Construction of a Model for Predicting the Risk of pT3 Based on Perioperative Characteristics in cT1 Renal Cell Carcinoma: A Retrospective Study at a Single Institution.

INTRODUCTION: This study explored the predictors of upstaging and multiple sites of extension, and constructed a predictive model based on perioperative characteristics to calculate the risk of upstaging of cT1 renal cell carcinoma to pT3. METHODS: We retrospectively reviewed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment at the Affiliated Hospital of Qingdao University between June 2016 and August 2021. The continuous and categorical variables were analyzed using the Mann-Whitney U test and Chi-square test, respectively. After randomly dividing patients into a training set and an internal validation set with a ratio of 7:3, univariate and multivariate logistic regression analyses were used to explore the predictors of upstaging and multiple sites of extension. A nomogram model was established based on the predictors of upstaging and was validated. RESULTS: Ninety-one cases (8.99%) of renal cell carcinoma were upstaged to pT3. In the training set, multivariate logistic regression identified the following predictors of upstaging: maximum tumor diameter, hilus involvement, tumor necrosis, tumor edge irregularity, symptoms, smoking, and platelet-lymphocyte ratio. A nomogram model was established based on the predictors. The area under the receiver operating characteristic curve was 0.810 in the training set, and 0.804 in the validation set. A 10-fold internal cross-validation conducted 200 times showed that the mean area under the curve was 0.797. The calibration curve and decision curve analysis suggested that the nomogram had robust clinical predictive power. Analyses showed higher neutrophil-lymphocyte ratio and tumor necrosis were associated with multiple sites of extrarenal extension in patients with pT3a renal cell carcinoma. CONCLUSIONS: We identified 7 predictors of upstaging to pT3 and 2 predictors of multiple sites of extension. A nomogram model was constructed with satisfactory accuracy for predicting upstaging to pT3.

Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). METHODS: We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. RESULTS: A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903-0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777-0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. CONCLUSIONS: We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

Tumor-associated macrophage enhances PD-L1-mediated immune escape of bladder cancer through PKM2 dimer-STAT3 complex nuclear translocation.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME) and strongly associated with poor prognosis and drug resistance, including checkpoint blockade immunotherapy in solid tumor patients. However, the mechanism by which TAM affects immune metabolism reprogramming and immune checkpoint signalling pathway in the TME remains elusive. In this study we found that transforming growth factor-beta (TGF-ß) secreted by M2-TAMs increased the level of glycolysis in bladder cancer (BLCA) and played important role in PD-L1-mediated immune evasion through pyruvate kinase isoenzymes M2 (PKM2). Mechanistically, TGF-ß promoted high expression of PKM2 by promoting the nuclear translocation of PKM2 dimer in conjunction with phosphorylated signal transducer and activator of transcription (p-STAT3), which then exerted its kinase activity to promote PD-L1 expression in BLCA. Moreover, SB-431542 (TGF-ß blocker) and shikonin (PKM2 inhibitor) significantly reduced PD-L1 expression and inhibited BLCA growth and organoids by enhancing anti-tumor immune responses. In conclusion, M2-TAM-derived TGF-ß promotes PD-L1-mediated immune evasion in BLCA by increasing the PKM2 dimer-STAT3 complex nuclear translocation. Combined blockade of the TGF-ß receptor and inhibition of PKM2 effectively prevent BLCA progression and immunosuppression, providing a potential targeted therapeutic strategy for BLCA.

External validation of a four-tiered grading system for chromophobe renal cell carcinoma.

