Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.

Predicting recurrence and survival in patients with non-metastatic renal-cell carcinoma after nephrectomy: a prospective population-based study with multicenter validation.

BACKGROUND: Accurate prognostication of oncological outcomes is crucial for the optimal management of patients with renal cell carcinoma (RCC) after surgery. Previous prediction models were developed mainly based on retrospective data in the Western populations, and their predicting accuracy remains limited in contemporary, prospective validation. We aimed to develop contemporary RCC prognostic models for recurrence and overall survival (OS) using prospective population-based patient cohorts and compare their performance with existing, mostly utilized ones. METHODS: In this prospective analysis and external validation study, the development set included 11  128 consecutive patients with non-metastatic RCC treated at a tertiary urology center in China between 2006 and 2022, and the validation set included 853 patients treated at 13 medical centers in the USA between 1996 and 2013. The primary outcome was progression-free survival (PFS), and the secondary outcome was OS. Multivariable Cox regression was used for variable selection and model development. Model performance was assessed by discrimination [Harrell's C-index and time-dependent areas under the curve (AUC)] and calibration (calibration plots). Models were validated internally by bootstrapping and externally by examining their performance in the validation set. The predictive accuracy of the models was compared with validated models commonly used in clinical trial designs and with recently developed models without extensive validation. RESULTS: Of the 11  128 patients included in the development set, 633 PFS and 588 OS events occurred over a median follow-up of 4.3 years [interquartile range (IQR) 1.7-7.8]. Six common clinicopathologic variables (tumor necrosis, size, grade, thrombus, nodal involvement, and perinephric or renal sinus fat invasion) were included in each model. The models demonstrated similar C-indices in the development set (0.790 [95% CI 0.773-0.806] for PFS and 0.793 [95% CI 0.773-0.811] for OS) and in the external validation set (0.773 [0.731-0.816] and 0.723 [0.731-0.816]). A relatively stable predictive ability of the models was observed in the development set (PFS: time-dependent AUC 0.832 at 1 year to 0.760 at 9 years; OS: 0.828 at 1 year to 0.794 at 9 years). The models were well calibrated and their predictions correlated with the observed outcome at 3, 5, and 7 years in both development and validation sets. In comparison to existing prognostic models, the present models showed superior performance, as indicated by C-indices ranging from 0.722 to 0.755 (all P <0.0001) for PFS and from 0.680 to 0.744 (all P <0.0001) for OS. The predictive accuracy of the current models was robust in patients with clear-cell and non-clear-cell RCC. CONCLUSIONS: Based on a prospective population-based patient cohort, the newly developed prognostic models were externally validated and outperformed the currently available models for predicting recurrence and survival in patients with non-metastatic RCC after surgery. The current models have the potential to aid in clinical trial design and facilitate clinical decision-making for both clear-cell and non-clear-cell RCC patients at varying risk of recurrence and survival.

Comparison of Transperitoneal and Retroperitoneal Robotic Partial Nephrectomy for Patients with Completely Lower Pole Renal Tumors.

(1) Background: For completely lower pole renal tumors, we compared the perioperative outcomes of robotic partial nephrectomy via transperitoneal and retroperitoneal approaches. (2) Methods: Complete lower pole renal tumors were defined as tumors that received 1 point for the "L" element of the R.E.N.A.L. and located at the lower pole of kidney. After confirming consistency in baseline characteristics, oncological and functional benefits were compared. Pentafecta achievement was used to represent the perioperative optimal outcome, followed by multivariate analysis of factors associated with the lack of pentafecta achievement. (3) Results: Among 151 patients identified, 116 (77%) underwent robotic partial nephrectomy via a transperitoneal approach and 35 (23%) via a retroperitoneal approach. Patients undergoing transperitoneal robotic partial nephrectomy experienced more blood loss than those undergoing retroperitoneal robotic partial nephrectomy (50 mL vs. 40 mL, p = 0.015). No significant differences were identified for operative time (120 min vs. 120 min), ischemia time (19 min vs. 20 min), positive surgical margins (0.0% vs. 2.86%), postoperative rate of complication (12.07% vs. 5.71%). No significant differences were identified in pathologic variables, eGFR decline in postoperative 12-month (3.9% vs. 5.4%) functional follow-up. Multivariate cox analysis showed that tumor size (OR: 0.523; 95% CI: 0.371−0.736; p < 0.001) alone was independently correlated to the achievement of pentafecta. (4) Conclusions: For completely lower pole renal tumors, transperitoneal and retroperitoneal robotic partial nephrectomy provide similar outcomes. These two surgical approaches remain feasible options for these cases.

