Integrated analysis of multiple transcriptomic approaches and machine learning integration algorithms reveals high endothelial venules as a prognostic immune-related biomarker in bladder cancer.

BACKGROUND: Despite the availability of established surgical and chemotherapy options, the treatment of bladder cancer (BCa) patients remains challenging. While immunotherapy has emerged as a promising approach, its benefits are limited to a subset of patients. The exploration of additional targets to enhance the efficacy of immunotherapy is a valuable research direction. METHOD: High endothelial venules (HEV) ssGSEA analysis was conducted using BEST. Through the utilization of R packages Limma, Seurat, SingleR, and Harmony, analyses were performed on spatial transcriptomics, bulk RNA-sequencing (bulk RNA-seq), and single-cell RNA sequencing (scRNA-seq) data, yielding HEV-related genes (HEV.RGs). Molecular subtyping analysis based on HEV.RGs was conducted using R package MOVICS, and various machine learning-integrated algorithm was employed to construct prognostic model. LDLRAD3 was validated through subcutaneous tumor formation in mice, HEV induction, Western blot, and qPCR. RESULTS: A correlation between higher HEV levels and improved immune response and prognosis was revealed by HEV ssGSEA analysis in BCa patients receiving immunotherapy. HEV.RGs were identified in subsequent transcriptomic analyses. Based on these genes, BCa patients were stratified into two molecular clusters with distinct survival and immune infiltration patterns using various clustering-integrated algorithm. Prognostic model was developed using multiple machine learning-integrated algorithm. Low LDLRAD3 expression may promote HEV generation, leading to enhanced immunotherapy efficacy, as suggested by bulk RNA-seq, scRNA-seq analyses, and experimental validation of LDLRAD3. CONCLUSIONS: HEV served as a predictive factor for immune response and prognosis in BCa patients receiving immunotherapy. LDLRAD3 represented a potential target for HEV induction and enhancing the efficacy of immunotherapy.

Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis).

ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is frequently mutated in various cancer types and has emerged as a potential therapeutic target. In this study, we observed that ARID1A-deficient colorectal cancer (CRC) cells showed synthetic lethal effects with a p53 activator, RITA (reactivating p53 and inducing tumor apoptosis). RITA, an inhibitor of the p53-MDM2 interaction, exhibits increased sensitivity in ARID1A-deficient cells compared to ARID1A wild-type cells. Mechanistically, the observed synthetic lethality is dependent on both p53 activation and DNA damage accumulation, which are regulated by the interplay between ARID1A and RITA. ARID1A loss exhibits an opposing effect on p53 targets, leading to decreased p21 expression and increased levels of proapoptotic genes, PUMA and NOXA, which is further potentiated by RITA treatment, ultimately inducing cell apoptosis. Meanwhile, ARID1A loss aggravates RITA-induced DNA damage accumulation by downregulating Chk2 phosphorylation. Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations.

Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-ß1/SMAD3/ANGPTL4 axis in colorectal cancer.

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

Development of a Silicone Rubber Mold with an Innovative Waterfall Cooling Channel.

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.

New Insights into the Cellular Toxicity of Carbon Quantum Dots to Escherichia coli.

In this study, the cytotoxicity and toxic mechanism of carbon quantum dots (CQDs) to E. coli were evaluated in vitro. The synthetic CQDs were extremely small in size (~2.08 nm) and displayed strong fluorescence. The results demonstrated that CQDs showed good biocompatibility with E. coli within a short culture time. However, when the exposure time exceeded 24 h, the toxicity of CQDs became apparent, and the contents of reactive oxygen species, lactate dehydrogenase, and the crystal violet absorption rate increased significantly. To further explore the cytotoxic mechanism, approaches including confocal laser scanning microscopy, scanning electron microscopy, and biological transmission electron microscopy combined with zeta potential tests, osmotic pressure measurement, and comet assays were performed. On the one hand, the CQDs altered the surface charges of cells and induced lipid peroxidation by adhesion on the surface of E. coli, leading to an increase in the permeability of the cell wall. On the other hand, when the concentration of CQDs reached 200 µg/mL, the osmotic pressure of the extracellular environment was significantly reduced. These are the main factors that lead to cell edema and death. Finally, the comet assays confirmed that CQDs could induce DNA damage, which could inhibit the proliferation of E. coli.