This study aimed to validate the prognostic value of a four-tiered grading system recently proposed by Avulova et al. and to explore the prognostic ability of another four-tiered classification grading system in which there is a separate Grade 3 for tumor necrosis. Grading of chromophobe renal cell carcinoma (ChRCC) by the Fuhrman system is not feasible because of the inherent nuclear atypia in ChRCC. We collected relevant data of 263 patients with ChRCC who had undergone surgery in our hospital from 2008 to 2020. The Kaplan-Meier method was used to calculate the survival rate and Cox proportional hazard regression models to assess associations with cancer-specific survival and distant metastasis-free survival by hazard ratios (HRs) and 95% confidence intervals (CIs). Ten patients died from ChRCC, and 12 developed metastases. The 5 year CSS rates were 95.9%. Grades 2 (HR = 10.9; CI 1.11-106.4; P = 0.04), 3 (HR = 33.6, CI 3.32-339.1; P = 0.003), and 4 (HR = 417.4, CI 35.0-4976.2; P < 0.001) in a four-tiered grading system were significantly associated with CSS in a multivariate setting. However, the difference in CSS between Grades 2 and 3 was not significant (HR = 2.14, 95% CI 0.43-10.63; P = 0.35). The HRs of the associations between an exploratory grading system that includes a separate Grade 3 for tumor necrosis and CSS were as follows: Grade 2, 10.2 (CI 1.06-97.9, P = 0.045); Grade 3, 11.4 (CI 1.18-109.6, P = 0.04); and Grade 4, 267.9 (CI 27.6-2603.3, P < 0.001). Similarly, Grades 2 and 3 did not differ significantly. The four-tiered grading system studied is useful for predicting death from ChRCC and metastasis. However, Grade 3 did not more accurately predict risk of death and metastasis than did Grade 2. This was also true for the novel exploratory grading system that classifies tumors with necrosis into a separate Grade 3.

Urogenital microbiota-driven virulence factor genes associated with recurrent urinary tract infection.

Urinary tract infections (UTIs) are a common health issue affecting individuals worldwide. Recurrent urinary tract infections (rUTI) pose a significant clinical challenge, with limited understanding of the underlying mechanisms. Recent research suggests that the urobiome, the microbial community residing in the urinary tract, may play a crucial role in the development and recurrence of urinary tract infections. However, the specific virulence factor genes (VFGs) driven by urobiome contributing to infection recurrence remain poorly understood. Our study aimed to investigate the relationship between urobiome driven VFGs and recurrent urinary tract infections. By analyzing the VFGs composition of the urinary microbiome in patients with rUTI compared to a control group, we found higher alpha diversity in rUTI patients compared with healthy control. And then, we sought to identify specific VFGs features associated with infection recurrence. Specifically, we observed an increased abundance of certain VGFs in the recurrent infection group. We also associated VFGs and clinical data. We then developed a diagnostic model based on the levels of these VFGs using random forest and support vector machine analysis to distinguish healthy control and rUIT, rUTI relapse and rUTI remission. The diagnostic accuracy of the model was assessed using receiver operating characteristic curve analysis, and the area under the ROC curve were 0.83 and 0.75. These findings provide valuable insights into the complex interplay between the VFGs of urobiome and recurrent urinary tract infections, highlighting potential targets for therapeutic interventions to prevent infection recurrence.

Identification and validation of a ferroptosis-related signature for prediction of the prognosis and tumor microenvironment in patients with chromophobe renal cell carcinoma.

BACKGROUND: Ferroptosis is a novel form of regulated cell death that is different from other forms, which has an important role in tumor growth inhibition. The purpose of this study was to construct and validate a prognostic signature related to ferroptosis in chromophobe renal cell carcinoma (ChRCC) and to explore its role in immune cell infiltration and systemic therapy. METHODS: The gene expression profiles of ChRCC patients obtained from The Cancer Genome Atlas (TCGA) database were used to identify differentially expressed prognostic ferroptosis-related genes (FRGs) by univariate Cox proportional hazards analyses. Ferroptosis molecular subtypes were obtained by consensus clustering analysis. The FRG-based signature in the training set was established by least absolute shrinkage and selection operator analysis and verified in the testing set. The association between molecular subtypes and the prognostic signature and immune microenvironment was explored to predict responses to immunotherapy. Immunohistochemistry was used to verify expression of the FRG-based signature externally. RESULTS: ChRCC patients were divided into two FRG subtypes. Two FRGs (TFRC and SLC7A11) were identified to construct the prognostic signature. The high-risk group and cluster 2 had worse overall survival than the low-risk group and cluster 1, respectively. The low-risk group and cluster 1 had higher levels of immune cell infiltration and expression of MHC and immune checkpoint molecules than the high-risk group and cluster 2. The risk score was a predictor of overall survival and had a good predictive ability, which was verified in the testing set and evaluated by ROC and calibration curves. The high-risk group had a higher tumor mutation burden. The different sensitivities of targeted drugs in patients with different risks were evaluated. External immunohistochemical analysis showed that TFRC and SLC7A11 were highly expressed in tumor tissues compared with para-cancer normal tissues, and the expression level was significantly associated with a more advanced stage and worse cancer-specific survival. CONCLUSIONS: An FRG signature was identified and validated to predict the clinicopathological features and prognosis of ChRCC. A significant association between the signature and immune cell infiltration, immune checkpoint expression, and drug response is helpful to guide comprehensive treatment of ChRCC.