Changing Patterns in Cancer Mortality from 1987 to 2020 in China.

BACKGROUND: China has the highest number of new cancer cases and deaths worldwide, posing huge health and economic burdens to society and affected families. This study comprehensively analyzed secular trends of national cancer mortality statistics to inform future prevention and intervention programs in China. METHODS: The annual estimate of overall cancer mortality and its major subtypes were derived from the National Health Commission (NHC). Joinpoint analysis was used to detect changes in trends, and we used age-period-cohort modeling to estimate cohort and period effects in Cancers between 1987 and 2020. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. RESULTS: The age-standardized cancer mortality in urban China has shown a steady downward trend but has not decreased significantly in rural areas. Almost all cancer deaths in urban areas have shown a downward trend, except for colorectal cancer in men. Decreasing mortality from cancers in rural of the stomach, esophagus, liver, leukemia, and nasopharynx was observed, while lung, colorectal cancer female breast, and cervical cancer mortality increased. Birth cohort risks peaked in the cohorts born around 1920-1930 and tended to decline in successive cohorts for most cancers except for leukemia, lung cancer in rural, and breast and cervical cancer in females, whose relative risks were rising in the very recent cohorts. In addition, mortality rates for almost all types of cancer in older Chinese show an upward trend. CONCLUSIONS: Although the age-standardized overall cancer mortality rate has declined, and the urban-rural gap narrowed, the absolute cancer cases kept increasing due to the growing elderly population in China. The rising mortality related to lung, colorectal, female breast, and cervical cancer should receive higher priority in managing cancer burden and calls for targeted public health actions to reverse the trend.

GTSE1 promotes tumor growth and metastasis by attenuating of KLF4 expression in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC.

Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity.

Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.

FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC), which is the most prevalent renal cell carcinoma subtype, has a poor prognosis. Emerging strategies for enhancing the immune response in ccRCC therapy are currently being investigated. Fibrinogen-like Protein 1(FGL1) is a novel mechanism that tumors may use to evade the immune system by binding LAG-3 and negatively regulating T cells. In this study, we aimed at investigating the underlying mechanism of FGL1 in ccRCC, and its expression and prognostic value. We found that FGL1 was upregulated in tumor tissues and plasma specimens of ccRCC patients. High FGL1 expression predicted a poor prognosis for ccRCC patients. We also discovered that overexpression of FGL1 enhances RCC cell migration, invasion, and metastasis by activating the epithelial-to-mesenchymal transition (EMT). Consistent with these results, we identified a significant positive correlation between expression of FGL1 and EMT-related genes through tissue microarray analysis. Gene-expression analysis revealed that FGL1-deficient ccRCC cell lines had altered transcriptional output in inflammatory response, cell-cell signaling, negative regulation of T cell activation, and intracellular signal transduction. Depletion of FGL1 significantly inhibited tumor growth and lung metastasis in orthotopic xenograft mouse model. Infiltration of myeloid-derived CD11b+ and Ly6G+ immune cells in tumor microenvironment (TME) was strikingly decreased when FGL1 expression reduced. Therefore, increased FGL1 expression in ccRCC is positively correlated with poor prognosis. Mechanistically, FGL1 facilitates the EMT process and modulates TME, which promotes ccRCC progression and metastasis. Consequently, targeting FGL1 can potentially improve clinical outcome of ccRCC patients.

A Risk Signature with Autophagy-Related Long Noncoding RNAs for Predicting the Prognosis of Clear Cell Renal Cell Carcinoma: Based on the TCGA Database and Bioinformatics.

