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Objectives: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC)., Materials and Methods: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety., Results: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study., Conclusion: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To determine the relationship between renal tumor complexity and vascular complications after partial nephrectomy using PADUA, RENAL, and ZS scores., Methods: Between January 2007 and December 2018, a total of 1917 patients with available cross-sectional imaging were enrolled in the study. Logistic regressions were used to identify independent predictors of vascular complications., Results: Of 1917 patients, 31 (1.6%) developed vascular complications, including 10 females and 21 males. The high-complexity category was significantly associated with a decreased risk of vascular complication in PADUA (OR = 0.256; 95%CI = 0.086-0.762; P = 0.014) and ZS score (OR = 0.279; 95%CI = 0.083-0.946; P = 0.040). Laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were independent risk factors for vascular complications. Meanwhile, the incidence was significantly reduced in the recent 4 years in the high score tumor group alone in PADUA (0.2% [1/474] vs. 2.2% [3/139], P = 0.038) and ZS score (0.2% [1/469] vs. 2.7% [3/112], P = 0.024). In the first 8 years, laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were the only two independent risk factors for vascular complications. In the recent 4 years, only the high-complexity category was significantly associated with a decreased risk of vascular complication in the PADUA score (OR = 0.110; 95%CI = 0.013-0.938; P = 0.044)., Conclusion: The renal anatomic classification system cannot predict the occurrence of vascular complications after partial nephrectomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To compare the oncologic outcomes and renal function discrepancy of salvage partial nephrectomy (sPN) and salvage radical nephrectomy (sRN) after an initial failed PN., Materials and Methods: Retrospective data from multiple centers between 2008 and 2022 were analyzed in this study. Patients who received sPN or sRN after an initial failed PN were identified. Comparative analysis and propensity score matching (PSM) was performed and the RENAL score, tumor size, and pathological T stage at salvage surgery were used to match the 2 groups. Local recurrence-free survival (LRFS) and recurrence-free survival (RFS) were assessed using the Cox proportional hazards model and log-rank tests. Renal function after salvage surgery was assessed using the Wilcoxon rank sum test., Results: A total of 140 patients who underwent salvage surgery were evaluated, of whom 60 were considered for PSM analysis after matching. At a median follow-up of 27.0 months, LRFS and RFS showed no significant difference between sPN and sRN, either before (LRFS, HR = 0.673 [95% CI: 0.171-2.644], P = 0.610; RFS, HR = 0.744 [95% CI: 0.271-1.344], P = 0.595) or after matching (LRFS, HR = 1.080 [95% CI: 0.067-17.30], P = 0.957; RFS, HR = 1.199 [95% CI: 0.241-5.983], P = 0.822). During long-term follow-up, sPN preserved renal function (after matching, eGFR, 71.4 vs. 54.0, P < 0.001) and prevented eGFR loss (after matching: 6.6% vs. 25.6%, P < 0.001)., Conclusion: Salvage partial nephrectomy offers a better alternative than sRN for recurrence after initial PN, as sPN preserves renal function better while maintaining parallel tumor control and acceptable complication rates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Complement C5a is an important component of the innate immune system. An increasing number of reports have revealed the relevance of C5a in tumor progression; however, its exact role in metastatic renal cell carcinoma (mRCC) remains unknown., Methods: We evaluated C5a expression in tumor tissue microarrays of 231 mRCC patients and analyzed the relationship between C5a levels and clinical outcomes, and the expression of epithelial-mesenchymal transition (EMT)-related proteins, programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). In-vitro functional experiments using exogenous C5a stimulation and C5a silencing in renal cell carcinoma cells were used to validate the tissue findings., Results: High C5a expression was associated with poor therapeutic responses, poor overall and progression-free survival, and high expression of EMT-related proteins and PD-1/PD-L1 in mRCC patients. Exogenous C5a promoted proliferation, migration, and invasion of renal cell carcinoma cells, and induced the expression of EMT-related proteins and PD-1/PD-L1. Conversely, C5a silencing inhibited migration and invasion of renal cell carcinoma cells and decreased the expression of EMT-related proteins and PD-1/PD-L1., Conclusions: Our findings indicate that elevated C5a expression is associated with poor outcomes in patients with mRCC, and this effect may be partly attributed to the ability of C5a to promote EMT and PD-1/PD-L1 expression. C5a may be a potential novel target for the treatment of mRCC.