Development and validation of a preoperative nomogram to predict lymph node metastasis in patients with bladder urothelial carcinoma.

PURPOSE: Predicting lymph node metastasis (LNM) in patients with bladder urothelial carcinoma (BUC) before radical cystectomy aids clinical decision making. Here, we aimed to develop and validate a nomogram to preoperatively predict LNM in BUC patients. METHODS: Patients with histologically confirmed BUC, who underwent radical cystectomy and bilateral lymphadenectomy, were retrospectively recruited from two institutions. Patients from one institution were enrolled in the primary cohort, while those from the other were enrolled in the external validation cohort. Patient demographic, pathological (using transurethral resection of the bladder tumor specimens), imaging, and laboratory data were recorded. Univariate and multivariate logistic regression analyses were performed to explore the independent preoperative risk factors and develop the nomogram. Internal and external validation was conducted to assess nomogram performance. RESULTS: 522 and 215 BUC patients were enrolled in the primary and external validation cohorts, respectively. We identified tumor grade, infiltration, extravesical invasion, LNM on imaging, tumor size, and serum creatinine levels as independent preoperative risk factors, which were subsequently used to develop the nomogram. The nomogram showed a good predictive accuracy, with area under the receiver operator characteristic curve values of 0.817 and 0.825 for the primary and external validation cohorts, respectively. The corrected C-indexes, calibration curves (after 1000 bootstrap resampling), decision curve analysis results, and clinical impact curves demonstrated that the nomogram performed well in both cohorts and was highly clinically applicable. CONCLUSION: We developed a nomogram to preoperatively predict LNM in BUC, which was highly accurate, reliable, and clinically applicable.

Comparison of Eco-friendly Ti-M Bimetallic Coordination Catalysts and Commercial Monometallic Sb- or Ti-Based Catalysts for the Synthesis of Poly(ethylene-co-isosorbide terephthalate).

Sustainable development greatly benefits from the effective synthesis of bio-based copolymers that are environmentally friendly. To enhance the polymerization reactivity for the production of poly(ethylene-co-isosorbide terephthalate) (PEIT), five highly active Ti-M (M = Mg, Zn, Al, Fe, and Cu) bimetallic coordination catalysts were designed. The catalytic activity of Ti-M bimetallic coordination catalysts and single Sb- or Ti-based catalysts was compared, and the effects of catalysts with a different type of coordination metal (Mg, Zn, Al, Fe, and Cu) on the thermodynamic and crystallization properties of copolyesters were explored. In polymerization, it was found that Ti-M bimetallic catalysts with 5 ppm (Ti) had higher catalytic activity than traditional antimony-based catalysts or Ti-based catalysts with 200 ppm (Sb) or 5 ppm (Ti). The Ti-Al coordination catalyst showed the best-improved reaction rate of isosorbide among the five transition metals used. Utilizing Ti-M bimetallic catalysts, a high-quality PEIT was successfully synthesized with the highest number-average molecular weight of 2.82 × 104 g/mol and the narrowest molecular weight distribution index of 1.43. The glass-transition temperature of PEIT reached 88.3 °C, allowing the copolyesters to be used in applications requiring a higher Tg, like hot filling. The crystallization kinetics of copolyesters prepared by some Ti-M catalysts was faster than that of copolyesters prepared by conventional titanium catalysts.

Granulomatous prostatitis after bacille Calmette-Guérin instillation resembles prostate carcinoma: A case report and review of the literature.