BACKGROUND: Disorders of autophagic processes have been reported to affect the survival outcome of clear cell renal cell carcinoma (ccRCC) patients. The purpose of our study was to identify and validate the candidate prognostic long noncoding RNA signature of autophagy. METHODS: Transcriptome profiles were obtained from The Cancer Genome Atlas. The autophagy gene list was obtained from the Human Autophagy Database. Based on coexpression analysis, we obtained a list of autophagy-related lncRNAs (ARlncRNAs). GO enrichment analysis and KEGG pathway analysis were conducted to explore the functional annotation of these ARlncRNAs. Univariate and multivariate Cox regression analyses were conducted to elucidate the correlation between overall survival and the expression level of each ARlncRNAs. We then established a prognostic signature that was a linear combination of the regression coefficients from the multivariate Cox regression model (ß) multiplied by the expression levels of the respective ARlncRNAs in the training cohort. The predictive performance was tested in the validation cohort. Additionally, the independence of the risk signature was assessed, and the relationship between the risk signature and conventional clinicopathological features was explored. RESULTS: Seven autophagy-related lncRNAs with prognostic value (SNHG3, SNHG17, MELTF-AS1, HOTAIRM1, EPB41L4A-DT, AP003352.1, and AC145423.2) were identified and integrated into a risk signature, dividing patients into low-risk and high-risk groups. The risk signature was independent of conventional clinical characteristics as a prognostic indicator of ccRCC (HR, 1.074, 95% confidence interval: 1.036-1.113, p < 0.001) and was valuable in the prediction of ccRCC progression. CONCLUSION: Our risk signature has potential prognostic value in ccRCC, and these ARlncRNAs may play a significant role in ccRCC tumor biology.

E2F1 promotes proliferation and metastasis of clear cell renal cell carcinoma via activation of SREBP1-dependent fatty acid biosynthesis.

Enhanced synthesis or uptake of lipids contributes to rapid cancer cell proliferation and tumor progression. In recent years, cell cycle regulators have been shown to be involved in the control of lipid synthesis, in addition to their classical function of controlling the cell cycle. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is characterized by lipid-rich cytoplasmic deposition. However, the relationship between altered lipid metabolism and tumor progression in ccRCC is poorly understood. Here, we demonstrated that E2F transcription factor 1 (E2F1), in addition to its key role in regulating the cell cycle, induces extensive lipid accumulation and elevated levels of lipogenic enzymes in ccRCC cells by upregulating sterol regulatory element-binding protein 1 (SREBP1). E2F1 knockdown or SREBP1 suppression attenuated fatty acid (FA) de novo synthesis, cell proliferation and epithelial-mesenchymal transition (EMT) in ccRCC cells. Furthermore, overexpression of E2F1 promoted lipid storage, tumor growth and metastasis in a mouse xenograft model, whereas E2F1 downregulation or SREBP1 inhibition reversed these effects. In ccRCC patients, high levels of E2F1 and SREBP1 were associated with increased lipid accumulation and correlated with poor prognosis. Our results demonstrate that E2F1 can increase proliferation and metastasis through SREBP1-induced aberrant lipid metabolism, which is a novel critical signaling mechanism driving human ccRCC progression.

Prognostic role of bland thrombus in patients treated with resection of renal cell carcinoma with inferior vena cava tumor thrombus.

OBJECTIVES: To assess the impact of the presence of bland thrombus (BT) on prognosis of patients treated with resection of renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT). MATERIALS AND METHODS: The medical records of a total of 145 consecutive postsurgical RCC patients with level I-IV IVCTT were reviewed from January 2008 to August 2018. Associations of BT with clinicopathological variables were estimated by chi-square test or Student's t-test. Kaplan-Meier method and multivariate Cox proportional hazard model were used. The eighth TNM staging system, "Spiess PE" model, University of California at Los Angeles Integrated Staging System and Stage, Size, Grade, and Necrosis (SSIGN) score were selected to assess whether BT could improve their predictive abilities. RESULTS: BT was observed in 34 (23.4%) patients and was significantly associated with increased levels of IVCTT (P = 0.004) and invasion of IVC wall (P = 0.030). Multivariable Cox analyses revealed that tumor grade, T stage, M stage, tumor thrombus consistency and BT were independent risk factors for both progression-free survival and overall survival. The concordance indexes ranged from a low of 0.652 in TNM to a high of 0.731 in SSIGN, and integrating BT into each base model led to an increased predictive accuracies of 6.2% for TNM (P = 0.025), 4.0% for "Spiess PE" model (P = 0.069), 2.1% for University of California at Los Angeles Integrated Staging System (P = 0.149) and 1.2% for SSIGN (P = 0.290), respectively. CONCLUSIONS: Presence of BT was independently associated with survival in postsurgical patients with RCC-IVCTT. Routine consideration of BT as an adjunct to TNM staging system may be suggested.

