Neoadjuvant everolimus in renal angiomyolipoma with or without tuberous sclerosis complex: Results from a multicenter, retrospective study.

OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

HER2 expression in upper tract urothelial carcinoma and the relationship with clinicopathological characteristics-an analysis of 155 patients in Southwest China.

OBJECTIVE: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters. MATERIALS AND METHODS: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44. RESULTS: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0-112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6-38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported. CONCLUSION: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

ABSTRACT: This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

DNA methylation urine test in the diagnosis of upper tract urothelial carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The DNA methylation urine test, a non-invasive early detection method for upper tract urothelial carcinoma (UTUC), is currently in full swing. This study aimed to systematically assess its diagnostic performance on UTUC. MATERIALS AND METHODS: PubMed, Scopus, Embase, and Cochrane were our main databases when searching articles published from January 2000 to December 2023. Sensitivity and specificity were study primary endpoints. I2 was used to evaluated heterogeneity, meanwhile subgroup and meta-regression analyses were adopted to investigated the source of heterogeneity. Sensitivity analysis was performed to evaluate the result robustness, while Deeks' funnel plot asymmetry test was for the publication bias. RESULTS: Nine studies with 1326 patients were included. The pooled sensitivity was 0.89 (95% confidence interval (CI), 0.83-0.93) and specificity were 0.91 (95% CI, 0.83-0.96). The area under the receiver operating characteristic curve was 0.96 (95% CI, 0.93-0.97). Substantial heterogeneity was found during the data synthesis, whereas the pooled results remained robust in the sensitivity analysis. None of the potential covariates-urine sample collection method, population, country, methylation test method, or tumor grade-could account for the heterogeneity. CONCLUSION: DNA methylation urine test is a promising method with high efficiency for UTUC early detection. Nevertheless, owing to the significant heterogeneity, more well-organized studies are warranted to further explore its diagnostic efficiency and application context.

Transperineal 3-Core Magnetic Resonance Imaging Ultrasound Fusion Targeted Plus Laterally 6-Core Systematic Biopsy in Prostate Cancer Diagnosis.

INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.

Wnt/ß-catenin signaling pathway in carcinogenesis and cancer therapy.

The Wnt/ß-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/ß-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/ß-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/ß-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/ß-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.

The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

Serum α-hydroxybutyrate dehydrogenase as a biomarker for predicting survival outcomes in patients with UTUC after radical nephroureterectomy.

PURPOSE: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy. RESULTS: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively. CONCLUSION: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored.

Preoperative Systemic Inflammation Score Predicts the Prognosis of Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan-Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan-Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11-3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07-3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients.

Utilization trend of prebiopsy multiparametric magnetic resonance imaging and its impact on prostate cancer detection: Real-world insights from a high-volume center in southwest China.

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients.

OBJECTIVE: The expression and significance of human epidermal growth factor receptor 2 (Her2) in upper tract urothelial carcinoma (UTUC) remains controversial. Thus, we aimed to systemically review the Her2 expression in UTUC patients and its relationship with pathological characters and clinical outcomes with meta-analysis. MATERIALS AND METHODS: A systematically computerized search in PubMed, Scopus, Embase and Cochrane was conducted. From a total of 454 related articles, 35 articles were finally reviewed and 16 papers were chosen for further analysis. Pathological characters included tumor stage, grade, lymph node metastasis (LNM) and lymphovascular invasion (LVI). The clinical outcomes included overall survival (OS), recurrence-free survival (RFS), cancer specific survival (CSS), metastatic-free survival (MFS) and progression-free survival (PFS). RevMan software was used for meta-analyses. RESULTS: In total 16 studies from 1994 to 2020 were chosen, 14 studies used immunohistochemistry to assess the expression of Her2 and 5 studies used in situ hybridization, with a positive rate of 0 to 74.0% and 7.2 to 18.1%, respectively. Her2-positive was significantly associated with stage (pooled HR 1.86; 95 % CI 1.43-2.42), grade (pooled HR 2.81; 95 % CI 1.01-7.85) and LNM (pooled HR 1.93; 95 % CI 1.18-3.15). However, there was no statistically relationship between Her2-positive with LVI (pooled HR 1.48; 95 % CI 0.64-3.46) and RFS (pooled HR 1.41; 95 % CI 0.98-1.83). CONCLUSIONS: This review indicated that UTUC patients with Her2-positive tended to develop higher stage and grade tumors and LNM. The Her2 expression in UTUC patients deserves further investigation in the future.

