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Abstract The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P

Abstract The methyltransferase Wilms’ tumor 1-associated protein (WTAP) has been reported to be dysregulated in various tumors. However, its role in renal cell carcinoma (RCC) remains elusive. Here, we explored whether WTAP was upregulated in RCC specimens compared to normal tissues. Functionally, WTAP promoted RCC cell proliferation and metastasis in vivo and in vitro. Mechanistically, WTAP act as an N6-methyladenosine transferase to regulate the m6A modification of long noncoding RNA TEX41. Then, the upregulated m6A modification destabilized TEX41 in a YTHDF2-dependent manner. Furthermore, TEX41 interacted with the SUZ12 protein and increased the histone methyltransferase activity of SUZ12, resulting in HDAC1 silencing. Totally, our study demonstrated the oncogenic the role of WTAP/TEX41/SUZ12/HDAC1 axis in RCC progression.

Abstract Objectives Renal cell carcinoma (RCC) is shown to have a tendency for late recurrence, occurring 5 or more years after curative surgery. Imaging diagnosis is required for follow‐up, and there is no definitive answer as to how long this should continue. Some patients discontinue follow‐up visits at their own discretion. How best to predict late recurrence and loss to follow‐up (LF) remains unclear. Patients and methods This study targeted patients diagnosed with non‐metastatic RCC who underwent either radical or partial nephrectomy at Chiba University Hospital between 1988 and 2021. Follow‐up for patients with RCC is typically lifelong. We used random survival forests (RSFs), a machine learning‐based survival analysis method, to predict late recurrence and LF. For verification of prediction accuracy, we applied the time‐dependent area under the receiver operating characteristic curve (t‐AUC). To analyse the risks of late recurrence and LF, SurvSHAP(t) and partial dependence plots were used. Results We analysed 1051 cases in this study. Median follow‐up was 58.5 (range: 0–376) months. The predictive accuracy of recurrence using RSF was t‐AUC 0.806, 0.761, 0.674 and 0.566 at 60, 120, 180 and 240 months postoperatively, respectively. The recurrence risk impact showed a time‐dependent increase up to approximately 50 months postoperatively. Beyond 50 months, there were no distinct risk factors characteristic of late recurrence. The predictive accuracy of LF using RSF was t‐AUC 0.542, 0.699, 0.685, 0.628 and 0.674 at 60, 120, 180, 240 and 300 months postoperatively, respectively. The risk of LF increased with advancing age beyond 70 years. Conclusion It is difficult to identify factors that predict late recurrence. For long‐term follow‐up observation, it is essential to pay particular attention to patients with RCC aged 70 years and above. Establishing frameworks to facilitate collaboration with local hospitals near patients' residences and providing care within the community is necessary.

Abstract Renal cell carcinoma (RCC) affects 10%–20% of patients annually, often with metastases present. This study evaluated the impact of systemic therapy before nephrectomy in patients with unresectable or metastatic renal cell carcinoma (RCC). Patients receiving upfront immune checkpoint inhibitor (ICI) combination therapy showed significantly improved progression‐free survival (PFS) compared to nephrectomy alone (2‐year PFS: 62.3% vs. 17.4%; p = 0.036), while upfront tyrosine kinase inhibitor (TKI) therapy did not (2‐year PFS: 18.2% vs. 12.3%; p = 0.545). Surgery‐related outcomes did not differ significantly between groups. ICI therapy maintained tumour reduction rates better than TKI therapy. The study highlights the potential benefits of ICI combination therapy over TKI therapy in advanced RCC, suggesting further research is needed to confirm these findings.

Solitary pulmonary nodule is a difficult case for differential diagnosis. The list of pathological processes manifested by pulmonary nodule is quite large, including organizing pneumonia, which has non-specific CT picture. A correct diagnosis requires comparing the radiation examination data with anamnesis, the results of invasive and morphological studies. The presented clinical case shows the difficulties of diagnosing a combination of pulmonary nodule and extensive renal mass.