Comparison of Transperitoneal and Retroperitoneal Robotic Partial Nephrectomy for Patients With Complete Upper Pole Renal Tumors.

OBJECTIVES: We compared the outcomes of transperitoneal robotic partial nephrectomy (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN) for complete upper pole renal masses (1 point for the "L" component of the RENAL scoring system). MATERIAL AND METHODS: We retrospectively reviewed patients who underwent either TRPN or RRPN from 2013 to 2016. Baseline demographics and perioperative, functional, and oncological results were compared. Multivariable analysis was performed to identify factors related to pentafecta achievement (ischemia time ≤25 min, negative margin, perioperative complication free, glomerular filtration rate (eGFR) preservation >90%, and no chronic kidney disease upstaging). RESULTS: No significant differences between TRPN vs. RRPN were noted for operating time (110 vs. 114 min, p = 0.870), renal artery clamping time (19 vs. 18 min, p = 0.248), rate of positive margins (0.0% vs. 3.3%, p = 0.502), postoperative complication rates (25.0% vs. 13.3%, p = 0.140). TRPN was associated with a more estimated blood loss (50 vs. 40 ml, p = 0.004). There were no significant differences in pathologic variables, rate of eGFR decline for postoperative 12-month (9.0% vs. 7.1%, p = 0.449) functional follow-up. Multivariate analysis identified that only RENAL score (odd ratio: 0.641; 95% confidence interval: 0.455-0.904; p = 0.011) was independently associated with the pentafecta achievement. CONCLUSIONS: For completely upper pole renal masses, both TRPN and RRPN have good and comparable results. Both surgical approaches remain viable options in the treatment of these cases.

Robotic-assisted laparoscopic pyeloplasty as management for recurrent ureteropelvic junction obstruction: a comparison study with primary pyeloplasty.

BACKGROUND: To analyze the perioperative parameters and outcomes of robotic-assisted laparoscopic pyeloplasty (RALP) for recurrent ureteropelvic junction obstruction (UPJO) and compare them with our series of RALP for primary UPJO. Secondary pyeloplasty can be a challenging procedure because of ureteral devascularization, fibrosis and dense stricture formation. Robotic approach could be adjunct to these repairs. METHODS: Between August 2015 to March 2019, 96 patients in our hospital underwent RALP, with 32 patients as secondary intervention for recurrent UPJO. We compared the perioperative parameters of RALP for both primary UPJO and recurrent UPJO. Patient demographics, perioperative parameters, postoperative outcomes and complications from both groups were analyzed and compared. RESULTS: RALP was successfully performed for all cases in both groups. The median operating time was longer for secondary RALP than for primary RALP [125 (108.5-155) vs. 151 (120-190) minutes, P=0.004]. There were no conversions to open surgery or significant perioperative complications. No difference in blood loss, transfusion rate and perioperative complication rates was noted between the two groups. The success rates were 98.44% (63/64) and 96.88% (31/32) at a median follow up of 32 and 20 months (P=0.001) for the primary and secondary groups, respectively. CONCLUSIONS: Secondary RALP is associated with significantly longer operative time as compared to primary RALP, especially during the exposure of the UPJO, however it is a safe surgical modality for recurrent UPJO with durable outcome. RALP should be an alternative treatment modality for recurrent UPJO whenever the facility and expert are available.

Prediction of pentafecta achievement following laparoscopic partial nephrectomy: Implications for robot-assisted surgery candidates.

BACKGROUND: In clinical practice, objective basis for the choice between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) is scarce. To evaluate surgical outcomes, assess the individual benefit from LPN to RAPN, which can guide clinical decision-making. METHODS: Patients underwent LPN or RAPN for a localized renal mass in our center between Jan 2013 and Dec 2016 were included. The surgical outcome of LPN and RAPN was the pentafecta achievement. A multivariable model was fitted to predict the probability of pentafecta achievement after LPN. Model-derived coefficients were applied to calculate the probability of pentafecta achievement in case of LPN among patients treated with RAPN. Locally weighted scatterplot smoothing method was applied to plot the observed probability of pentafecta achievement against the predicted pentafecta probability in case of LPN. RESULTS: RAPN group had a significantly higher pentafecta achievement (54.6% vs. 41.1%, P < 0.001) than LPN. Multivariable analyses identified that tumor size, distance of the tumor to collecting system or sinus, and preoperative eGFR were independent predictors of pentafecta after LPN. When RAPN was chosen over LPN, the increase in the probability of pentafecta achievement was greatest in intermediate-probability patients. With the increase or decrease of the probability of pentafecta, the benefit of RAPN decreased. CONCLUSION: When pentafecta achievement are assessed, the benefit of RAPN over LPN varies from patient to patient. Patients at intermediate-probability of pentafecta achievement after LPN benefit the most from robotic surgery, which may be the potential ideal candidates for RAPN.