Introduction: Local retroperitoneal recurrence (RPR) after racial nephrectomy (RN) of renal cell carcinoma (RCC) remains a therapeutic challenge and has a poor prognosis. We aimed to compare the oncological outcomes of patients with RPR treated with RPR surgery or targeted therapy alone and assess the prognostic factors of these patients., Patients and Methods: This is a retrospective multi-center study of patients with RPR after prior RN treated with or without surgical treatment from 2008 to 2020. RPR of RCC is defined as an ipsilateral recurrence confined to the renal fossa, adrenal gland or retroperitoneal lymph nodes after prior nephrectomy, which was diagnosed by cross-sectional imaging. Clinical and pathological features, perioperative complications were reported using descriptive statistics. Cancer-specific survival (CSS) was evaluated by Kaplan-Meier method and studied using Cox proportional hazards model., Results: Median follow-up period was 35 months (IQR 20-61) for the RPR surgery group and 23 months (IQR 9-40.5) for the targeted therapy group. No patients had distant metastatic disease at the time of RPR diagnosis. Treatment with RPR surgery resulted in significantly longer CSS than targeted therapy alone (P < .001). In multivariable analysis, high Fuhrman grade, size of RPR tumor, mixed type of RPR, multiple recurrence lesions and the absence of RPR surgery were associated with a significantly increased risk of death from RCC., Conclusion: Aggressive surgical resection of RPR after RN represents a potentially curative treatment for selected RCC patients without synchronous metastases, resulting in significantly longer CSS than targeted therapy alone., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS)., Results: The median follow-up time was 55 months (interquartile range, 40-81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III-IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008-1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III-IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020-3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776-16.100; p < 0.001), and WHO/ISUP grade III-IV (HR, 1.950; 95 % CI, 1.100-3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065-3.942; p = 0.032) and WHO/ISUP grade III-IV (HR, 2.148; 95 % CI, 1.189-3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group., Conclusions: CID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) is rare in patients with renal cell carcinoma (RCC); however, it is associated with poor prognosis and lacks standard treatment. Our study aimed to assess oncological outcomes and prognostic factors of patients that underwent targeted therapy for RPR after RN, and to evaluate the role of presurgical targeted therapy in this context. This was a retrospective multicenter study of 85 patients with RPR treated with targeted therapy for RPR after RN (July 2008-October 2020). Clinical and pathological characteristics were reported using descriptive statistics. Cancer-specific survival (CSS) was examined using the Cox proportional hazards model. The median follow-up time was 50 months (95% confidence interval [CI]: 33.3-66.7) after the RPR diagnosis. The median CSS was 96 months in the presurgical targeted therapy followed by surgical resection group and 42 months (95% CI: 28.8-55.2) in the targeted therapy alone group (P = .0011). In multivariate analysis, International Metastatic RCC Database Consortium classification intermediate/poor risk, number of recurrence lesions and surgical resection were independent predictors of CSS. Presurgical targeted therapy may increase the feasibility of tumor resection for RPR after RN. Patients who underwent surgical resection following presurgical targeted therapy had better CSS than those treated with targeted therapy alone., (© 2022 UICC.)

Objective: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib., Methods: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS., Results: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8 + and CD4 + T-cell infiltration in tumors., Conclusion: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.

Background: To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes., Methods: The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture., Results: Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839-29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804-36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183-42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018-0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029)., Conclusions: Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes., (© 2022. The Author(s).)