Abstract Background With the increasing incidence of renal lesions, pretreatment differentiation between benign and malignant lesions is crucial for optimized management. This study aimed to develop a machine learning model utilizing radiomic features extracted from various regions of interest (ROIs), intratumoral ecological diversity features, and clinical factors to classify renal lesions. Methods CT images (arterial phase) of 1,795 renal lesions with confirmed pathology from three hospital sites were split into development (1184, 66%) and test (611, 34%) cohorts by surgery date. Conventional radiomic features were extracted from eight ROIs of arterial phase images. Intratumoral ecological diversity features were derived from intratumoral subregions. The combined model incorporating these features with clinical factors was developed, and its performance was compared with radiologists’ interpretation. Results Combining intratumoral and peritumoral radiomic features, along with ecological diversity features yielded the highest AUC of 0.929 among all combinations of features extracted from CT scans. After incorporating clinical factors into the features extracted from CT images, our combined model outperformed the interpretation of radiologists in the whole (AUC = 0.946 vs 0.823, P

Immune checkpoint inhibitors (ICI)-based combinations have become the standard first-line treatment for advanced clear cell renal cell carcinoma (ccRCC). Despite significant improvements in survival and the achievement of sustained long-term responses, a subset of patients remains refractory to ICI, and most will eventually develop resistance. Thus, identifying predictive biomarkers for ICI efficacy and resistance is essential for optimizing therapeutic strategies. Up to now, tissue-based biomarkers have not been successful as predictive biomarkers in RCC. Circulating blood-based biomarkers offer a promising alternative. These biomarkers, including circulating immune cells, soluble factors, tumor-derived markers, and those based on metabolomics, are less invasive, offer reproducibility over time, and provide a comprehensive assessment of tumor biology and patient immune status, as well as allow dynamic monitoring during treatment. This review aims to evaluate the current evidence on the different candidate circulating biomarkers being investigated for their potential to predict ICI efficacy in RCC patients.

Aim: We aimed to investigate the prognostic factors, factors affecting survival and the prognostic value of the Memorial Sloan-Kettering Cancer Centre (MSKCC) risk score in renal cell carcinoma (RCC) patients. In addition, we assessed the survival and potential adverse effects of sunitinib and pazopanib tyrosine kinase inhibitors. Materials and Methods: The study included patients diagnosed with RCC aged ≥18 years, who were followed up in our clinic between 2006 and 2020. The clinicopathological characteristics were recorded in the hospital’s electronic data system. In the entire patient population, survival and prognostic factors were investigated. Furthermore, prognostic factors in terms of treatment (pazopanib vs. sunitinib) for advanced stage patients were evaluated as well. Results: Two hundred and two patients were included in this study. Fifty-five of the patients were female, 147 patients were male. Most common histological type was clear cell carcinoma (59%). At the time of presentation, 57% of the patients were in the early stage (stage 1,2,3). The median overall survival (mOS) was 16.8 months in stage 4 patients and 82.5 months in early stage patients. mOS was 69.1 months in the favorable MSKCC risk group while it was 6.8 months in the poor risk group. In the sunitinib arm, the median progression-free survival (mPFS) was 11.1 months, and mOS was 18.1 months. In the pazopanib arm, mPFS was 12.2 months, and mOS was 17.4 months. There was no significant difference in response rate, mPFS, and mOS between the two drugs. Conclusion: In this study, we have shown that risk and performance scorings with some laboratory and clinical evaluations, which are still cheap and easily accessible, are valuable and usable in showing prognosis in RCC patients. Disease stage, MSKCC risk score, Eastern Cooperative Oncology Group, and Karnofsky performance scores showed prognostic characteristics in RCC. There was no survival difference between histological subtypes. The efficacy of sunitinib and pazopanib in metastatic first-line treatment was similar, but pazopanib was superior in terms of any grade adverse events.