A modified sequential vascular control strategy in robot-assisted level III-IV inferior vena cava thrombectomy: initial series mimicking the open 'milking' technique principle.

OBJECTIVE: To introduce a modified sequential vascular control strategy, mimicking the open 'milking' technique principle, for the early release of the first porta hepatis (FPH) and to stop cardiopulmonary bypass (CPB) in level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCTE). PATIENTS AND METHODS: From November 2014 to June 2019, 27 patients with a level III-IV IVC tumour thrombus (IVCTT) underwent RA-IVCTE in our department. The modified sequential control strategy was used in 12 cases. Previously, we released the FPH after the thrombus was resected and the IVC was closed completely, and CPB was stopped at the end of surgery (15 patients). Presently, using our modified strategy, we place another tourniquet inferior to the second porta hepatis (SPH) once the proximal thrombus is removed from the IVC below the SPH. Then, we suture the right atrium and perform early release of the FPH, and stop CPB. Finally, tumour thrombectomy, vascular reconstruction, and radical nephrectomy are performed. RESULTS: Compared with the previous strategy, the modified steps resulted in a shorter median FPH clamping (19 vs 47 min, P < 0.001) and CPB times (60 vs 87 min, P < 0.05); a lower rate of Grade II-IV perioperative complications (25% vs 60%, P < 0.05); and better postoperative hepatorenal and coagulation function, including better median serum alanine aminotransferase (172.7 vs 465.4 U/L, P < 0.001), aspartate aminotransferase (282.4 vs 759.8 U/L, P < 0.001), creatinine (113.4 vs 295 µmol/L, P < 0.01), blood urea nitrogen (7.3 vs 16.7 mmol/L, P < 0.01), and D-dimer (5.9 vs 20 mg/L, P < 0.001) levels. CONCLUSION: With the early release of the FPH and stopping CPB, the modified sequential vascular control strategy in level III-IV RA-IVCTE reduced the perioperative risk for selected patients and improved the feasibility and safety of the surgery. We would recommend this approach to other centres that plan to develop robotic surgery for renal cell carcinoma with level III-IV IVCTT in the future.

The Mayo Adhesive Probability Score Predicts Longer Dissection Time During Laparoscopic Partial Nephrectomy.

Background: To examine the impact of the Mayo adhesive probability (MAP) score on the surgical complexity of exposing the tumor during laparoscopic partial nephrectomy (LPN). Patients and Methods: Our study included 318 patients who underwent LPN from January 2017 to December 2018 at our institution. Patients were divided into a lower MAP score group (≤2, n = 172) and a higher MAP score group (≥3, n = 146). Perioperative outcomes were compared between the groups. The operative time was predominantly occupied by the dissection time and the warm ischemia time (WIT). Results: A higher MAP score was associated with a longer operative time (131 vs 110 minutes, p < 0.001) and longer dissection time (71 vs 54 minutes, p < 0.001), respectively. The estimated blood loss (EBL) increased in patients with a higher MAP score (50 vs 20 mL, p < 0.001). No significant difference was found with respect to the WIT (21 vs 20 minutes, p = 0.370). In the multivariate linear regression model, male gender (ß = 11.199, p = 0.001), body mass index (ß = 1.197, p = 0.008), and MAP score (ß = 9.958, p = 0.002) were significantly associated with the prolongation of dissection time. Conclusions: The MAP score was significantly associated with the prolongation of dissection time during LPN. In addition, the EBL increased in patients with a higher MAP score. Therefore, the MAP score can predict surgical complexity of exposing the tumor in patients undergoing LPN.

Esculetin inhibits proliferation, migration, and invasion of clear cell renal cell carcinoma cells.

