our experiences with partial nephrectomy (PN) through retroperitoneal approach (RP) with the Kangduo robotic system. METHODS: From December 2020 to February 2021, the perioperative data of 11 patients underwent PN through RP with the Kangduo robotic system were collected prospectively. RESULTS: For the R.E.N.A.L. nephrometry score, 72.7% of patients had a low score (4-6) and 27.3% of patients had a medium score (7-9). Seven tumours were posterior (P), four tumours were on the midline (X). All procedures were completed successfully. The median warm ischemia time was 18.5 (IQR, 13.7-21.0) min. None of the patients had positive surgical margins at definitive histology (all pT1a). No high-grade perioperative complications or device-related adverse events occurred. At a mean follow-up of 8 ± 0.8 months, no complications occurred in all patients. CONCLUSIONS: RPPN using the novel Kangduo robotic system is a safe and effective option for managing posterior and lateral renal tumours with R.E.N.A.L. nephrometry scores ≤9.

Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer.

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy. Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset. Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively. Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

Fluoroscopy-free minimally invasive ureteral stricture balloon dilatation: a retrospective safety and efficacy cohort study.

BACKGROUND: Traditional ureteral stricture balloon dilation was performed with fluoroscopic assistance. The use of a C-arm X-ray machine delivered hazardous radiation to both surgeons and patients. In attempt to eliminate the radiation hazard, we developed a F4.5/6.5 ureteroscope assisted intraoperative X-ray free balloon dilation surgical approach to treat ureteral stricture and to verify its safety and efficacy. Specifically, this method had not been previously reported in the literature. METHODS: We demonstrated an intraoperative X-ray free balloon dilation with detailed step-by-step procedures description and video illustration. Clinical data of patients undergoing minimally invasive endourological treatment for ureteral stricture between February 2015 and November 2019 were retrospectively analyzed. All steps of X-ray free balloon dilation were carried out under direct vision of a ureteroscope, and two indwelling F7 ureteral stents were used for 3 months postoperatively. Preoperative, intraoperative, and postoperative clinical data were evaluated, and follow-up results were reported. Successful outcome was defined as disappearance of preoperative symptoms, relief of hydronephrosis and stable of renal function. Univariate and multivariate prognostic analyses were performed. RESULTS: We identified 109 patients who received endourological treatment for ureteral stricture in our hospital's medical database. After excluding patients undergone simple catheter dilation, endoureterotomy and other treatment method, 76 patients received balloon dilation without intraoperative fluoroscopic guidance were included in our study. 4/76 patients report a grade II complication (urinary tract infections, UTIs) according to Clavien Dindo classification. In the 22.5 months median follow-up time, the one-year cumulative success rate and two-year cumulative success rate were 85.9% and 80.2% (61/76), respectively, and the majority (13/15, 86.7%) recurrence of ureteral stricture or hydronephrosis deterioration were found within two years after surgery. The longer stenotic lesion length (>5 mm) or multiple ureter stenosis and compromised blood supply of ureter were significantly associated with postoperative stenosis recurrence. CONCLUSIONS: X-ray free endoscopic balloon dilation is a safe and effective procedure that could be performed on patients with ureteral stenosis.

Natural history and growth kinetics of clear cell renal cell carcinoma in sporadic and von Hippel-Lindau disease.