Abstract Background Renal cell carcinoma is the most fatal form of renal tumors, representing about ninety percent of all renal cancers. There are different variations in prognosis among various histological types of RCC. In recent years, there has been a greater emphasis on differentiating between RCC subtypes. Evaluation of different subtypes of renal cell carcinoma using intravoxel incoherent motion (IVIM) diffusion-weighted MRI is the aim of this study. Results Clear cell renal cell carcinoma (CCRCCs) showed highest f and D values, followed by chromophobe renal cell carcinoma (ChRCCs), while papillary renal cell carcinoma (PRCCs) had the lowest values. CCRCCs had significantly different D and f values compared to non-clear types (PRCC and ChRCC) (P

Abstract Background The population diagnosed with renal cell carcinoma, especially in Asia, represents 36.6% of global cases, with the incidence rate of renal cell carcinoma in Korea steadily increasing annually. However, treatment options for renal cell carcinoma are diverse, depending on clinical stage and histologic characteristics. Hence, this study aims to develop a machine learning based clinical decision-support system that recommends personalized treatment tailored to the individual health condition of each patient. Results We reviewed the real-world medical data of 1,867 participants diagnosed with renal cell carcinoma between November 2008 and June 2021 at the Pusan National University Yangsan Hospital in South Korea. Data were manually divided into a follow-up group where the patients did not undergo surgery or chemotherapy (Surveillance), a group where the patients underwent surgery (Surgery), and a group where the patients received chemotherapy before or after surgery (Chemotherapy). Feature selection was conducted to identify the significant clinical factors influencing renal cell carcinoma treatment decisions from 2,058 features. These features included subsets of 20, 50, 75, 100, and 150, as well as the complete set and an additional 50 expert-selected features. We applied representative machine learning algorithms, namely Decision Tree, Random Forest, and Gradient Boosting Machine (GBM). We analyzed the performance of three applied machine learning algorithms, among which the GBM algorithm achieved an accuracy score of 95% (95% CI, 92–98%) for the 100 and 150 feature sets. The GBM algorithm using 100 and 150 features achieved better performance than the algorithm using features selected by clinical experts (93%, 95% CI 89–97%). Conclusions We developed a preliminary personalized treatment decision-support system (TDSS) called “RCC-Supporter” by applying machine learning (ML) algorithms to determine personalized treatment for the various clinical situations of RCC patients. Our results demonstrate the feasibility of using machine learning-based clinical decision support systems for treatment decisions in real clinical settings.

Abstract Purpose The purpose of this study was to analyze the expression patterns of immune cells in renal cancer patients, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), CD3 + /CD4 + T cells, CD3 + / CD8 + T cells, and CD3- CD16 + CD56 + cells. In addition, this study will explore the correlation between these immune markers and the progression of renal cell carcinoma and evaluate their potential application in predicting the therapeutic effect of renal cell carcinoma. Methods In this study, 80 renal cancer patients who received treatment in our hospital from October 2022 to December 2023 were selected as the research object and 50 healthy people who underwent a physical examination at the same time were selected as the control group. All participants had a 3 ml venous blood sample taken in the morning on an empty stomach. All patients with renal cell carcinoma have been confirmed by histopathological diagnosis. Clinicopathological data including age, gender, BMI, clinical stage, tumor size and pathological type were collected.MDSC, Treg, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, the ratio of CD3 + /CD4 + T cells/CD3 + /CD8 + T cell and the expression level of CD3-CD16 + CD56 + cells were detected by flow cytometry. Results Through the detection of flow cytometry, we observed that there was no significant difference in gender, age, BMI and other baseline characteristics between renal cancer patients and healthy controls, and the P value was greater than 0.05. However, in the analysis of peripheral blood immune cell subsets, including CD3 + /CD4 + , CD3 + /CD8 + , CD3 + /CD4 + /CD3 + /CD8 + ratio, NK cells, regulatory T cells (T-reg), polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and mononuclear myeloid-derived suppressor cells (M-MDSC) were significantly different between renal cell carcinoma group and normal control group (P 0.05).At the same time, CD3 + /CD8 + T cells, the ratio of CD3 + /CD4 + /CD3 + /CD8 + and the expression level of NK cells were not significantly correlated with tumor size and clinical stage (P > 0.05). However, the expression levels of CD3 + /CD4 + cells, M-MDSC, PMN-MDSC, and T-reg cells were statistically significantly different with tumor size and clinical stage (P