Industry Distribution Characteristics of Benzene-Induced Leukemia - 7 PLADs, China, 2005-2019.

What is already known about this topic?: In the 1980s. benzene-induced leukemia (BIL) mainly occurred in shoemaking and painting industries. Now the industry distribution of benzene-induced leukemia may have changed over time. What is added by this report?: BlL cases mainly occurred in the manufacturing industry from 2005-2019, especially in private enterprises and small/medium-sized enterprises. The industry with the largest number of new cases of BIL was the general and special equipment manufacturing. The number of leukemia cases in emerging industries such as computer/electronic product manufacturing was found to be increasing. What are the implications for public health practice?: Strengthening supervision and regulation of manufacturing, especially of small/medium-sized enterprises and emerging manufacturing industry, may be effective in reducing BIL.

Occupational risk factors and breast cancer in Beijing, China: a hospital-based case-control study.

INTRODUCTION: Studies on the association between breast cancer and occupational hazards are limited, especially in China. This is the first study to explore the relationship between breast cancer and occupational hazards in Beijing, China. DESIGN: A hospital-based case-control study. SETTING: Eight local hospitals in Beijing, China. PARTICIPANTS: A total of 973 female participants, comprising 495 cases and 478 controls, were recruited in our study. We identified patients who underwent diagnosis for breast cancer at one of the eight local hospitals in Beijing between 1 January 2015 and 31 December 2019; controls were individuals randomly matched from the same hospital where the cases were confirmed. MAIN OUTCOME AND MEASURE: Least absolute shrinkage and selection operator (LASSO) regression was used to estimate the occupational risk factors associated with breast cancer, including night shift work history and work posture. RESULTS: In the case group, the breast cancer type was mainly invasive, which accounted for 85.66% of all the breast cancer patients. Five risk factors were included in the final LASSO model, including body mass index (BMI), marital status, menopause, night shift work history and work posture. Furthermore, these risk factors were considered for multivariate logistic regression, and the analyses suggested that the risk of breast cancer was significantly associated with higher BMI (≥28.0 kg/m2, OR: 2.85, 95% CI: 1.29 to 6.30); married status: married (OR: 2.67, 95% CI: 1.28 to 5.56) or divorced (OR: 4.51, 95% CI: 1.84 to 11.07); menopause (OR: 6.89, 95% CI: 5.07 to 9.36); night shift work (OR: 1.53, 95% CI: 1.11 to 2.11); and maximum standing or walking, and minimal sitting (OR: 1.80, 95% CI: 1.19 to 2.73). CONCLUSION: Breast cancer is associated with occupational risk factors. Night shift work, especially in a standing posture, can increase the incidence of breast cancer in women in Beijing, China.

The functions of clusterin in renal mesenchymal stromal cells: Promotion of cell growth and regulation of macrophage activation.

Clusterin (CLU) increases resistance to renal ischemia-reperfusion injury and promotes renal tissue repair. However, the mechanisms underlying of the renal protection of CLU remain unknown. Mesenchymal stromal cells (MSCs) may contribute to kidney cell turnover and injury repair. This study investigated the in vitro functions of CLU in kidney mesenchymal stromal cells (KMSCs). KMSCs were grown in plastic culture plates. Cell surface markers, apoptosis and phagocytosis were determined by flow cytometry, and CLU protein by Western blot. There were no differences in the expression of MSC markers (positive: CD133, Sca-1, CD44, CD117 and NG2, and negative: CD34, CD45, CD163, CD41, CD276, CD138, CD79a, CD146 and CD140b) and in the trilineage differentiation to chondrocytes, adipocytes and osteocytes between wild type (WT) and CLU knockout (KO) KMSCs. CLU was expressed intracellularly and secreted by WT KMSCs, and it was up-regulated by hypoxia. CLU did not prevent hypoxia-induced cell apoptosis but promoted cell growth in KMSC cultures. Furthermore, incubation with CLU-containing culture medium from WT KMSCs increased CD206 expression and phagocytic capacity of macrophages. In conclusion, our data for the first time demonstrate the function of CLU in the promotion of KMSCs proliferation, and it may be required for KMSCs-regulated macrophage M2 polarization and phagocytic activity.