The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.

This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.

Survival impact of variant histology in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To investigate the prognostic impact of variant histology (VH) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: Data from 635 UTUC patients who underwent RNU at our institution from May 2003 to June 2019 were retrospectively acquired and analyzed. After propensity score matching (PSM), we investigated the impact of VH on overall survival (OS) and cancer-specific survival (CSS) by using cumulative incidence plots with the log-rank test, Cox regression models, and competing risk regression models. RESULTS: Overall, 121 (19.1%) patients were diagnosed with VH, including 68 (10.7%) with squamous cell differentiation (SCD) and 28 (4.4%) with adenocarcinoma differentiation (AD). After PSM, the presence of VH was significantly associated with worse OS (HR 1.70, 95% CI 1.25-2.32) and CSS (HR 1.64, 95% CI 1.17-2.31) only in locally advanced UTUC patients (pT>2). In the subgroup analysis, SCD revealed inferior outcomes (OS: HR 1.81, 95% CI 1.28-2.57; CSS: HR 1.73, 95% CI 1.18-2.54) compared with pure urothelial carcinoma (pUC), whereas AD conferred comparable outcomes. In addition, compared with pUC patients, SCD patients with extensive squamous components had significantly decreased OS (HR 4.17, 95% CI 1.84-9.44) and CSS (HR 1.10, 95% CI 0.61-1.99), whereas those with regional squamous components had similar survival outcomes. CONCLUSION: For UTUC patients after RNU, the presence of VH is associated with aggressive clinicopathological features and inferior survival outcomes. However, the survival outcomes of localized UTUC patients (pT≤2) with VH, and patients with the AD or regional SCD subtype are comparable to those of patients with pUC.

Advanced Age May Not Be an Absolute Contraindication for Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma: A Single-Center Case Series and a Systematic Review with Meta-Analyses.

OBJECTIVE: This study aims to investigate whether advanced age is an absolute contraindication for radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) through a single-center case series and a systematic review with meta-analysis. MATERIALS AND METHODS: In the single-center case series, 588 UTUC patients who underwent RNU between May 2003 and June 2019 in West China Hospital were enrolled, and cancer-specific survival (CSS) was the primary outcome of interest. In the systematic review with meta-analysis, PubMed, Scopus, Embase, and Cochrane databases were systematically searched for related articles for further analysis. The endpoints for meta-analyses were overall survival (OS) and CSS. RESULTS: The single-center case series included 57 (9.7%) octogenarians. The CSS of octogenarians after RNU was comparable to that of younger people. Advanced age (≥80) was not an independent risk factor for poor CSS (HR, 1.08; 95% CI, 0.48, 2.40). In a systematic review with meta-analysis, the cut-off value of advanced age is 70, and the results showed that advanced age was associated with inferior OS (pooled HR, 1.55; 95% CI, 1.29, 2.01) and CSS (pooled HR, 1.37; 95% CI, 1.08, 1.65). However, the subgroup analysis of countries found no positive correlation between advanced age and CSS (pooled HR, 1.33; 95% CI 0.92, 1.74) in Chinese. CONCLUSIONS: Advanced age may no longer be an absolute contraindication for RNU. RNU can be safely and effectively performed on UTUC patients of advanced age after a comprehensive presurgical evaluation.

Prognostic value of preoperative albumin-to-alkaline phosphatase ratio in patients with surgically treated urological cancer: a systematic review and meta-analysis.

Objective: A novel albumin-to-alkaline phosphatase ratio (AAPR) is associated with the prognosis of several cancers. In the present study, we evaluate the prognostic significance of perioperative AAPR in urological cancers. Method: Relevant studies were searched comprehensively from CNKI, PubMed, Embase and Web of Science up to March 2023. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of perioperative AAPR in patients with surgically treated urological cancers. Results: A total of 8 studies consisting of 3,271 patients were included in the final results. A low AAPR was significantly associated with a worse OS (HR=2.21; P<0.001), CSS (HR=2.61; P<0.001) and RFS/DFS (HR=2.87; P=0.001). Stratified by disease, a low AAPR was also associated with worse OS in renal cell carcinoma (HR=2.01; P<0.001), bladder cancer (HR=3.37; P<0.001) and upper tract urothelial carcinoma (HR=1.59; P=0.002). Conclusion: In conclusion, low AAPR could serve as an unfavorable factor in patients with surgically treated urological cancers. Stratified by tumor type, the low AAPR was also associated with inferior survival. While more prospective and large-scale studies are warranted to validate our findings.