Purpose: To explore the predictive value of renal tumor contour irregular degree (CID) in pathological T3a upstaging of clinical T1 renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective multi-institutional review of 1,487 patients with clinical T1N0M0 RCC between January 2009 and June 2019. Kaplan-Meier survival curve and Cox regressions were used to analyze the prognostic factors of disease-free survival (DFS). Logistic regressions were performed to determine predictors of pathological T3a upstaging in clinical T1 RCC., Results: Among 1,487 patients with cT1 RCC, 96 (6.5%) were pathological T3a upstaging. Multivariable logistic regression analysis showed that age (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.001-1.042, P = 0.036), tumor maximum diameter(OR = 1.242, 95% CI = 1.042--1.480, P = 0.015) and CID (OR = 1.067, 95% CI = 1.051-1.083, P < 0.001) were independent predictors of pathological T3a upstaging. The area under the curve (AUC) of the prediction model that included the CID was 0.846, while the AUC of the prediction model that did not include CID was only 0.741, the difference was statistically significant (P < 0.001). Kaplan-Meier survival curve showed that patients with pathological T3a upstaging had significantly worse DFS than patients without pathological T3a upstaging (P < 0.001). Multivariable Cox analysis showed that pathological T3a upstaging (HR = 1.836, 95% CI = 1.013-3.329, P = 0.002) is an independent prognostic factor for DFS in patients with cT1N0M0 RCC., Conclusions: The predictive model of CID combined with tumor maximum diameter and age significantly improved the ability to predict pathological T3a upstaging in clinical T1 RCC, compared with the prediction model of tumor maximum diameter combined with age. The predictive model of CID combined with tumor maximum diameter and age may be applicable to patients considering partial vs. radical nephrectomy., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins., Competing Interests: HH, YL, WM, JL, JH, XH, MT, SY, MA, CZ, QG, WZ No competing interests declared, (© 2021, Huang et al.)

Objectives: To illustrate tumor contour irregularity on preoperative imaging with a practical method and further determine its value in predicting disease-free survival (DFS) in patients with pRCC (papillary renal cell carcinoma)., Methods: We performed a retrospective single-institution review of 267 Chinese pRCC patients between March 2009 and May 2019. Contour irregularity on cross-section was classified into smooth but distorted margin, unsmooth and sharply nodular margin, and blurred margin. Then, the ratio of the cross-section numbers of irregularity and the total tumor was defined as the contour irregular degree (CID). Cox regression and Kaplan-Meier analysis were performed to analyze the impact of CID on DFS. Then, the prognostic performance of CID was compared with pRCC risk stratification published by Leibovich et al. RESULTS: The median follow-up was 45 months (IQR: 23-69), in which 27 (10%) patients had metastasis or recurrence. Observed DFS rates were 95%, 90%, and 88% at 1, 3, and 5 years. The CID was an independent prognostic factor of DFS (HR = 1.048, 95% CI = 1.029-1.068, p < 0.001). The Kaplan-Meier plot showed that high-risk patients (CID ≥ 50%) tended to have a significantly shorter DFS (p < 0.001). The CID and Leibovich's pRCC model for DFS prediction had a C-index of 0.934 (95% CI = 0.907-0.961) and 0.833 (95% CI = 0.739-0.927) respectively., Conclusions: With our standard and practical method, the CID can be a reliable imaging marker for DFS prediction in patients with pRCC., Key Points: • The updated contour irregularity was an independent parameter for predicting disease-free survival in patients with pRCC. • High-risk pRCC patients (contour irregular degree ≥ 50%) tended to have a shorter disease-free survival. • Tumor contour irregularity in pRCC risk stratification outperformed Leibovich's model from our cohort.

Tumour-infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumour-infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 patients with mRCC; TIMs (mast cells density positive to tryptase), along with CD8 + and CD4 + TILs, were evaluated by immunohistochemistry using a tissue microarray. The log-rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression-free survival (OS, P = .008, and PFS, P = .016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR = 0.624, 95% CI: 0.420-0.927, P = .020) and PFS (HR = 0.658, 95% CI: 0.466-0.930, P = .019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one- and two-year OS (P = .002 and P = .004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8 + and CD4 + TILs (P = .008 and P = .001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co-existence of CD8 + and CD4 + TILs, which have anti-tumour effects on activation status., (© 2020 The Scandinavian Foundation for Immunology.)

Objective: To quantitatively compare the diagnostic values of conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) in differentiating between malignant and benign renal tumors., Methods: Multiple b value DWIs and DKIs were performed in 180 patients with renal tumors, which were divided into clear cell renal cell carcinoma (ccRCC), non-ccRCC, and benign renal tumor group. The apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) maps were calculated. The diagnostic efficacy of various diffusion parameters for predicting malignant renal tumors was compared., Results: The ADC, D, and MD values of ccRCCs were higher, while D*, f, and MK values were lower than those of benign renal tumors (all p < 0.025). The D* and f values of non-ccRCCs were lower than those of benign renal tumors (p = 0.002 and p < 0.001, respectively). The difference of ADC, D, MD, and MK values between non-ccRCCs and benign renal tumors was not statistically significant (p > 0.05). The ADC, D, MD, and f values of ccRCCs were higher, while MK values were lower than those of non-ccRCCs (all p < 0.001). The AUC values of ADC, D, D*, f, MK, and MD were 0.849, 0.891, 0.708, 0.656, 0.862, and 0.838 for differentiating ccRCCs from benign renal tumors, respectively. The AUC values of D* and f were 0.772 and 0.866 for discrimination between non-ccRCCs and benign renal tumors, respectively., Conclusion: IVIM parameters are the best, while DWI and DKI parameters have similar performance in differentiating malignant and benign renal tumors., Key Points: • The D value is the best parameter for differentiating ccRCC from benign renal tumors. • The f value is the best parameter for differentiating non-ccRCC from benign renal tumors. • Conventional DWI and DKI have similar performance in differentiating malignant and benign renal tumors.

