SLC11A1 promotes kidney renal clear cell carcinoma (KIRC) progression by remodeling the tumor microenvironment.

Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.

m6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression.

BACKGROUND: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserves to be further revealed. METHODS: The mRNA and protein levels of IGF2BP2 and neuronilin-1 (NRP1) were detected by real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation, apoptosis, migration and invasion were determined using colony formation assay, EdU assay, CCK8 assay, flow cytometry and transwell assay. Xenograft tumor model was conducted to evaluate the role of IGF2BP2 in vivo. THP-1-M0 macrophages were co-cultured with the condition medium (CM) of BCa cells to induce polarization. M2 macrophage polarization was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry. Moreover, MeRIP and RIP assay were performed to assess m6A level and the interaction between IGF2BP2 and NRP1. RESULTS: IGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown. IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression. CONCLUSION: m6A-reader IGF2BP2 enhanced M2 macrophage polarization and BCa cell progression by promoting NRP1 mRNA stability.

Vector solitonic pulses excitation in microresonators via free carrier effects.

We numerically investigate the excitation of vector solitonic pulse with orthogonally polarized components via free-carrier effects in microresonators with normal group velocity dispersion (GVD). The dynamics of single, dual and oscillated vector pulses are unveiled under turn-key excitation with a single frequency-fixed CW laser source. Parameter spaces associated with detuning, polarization angle, interval between the pumped orthogonal resonances and pump amplitude have been revealed. Different vector pulse states can also be observed exploiting the traditional pump scanning scheme. Simultaneous and independent excitation regimes are identified due to varying interval of the orthogonal pump modes. The nonlinear coupling between two modes contributes to the distortion of the vector pulses' profile. The free-carrier effects and the pump polarization angle provide additional degrees of freedom for efficiently controlling the properties of the vector solitonic microcombs. Moreover, the crucial thermal dynamics in microcavities is discussed and weak thermal effects are found to be favorable for delayed vector pulse formation. These findings reveal complex excitation mechanism of solitonic structures and could provide novel routes for microcomb generation.

[Long-term effect of finasteride on high-risk patients with benign prostatic hyperplasia after implantation of thermo-expandable spiral prostatic stent].

OBJECTIVE: To investigate the long-term effect of finasteride (FS) on high-risk BPH patients after treated by implantation of thermo-expandable spiral prostatic stent (TESPS). METHODS: We retrospectively analyzed the clinical data on 63 cases of BPH treated by implantation of TESPS in our Department of Urology from January 2017 to January 2019. All the patients received oral FS after operation except two cases of stent removal because of infection, 37 for more than 12 months (the long-term FS group) and the other 24 for less than 12 months (the control group). We followed up the patients at 3, 6, 12, 24, 36 and 48 months postoperatively, recorded the incidence of hematuria and infection, IPSS, maximum urinary flow rate (Qmax) and residual urine volume (PVR), and compared them between the two groups of patients. RESULTS: At 48 months after operation, the incidence rates of postoperative hematuria and infection were significantly lower in the long-term FS group than in the control (P < 0.05), but evidently increasing with the prolonging of medication time. The total effectiveness rate was as high as 95.1% at 3 months, but only 63.6% at 48 months, significantly higher, however, in the long-term FS than in the control group (69.2% vs 55.6%, P < 0.05), and the IPSS, Qmax and PVR were also remarkably higher in the former than in the latter group (P < 0.05). CONCLUSION: The long-term effect of TESPS implantation is definite in the treatment of BPH-induced dysuria, and it can be used as a first-choice method for the patients at high risk and unsuitable for surgery. Finasteride has an evident advantage in preventing hematuria and infection after prostatic stent implantation, and long-term medication of finasteride improves long-term outcomes.

Nobiletin inhibits viability of human renal carcinoma cells via the JAK2/STAT3 and PI3K/Akt pathway.