BACKGROUND: Bacille Calmette-Guérin (BCG) instillation is recommended in patients with non-muscle-invasive bladder cancer who have intermediate-risk and high-risk tumors. However, granulomatous prostatitis is a rare complication induced by BCG instillation, which can easily be misdiagnosed as prostate cancer. Here, we report a case of granulomatous prostatitis that resembled prostate cancer. CASE SUMMARY: A 64-year-old Chinese man with bladder cancer received BCG instillation. Three days later, he stopped BCG instillation and received anti-infective therapy due to the urinary tract infection. Three months after BCG restart, he had rising total prostate-specific antigen (PSA) (9.14 ng/mL) and decreasing free PSA/total PSA (0.09). T2-weighted images of magnetic resonance imaging (MRI) showed a 28 mm × 20 mm diffuse low signal abnormality in the right peripheral zone, which was markedly hyperintense on high b-value diffusion-weighted MRI and hypointense on apparent diffusion coefficient map images. Considering Prostate Imaging Reporting and Data System score of 5 and possibility of prostate cancer, a prostate biopsy was conducted. Histopathology showed typical features of granulomatous prostatitis. The nucleic acid test for tuberculosis was positive. He was finally diagnosed with BCG-induced granulomatous prostatitis. Thereafter, he stopped BCG instillation and received anti-tuberculosis treatment. During 10 mo follow-up, he had no evidence of tumor recurrence or symptoms of tuberculosis. CONCLUSION: Temporarily elevated PSA and high followed by low signal abnormality on diffusion-weighted MRI are important indicators of BCG-induced granulomatous prostatitis.

Prognostic Factors of Adrenocortical Carcinoma: Experience from a Regional Medical Center in Eastern China.

Objective: This study aimed to summarize and analyze the clinical and pathological features and prognostic risk factors of adrenocortical carcinoma (ACC). Methods: We retrospectively analyzed clinical and pathological data and the prognoses of 39 adult ACC patients confirmed by pathologic diagnosis at the Affiliated Hospital of Qingdao University between August 2009 and October 2021. Kaplan-Meier curves and univariate and multivariate Cox regression models were used to analyze correlations between clinical and pathological parameters and prognosis. A nomogram prediction model was constructed for overall survival (OS) based on the independent prognostic factors and externally validated it with The Cancer Genome Atlas (TCGA) dataset. Results: The mean age of the patient cohort was 53.87 ± 11.1 years (range: 29-80 years), which included 17 men and 22 women. The 1-, 2-, and 5-year OS rates were 83.7%, 64.4%, and 59.8%, respectively; the recurrence-free survival (RFS) rates at the same time points were 76.1%, 45.8%, and 23.5%, respectively. Kaplan-Meier curves showed that patients with poor OS were associated with M1 stage (P = 0.008), late ENSAT stage (P = 0.017), presence of venous tumor thrombus (P = 0.015), Ki67 >20% (P = 0.006), R1/R2 status (P = 0.018), and poorly differentiated tumors (P = 0.047). Patients with late ENSAT stage (P = 0.017), combined with venous tumor thrombus (P = 0.008), Ki67 >20% (P = 0.022) were more likely to have tumor recurrence. However, age, gender, BMI, tumor diameter, clinical symptoms and postoperative treatment were not correlated with OS or RFS (P > 0.05). Univariate and multivariate COX analyses showed that Ki67 >20% (P = 0.013) and R1/2 status (P = 0.040) were independent risk factors for OS, while only Ki67 >20% (P = 0.032) was an independent risk factor for RFS. A nomogram for predicting OS was constructed based on the above factors, and the area under the receiver characteristic curve (ROC)-1, 3, and 5-year survival were 0.8, 0.825 and 0.902, respectively. The C-index of the predicted nomogram was 0.813 and a high C-index value of 0.846 could still be achieved in the external validation of TCGA. Conclusion: ACC is a rare and deadly endocrine malignancy with a high rate of recurrence. High Ki67 index (>20%) and R1/R2 resection status were independent risk factors for poor prognosis in ACC patients. A novel nomogram with a relatively good accuracy was established to assist clinicians in assessing the risk of OS in patients with ACC.

Prognostic value of the sarcomatoid component in bladder cancer: A propensity score matching study.