Background: Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown., Objective: We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics., Methods: Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman's correlation coefficient., Results: Among all SPF components, high α 1 -globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399-3.966, p = 0.001; and HR 1.994; 95% CI 1.360-2.923, p < 0.001, respectively). In our cohort, α 1 -globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α 1 -globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001)., Conclusions: High serum α 1 -globulin correlates with high tumor load. Serum α 1 -globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.

Objectives: To develop and prospectively validate a novel weighted quantitative scoring system based on CT findings, namely, the renal cyst index (RCI), aimed at preoperatively predicting the pathological features of cystic renal masses (CRMs)., Methods: The RCI was based on four critical features of CRMs: the cyst wall, septal, nodule, and cyst contents. These parameters were scored with 1, 2, or 3 points. Weight coefficients for these parameters were determined by the multivariable logistic regression. The odds ratio (OR) and 95% confidence interval (95% CI) were used to summarise the results. The RCI was defined as the sum of these four weight coefficients. Malignancy risk prediction models were built based on the retrospective evaluation of 441 patients. We also compared the prediction ability of the RCI with the Bosniak classification in the 441 patients and applied these novel models to 152 masses resected in our institution to prospectively validate the efficiency of the RCI., Results: The wall point (OR = 5.71 [95% CI = 1.734-18.808, p = 0.004, point = 2], OR = 12.665 [95% CI = 3.750-42.770, p < 0.001, point = 3]), septal point (OR = 3.325 [95% CI = 1.272-8.692, p = 0.014, point = 3]), nodule point (OR = 4.588 [95% CI = 1.429-14.729, p < 0.001, point = 2], OR = 17.032 [95% CI = 5.017-57.820, p = 0.010, point = 3]), content point (OR = 22.822 [95% CI = 1.041-495.995, p = 0.047, point = 2], OR = 2.723 [95% CI = 1.296-10.696, p = 0.015, point = 3]), and RCI (OR = 1.247 [95% CI = 1.197-1.299, p < 0.001]) were significantly associated with malignancy. Masses with an RCI < 6 were regarded as benign masses; masses with an RCI ≥ 10 were regarded as malignant masses. The malignancy risk of masses with an RCI > 6 but < 10 were determined by a nomogram. The prediction ability of the RCI was significantly superior to the Bosniak classification for Bosniak IIF and III masses (AUC: 0.912 vs. 0.753, p = 0.001). The RCI also accurately predicted the pathological features of 152 masses., Conclusion: The RCI is a reliable quantitative scoring system in predicting the malignancy risk of CRMs, and it outperformed the Bosniak classification system in some ways., Key Points: • The renal cyst index (RCI) is a useful weighted quantitative classification system based on CT findings for diagnosing cystic renal masses. • The RCI outperforms the Bosniak classification system in some ways, especially for Bosniak IIF and III masses. • Masses with an RCI < 6 can be regarded as a simple cyst, while those with an RCI > 10 can be regarded as malignant masses.

Objectives: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus., Methods: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy., Results: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy., Conclusions: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously., (© 2018 S. Karger AG, Basel.)