Nobiletin, a flavonoid found chiefly in oranges and lemons, has exhibited potential anti-proliferative and pro-apoptotic activities in various types of cancers. However, the inhibitory effect and mechanisms of nobiletin on renal cancer cells are unclear.  CCK8 and plate clone formation assay were used to determine the effect of nobiletin on the proliferation of renal cancer cells, while scratch healing test was used to assay its effect on migration ability. The effect of nobiletin on the invasion of renal cancer cells was determined using Trans well chamber assay. Flow cytometry was used to determine the effect of nobiletin on apoptosis of renal cancer cells, while Western blotting assay was used to determine its effect on the expressions of JAK2/STAT3 and PI3K/Akt pathway proteins, and apoptosis-related proteins. Nobiletin inhibited the proliferation of renal carcinoma cells in a time- and dose-dependent manner. It inhibited the migration and invasion of renal cancer cells, and promoted their apoptosis. Western blot results showed that nobiletin inhibited the phosphorylations of JAK2, STAT3, PI3K, and Akt, and promoted the expressions of apoptosis-related proteins. Nobiletin inhibits the proliferation, invasion and migration of renal cell carcinoma by inhibiting JAK2/STAT3 and PI3K/Akt pathways, and promotes their apoptosis. These findings provide a new experimental basis for the application of nobiletin in the treatment of renal cancer.

Molecular dynamics investigation of the local structure in iron melts and its role in crystal nucleation during rapid solidification.

A comprehensive investigation on local structures in iron melts and their role in nucleation under various cooling rates was performed by means of large-scale molecular dynamics simulations. The embedded atoms method (EAM) was adopted to describe the interactions between iron atoms. Connections between short-range order (SRO), medium-range order (MRO), and crystalline nucleation from iron melts were constructed using several structural analysis techniques, including the radial distribution function, common neighbor analysis method, the Voronoi tessellation, and bond order analysis. The simulation results showed that abundant types of atomic clusters with SRO, mainly including the icosahedral-like (ICO-like) and fcc-like clusters, were predominant in undercooled iron melts. The obtained microstructures were determined by the competition between the ICO-like and crystal-like configurations. There existed a critical cooling rate, below which the fcc-like configurations gain the advantage upon cooling and where crystallization could take place; otherwise, the ICO-like configurations are favored and the glass phases could be obtained. Furthermore, it was proved that the crystal nucleation could be divided into three stages: first, a fluctuation and competition between crystal-like and ICO-like clusters in undercooled melts; second, the formation and growth of MRO clusters via the transformation of atomic configurations from ICO-like to crystal-like; finally, the nucleation of bcc nuclei from the core of steady MRO clusters. This process agrees with the Ostwald's step rule and the findings from other investigations. Based on the analysis of the compositional origin of MRO clusters, we further found that the MRO clusters were mainly composed of fcc-like instead of ICO-like configurations, indicating a negative role of ICO-like configurations in crystal nucleation.

[Spiral thermo-expandable prostatic stent implantation for benign prostatic hyperplasia: Clinical analysis of 26 cases].

OBJECTIVE: To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH. METHODS: From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62－91 years old, with a prostate volume of 32－78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation. RESULTS: The operations lasted 15－30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (ï¼»21.4 ± 7.7ï¼½ ml), Qmax (ï¼»18.3 ± 4.7ï¼½ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P > 0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases. CONCLUSIONS: Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.

Crosstalk between long non-coding RNAs and Wnt/ß-catenin signalling in cancer.

Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/ß-catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/ß-catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/ß-catenin signalling pathway-related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/ß-catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/ß-catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/ß-catenin signalling pathway may be a feasible therapeutic method in the future.

NPTX1 inhibits colon cancer cell proliferation through down-regulating cyclin A2 and CDK2 expression.

Colon cancer is the third most common malignancy and one of the leading causes of cancer-associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated with tumor progression in some types of tumors. However, its expression and role in colon cancer has not been yet reported. Here we observed that NPTX1 was down-regulated in colon cancer. Additionally, we explored the functional significance of NPTX1 in colon cancer. We found that over-expression of NPTX1 inhibited colon cancer cell growth by performing MTT, colony formation, Edu corporation assays, and cell cycle analysis. In vivo mouse experiments also confirmed the anti-proliferative role of NPTX1 in colon cancer. Further mechanistic study showed that over-expression of NPTX1 inhibited the expression of cyclin A2 and CDK2 in colon cancer cells, thereby regulating the Rb-E2F signaling. In summary, these findings reveal that NPTX1 suppress the colon cancer cell growth and might serve as a useful potential target for treatment of colon cancer.

Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa.