Industry Distribution Characteristics of Benzene-Exposed Workers with Cytopenia - Four Provinces, China, 2020.

What is already known about this topic?: Benzene is harmful to the hematopoietic system and can cause leukemia. However, benzene is still being used in various industries including furniture, rubber, plastic products, and metal product manufacturing. What is added by this report?: The white blood cell count of workers in general equipment, special equipment, chemical raw materials, and chemical products manufacturing decreased significantly. The enterprises in which benzene concentration exceeded the occupational exposure limit were small enterprises and private enterprises. What are the implications for public health practice?: Regular health examinations are necessary for benzene-exposed workers. In addition, the monitoring of benzene concentration in small enterprises and private enterprises should be strengthened.

VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression.

Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.

Structural and Emulsifying Properties of Soybean Protein Isolate-Sodium Alginate Conjugates under High Hydrostatic Pressure.

Soybean protein isolate (SPI) is a kind of plant derived protein with high nutritional value, but it is underutilized due to its structural limitations and poor functionalities. This study aimed to investigate the effects of high hydrostatic pressure (HHP) treatment on SPI and sodium alginate (SA) conjugates prepared through the Maillard reaction. The physicochemical properties of the conjugate synthesized under 200 MPa at 60 °C for 24 h (SPI-SA-200) were compared with those of the conjugate synthesized under atmospheric pressure (SPI-SA-0.1), SPI-SA mixture, and SPI. The HHP (200 MPa) significantly hindered the Maillard reaction. This effect was confirmed by performing SDS-PAGE. The alterations in the secondary structures, such as α-helices, were analyzed using circular dichroism spectroscopy and the fluorescence intensity was determined. Emulsifying activity and stability indices of SPI-SA-200 increased by 33.56% and 31.96% respectively in comparison with the SPI-SA-0.1 conjugate. Furthermore, reduced particle sizes (356.18 nm), enhanced zeta potential (‒40.95 mV), and homogeneous droplet sizes were observed for the SPI-SA-200 emulsion. The present study details a practical method to prepare desirable emulsifiers for food processing by controlling the Maillard reaction and improving the functionality of SPI.

PRMT5 regulates colorectal cancer cell growth and EMT via EGFR/Akt/GSK3ß signaling cascades.

Emerging evidence shows that type II protein arginine methyltransferase 5 (PRMT5) serves as an oncoprotein and plays a critical role in many types of human cancer. However, the precise role and function of PRMT5 in human colorectal cancer (CRC) growth and epithelial-mesenchymal transition (EMT) are still unclear, and the related molecular mechanism and signaling axis remains largely obscure. Here, we show that PRMT5 is highly expressed in CRC cell lines and tissues. Using PRMT5 stable depletion cell lines and specific inhibitor, we discover that down-regulation of PRMT5 by shRNA or inhibition of PRMT5 activity by specific inhibitor GSK591 markedly suppresses CRC cell proliferation and cell cycle progression, which is closely associated with PRMT5 enzyme activity. Moreover, PRMT5 regulates CRC cell growth and cycle progression via activation of Akt, but not through ERK1/2, PTEN, and mTOR signaling pathway. Further study shows that PRMT5 controls EMT of CRC cells by activation of EGFR/Akt/GSK3ß signaling cascades. Collectively, our results reveal that PRMT5 promotes CRC cell proliferation, cell cycle progression, and EMT via regulation of EGFR/Akt/GSK3ß signaling cascades. Most importantly, our findings also suggest that PRMT5 may be a potential therapeutic target for the treatment of human colorectal cancer.

Overproduction of the AlgT Sigma Factor Is Lethal to Mucoid Pseudomonas aeruginosa.