Purposes: Although several anatomical classification systems that aimed to standardize the description of renal tumors were previously reported, a special classification system is required to help predict the complexity and perioperative outcomes of off-clamp nephron-sparing surgery (NSS). We developed a novel criterion-zero ischemia index (ZII), aiming to help predict the perioperative outcomes after off-clamp NSS and guide patient selection., Methods: We retrospectively evaluated 149 patients between June 2009 and July 2014 in our institution who underwent off-clamp NSS with available computed tomography images. ZII was defined as the product of the tumor diameter and depth within renal parenchyma. ZII was then analyzed to investigate its association with perioperative outcomes. A specific ZII score was further selected to best guide patient selection in off-clamp NSS., Results: ZII was significantly associated with estimated blood loss >500 mL (OR 1.270, 95% CI 1.036-1.557, p = 0.021), operative time >2 h (OR 1.286, 95% CI 1.051-1.573, p = 0.014), surgical complications (OR 1.251, 95% CI 1.035-1.511, p = 0.020), overall complications (OR 1.208, 95% CI 1.016-1.436, p = 0.032), and >10% decrease in estimated glomerular filtration rate (OR 1.362, 95% CI 1.045-1.776, p = 0.022). Patients with ZII > 6 may bear a higher risk of hemorrhage, perioperative complications, and a longer operative time, if they underwent an off-clamp NSS, compared to those with ZII ≤ 6., Conclusions: The ZII is a novel and readily measurable criterion which can help predict renal complexity of tumor and risk of perioperative outcomes after off-clamp NSS. ZII = 6 is established as a preliminary threshold for patient selection of off-clamp NSS. A more robust criterion is to be validated with more samples in a prospective study.

Objective: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy., Methods: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively. Tumor growth and animal survival were observed. The myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in peripheral blood and spleen were determined by flow cytometry. The MDSCs protein was extracted for STAT3 analysis by western blot., Results: 769-p cell lines were suppressed in a dose and time-dependent manner. The expression of GM-CSF was substantially inhibited by celecoxib and sunitinib. Combination of sunitinib and celecoxib in vivo could effectively reduce the MDSCs than those in control group. Meanwhile, the CD4+ lymphocytes were strongly increased and the expression of signal transducer and activator of transcription 3 (STAT3) in MDSCs were significantly reduced., Conclusion: Combination therapy with sunitinib and celecoxib intensified the curative effects to renal cell carcinoma by suppressing immune regulatory cells.

The incidence of kidney cancer has been increasing globally during the past two decades. Renal cell carcinoma (RCC) is the most aggressive subtype of kidney cancer, which usually deteriorates with epithelial-mesenchymal transition (EMT) that facilitates the migration and invasion of cancer cells. Till now, the underlying mechanism remains unclear. In this study, we demonstrated that programmed death ligand 1 (PD-L1/B7-H1/CD274) could induce EMT and enhance RCC cell cancer stemness through up-regulation of SREBP-1c. Furthermore, we found that PD-L1 is up-regulated in human RCC metastases. These results, taken together, provide evidence for a novel mechanism of PD-L1 in RCC progression, suggesting that there is a close relationship between EMT and immune escape signaling pathways in RCC.

Although multitargeted tyrosine kinase inhibitor sunitinib has been used as first-line therapeutic agent against metastatic renal cell carcinoma (mRCC), the molecular mechanism and functional role per se for its therapeutic performance remains obscure. Our present study revealed that sunitinib-treated RCC cells exhibit senescence characteristics including increased SA-β-gal activity, DcR2 and Dec1 expression, and senescence-associated secretary phenotype (SASP) such as proinflammatory cytokines interleukin (IL)-1α, IL-6 and IL-8 secretion. Moreover, sunitinib administration also led to cell growth inhibition, G1-S cell cycle arrest and DNA damage response in RCC cells, suggesting therapeutic significance of sunitinib-induced RCC cellular senescence. Mechanistic investigations indicated that therapy-induced senescence (TIS) following sunitinib treatment mainly attributed to p53/Dec1 signaling activation mediated by Raf-1/NF-κB inhibition in vitro. Importantly, in vivo study showed tumor growth inhibition and prolonged overall survival were associated with increased p53 and Dec1 expression, decreased Raf-1 and Ki67 staining, and upregulated SA-β-gal activity after sunitinib treatment. Immunohistochemistry analysis of tumor tissues from RCC patients receiving sunitinib neoadjuvant therapy confirmed the similar treating phenotype. Taken together, our findings suggested that sunitinib treatment performance could be attributable to TIS, depending on p53/Dec1 activation via inhibited Raf-1/nuclear factor (NF)-κB activity. These data indicated potential insights into therapeutic improvement with reinforcing TIS-related performance or overcoming SASP-induced resistance., (© 2013 Japanese Cancer Association.)