NalD was reported to be the secondary repressor of the MexAB-OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa. Here, we show that novobiocin binds directly to NalD, which leads NalD to dissociate from the DNA promoter, and thus de-represses the expression of the MexAB-OprM pump. In addition, we have solved the crystal structure of NalD at a resolution of 2.90 Å. The structural alignment of NalD to its homologue TtgR reveals that the residues N129 and H167 in NalD are involved in its novobiocin-binding ability. We have confirmed the function of these two amino acids by EMSA and plate assay. The results presented here highlight the importance and diversity of regulatory mechanism in bacterial antibiotic resistance, and provide further insight for novel antimicrobial development.

Structural Basis for the Selective Pb(II) Recognition of Metalloregulatory Protein PbrR691.

The transcription regulator PbrR691, one of the MerR family proteins, shows extremely high sensitivity and selectivity toward Pb(II) in Ralstonia metallidurans CH34. Here, we present the crystal structure of PbrR691 in complex with Pb(II) at 2.0 Å resolution. The Pb(II) coordinates with three conserved cysteines and adopts a unique trigonal-pyramidal (hemidirected) geometry. To our knowledge, the PbrR691-Pb(II) structure provides the first three-dimensional visualization of a functional hemidirected lead(II) thiolate coordinate geometry in a protein.

[Robot-assisted laparoscopic prostatectomy versus laparoscopic radical prostatectomy for the management of prostate cancer].

OBJECTIVE: To compare robot-assisted laparoscopic radical prostatectomy (RALRP) with laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer and investigate the clinical application value of RLRP. METHODS: We retrospectively analyzed 70 cases of prostate cancer treated by RALRP and another 32 cases treated by LRP. We compared the operation time, intraoperative blood loss and transfusion, catheter-indwelling time, postoperative hospital stay, incisal margin positive rate, biochemical recurrence, and normal postoperative urinary continence and penile erectile function between the two groups of patients. RESULTS: All the operations were successfully accomplished. RALRP exhibited a significant superiority over LRP in intraoperative blood loss and transfusion, catheter-indwelling time, and postoperative hospital stay, urinary continence and erectile function (P < 0.05). CONCLUSION: Robot-assisted laparoscopic radical prostatectomy, with its advantages of few postoperative complications and well-preserved urinary continence and penile erectile function, is an effective, safe and minimally invasive surgical option for prostate cancer.

A modified adrenal gland-sparing surgery based on retroperitoneal laparoscopic radical nephrectomy.

BACKGROUND: The objective of this study was to modify the adrenal gland-sparing strategy based on retroperitoneal laparoscopic radical nephrectomy by reviewing the anatomic relationship between the kidney and the adrenal gland. METHODS: From June 2010 to October 2012, a total of 68 patients (45 males and 23 females) with localized renal cell carcinoma were treated at our hospital. The study included 35 cases that were right side and 33 cases that were left, and average patient age was 54.06 years. The average tumor size was 4.7 cm. Tumors were classified via the TNM staging system. All patients underwent adrenal gland-sparing surgery based on retroperitoneal laparoscopic radical nephrectomy. RESULTS: For each patient, surgery was successful without conversion to open surgery. The average operative time was 56.65 ± 26.60 min, and the mean blood loss was 70.61 ± 60.96 ml. All patients were discharged from the hospital 3 to 8 days after surgery. During surgery, the adrenal gland was slightly lacerated in three cases and the peritoneum showed perforation in six cases. Only one case recurred during the study follow-up. CONCLUSIONS: Based on retroperitoneal laparoscopy radical nephrectomy, this effective adrenal gland-sparing surgery showed direct exposure of tissue and little interference of the upper pole of the kidney. Elevation of the adrenal gland could help with the complete dissection of the adrenal gland from the kidney. The separation of the kidney was rapid, simple and accurate. The probability of adrenal gland damage was reduced. This strategy is recommended for widespread use in T1-2 renal neoplasms.

[Inhibitory effect of ONO-AE3-208 on the formation of bone metastasis of prostate cancer in mice].

OBJECTIVE: To examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate cancer in mice. METHODS: Thirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice. RESULTS: At 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P < 0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P < 0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P < 0.001). CONCLUSION: EP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate cancer in mice.

