Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Venous Tumor Thrombus Consistency in Renal Cell Carcinoma.

BACKGROUND: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking. PURPOSE: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (Dt , Dp , f, and ADC) and the apparent diffusion coefficient (ADC) value. STUDY TYPE: Retrospective. POPULATION: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection. FIELD STRENGTH/SEQUENCES: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm2 ). ASSESSMENT: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded. STATISTICAL TESTS: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05. RESULTS: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of Dt of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining Dp and Dt of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining Dp and Dt of VTT and Dt of the primary tumor was 0.886 (95% CI 0.814-0.937). CONCLUSION: IVIM-derived parameters had the potential to predict VTT consistency of RCC. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Can the extension of the global value chain production length promote carbon emissions reduction in China's equipment manufacturing industry?

In the context of localization of Global Value Chain (GVC) and stricter carbon emission requirements, the impact of participating in GVC on carbon emission reduction has become one of the most crucial criteria for China's manufacturing industry to consider whether to deepen its participation in GVC. In order to clearly and directly reflect the change in the production distance between the original input and the final product, we use the GVC production length to express the degree of participation in GVC. And in order to make the research more targeted and typical, we select the equipment manufacturing industry as the research object. Using the data from the World Input-Output Database (WIOD), we empirically analyze the GVC production length under different cross-border production activities on the basis of the theoretical mechanism. The results show that the extension of the GVC production length can significantly promote the carbon emissions reduction. In the decomposition part, the extension of simple GVC production length can effectively promote carbon emissions reduction. Therefore, it is suggested that China's equipment manufacturing industry should continue to deeply participate in the high-end production links of GVC and improve its status in the complex GVC production activities.

MRI radiomics-based nomogram for individualised prediction of synchronous distant metastasis in patients with clear cell renal cell carcinoma.

OBJECTIVE: To evaluate the performance of a multiparametric MRI radiomics-based nomogram for the individualised prediction of synchronous distant metastasis (SDM) in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Two-hundred and one patients (training cohort: n = 126; internal validation cohort: n = 39; external validation cohort: n = 36) with ccRCC were retrospectively enrolled between January 2013 and June 2019. In the training cohort, the optimal MRI radiomics features were selected and combined to calculate the radiomics score (Rad-score). Incorporating Rad-score and SDM-related clinicoradiologic characteristics, the radiomics-based nomogram was established by multivariable logistic regression analysis, then the performance of the nomogram (discrimination and clinical usefulness) was evaluated and validated subsequently. Moreover, the prediction efficacy for SDM in ccRCC subgroups of different sizes was also assessed. RESULTS: Incorporating Rad-score derived from 9 optimal MR radiomics features (age, pseudocapsule and regional lymph node), the radiomics-based nomogram was capable of predicting SDM in the training cohort (area under the ROC curve (AUC) = 0.914) and validated in both the internal and external cohorts (AUC = 0.854 and 0.816, respectively) and also showed a convincing predictive power in ccRCC subgroups of different sizes (≤ 4 cm, AUC = 0.875; 4-7 cm, AUC = 0.891; 7-10 cm, 0.908; > 10 cm, AUC = 0.881). Decision curve analysis indicated that the radiomics-based nomogram is of clinical usefulness. CONCLUSIONS: The multiparametric MRI radiomics-based nomogram could achieve precise individualised prediction of SDM in patients with ccRCC, potentially improving the management of ccRCC. KEY POINTS: • Radiomics features derived from multiparametric magnetic resonance images showed relevant association with synchronous distant metastasis in clear cell renal cell carcinoma. • MRI radiomics-based nomogram may serve as a potential tool for the risk prediction of synchronous distant metastasis in clear cell renal cell carcinoma.

A three-dimensional, anatomy-based nephrometry score to guide nephron-sparing surgery for renal sinus tumors.