Pseudomonas aeruginosa isolates from chronic lung infections often overproduce alginate, giving rise to the mucoid phenotype. Isolation of mucoid strains from chronic lung infections correlates with a poor patient outcome. The most common mutation that causes the mucoid phenotype is called mucA22 and results in a truncated form of the anti-sigma factor MucA that is continuously subjected to proteolysis. When a functional MucA is absent, the cognate sigma factor, AlgT, is no longer sequestered and continuously transcribes the alginate biosynthesis operon, leading to alginate overproduction. In this work, we report that in the absence of wild-type MucA, providing exogenous AlgT is toxic. This is intriguing, since mucoid strains endogenously possess high levels of AlgT. Furthermore, we show that suppressors of toxic AlgT production have mutations in mucP, a protease involved in MucA degradation, and provide the first atomistic model of MucP. Based on our findings, we speculate that mutations in mucP stabilize the truncated form of MucA22, rendering it functional and therefore able to reduce toxicity by properly sequestering AlgT.IMPORTANCEPseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing chronic lung infections. Phenotypes important for the long-term persistence and adaption to this unique lung ecosystem are largely regulated by the AlgT sigma factor. Chronic infection isolates often contain mutations in the anti-sigma factor mucA, resulting in uncontrolled AlgT and continuous production of alginate in addition to the expression of ∼300 additional genes. Here, we report that in the absence of wild-type MucA, AlgT overproduction is lethal and that suppressors of toxic AlgT production have mutations in the MucA protease, MucP. Since AlgT contributes to the establishment of chronic infections, understanding how AlgT is regulated will provide vital information on how P. aeruginosa is capable of causing long-term infections.

Generation of sphingosine-1-phosphate by sphingosine kinase 1 protects nonalcoholic fatty liver from ischemia/reperfusion injury through alleviating reactive oxygen species production in hepatocytes.

BACKGROUND: Nonalcoholic fatty liver (NAFL) is emerging as a leading risk factor of hepatic ischemia/reperfusion (I/R) injury lacking of effective therapy. Lipid dyshomeostasis has been implicated in the hepatopathy of NAFL. Herein, we investigate the bioactive lipids that critically regulate I/R injury in NAFL. METHODS: Lipidomics were performed to identify dysregulated lipids in mouse and human NAFL with I/R injury. The alteration of corresponding lipid-metabolizing genes was examined. The effects of the dysregulated lipid metabolism on I/R injury in NAFL were evaluated in mice and primary hepatocytes. RESULTS: Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) were uncovered to be substantially activated by I/R in mouse NAFL. Sphingosine kinase 1 (Sphk1) was found to be essential for hepatic S1P generation in response to I/R in hepatocytes of NAFL mice. Sphk1 knockdown inhibited the hepatic S1P rise while accumulating ceramides in hepatocytes of NAFL mice, leading to aggressive hepatic I/R injury with upregulation of oxidative stress and increase of reactive oxygen species (ROS). In contrast, administration of exogenous S1P protected hepatocytes of NAFL mice from hepatic I/R injury. Clinical study revealed a significant activation of S1P generation by I/R in liver specimens of NAFL patients. In vitro studies on the L02 human hepatocytes consolidated that inhibiting the generation of S1P by knocking down SPHK1 exaggerated I/R-induced damage and oxidative stress in human hepatocytes of NAFL. CONCLUSIONS: Generation of S1P by SPHK1 is important for protecting NAFL from I/R injury, which may serve as therapeutic targets for hepatic I/R injury in NAFL.

Effect of high hydrostatic pressure on solubility and conformation changes of soybean protein isolate glycated with flaxseed gum.

Soybean protein isolate (SPI) was incubated with flaxseed gum (FG) at 60 °C for 3 days under high hydrostatic pressure (HHP 0.1-300 MPa). Results showed improvement in solubility of SPI upon glycation with FG. The maximum solubility reached 86.84% when SPI-FG was treated at pH 8.0 and 200 MPa. The occurrence, degrees and sites of SPI-FG glycation suggested that moderate pressure (100 MPa) significantly promoted Maillard reactions, but higher pressures (greater than 200 MPa) suppressed these reactions. The secondary structure of the glycated proteins varied greatly with respect to α-helix and random coil contents and vibrations of the amide II band at 200 MPa. These microstructural changes increased the solubility over a broad pH range. The conformational changes in the glycated SPI supported the improved solubility of SPI-FG. Overall, HHP represents a potential method of controlling glycation to improve protein processability and expand their applicability in the food industry.

Electrolyte disorders are ERAS-associated in patients undergoing hepato-pancreato-biliary surgery.

PURPOSE: Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. METHODS: Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. RESULTS: The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76 mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41 mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. CONCLUSIONS: ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.

Characteristics in the Distribution of Chronic Benzene Poisoning Associated Industries - 6 PLADs, China, 2005-2019.