Sarcomatoid carcinoma of the bladder is rare, and little is known about the prognostic impact of the proportion of sarcomatoid components of the bladder. The present study aimed to assess the prognostic value of the proportion of sarcomatoid components with regard to death and recurrence rates in patients with bladder cancer (BC), and to validate the worse survival results of sarcomatoid carcinomas of the bladder using propensity score matching. Patients with sarcomatoid carcinoma of the bladder who were treated at the Affiliated Hospital of Qingdao University between August 2010 and May 2021 were included in the study. A 1:2 propensity score matching system based on age, sex and pathological T stage was used for sarcomatoid and non-sarcomatoid carcinoma matching. Finally, 114 patients with BC were included. Patients with sarcomatoid carcinoma had worse 5-year cancer-specific survival (CSS) (69.1 vs. 86.9%; log-rank P=0.008) and recurrence-free survival (RFS) (64.1 vs. 83.6%; log-rank P=0.001) rates compared with patients with non-sarcomatoid carcinoma, as had the subgroup with muscle invasion. Multivariate analysis revealed sarcomatoid carcinoma as an independent prognostic factor. Patients with a low proportion of sarcomatoid components (1-50%) had a better prognosis than patients with a high proportion (>50%), and no significant difference was found compared with the non-sarcomatoid group. Overall, a proportion of sarcomatoid components >50% was a predictor of CSS and RFS. Sarcomatoid components markedly increased the risk of death and recurrence in muscle-invasive BC, but not in non-muscle-invasive BC. A higher proportion of sarcomatoid components was significantly associated with poorer survival.

Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4.

Objective: The aim of this study was to investigate the role of deubiquitinase (DUB) 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in patients with bladder cancer. Methods: From 2016 to 2018, 181 patients diagnosed with primary bladder cancer at the Affiliated Hospital of Qingdao University were recruited. The expression of PSMD14 in bladder cancer tissues was tested by immunochemistry. The association between PSMD14 expression and clinical and pathological data and outcomes of bladder cancer patients was determined. Overexpression and knockdown cells were constructed to evaluate the effects of PSMD14 on proliferation of bladder cancer cells. Results: Our results showed that PSMD14 was significantly overexpressed in bladder cancer tissues compared to adjacent non-tumor tissues (76.24% vs 23.76%, P = 0.02). The expression of PSMD14 was significantly higher in patients with larger tumor diameters (85.14% vs 70.09%, P = 0.019) and patients with a family history of cancer (92.16% vs 70.00%, P = 0.002). Patients with high expression of PSMD14 had poor disease-free survival (DFS) (HR = 2.89, 95% CI [1.247-6.711], P = 0.013). Gain and loss of function experiments demonstrated that PSMD14 deficiency inhibited bladder cancer cell proliferation. Additionally, depletion of PSMD14 suppressed bladder cancer cell growth via down-regulation of GPX4, and the promotion of PSMD14-induced cell growth was observably reversed by the GPX4 inhibitor RSL3. Conclusion: We determined that PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation of bladder cancer cells through the downregulation of GPX4. Therefore, PSMD14 may be an effective target for the treatment of bladder cancer.

Testis and epididymis-unusual sites of metastatic gastric cancer: A case report and review of the literature.

BACKGROUND: Although gastric cancer is one of the most prevalent cancers worldwide, cases of gastric cancer metastasis to the male reproductive system are rare. Here, we report a case involving testicular and epididymal gastric cancer metastases. CASE SUMMARY: A 75-year-old Chinese man complained of experiencing a palpable painful mass in the right scrotum for 6 mo. He had undergone distal gastrectomy with chemotherapy for pT3N3aMx poorly differentiated gastric adenocarcinoma 9 mo before. Physical examination revealed a moderate right hydrocele and a painful mass in the right testis and epididymis. Serum tumor biomarkers were all normal except for elevated beta-human chorionic gonadotropin levels. Computed tomography urography and B-ultrasound imaging revealed a moderate right hydrocele and a mixed solid-cystic mass in the right testicular and epididymal area. Thus, the patient underwent right radical orchiectomy. Immunohistochemical analysis revealed that the tumor cells were positive for pancytokeratins and caudal related homeodomain transcription 2. Metastatic, poorly differentiated gastric adenocarcinoma of the testis and epididymis was confirmed by pathology. He continued to undergo chemotherapy at the department of oncology of our hospital. Mesenteric lymph node metastases were found at the postoperative 1-mo follow-up. CONCLUSION: Palpable, painful scrotal mass, history of gastric cancer, and imaging features may indicate testicular and epididymal metastatic gastric cancer.

Neoadjuvant Chemotherapy for Different Stages of Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis.

