Targeting STING elicits GSDMD-dependent pyroptosis and boosts anti-tumor immunity in renal cell carcinoma.

While Stimulator-of-interferon genes (STING) is an innate immune adapter cruicial for sensing cytosolic DNA and modulating immune microenvironment, its tumor-promoting role in tumor survival and immune evasion remains largely unknown. Here we reported that renal cancer cells are exceptionally dependent on STING for survival and evading immunosurveillance via suppressing ER stress-mediated pyroptosis. We found that STING is significantly amplified and upregulated in clear cell renal cell carcinoma (ccRCC), and its elevated expression is associated with worse clinical outcomes. Mechanically, STING depletion in RCC cells specifically triggers activation of the PERK/eIF2α/ATF4/CHOP pathway and activates cleavage of Caspase-8, thereby inducing GSDMD-mediated pyroptosis, which is independent of the innate immune pathway of STING. Moreover, animal study revealed that STING depletion promoted infiltration of CD4+ and CD8+ T cells, consequently boosting robust antitumor immunity via pyroptosis-induced inflammation. From the perspective of targeted therapy, we found that Compound SP23, a PROTAC STING degrader, demonstrated comparable efficacy to STING depletion both in vitro and in vivo for treatment of ccRCC. These findings collectively unveiled an unforeseen function of STING in regulating GSDMD-dependent pyroptosis, thus regulating immune response in RCC. Consequently, pharmacological degradation of STING by SP23 may become an attractive strategy for treatment of advanced RCC.

Neoadjuvant therapy in renal cell carcinoma with tumor thrombus: A systematic review and meta-analysis.

To evaluate the efficacy, feasibility and safety of neoadjuvant therapy (NAT) for renal cell carcinoma with tumor thrombus (RCC-TT) in terms of response, perioperative and oncological outcomes, and compare the results between neoadjuvant and non-neoadjuvant groups. Overall, 29 single-arm studies and 5 cohort studies were included. Of the 204 patients undergoing NAT, 16.2% were level I, 35.3% level II, 24.0% level III and 18.6% level IV thrombus. Most of patients underwent preoperative targeted therapy, immunotherapy-based combination therapy was applied in 5.4% patients. The total reduction rate of thrombus level was 29.4%. NAT is associated with a shorter operative time, less blood loss (p<0.05 for both). Rate of complications and oncological outcomes were similar between two groups. Overall, 32.1% (34/106) ≥ grade 3 adverse events occurred in patients undergoing NAT. Neoadjuvant therapy is safe and feasible with acceptable perioperative outcomes in RCC-TT.

A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: a retrospective case-control study.

BACKGROUND: Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized. OBJECTIVES: To identify preoperative thrombotic risk factors in patients with RT-IVCTT. PATIENTS/METHODS: Two hundred fifty-seven consecutive postsurgical patients with RT-IVCTT aged 18-86 years were enrolled between January 2008 and September 2022. Clinicopathological variables were retrospectively reviewed. A multivariate logistic regression model was performed. Preoperative hemoglobin, neutrophils, and serum albumin levels were analyzed as both continuous and categorical variables. RESULTS: VTE was identified in 63 patients (24.5%). On both continuously and categorically coded variables, advanced IVC thrombus (OR 3.2, 95% CI: 1.4-7.0; OR 2.7, 95% CI: 1.2-6.1), renal sinus fat invasion (OR 3.4, 95% CI: 1.6-7.0; OR 3.7, 95% CI: 1.8-7.7), IVC wall invasion (OR 3.6, 95% CI: 1.6-7.9; OR 4.3, 95% CI: 1.9-10.0), IVC blockage status of greater than 75% (OR 5.2, 95% CI: 1.7-15.8; OR 6.1, 95% CI: 1.9-19.7), and higher neutrophils (OR 1.3, 95% CI: 1.0-1.7; OR 2.4, 95% CI: 1.1-5.4) were significantly associated with increased VTE risk in patients with RT-IVCTT. Except hemoglobin, categorically coded serum albumin (OR 0.36, 95% CI: 0.17-0.75) was validated as an independent risk factor for VTE. CONCLUSIONS: This study provided an insight of risk factors contributing to preoperative VTE in patients with RT-IVCTT, which may be beneficial for optimizing strategies to manage VTE in clinical practice.