BACKGROUND: A quantitative nephrometry scoring system specifically for renal sinus tumors will assist in classifying surgical complexity and treatment planning. METHODS: By using preoperative computed tomography, magnetic resonance imaging, and 3-dimensional image reconstruction, 5 critical components were assessed: the ratio of the sinus area occupied by the tumor in relation to the whole sinus area (R), the compression of the renal segmental vessels or collection system by the tumor (O), the anteroposterior relation of the tumor relative to the segmental vessels or collection system (A), the tumor diameter (D), and whether the tumor affects a solitary kidney (S) ("ROADS"). The ROADS score, indicating low, moderate, or high surgical complexity, was then used to guide surgical strategy planning, including cooling techniques, surgical approaches, and parenchyma incision techniques. A cohort of 134 patients with renal sinus tumors was treated based on their ROADS score and was retrospectively analyzed. RESULTS: The authors successfully performed 113 nephron-sparing surgeries and 21 radical nephrectomies with a complication rate of 7.9%. During follow-up, 3 cases were classified according to surgical margin status because they lacked an intact tumor capsule. There was only 1 case of local recurrence, and there were no cases of metastasis. A high ROADS score was correlated with greater operative complexity, such as longer operation and ischemia times and higher estimated blood loss and complication rates. However, renal function and short-term oncologic outcomes were not related to the score. CONCLUSIONS: The ROADS scoring system provides a standardized, quantitative, 3-dimensional anatomic classification to guide surgical strategy in renal sinus tumors.

MRI-based Bosniak Classification of Cystic Renal Masses, Version 2019: Interobserver Agreement, Impact of Readers' Experience, and Diagnostic Performance.

Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

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.

Multiparametric MRI Radiomic Model for Preoperative Predicting WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

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.

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.

miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating Dicer.

Although overall downregulation of microRNAs (miRNAs) is a general feature of clear-cell renal cell carcinoma (ccRCC), several miRNAs are consistently upregulated, among which miR-122 was markedly increased in ccRCC tissues. Our study aims to determine the functional importance and underlying mechanism of miR-122 in ccRCC metastasis. Here, we demonstrate that the expression of miR-122 increased in ccRCC tissues, and higher miR-122 expression was found in ccRCC tissues with metastatic disease than in those without metastasis. The increased miR-122 levels were associated with poor metastasis-free survival in ccRCC patients with localized disease. Dicer was validated as a direct functional target of miR-122. Overexpression of miR-122 promoted migration and invasion of ccRCC cells in vitro and metastatic behavior of ccRCC cells in vivo. Inhibition of miR-122 attenuated this metastatic phenotype in vitro. Importantly, miR-122 exerted its pro-metastatic properties in ccRCC cells by downregulating Dicer and its downstream effector, the miR-200 family, thereby inducing epithelial-mesenchymal transition (EMT). Our results suggest an important role of the miR-122/Dicer/miR-200s/EMT pathway in ccRCC metastasis. Furthermore, miR-122 may serve as a biomarker for discriminating ccRCC with metastatic potential.

Laparoscopic vs robot-assisted partial nephrectomy for renal tumours of >4 cm: a propensity score-based analysis.

OBJECTIVES: To compare perioperative data, functional and oncological outcomes between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) for renal tumours of >4 cm. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent either LPN or RAPN between 2008 and 2015. To adjust for potential baseline confounders, propensity score matching (1:1) was performed. Perioperative data, functional and oncological outcomes were reviewed. Disease-free survival, cancer-specific survival and overall survival were analysed using Kaplan-Meier survival curves with log-rank tests. RESULTS: In all, 197 patients underwent LPN and 96 underwent RAPN during the study period. After matching, there was no significant difference between the groups for baseline characteristics. Within the matched cohort, the LPN group was associated with significantly higher estimated blood loss (150 vs 100 mL; P < 0.001), longer renal artery clamp time (25 vs 20 min; P < 0.001), longer postoperative hospital stay (7 vs 5 days; P < 0.001), and lower rate of Margin, Ischaemia, and Complications (MIC) achievement (30.2% vs 46.9%; P = 0.018). The postoperative percentage of estimated glomerular filtration rate decline was higher in the LPN group (11.3% vs 5.5%; P = 0.018). Complication and surgical conversion outcomes were similar between LPN and RAPN. There was no significant difference in oncological outcomes between the groups. CONCLUSIONS: For patients with renal tumours of >4 cm, RAPN is more favourable than LPN in terms of perioperative outcomes (i.e. estimated blood loss, renal artery clamp time and postoperative hospital stay) and early renal functional preservation.

Identification of Missing Proteins in the Phosphoproteome of Kidney Cancer.