Abstract Background Metastasis, the leading cause of renal cell carcinoma (RCC) mortality, involves cancer cells resisting anoikis and invading. Until now, the role of the matrix metalloproteinase (MMP)-related enzyme, A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1), in RCC anoikis regulation remains unclear. Methods The clinical significance of ADAMTS1 and its associated molecules in patients with RCC was investigated using data from the Gene Expression Omnibus (GEO) and TCGA datasets. Human phosphoreceptor tyrosine kinase (RTK) array, luciferase reporter assays, immunoprecipitation (IP) assays, western blotting, and real-time reverse-transcription quantitative polymerase chain reaction (RT–qPCR) were used to elucidate the underlying mechanisms of ADAMTS1. Functional assays, including anoikis resistance assays, invasion assays, and a Zebrafish xenotransplantation model, were conducted to assess the roles of ADAMTS1 in conferring resistance to anoikis in RCC. Results This study found elevated ADAMTS1 transcripts in RCC tissues that were correlated with a poor prognosis. ADAMTS1 manipulation significantly affected cell anoikis through the mitochondrial pathway in RCC cells. Human receptor tyrosine kinase (RTK) array screening identified that epidermal growth factor receptor (EGFR) activation was responsible for ADAMTS1-induced anoikis resistance and invasion. Further investigations revealed that enzymatically active ADAMTS1-induced versican V1 (VCAN V1) proteolysis led to EGFR transactivation, which in turn, through positive feedback, regulated ADAMTS1. Additionally, ADAMTS1 can form a complex with p53 to influence EGFR signaling. In vivo, VCAN or EGFR knockdown reversed ADAMTS1-induced prometastatic characteristics of RCC. A clinical analysis revealed a positive correlation between ADAMTS1 and VCAN or the EGFR and patients with RCC with high ADAMTS1 and VCAN expression had the worst prognoses. Conclusions Our results collectively uncover a novel cyclic axis involving ADAMTS1–VCAN–EGFR, which significantly contributes to RCC invasion and resistance to anoikis, thus presenting a promising therapeutic target for RCC metastasis.

Ling Wang,1– 3,* Fangqing Cai,3,* Yixuan Li,3,* Xiaolan Lin,3 Yuting Wang,3 Weijie Liang,3 Caiyu Liu,4 Cunze Wang,3 Junshan Ruan1– 3 1School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junshan Ruan, School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, 134 Dongjie, Fuzhou, 350001, People’s Republic of China, Tel +86 591-88216343, Fax +86 591-87532356, Email ruanjunshan@163.comPurpose: Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC.Methods: In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEG-PBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic–hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated.Results: TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 μg/mL to more than 5 mg/mL. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity.Conclusion: In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.Keywords: renal cell carcinoma, drug delivery, pH-responsive, mPEG-PBAE, nanomicelles

Abstract Background Open partial nephrectomy (OPN) has previously been considered the gold standard procedure for treatment of T1 localized renal tumors. After introduction of robot assisted partial nephrectomy (RAPN) as an alternative method to OPN, OPN was gradually abandoned at our department. The aim of the study was to retrospectively compare the results of patients treated with either OPN or RAPN for suspected renal carcinoma. Methods Patients who underwent either open or robotic assisted partial nephrectomy between January 1st 2010 and December 31st 2020 were retrospectively included in the study. Each tumor subjected to surgery was scored preoperatively by the RENAL nephrometry score. Complications within 30 days were assessed according to the Clavien-Dindo classification system. Results A total of 197 patients who underwent partial nephrectomy were identified; 75 were subjected to OPN and 122 were treated with RAPN. There were no significant differences between the groups with respect to age (OPN: 63 years ± 11, RAPN: 62 years ± 10), gender (OPN: 71/29%, RAPN: 67/33%), body mass index (OPN: 28 ± 5, RAPN: 28 ± 5), ASA score (OPN: 2.4 ± 0.6, RAPN: 2.2 ± 0.5), or nephrometry score (OPN: 6.6 ± 1.7, RAPN: 6.9 ± 1.7, p = 0.2). The operative time was significantly shorter in the OPN group (81 min) compared to the RAPN group (144.5 min, p