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.

Renal angiomyolipoma with tumor thrombi: Clinical analysis of 18 cases in a single-center experience.

PURPOSE: To improve understanding of the clinical features of renal angiomyolipoma (AML) accompanied by tumor thrombus (TT). METHODS: From January 2017 to February 2022, 18 patients with AML and TT were enrolled. We retrospectively analyzed them and there were 6 cases of epithelial AML (EAML) and 12 of classical AML (CAML). We compared the key variables between the two cohorts. RESULTS: The mean age of the 18 cases was 42.0 (standard deviation [SD] 13.4) years and 14 (77.8%) were female. Eleven (61.1%) tumors were on the right side. Only two (11.1%) cases presented with flank pain. The mean follow-up time was 33.6 (IQR: 20.1-48.5) months. All participants were alive at the end of follow-up. One case developed lung metastases 21 months after operation but entered remission after 2 years of everolimus treatment. The imaging diagnoses of all CAML cases were consistent with the pathology, while all imaged EAML cases were diagnosed with carcinomas. Five EAML cases, but only one CAML case, exhibited necrosis (83.3 vs. 8.3%, P = 0.001). The Ki-67 index of the EAML group was significantly higher than that of the CAML group (7 vs. 2, P = 0.004). CONCLUSIONS: Compared to CAML, EAML tended to be associated with a higher imaging misdiagnosis rate, and was more commonly associated with necrosis and a higher Ki-67 index. Surgery remains the prime treatment for nonmetastatic AML with TT; such cases have a relatively good prognosis despite the malignant potential.

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.

Clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with sarcomatoid dedifferentiation: A PRISMA-compliant systematic review and meta-analysis.

Background: There are still differences in the prognostic factors of renal cell carcinoma with sarcomatoid dedifferentiation (sRCC). The aim of this study was to evaluate important predictors of survival in patients with sRCC. Patients and methods: A comprehensive search of PubMed, Embase, and Cochrane Library was conducted to identify eligible studies. The endpoints embraced overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Hazard ratios (HRs) and related 95% confidence intervals (CIs) were extracted. Results: A total of 13 studies were included for analyses. The pooled results showed that high European Cooperative Oncology Group performance score (HR 2.39, 95% CI 1.32-4.30; P = 0.004), high T stage (HR 2.18, 95% CI 1.66-2.86; P < 0.001), positive lymph node (HR 1.54, 95% CI 1.40-1.69; P < 0.001), distant metastasis (HR 2.52, 95% CI 1.99-3.21; P < 0.001), lung metastases (HR 1.45, 95% CI 1.16-1.80; P < 0.001), liver metastases (HR 1.71, 95% CI 1.30-2.25; P < 0.001), tumor necrosis (HR 1.78, 95% CI 1.14-2.80; P = 0.010), and percentage sarcomatoid ≥50% (HR 2.35, 95% CI 1.57-3.52; P < 0.001) were associated with unfavorable OS. Positive lymph node (HR 1.57, 95% CI 1.33-1.85; P < 0.001) and high neutrophil to lymphocyte ratio (HR 1.16, 95% CI 1.04-1.29; P = 0.008) were associated with unfavorable CSS. High T stage (HR 1.93 95% CI 1.44-2.58; P < 0.001) was associated with unfavorable progression-free survival. Conclusions: A meta-analysis of available data identified important prognostic factors for CSS, OS, and PFS of sRCC, which should be systematically evaluated for patient counseling, risk stratification, and treatment selection. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=249449.

Nerve-spring technique could achieve a functional trifecta outcome of robotic intracorporeal studer's orthotopic neobladder in the male.