Identifying missing proteins (MPs) has been one of the critical missions of the Chromosome-Centric Human Proteome Project (C-HPP). Since 2012, over 30 research teams from 17 countries have been trying to search adequate and accurate evidence of MPs through various biochemical strategies. MPs mainly fall into the following classes: (1) low-molecular-weight (LMW) proteins, (2) membrane proteins, (3) proteins that contained various post-translational modifications (PTMs), (4) nucleic acid-associated proteins, (5) low abundance, and (6) unexpressed genes. In this study, kidney cancer and adjacent tissues were used for phosphoproteomics research, and 8962 proteins were identified, including 6415 phosphoproteins, and 44 728 phosphosites, of which 10 266 were unreported previously. In total, 75 candidate detections were found, including 45 phoshoproteins. GO analysis for these 75 candidate detections revealed that these proteins mainly clustered as membrane proteins and took part in nephron and kidney development. After rigorous screening and manual check, 9 of them were verified with the synthesized peptides. Finally, only one missing protein was confirmed. All mass spectrometry data from this study have been deposited in the PRIDE with identifier PXD006482.

Comparison of robot-assisted and laparoscopic partial nephrectomy for complex renal tumours with a RENAL nephrometry score ≥7: peri-operative and oncological outcomes.

OBJECTIVE: To evaluate the peri-operative, functional and oncological outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for moderately or highly complex tumours (defined as RENAL nephrometry score ≥7). PATIENTS AND METHODS: We retrospectively analysed the medical charts of 216 patients with complex tumours who underwent LPN (n = 135) or RAPN (n = 81) between 2008 and 2014. Peri-operative data, pathological variables, complications, functional and oncological outcomes were reviewed. RESULTS: Demographic characteristics were similar in the two groups. LPN was associated with a longer operating time (149.6 vs 135.6 min; P = 0.017) and greater estimated blood loss (220.8 vs 196.5 mL; P = 0.013). RAPN was associated with a higher direct cost. There were no differences in warm ischaemia time, transfusion rate, conversion rate, hospital stay, operative complications and estimated glomerular filtration rate change at 6 months after surgery. The mean follow-ups for LPN and RAPN were 31.4 and 16.5 months, respectively. The 3-year recurrence-free survival rate was 95.2% for LPN and 97.1% for RAPN (P = 0.71). CONCLUSION: In patients with complex tumours, RAPN and LPN provided acceptable and similar results in terms of peri-operative, functional and oncological outcomes. RAPN was superior to LPN in terms of estimated blood loss and operating time, and LPN was the more cost-effective approach. Both surgery techniques remain viable options in the management of complex tumours with RENAL scores ≥7.

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma.

BACKGROUND: Although metastasis of clear cell renal cell carcinoma (ccRCC) is predominantly observed in late stage tumors, early stage metastasis of ccRCC can also be found with indefinite molecular mechanism, leading to inappropriate clinical decisions and poor prognosis. Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in calcium/phosphate homeostasis, which regulates various cellular processes in normal development and tumorigenesis. This study aimed to investigate the role and mechanism of regulation of STC1 in the metastasis of early stage ccRCC. METHODS: STC1 mRNA and protein expression was determined in ccRCC surgical specimens, RCC cell lines, and human kidney tubule epithelial cell line HKC by real-time polymerase chain reaction (RT-PCR) and western blotting. Immunohistochemistry staining (IHC) and immunofluorescence were also used to examine the expression and localization of STC1 in ccRCC tissues and cancer cells. Knockdown and overexpression studies were conducted in vitro in RCC cell lines using small interfering RNAs (siRNA) and lentiviral-mediated gene delivery to evaluate the role of STC1 in cell proliferation, anchorage-dependent and independent growth, cell cycle control, and migration and invasion. RESULTS: STC1 mRNA and protein expression were significantly up-regulated in tumors when compared with non-tumor tissues, with the greatest increase in expression observed in metastatic tissues. Clinicopathological analysis revealed that STC1 mRNA expression was associated with Fuhrman tumor grade (P = 0.008) and overall Tumor Node Metastasis (TNM) staging (P = 0.018). STC1 expression was elevated in T1 stage metastatic tumors when compared with localized tumors, and was positively correlated with average tumor diameter. Silencing of STC1 expression by Caki-1 and A498 resulted in the inhibition of cell proliferation, migration, and invasion, meanwhile down-regulation of STC1 impaired epithelial-mesenchymal transition (EMT) of ccRCC cell lines. Overexpression of STC1 in Caki-2 enhanced cell growth and proliferation but not migration and invasion. Further investigation identified hypoxia and HIF-1α as candidate regulators of STC1 expression. CONCLUSIONS: Our findings demonstrate a role for STC1 in metastasis of early stage ccRCC and suggest that STC1 may be a biomarker of potential value both for the prognosis of this disease and for guiding clinical decisions regarding surgical strategies and adjuvant treatment.

Laparoendoscopic single-site urethrovesical anastomosis training in an economical porcine model.