This study aimed to assess the prognostic role of body mass index (BMI) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. We searched for relevant studies in the MEDLINE, Embase, and Cochrane Library databases. The initial search yielded 599 records, of which seven articles (2,517 patients) were selected for analysis. Patients with a high BMI had a favorable overall survival (OS) based on hazard ratio (HR) (crude HR 0.69, 95% confidence interval [CI] 0.57–0.83, p

Introduction Paraneoplastic syndromes are frequent in patients with renal cell carcinoma. Dermatomyositis is an idiopathic inflammatory myopathy that may be associated with neoplasms. This case aims to describe the rare association of dermatomyositis with renal cell carcinoma and to increase clinical suspicion of this neoplasm when systemic rheumatologic symptoms are present. Case presentation A 35‐year‐old female developed severe rheumatologic symptoms (progressive muscle weakness, heliotrope rash, and Gottron's papules). Clinical and laboratory findings indicated dermatomyositis. During the investigation, computed tomography revealed a left kidney solid mass. She underwent a left radical nephrectomy, and histology confirmed renal cell carcinoma. After 3 months, dermatomyositis manifestations disappeared and the patient withdrawn steroid therapy. Conclusion Most paraneoplastic syndromes associated with renal cell carcinoma are only cured with nephrectomy. We highlight the potential role of surgery in dermatomyositis caused by renal cell carcinoma. The recurrence of symptoms related to the syndrome should alert for disease progression.

Abstract Objective To assess the rate at which sutureless partial nephrectomy (SLPN) transitions to standard partial nephrectomy (SPN), focusing on preoperative factors that might prompt such conversions. Patients and methods In this retrospective study, we analyzed the efficacy of SLPN performed on adults at our institution from 2016 to 2023. The subjects were patients diagnosed with localized solid renal tumors. The primary technique employed was resection with scissors and argon beam coagulation for hemostasis, with suturing techniques used only when necessary. Predictive factors necessitating conversion to SPN were identified, and the associations among multiple variables were explored using various statistical analysis methods, including logistic regression, to identify key preoperative predictive factors. Results Our institution performed 353 SLPN, with 21 cases (5.9%) necessitating conversion to SPN. The conversion rates for the Laparoscopic Partial Nephrectomy (LPN) subgroup and the Robotic-assist Partial Nephrectomy (RPN) subgroup were 7.9% (17/215) and 2.9% (4/138), respectively, nearing statistical significance (P = .066). Significant differences were observed between the conversion group and the no conversion group in terms of preoperative estimated Glomerular Filtration Rate (eGFR), age at surgery, tumor size, and exophytic/endophytic characteristics. Multivariate analysis identified age at surgery, preoperative eGFR, radiological tumor size, and tumor exophytic/endophytic nature as significant predictors for conversion to SPN. Conclusion This investigation highlights the efficacy and feasibility of SLPN while identifying critical factors influencing the necessity for conversion to SPN. The identified predictors, including younger surgical age, superior preoperative eGFR, and specific tumor characteristics, provide valuable insights for refining surgical strategies.