Objectives: To summarize some key steps of functional improvement in robotic intracorporeal studer's orthotopic neobladder (RISON) of males, especially for nerve-spring technique. We also presented the result of 1-year follow-up aimed to illustrate its functional trifecta outcomes. Methods: Robotic radical cystectomy with intracorporeal studer's orthotopic neobladder was performed on 33 male patients by the same surgeon from April 2018 to March 2019. Nerve-sparing technique had been used in 11 of the 33 patients. A prospectively maintained dataset was retrospectively searched and the related perioperative and follow-up data were analyzed. The functional trifecta outcomes referred to the freedom from recurrence, urinary continence and sexual function recovery after one year. Results: A total of 33 males were included in our study. All perioperative information was recorded in detail. Thirty-two cases were confirmed to have negative surgical margin, except one pT3a case. And another case of incidental prostate cancer was diagnosed pathologically. All patients (100%) were recurrence-free one year after the operation. Eleven patients underwent nerve-sparing surgeries, including inter-fascial techniques or intra-fascial techniques. All these patients attained daytime continence (0 pad) at 1 month. With the nighttime continence, nerve-sparing group (2, 2,1) used fewer pads than other 22 cases (3, 3,2) at 1, 6 or 12 month(s) respectively. We defined urinary continence as 0 pad in daytime and no more than 1 pad in nighttime. The median preoperative score of International Index of Erectile Function (IIEF-6) in the 11 cases was 24. The sexual function recovery was defined as IIEF-6 > 20. The final trifecta rate was 54.5% and the median follow-up time lasted 17 months (range, 12 to 22 months). Conclusions: RISON could be a safe and feasible choice of urinary diversion. Nerve sparing techniques might help the patients achieve a relatively higher functional trifecta rate.

Robotic versus Laparoscopic Retroperitoneal Lymph node Dissection for Clinical Stage I Non-seminomatous Germ Cell Tumor of Testis: A Comparative Analysis.

PURPOSE: To compare the treatment outcomes of robotic retroperitoneal lymph node dissection (R-RPLND) versus laparoscopic RPLND (L-RPLND) for clinical stage I non-seminomatous germ cell testicular tumors (NSGCTs). MATERIALS AND METHODS: We retrospectively reviewed the data of patients with stage I NSGCTs who underwent robotic or laparoscopic RPLND between 2008 and 2017. Perioperative data and oncologic outcomes were reviewed and compared between the two groups. Progression-free survival was analyzed using Kaplan-Meier survival curves and compared between two groups. RESULTS: A total of 31 and 28 patients underwent R-RPLND and L-RPLND respectively. The preoperative characteristics of the patients were comparable in the two groups. Patients in R-RPLND group had significantly shorter median operative time (140 vs. 175 minutes, P < .001), a shorter median duration to surgical drain removal (2 vs. 4 days, P = .002) and a shorter median postoperative hospital stay (5 vs. 6 days, P = .001). There were no statistical differences in intra- and post-operative complication rate between the groups and the oncologic outcomes were similar in the two groups. CONCLUSION: In expert hands, R-RPLND and L-RPLND were comparable in oncological parameter and morbidity rate; R-RPLND showed superiority in operation duration, median days to surgical drain removal and postoperative hospital stay for stage I NSGCTs. Multicenter and randomized studies with good power of study and sufficient follow-up duration are required to validate our result.

Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study.

BACKGROUND: To evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC). METHODS: In this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. The standard treatment group maintained 10 mg QD for 12 months, while the sequential treatment group reduced the dose to 5 mg QD from the 4th month. The efficacy, serum everolimus concentration and safety were evaluated at 1, 3, 6, 9 and 12 months after treatment. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in the total volume of target AML relative to baseline. RESULTS: Between June 1, 2016 and June 1, 2017, a total of 53 patients were included. Twenty-three patients received standard treatment, 30 patients received sequential treatment. At 1, 3, 6, 9 and 12 months after treatment, the proportion of patients whose total target tumor volume decreased by ≥ 50% from baseline was 39.1% versus 36.7%, 43.5% versus 56.7%, 47.8% versus 50%, 47.8% versus 60% and 47.8% versus 23.3% respectively (P > 0.05 for all). The overall response rate of skin lesions in the two groups was 40.4%, and the response rates of skin lesions at different times were similar for two groups (P > 0.05 for all). Major adverse effects (AEs) included mouth ulceration, hypertriglyceridemia, hypercholesterolemia, menstrual disorders. There was no significant difference between the two groups in the incidence of AEs at 3 months after treatment. The incidence of overall and grade 3/4 AEs at 12 months after treatment were significantly lower in the sequential treatment group. The average direct cost of the two groups in 12 months was $15,466 and $11,120, respectively. CONCLUSIONS: Compared to standard treatment, sequential treatment was equally effective, with a lower incidence of adverse events and a lower direct cost, suggesting that it may be an alternative treatment for AML associated with TSC.