[Retracted] miR­141 inhibits prostatic cancer cell proliferation and migration, and induces cell apoptosis via targeting of RUNX1.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that a number of plates showing colony formation assay data in Fig. 3A appeared to be overlapping, such that data purportedly showing the results from differently performed experiments may have been derived from the same original source(s); furthermore, certain of the cell­cycle histograms shown in Fig. 4B were duplicated, again where they were intended to have shown results obtained under different experimental conditions. Subsequently, following an independent enquiry in the office, it was also noted that, in Fig. 2B, the data shown for the RUNX1 western blots were apparently the same for both the DU145 and PC­2 cell lines. Although a corrigendum was requested by the authors, given the extent of the errors that were identified with respect to the compilation of as many as three of the figures in this paper, the Editor of Oncology Reports has decided that this article should be retracted from the publication owing to a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience that might result from the retraction of this article. [Oncology Reports 39: 1454­1460, 2018; DOI: 10.3892/or.2018.6209].

A novel variant in the FLCN gene in a Chinese family with Birt-Hogg-Dubé syndrome.

BACKGROUND: This study aimed to identify disease-causing variants within a Chinese family affected by Birt-Hogg-Dubé syndrome (BHDS), which arises from an autosomal dominant inheritance pattern attributed to variants in the folliculin (FLCN) gene, recognized as a tumor suppressor gene. METHODS: A Chinese proband diagnosed with BHDS due to renal tumors underwent next-generation sequencing (NGS), revealing a novel variant in the FLCN gene. Sanger sequencing was subsequently performed on blood samples obtained from family members to confirm the presence of this variant. RESULTS: A novel germline frameshift variant (NM_144997.5:c.977dup) was identified in five individuals among the screened family members, marking the first report of this variant. Additionally, a somatic frameshift variant (NM_144997.5:c.1252del) was detected in the renal tumors of the proband. No variant was detected in unaffected family members. CONCLUSIONS: A novel heterozygous variant was identified in exon 9 of the FLCN gene, which broadens the spectrum of FLCN variants. We recommend that molecular analysis of the FLCN gene be performed in patients with suspected BHDS and their families.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Collecting Duct Carcinoma of the Kidney: A Single-Center Retrospective Study of 23 Cases.

Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan-Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.

Prognostic value of systemic immune-inflammation index in non-metastatic clear cell renal cell carcinoma with tumor thrombus.

This study aims to determine the prognostic value of SII for non-metastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). We retrospectively collected and analyzed 328 non-metastatic ccRCC patients with VTT who underwent radical nephrectomy and thrombectomy from 3 tertiary centers in China between 2011 to 2021. Kaplan-Meier analyses and Cox proportional hazard analyses were used to determine its prognostic value for overall survival (OS) and disease free survival (DFS). The Harrell concordance index (C-index), receiver operating characteristic curve (ROC) analysis, and decision curve analysis (DCA) were used to evaluate its role in the improvement of prognostic accuracy of the existing models. Nomogram models containing the SII were then developed and evaluated by R. Patients were divided into low-SII and high-SII groups based on the SII optimal cut-off value 912 calculated by the Youden index in all patients. Higher SII was correlated with more symptoms, longer surgical time, higher WHO/ISUP grade, and longer tumor diameter. Kaplan-Meier analyses revealed significant differences in OS and DFS between two groups. Multivariate analyses revealed that SII was an independent prognostic factor for OS (HR:2.220, p=0.002) and DFS (HR:1.846, p=0.002). Compared with other indicators, SII had a superior accuracy (c-index=0.630 for OS and 0.595 for DFS). It also improved the performance of models for predicting OS and DFS (all p <0.01). Based on the results of LASSO Cox regression analysis, we constructed a nomogram to predict OS and it performed well on both the training cohort (AUC=0.805) and the validation cohort (AUC=0.795). Risk stratification based on nomogram can distinguish patients with different risks (all p <0.001). Preoperative SII is an independent predictive factor for OS and DFS of non-metastatic ccRCC patients with VTT. It can be used to improve the performance of current risk models.

Establishment and validation of a nomogram to select patients with metastatic sarcomatoid renal cell carcinoma suitable for cytoreductive radical nephrectomy.

Introduction: Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods: Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results: Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687-0.845), internal validation set (AUC = 0.796, 95% CI: 0.684-0.908), and external validation set (AUC = 0.911, 95% CI: 0.831-0.991). Conclusions: A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.