What is already known on this topic? Starting in the early 1950s, the main industries in China associated with chronic benzene poisoning (CBP) included painting, pharmaceuticals, and shoemaking. However, because of rapid socioeconomic development, the distribution of industries associated with CBP likely changed. What is added by this report? From 2005 to 2019, CBP has become an increasingly important type of chronic occupational poisoning (COP) in China. CBP was mainly found to have occurred in manufacturing industries, especially private enterprises and small and medium-sized enterprises. The sub-industry with the highest proportion of CBP cases was general and special equipment manufacturing, followed by chemical raw materials and chemical manufacturing. What are the implications for public health practice? CBP was found to be the main component of COP in China, so the supervision and management in manufacturing, especially in the medium-sized and small enterprises, need to be strengthened. Occupational benzene exposure limits should also be adjusted accordingly.

Adaptive Weighted Nuclear Norm Minimization for Removing Speckle Noise from Optical Coherence Tomography Images.

Low-rank matrix approximation is widely used in various fields of computer science, and weighted nuclear norm minimization (WNNM) has demonstrated improved results by shrinking the different weights of singular values. In this paper, an adaptive WNNM is proposed, considering the relative significance of image information by modifying the WNNM. As a result, singular values that contain more important information are relatively saved, whereas those that contain less crucial information are drastically reduced. When applying this method to noised image with black and white dot-noised images, the algorithm showed improved performance in both instances. Especially, when applied to images with white dot noise, the denoised results were outstanding. In addition, the proposed algorithm was successfully applied onto the optical coherence tomography images, numerically and visually.

A systematic review and meta-analysis of clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with tumor thrombus treated by radical nephrectomy with thrombectomy.

BACKGROUND: There remain discrepancies over the factors that influence oncologic outcomes after radical nephrectomy with thrombectomy (RNTE). To assess significant predictors of oncologic outcomes after RNTE from a systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library and Web of Science was performed to identify eligible studies. The endpoints included cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). A formal meta-analysis was performed for studies containing non-metastatic and metastatic tumors. Additionally, a sensitivity analysis including the subgroup of studies containing non-metastatic tumors only was conducted. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were conducted. RESULTS: Overall, 35 retrospective studies of low to moderate risk of bias including 11,929 patients were included. The results indicated that large tumor size, high Fuhrman grade, tumor necrosis, positive lymph node, and metastasis at surgery were adverse significant predictors for both CSS and OS. Also, IVC tumor thrombus, sarcomatoid differentiation, perinephretic fat invasion, and adrenal gland invasion were associated with poor CSS. In the subset of non-metastatic patients, the significant predictors were clinical symptom, thrombus level, Fuhrman grade and adrenal gland invasion for CSS; thrombus consistency, Fuhrman grade and tumor necrosis for OS; tumor size, Fuhrman grade and perinephretic fat invasion for RFS. CONCLUSIONS: A meta-analysis of available data identified significant prognostic factors of CSS, OS and RFS that should be systematically evaluated to propose a risk-adapted approach to postoperative patient counseling, risk stratification, and therapy selection.

A proposal of post-operative nomogram for overall survival in patients with renal cell carcinoma and venous tumor thrombus.

OBJECTIVE: To identify the predictors of overall survival (OS) and create a post-operative prognostic model for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). PATIENTS AND METHODS: The study cohort included patients with RCC and VTT that underwent full surgical resection between 2006 and 2016. Univariate and multivariate analyses were used to determine the prognostic factors of OS. A nomogram was developed and internally calibrated by bootstrap resampling method. RESULTS: A total of 185 patients were identified, including patients with thrombus present in the renal vein (109 patients, 58.9%), infrahepatic inferior vena cava (IVC; 68 patients, 36.8%), and suprahepatic IVC (8 patients, 4.3%). After a median follow-up of 30.2 months (interquartile range, 12.1-48.4 months), 63 (34.1%) patients died. Independent prognostic factors for OS included histological subtype, collecting system invasion, metastasis at surgery, De Ritis ratio (AST/ALT), and serum albumin. Independently predictive variables were used to create a nomogram, which achieved a concordance index of 0.75 for OS. CONCLUSIONS: For patients with RCC and VTT, the developed and internally validated post-operative nomogram can be used to select patients who may benefit from aggressive surveillance regimens or adjuvant therapy clinical trials.