BACKGROUND: Esculetin, the main active ingredient in the Chinese herbal medicineCortex Fraxini, has been shown to possess antitumor activity. However, the effect of esculetin on clear cell renal cell carcinoma (ccRCC) has not been investigated. METHODS: MTS assays and colony formation assays were used to study the cytotoxicity of esculetin. The effects of esculetin on cell cycle and apoptosis were analyzed by flow cytometry. Western blot was used to detect cell cycle-, apoptosis-, and EMT-related proteins. Wound-healing assays and transwell assays were performed to study the effect of esculetin on cell migration and invasion in the ccRCC cell lines 786-O and SN12-PM6. RESULTS: Esculetin exerted cytotoxic activities in 786-O and SN12-PM6 cells in a dose- and time-dependent manner. The compound arrested the cell cycle in G0/G1 and G2/M phase with down-regulation of Cyclin D1, CDK4, CDK6, and c-Myc expression. Esculetin also induced apoptosis and the expression of cleaved caspase 3 increased. Additionally, esculetin significantly inhibited 786-O and SN12-PM6 cell migration and invasion, the expression of E-Cadherin increased, and the expression of N-cadherin and vimentin decreased. CONCLUSION: Taken together, these results suggest that esculetin inhibits proliferation, migration, and invasion of ccRCC and is a potential novel therapeutic agent for the treatment of ccRCC.

Cumulative Sum Analysis of the Operator Learning Curve for Robot-Assisted Mayo Clinic Level I-IV Inferior Vena Cava Thrombectomy Associated with Renal Carcinoma: A Study of 120 Cases at a Single Center.

BACKGROUND This study aimed to use cumulative sum analysis of the operator learning curve for robot-assisted Mayo Clinic level I-IV inferior vena cava (IVC) thrombectomy associated with renal carcinoma, and describes the development of an optimized operative procedure at a single center. MATERIAL AND METHODS A retrospective study included 120 patients with Mayo Clinic level I-IV IVC thrombus who underwent robotic surgery between 2013 and 2018. Points in the learning curve were identified using cumulative sum analysis, and their impact was assessed by multiple regression analysis. Perioperative indicators analyzed included operative time, estimated blood loss, early complications, and the 90-day progression rate. RESULTS Cumulative sum analysis identified three phases in the learning curve of robot-assisted IVC thrombectomy. The median operative time decreased from 265 min (range, 212-401 min) to 207 min (range, 146-276 min) (p=0.003), the median estimated blood loss decreased from 775 ml (range, 413-1500 ml) to 300 ml (range, 163-813 ml) (p=0.006), and the early complication rate decreased from 52.5% to 15.0% (p<0.001). Multivariate analysis showed that for an initial 40 cases and a further 80 cases, the learning phase, the affected side, the Mayo Clinic level, and the surgical method were independent factors that affected operative time, estimated blood loss, and the rate of early complications. CONCLUSIONS Experience from an initial 40 cases and a further 80 cases of Mayo Clinic level I-IV IVC thrombectomy associated with renal carcinoma were found to provide acceptable surgical and clinical outcomes.

Long noncoding RNA LINC-PINT promotes proliferation through EZH2 and predicts poor prognosis in clear cell renal cell carcinoma.

Background: Renal cell carcinoma (RCC) is one of the most common types of urological malignant tumors. Despite recent advances in diagnosis and management of RCC, its prognosis remains poor. Emerging evidence has shown that long noncoding RNAs (lncRNAs) play crucial regulatory roles in cancer biology. Materials and methods: The most abundant transcript of long intergenic non-protein coding RNA p53 induced transcript (LINC-PINT) in clear cell RCC (ccRCC) was determined by RT-PCR. Quantitative real-time PCR was performed to examine LINC-PINT expression in paired ccRCC samples and cell lines. The relationship of LINC-PINT expression with clinicopathologic characteristics and clinical outcome was analyzed. The biological function of LINC-PINT was studied by MTS and colony formation. The flow cytometry was used to analyze cell cycle distribution and apoptosis. The subcelluar fractionation and RIP assay was performed to explore the molecular mechanism of LINC-PINT. Western blotting and immunofluorescence was carried out to examine EZH2 and p53. Results: We found that the LINC-PINT was frequently upregulated in ccRCC samples. Furthermore, we observed that the level of LINC-PINT depended on gender as well as on pT and TNM stage of patients with ccRCC. Moreover, patients with high LINC-PINT expression had poor disease-free survival and overall survival. Functionally, overexpression of LINC-PINT promoted ccRCC cell proliferation, induced cell cycle progression, and inhibited apoptosis. LINC-PINT was primarily located in cell nuclei and interacted with EZH2. When EZH2 was knocked down in 769P and OS-RC-2 cells overexpressing LINC-PINT, the effect of LINC-PINT on cell proliferation, cell cycle, and apoptosis was partially reversed. Additionally, inducing p53 by doxorubicin (Dox) promoted LINC-PINT expression. Conclusion: Collectively, our results provide novel insights into the important role of LINC-PINT in ccRCC development and indicate that LINC-PINT may serve as a valuable prognostic biomarker for ccRCC.