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.

A new index (A/G) associated with early complications of radical cystectomy and intestinal urinary diversion.

OBJECTIVES: To put forward a new index (A/G, the postoperative ratio of albumin to blood glucose) associated with complications occurring within 30-day of radical cystectomy and intestinal urinary diversion (RC-IUD). PATIENTS AND METHODS: The charts of 565 patients undergoing RC-IUD at our single center between 2008 and 2018 were reviewed. All baseline information and perioperative data were collected. We finally picked up 360 of them with complete postoperative laboratory test results to find a new index. Early complications (within 30-day) after surgery were graded using the standardized Clavien-Dindo scale. Single and multivariate logistic regression determined the association between perioperative variables and post RC-IUD complications. RESULTS: A total of 485 men and 80 women with a median age of 61 years and BMI of 24.8 were included. As for intestinal urinary diversion, most patients (n = 513, 90.8%) received ileal conduits, 47 (8.3%) received Ileal orthotopic neobladders and 5 received Mainz pouch bladders (0.9%). Robotic surgeries were conducted in 311(55.0%) patients and other 254 (45.0%) accepted laparoscopic surgeries. Available laboratory markers were obtained from 359 cases. Postoperative complications occurred in 129 patients (22.8%), including 117 (90.7%) Minor (Clavien I or Clavien II events) complications, and 12 (9.3%) major (Clavien III or greater events) complications. A single logistic regression identified 4 variables associated with postoperative complications, including hypertension, surgical procedures, postoperative A/G, operating time, and blood loss. A further multivariate logistic regression identified 2 significant indices: operating time and postoperative A/G. Moreover, we built a receiver operating characteristic curve of A/G to identify a threshold of 3.65 as a new indicator of postoperative complication. CONCLUSIONS: We put forward a new index named A/G associated with complications after radical cystectomy, not singular considering albumin or blood glucose any more. This novel related index may provide an early alert for RC-IUD patients thus aiding in directing individual rehabilitation and improving postoperative outcomes after RC-IUD.

Sarcomatoid variant urothelial carcinoma of the bladder: a systematic review and meta-analysis of the clinicopathological features and survival outcomes.

BACKGROUND: A systematic review and meta-analysis was performed to compare the clinicopathological features and survival outcomes between sarcomatoid variant (SV)-urothelial carcinoma of the bladder (UCB) and conventional UCB (C-UCB). METHODS: A comprehensive search of PubMed, Embase, and Cochrane Library was performed. Endpoints included clinicopathological features and survival outcomes (overall survival [OS], cancer-specific survival [CSS], and progression-free survival [PFS]). The survival benefits of neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) for SV-UCB also have been studied. RESULTS: A total of 8 observational studies were included. Patients with SV-UCB had a higher rate of ≥ stage pT3 (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.64-2.59; p < 0.001) and a lower rate of concomitant carcinoma in situ (OR, 0.25; 95% CI, 0.09-0.72; p = 0.010). The other clinicopathological variables were similar between SV-UCB and C-UCB. With unadjusted data, patients with SV-UCB had a significant inferior OS (HR, 1.24; 95% CI, 1.07-1.44; p = 0.004) and CSS (HR, 2.08; 95% CI, 1.63-2.66; p < 0.001). However, after adjusted, SV-UCB had worse OS (HR, 1.41; 95% CI, 0.95-2.08; p = 0.090) and CSS (HR, 1.54; 95% CI, 0.95-2.52; p = 0.080) approaching the borderline of significance. For SV-UCB, NAC (HR, 0.73; 95% CI, 0.51-1.05; p = 0.090) and AC (HR, 0.88; 95% CI, 0.66-1.17; p = 0.370) seemed to have no benefit on OS. CONCLUSIONS: Compared to C-UCB, SV-UCB was associated with more advanced disease and more inferior OS and CSS. NAC and AC had no survival benefit for SV-UCB.

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/ß-catenin signaling.

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/ß-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/ß-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

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.

miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1.

BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. RESULTS: we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. CONCLUSIONS: Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.