Clinical outcomes of immune checkpoint inhibitor plus nab-paclitaxel in metastatic upper tract urothelial carcinoma.

Background: Metastatic upper tract urothelial carcinoma (mUTUC) is a malignant cancer associated with poor prognosis. Few studies have investigated the clinical outcome of a recently developed combination regimen of programmed cell death 1 (PD-1) inhibitor plus nab-paclitaxel in mUTUC. Methods: We retrospectively retrieved data from the electronic medical records of cisplatin-ineligible or cisplatin-refractory mUTUC patients from five participating Chinese centers, who received treatment of PD-1 inhibitor plus nab-paclitaxel between April 2018 and January 2022. Clinical response was assessed according to Response Evaluation Criteria in Solid Tumors criteria version 1.1 (RECIST 1.1). Duration of response (DOR), overall survival (OS), and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. Results: The confirmed overall response rate (ORR) was 14/34 (41.2%), and the disease control rate (DCR) was 24/34 (70.6%). Complete response (CR) was achieved in one case, partial response (PR) in 13 cases (38.2%), stable disease (SD) in 10 cases (29.4%), and progressive disease (PD) occurred in 10 cases (29.4%). After a median follow-up period of 16.0 months [95% confidence interval (CI): 9.9-22.1], 14 deaths were reported, with a median OS of 15.0 months (95% CI: 9.9-20.1); 22 progressions were reported, with a median PFS of 6.0 months (95% CI: 2.4-9.6). Patients with visceral metastasis had a similar PFS [hazard ratio (HR): 1.28, 95% CI: 0.53-3.09, P=0.574) and OS (HR: 1.94, 95% CI: 0.64-5.83, P=0.279] to patients with lymph node metastasis only. Conclusions: This real-world study suggests that PD-1 inhibitor plus nab-paclitaxel is effective in cisplatin-ineligible and cisplatin-refractory mUTUC patients with acceptable toxicity, especially for patients with visceral metastasis.

Transperineal magnetic resonance imaging targeted biopsy versus transrectal route in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: Magnetic resonance imaging (MRI) has deeply altered the prostate biopsy strategy to detect prostate cancer. However, it is still debatable whether the detection rate differs between transrectal (TR) and transperineal (TP) MRI-targeted biopsy (MRI-TB). To compare the effectiveness of these two methods for detecting both overall prostate cancer (PCa) and clinically significant PCa (csPCa), We performed a review and meta-analysis. METHODS: Until January 2023, we conducted a thorough search of Cochrane, Embase, Ovid, and PubMed. In total, 1482 references were identified, and 15 records were finally included. For PCa and csPCa discovered by TP and TR MRI-TB, we combined the relative sensitivity (RR) with 95% confidence intervals (CI). The RR between the TP and TR routes was established. RESULTS: Our study included 8826 patients in total and revealed that TP MRI-TB detected more PCa (RR 1.25 [95% CI 1.12, 1.39], p < 0.0001). In patients who underwent TP MRI-TB and TR MRI-TB at the same time or separately, TP MRI-TB had a greater detection rate of csPCa in per-patient analysis (one cohort (RR 1.33 [95% CI 1.09, 1.63], p = 0.005); two cohorts (RR 1.37 [95% CI 1.16, 1.61], p = 0.0002)). However, the detection rate of csPCa between the TP route and the TR route was comparable in per-lesion analysis (RR 0.91 [95% CI 0.76, 1.08], p = 0.28). Additionally, in the prostate's anterior region, we found that TP MRI-TB detected more csPCa (per-lesion (RR 1.52 [95% CI 1.04, 2.23], p = 0.03); per-patient (RR 2.55 [95% CI 1.56, 4.16], p = 0.0002)). CONCLUSION: According to this comprehensive study, TP MRI-TB is more effective than TR MRI-TB at detecting PCa and csPCa. Significant results persisted for detecting csPCa located in the anterior zone. The results need to be taken carefully notwithstanding the heterogeneity among the included studies.

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.