Radical Nephrectomy with or without Lymph Node Dissection for pT3 Renal Cell Carcinoma: A Propensity Score-based Analysis.

OBJECTIVES: To study whether radical nephrectomy (RN) with lymph node dissection (LND) can benefit pT3 renal cell carcinoma (RCC) patients versus no LND under the 2018 American Joint Committee on Cancer TNM classification system. Subjects/Patients and Methods: We performed a retrospective cohort study of clinicopathological data for 245 T3 RCC patients, who underwent radical nephrectomy between January 2006 and December 2013 at our center, including 67 (27.1%) who underwent LND. The relationships between the LND and progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using 1:1 propensity score (PS) matching. Then, Kaplan-Meier survival analysis and Cox regression analysis were conducted to study whether these patients can benefit from LND. Depending on the LND number, we divided the cohort into two groups for further comparation. At last, we validated the results with the TCGA database KIRC patients. RESULTS: The median follow-up time was 4.9 years. Sixty-seven pairs of patients were screened by the PS and were further analyzed. We conducted a Cox regression with the survival data and found that the LND group, compared with the non-LND group, showed no survival benefit on PFS, CSS, and OS (p = 0.444, 0.809, and 0.816, respectively). However, the removal of 5 or more LNs showed negative effect on OS (p = 0.0387). TCGA cohort results are mostly consistent with our findings. CONCLUSION: RN with LND cannot improve the PFS, CSS, or OS for pT3 renal cell carcinoma patients.

Risk Factors Influencing the Thickness and Stranding of Perinephric Fat of Mayo Adhesive Probability Score in Minimally Invasive Nephrectomy.

BACKGROUND Mayo adhesive probability (MAP) score, an accurate and reliable predictor of adherent perinephric fat (APF), consists of posterior perinephric fat thickness and perinephric fat stranding. The present study aimed to identify the potential clinical characteristics associated with these 2 variables to further our understanding of APF. MATERIAL AND METHODS Clinical data of 346 patients subjected to minimally invasive nephrectomy was collected within our prospectively maintained database, between January 2015 and December 2016. Radiological data was assessed by 2 readers in an independent blinded - to each other and APF patient status - fashion. Ordinal logistic regression analyses were performed to evaluate risk factors of posterior perinephric fat thickness and perinephric fat stranding. RESULTS On multivariate analysis, posterior perinephric fat thickness was associated with older age (ß=1.05 [range, 1.03-1.07], P<0.01); male gender (ß=6.06 [3.18-11.54], P<0.01), and higher body mass index (BMI) (ß=1.31 [1.21-1.41], P<0.01). Perinephric fat stranding was associated with older age (ß=1.05 [1.02-1.07], P<0.01), male gender (ß=3.64 [2.09-6.34], P<0.01) and history of diabetes (ß=2.09 [1.24-3.52], P<0.01). MAP score was associated with older age (ß=1.05 [1.03-1.07], P<0.01), male gender (ß=5.07 [2.96-8.71], P<0.01), higher BMI (ß=1.14 [1.07-1.21], P<0.01), history of diabetes (ß=1.72 [1.06-2.78], P=0.03) and alcoholism (ß=1.88 [1.10-3.20], P=0.02). CONCLUSIONS The current study highlights that different risk factors influence the posterior perinephric fat thickness and perinephric fat stranding. Posterior perinephric fat thickness was correlated with age, gender, and BMI, while perinephric fat stranding was associated with age, gender, and history of diabetes.