The purpose of this meta-analysis is to determine the survival benefits and pathological outcomes of neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) administered to patients with cT2 or cT3-4N0M0 muscle-invasive bladder cancer (MIBC). PubMed, Embase, and the Cochrane Library were searched for comparing the use of NAC in combination with RC and RC alone in patients with different MIBC stages. A fixed effects model was used to calculate hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs), and the I 2 statistic was used to assess heterogeneity. Moreover, we determined possible sources of heterogeneity by subgroup and sensitivity analyses. Fifteen studies were finally selected. For cT2 bladder cancer, NAC combined with RC significantly increased the rates of pathological complete response (pCR) (OR = 4.84, 95% CI: 1.18-19.92, p = 0.029) but did not improve overall survival (OS) (HR = 0.86, 95% CI: 0.72-1.02, p = 0.078) across six studies. Regarding cT3-4 bladder cancer, NAC has a significantly improved effect on OS (HR = 0.69; 95% CI: 0.59-0.81, p < 0.001, across seven studies and 5726 patients) and pCR (pooled OR = 4.80; 95% CI: 2.06-11.23, p < 0.001, across two studies) than RC alone. Most studies were randomized prospective trials (level 1 evidence), and all the effects were irrespective of the type of study design and did not vary between subgroups of patients. In conclusion, NAC combined with RC is recommended for patients with T3-4aN0M0 but not for patients with T2N0M0.

LDLR promotes growth and invasion in renal cell carcinoma and activates the EGFR pathway.

Previous studies identified an association of low-density lipoprotein (LDL) levels and LDL receptor (LDLR) with renal cell carcinoma (RCC) development. This study investigated the expression and roles of LDLR in RCC. LDLR expression was examined in clear cell RCC (ccRCC) and adjacent normal kidney tissues, and its clinicopathological significance was analyzed. The role of LDLR in RCC cell proliferation, cell cycle, and invasion were assessed in RCC cells with LDLR stable knockdown. LDLR expression was higher in ccRCC tissues than in normal kidney tissues and increased with RCC progression. LDLR knockdown in RCC cells inhibited cell growth, migration and invasion, and induced G1/S cell cycle arrest. We identified an interaction between LDLR and EGFR, and EGFR signaling protein expression was reduced after LDLR knockdown. Our findings reveal that LDLR plays an important role in RCC carcinogenesis, suggesting that LDL and LDLR might be potential targets for therapeutic intervention in RCC.

Efficacy and adverse reactions of intra-arterial chemotherapy in patients with bladder cancer: A systematic review and meta-analysis.

This meta-analysis investigated the efficacies of intra-arterial chemotherapy (IAC) plus intravesical chemotherapy (IVC) versus IVC alone in patients with non-muscle-invasive bladder cancer (NMIBC), and preoperative IAC versus preoperative intravenous chemotherapy (IV) in patients with bladder cancer. We also assessed the adverse reactions (ARs) of IAC. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English articles published before April 2021. The qualities of cohort studies and randomized controlled trials were analyzed using the Newcastle-Ottawa Scale and Cochrane risk-of-bias tool, respectively. Effect outcomes were computed by random-effects and fixed-effects models. Statistical analyses were conducted using Stata 16.0 and RevMan v5.3.0. A total of seven articles were included. The analysis revealed that IAC plus IVC significantly prolonged recurrence-free survival (RFS) (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.40-0.76, I2 = 0%) and progression-free survival (PFS) (HR = 0.59, 95% CI = 0.37-0.97, I2 = 0%) compared with IVC alone in NMIBC patients after transurethral resection of bladder tumor (TURBT), but had no effect on overall survival (OS), tumor recurrence interval, or tumor-specific death rate. Preoperative IAC had no significant OS benefit compared with preoperative IV in bladder cancer patients. Regarding ARs, patients treated with IAC were significantly more likely to develop grade 1-2 ARs, including nausea/vomiting (odds ratio [OR] = 26.38, 95% CI = 1.88-370.79, I2 = 78%), neutropenia (OR = 10.15, 95% CI = 3.01-34.24, I2 = 0%), hypoleukemia (OR = 5.49, 95% CI = 1.38-21.82, I2 = 26%), and increased alanine aminotransferase (OR = 12.28, 95% CI = 2.24-67.43, I2 = 0%), but there was no significant difference between grade 1-2 ARs and grade 3-4 ARs in terms of increased creatinine in patients treated with IAC. Therefore, administration of IAC plus IVC after TURBT improved RFS and PFS compared with IAC alone in patients with NMIBC. IAC was associated with mild ARs and was well tolerated by most patients.

Urine Culture in Hospitalized Patients during 2014-2018: An Analysis on Pathogen Distribution and Drug Sensitivity.