PURPOSE: To develop an economical animal model for laparoendoscopic single-site surgery (LESS) urethrovesical anastomosis (UVA) training. MATERIALS AND METHODS: A homemade single-port device was used and the uterus cervix and the ileum were chosen to simulate UVA to reduce costs. Ten trainees were randomly divided into two groups: the conventional LESS UVA (CLUVA) group and the transurethral assistant LESS UVA (TALUVA) group. In TALUVA, a laparoscopic forceps was inserted through the urethra to assist operation after the bladder neck was disconnected, whereas CLUVA followed the conventional steps. Anastomosis time and knotting time were recorded, and the learning curves of both groups were analyzed. After training, questionnaires were given to the trainees to assess the difficulties and the satisfaction of the training. RESULTS: The final mean operating time significantly declined in both groups. Except for the first lesson, the trainees in the TALUVA group operated faster than those in the other group. The results from the questionnaires show that all trainees were satisfied with the training, and LESS UVA was considered more difficult in the CLUVA group than in the TALUVA group. CONCLUSIONS: The female porcine model for LESS UVA was feasible and cost-effective. TALVUA could effectively reduce the difficulties involved in LESS UVA.

Identification of HDAC10 as a candidate oncogene in clear cell renal carcinoma that facilitates tumor proliferation and metastasis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood. METHOD: Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The 'oncoPredict' algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2'-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients. RESULT: Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ). CONCLUSION: Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.

Development and Validation of a Nomogram for Predicting Postoperative Recurrence-Free Survival in Patients With Nonmetastatic Pathological T3a Stage Renal Cell Carcinoma.

BACKGROUND: To establish a nomogram predicting postoperative recurrence-free survival (RFS) in patients with nonmetastatic renal cell carcinoma (RCC) of pathological T3a (pT3a) stage undergoing nephrectomy. MATERIALS AND METHODS: A retrospective review included 668 patients with pT3a RCC between 2008 and 2019, randomly divided into training and validation groups (7:3 ratio). Cox regression analysis established the RFS-predicting nomogram in the training group. Nomogram performance was assessed using Harrell's concordance index (C-index), time-dependent receiver operating characteristic curve, decision curve analysis, and Kaplan-Meier survival analysis. RESULTS: Of the 668 patients with pT3a RCC, 167 patients experienced local recurrence or distant metastasis. Using multivariable Cox regression analysis, tumor size, ISUP grade, necrosis, capsular invasion, pT3a invasion pattern were identified as the significant predictors for RFS to establish the nomogram. The C-index of the nomogram was 0.753 (95% CI, 0.710-0.796) and 0.762 (95% CI, 0.701-0.822) for the training and validating group, respectively. The areas under the 1-year, 3-year and 5-year RFS receiver operating characteristic curves were 0.814, 0.769 and 0.768, respectively. Decision curve analysis showed the optimal application of the model in clinical decision-making. Patients with low risk T3a RCC have better RFS than those with high risk T3a RCC. CONCLUSION: Tumor size, ISUP grade, necrosis, capsular invasion and T3a invasion patterns were independent risk factors for worse RFS in patients with nonmetastatic pT3a RCC. The current nomogram could effectively predict the RFS of patients with nonmetastatic pT3a RCC.

Case report: Retroperitoneal solid pseudopapillary neoplasm associated with multiple hepatic metastases.

Solid pseudopapillary neoplasm (SPN) is a rare tumor mostly occurring in the pancreas. They are low-grade malignant tumors of the exocrine pancreas that occasionally metastasize, usually to the liver or peritoneum. Additionally, multiple metastases of extrapancreatic SPN to the liver are extremely rare and have been reported before. This study presents a case of a 13-year-old male patient with retroperitoneal SPN and multiple hepatic metastases. The patient presented with abdominal trauma and underwent enhanced CT, which revealed upper pancreatic occupancy and three hypodense foci in the right lobe of the liver. Moreover, increased spleen size was noted. The patient's serum tumor marker CA125 was increased to 39.00 U/mL (N < 35.0 U/mL), and circulating tumor cells were elevated to 10.2 FU/3 mL (N < 8.7 FU/3 mL). The patient underwent retroperitoneal occupancy resection and splenectomy, followed by resection of liver metastases 7 months after the surgery. Furthermore, multiple liver metastases from retroperitoneal SPN were confirmed postoperatively. The patient recovered for 1 year without tumor recurrence. This case emphasizes the importance of evaluating serum tumor markers and medical imaging in young patients as well as the fact that surgery appears to be the preferred treatment option for multiple metastases in SPN.

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.