BACKGROUND: To evaluate and compare the natural history and growth kinetics of sporadic clear cell renal cell carcinoma (ccRCC) with those of ccRCC in von Hippel-Lindau disease (VHL). METHODS: Sixty patients in the sporadic group with 61 tumors and 15 patients in the VHL group with 30 tumors whom all underwent delayed surgery after at least 12 months of active surveillance (AS) were enrolled to conduct a retrospective cohort study. The growth rate was calculated, and the growth kinetics between the sporadic and VHL groups were compared. The patient and tumor characteristics were reviewed, and their correlation with growth rate was analyzed. RESULTS: The mean growth rate of sporadic ccRCC was 0.91 cm/year (ranging from 0-4.74 cm/year) and that of VHL ccRCC was 0.47 cm/year (ranging from 0.04-1.89 cm/year). The growth rate of sporadic ccRCC showed a tendency of being faster than that of VHL ccRCC but did not reach statistical significance (P=0.07). The factors affecting the growth rate were different between the two groups. For VHL ccRCC, the only factor that correlated with growth rate was initial tumor diameter (P<0.001), but for sporadic ccRCC, the only factor was pathological nuclear grade (P<0.001). CONCLUSIONS: The growth rate of VHL-associated ccRCC might be slower than that of sporadic ccRCC. Furthermore, we identified a disparity in growth kinetics between sporadic and VHL-associated ccRCC.

Potent antitumour of the mTORC1/2 dual inhibitor AZD2014 in docetaxel-sensitive and docetaxel-resistant castration-resistant prostate cancer cells.

Recent studies indicate mammalian target of rapamycin (mTOR) may play an important role in PCa progression and drug resistance. Here, we investigated the effects of a novel mTORC1/C2 dual inhibitor, AZD2014, on naive and docetaxel (Doc)-pre-treated castration-resistant PCa (CRPC) cells and explored its therapeutic potential in CRPCs. In the current study, AZD2014 has a greater inhibitory effect against 4EBP1 and AKT phosphorylation than rapamycin in CRPC cells and prevented the feedback activation of AKT signalling. Importantly, AZD2014 suppressed CRPC cell growth in vitro by suppressing proliferation, apoptosis, cell cycle arrest at G1 phase and autophagy to a greater extent than rapamycin. Moreover, AZD2014 was more efficacious than rapamycin in inhibiting migration, invasion and EMT progression in Doc-sensitive and Doc-resistant CRPC cells. Overall, AZD2014 showed significant antitumour effects. Thereby, the current study highlights a reliable theoretical basis for the clinical application of AZD2014 in both Doc-sensitive and Doc-resistant CRPCs.

Identification of the Six-RNA-Binding Protein Signature for Prognosis Prediction in Bladder Cancer.

RNA-binding proteins (RBPs) are a kind of gene regulatory factor that presents a significant biological effect in the initiation and development of various tumors, including bladder cancer (BLCA). However, the RBP-based prognosis signature for BLCA has not been investigated. In this study, we attempted to develop an RBP-based classifier to predict overall survival (OS) for BLCA based on transcriptome analysis. We extracted data of BLCA patients from The Cancer Genome Atlas database (TCGA) and UCSC Xena. Finally, a total of 398 cases without missing clinical data were enrolled and six RBPs (FLNA, HSPG2, AHNAK, FASTKD3, POU5F1, and PCSK9) associated with OS of BLCA were identified through univariate and multivariate Cox regression analysis. Online analyses and immunohistochemistry validated the prognostic value and expression of six RBPs. Risk scores were calculated to divide patients into high-risk and low-risk level, and patients in the high-risk group tended to have a poor prognosis. In addition, the receiver operating characteristic (ROC) curve analysis was performed to assess the prognostic value of RBPs, and the area under the curve (AUC) values were 0.711 and 0.706, respectively, in the training set and validating set. The findings were further validated in an external validation set. Subsequently, the 6-RBP-based signature and pathological stage were used to construct the nomogram to predict the 3- and 5-years OS of BLCA patients. Also, this 6-RBP-based signature was highly related to recurrence-free survival of BLCA. Weighted co-expression network analysis (WGCNA) combined with functional enrichment analysis contributed to study the potential pathways of six RBPs, including keratinocyte differentiation, RHO GTPases activate PNKs, epithelial tube morphogenesis, establishment or maintenance of cell polarity, and so on. In summary, the 6-RBP-based signature holds the potentiality to serve as a novel prognostic predictor of OS for BLCA.