OBJECTIVE: We sought to analyze the distribution and antibiotic sensitivity of pathogens in hospitalized patients and to provide a scientific reference for the rational application of antibiotics. METHODS: From January 2014 to December 2018, urine cultures from patients in our hospital were collected and analyzed retrospectively for the presence, distribution, and drug sensitivity of pathogens. RESULTS: A total of 42,854 midstream urine cultures were collected from which 11,891 (27.75%) pathogens were isolated, including 8101 (68.13%) strains of gram-negative bacteria, 2580 (21.69%) strains of gram-positive bacteria, and 1210 (10.18%) strains of fungi. Escherichia coli and Enterococci were the most common species of gram-negative and gram-positive bacteria, respectively. Drug sensitivity varied among different pathogens. Clear drug resistance was observed in bacteria, while fungus exhibited relatively lower resistance. CONCLUSION: Pathogens responsible for urinary tract infections in hospitalized patients are diversiform and display resistance to some antibiotics. Drug resistance monitoring should be enhanced to optimize antimicrobial therapy.

Cancer-Associated Fibroblasts Regulate Bladder Cancer Invasion and Metabolic Phenotypes through Autophagy.

Recently, both cancer-associated fibroblasts (CAFs) and autophagy have been proven to play an important role in tumor development, including bladder cancer (BCa). However, the real mechanisms remain largely unclear. Here, we reconstruct a mimic tumor microenvironment to explore the interaction between CAFs and the BCa cell line T24 using a coculture system. Autophagy in CAFs was induced or inhibited by rapamycin or siRNA, respectively. After coculture with CAFs, T24 cell proliferation, invasion, and aerobic glycolysis were tested in vitro. Rapamycin induced and siAtg5 inhibited autophagy in CAFs. Enhanced autophagy in CAFs promoted cell proliferation and invasion in T24 cells in vitro, while there was no significant difference between the autophagy-inhibited group and the controls. Lactate concentration was elevated in both rapamycin-treated and siAtg5-treated groups compared with the control group. In addition, the expression levels of MCT1, MCT4, HK2, SLC2A1, and MMP-9 were all increased in T24 cells in the autophagy-enhanced group. Our results indicated that CAFs could regulate BCa invasion and metabolic phenotypes through autophagy, providing us with new alternative treatments for BCa in the future.

A 5-lncRNA Signature Associated with Smoking Predicts the Overall Survival of Patients with Muscle-Invasive Bladder Cancer.

Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a P value < 0.05 through the limma package. Subsequently, a comparison between patients with no tobacco smoke exposure for <15 years and patients who had been exposed to tobacco smoke for >15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation.

Development and validation of a nomogram including lymphocyte-to-monocyte ratio for initial prostate biopsy: a double-center retrospective study.

Here, we developed a prostate cancer (PCa) risk nomogram including lymphocyte-to-monocyte ratio (LMR) for initial prostate biopsy, and internal and external validation were further conducted. A prediction model was developed on a training set. Significant risk factors with P < 0.10 in multivariate logistic regression models were used to generate a nomogram. Discrimination, calibration, and clinical usefulness of the model were assessed using C-index, calibration plot, and decision curve analysis (DCA). The nomogram was re-examined with the internal and external validation set. A nomogram predicting PCa risk in patients with prostate-specific antigen (PSA) 4-10 ng ml-1 was also developed. The model displayed good discrimination with C-index of 0.830 (95% confidence interval [CI]: 0.812-0.852). High C-index of 0.864 (95% CI: 0.840-0.888) and 0.871 (95% CI: 0.861-0.881) was still reached in the internal and external validation sets, respectively. The nomogram exhibited better performance compared to the nomogram with PSA only (C-index: 0.763, 95% CI: 0.746-0.780, P < 0.001) and the nomogram with LMR excluded (C-index: 0.824, 95% CI: 0.804-0.844, P < 0.010). The calibration curve demonstrated good agreement in the internal and external validation sets. DCA showed that the nomogram was useful at the threshold probability of >4% and <99%. The nomogram predicting PCa risk in patients with PSA 4-10 ng ml-1 also displayed good calibration and discrimination performance (C-index: 0.734, 95% CI: 0.708-0.760). This nomogram incorporating age, PSA, digital rectal examination, abnormal imaging signals, PSA density, and LMR could be used to facilitate individual PCa risk prediction in initial prostate biopsy.