Sangmin Lee,1 Jae-Hun Kim,2 Wan Song,1 Hyun Hwan Sung,1 Hwang Gyun Jeon,1 Byong Chang Jeong,1 Seong Il Seo,1 Seong Soo Jeon,1 Se Hoon Park,3 Ji Hyun Lee,2 Jiwoong Yu,1,* Minyong Kang1,4,5,* 1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea; 5Samsung Genome Institute, Samsung Medical Center, Seoul, Korea*These authors contributed equally to this workCorrespondence: Minyong Kang; Jiwoong Yu, Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea, Tel +82-2-3410-1138 ; +82-2-3410-3559, Fax +82-2-3410-6992 ; +82-2-3410-6990, Email dr.minyong.kang@gmail.com; darwin082smart@gmail.comPurpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy.Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan–Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes.Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively).Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.Keywords: immunotherapy, renal cell carcinoma, body composition, prognosis

Introduction: Combined immuno-oncology (IO) regimens are the cornerstone of the current front-line systemic therapy for metastatic renal cell carcinoma (mRCC). Despite the fact that combined IO regimens show high efficacy, they are often accompanied by a wide spectrum of immune-related adverse effects (irAEs). Case Presentation: We describe a case of rare irAEs manifested as giant cell temporal arteritis (GCA) followed by severe encephalopathy occurring after continuing immunotherapy in a 66-year-old man with mRCC receiving a combination of ipilimumab and nivolumab in the first line of systemic therapy. GCA occurred 4 months after the initiation of IO and responded promptly to the low-dose prednisone therapy. Four months after the continuation of nivolumab maintenance, the patient was hospitalized due to severe irAE encephalopathy which presented as psycho-behavioral abnormalities and progressive cognitive decline. He was treated with high-dose methylprednisolone which led to complete resolution of the symptoms and IO was permanently discontinued. The patient achieved a durable partial response. Conclusion: Both GCA and the subsequent encephalopathy in our patient responded well to the corticosteroid therapy, leading to the complete resolution of the symptoms and the patient achieved a durable partial response. Although the risk of severe neurologic irAEs affecting the central nervous system induced by IO re-administration, following previous discontinuation due to irAE, is not well-defined because of their rarity, this case highlights the need for caution, particularly in cases with a history of previous irAE-associated GCA.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13–0.68) and CN-ST (HR 0.68, CI 0.47–0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26–0.77) and CN-ST (HR 0.9, CI 0.68–1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

Renal cell carcinoma accounts for a significant proportion of cancer diagnoses in Canadians. Over the past several years, the management of renal cell cancers has undergone rapid changes in all prognostic risk categories, resulting in improved oncologic outcomes. Novel strategies for metastatic disease make use of the synergy between checkpoints and angiogenesis inhibition. Moreover, combination checkpoint inhibition has demonstrated durable efficacy in some patients. Adjuvant immunotherapy has recently shown a survival benefit for the first time in select cases. Significant efforts are underway to explore new compounds or combinations for later-line diseases, such as inhibitors of hypoxia-inducible factors and radiolabeled biomolecules targeting tumor antigens within the neoplastic microenvironment for precise payload delivery. In this manuscript, we provide a comprehensive review of the available data addressing key therapeutic areas pertaining to systemic therapy for metastatic and localized disease, review the most relevant prognostic tools, describe local therapies and management of CNS disease, and discuss practice-changing trials currently underway. Finally, we focus on some of the practical aspects for general practitioners in oncology caring for patients with renal cell carcinoma.

Abstract Renal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90–95% of kidney cancer cases. Although its incidence has increased over the past decades, its pathogenesis is still unclear. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising more than 50% of the tumor volume. By interacting with cancer cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In the TME, M2-type TAMs, which are known to promote tumorigenesis, are more abundant than M1-type TAMs, which are known to suppress tumor growth. This ratio of M1 to M2 TAMs can create an immunosuppressive environment that contributes to tumor cell progression and survival. This review focused on the role of TAMs in RCC, including their polarization, impacts on tumor proliferation, angiogenesis, invasion, migration, drug resistance, and immunosuppression. In addition, we discussed the potential of targeting TAMs for clinical therapy in RCC. A deeper understanding of the molecular biology of TAMs is essential for exploring innovative therapeutic strategies for the treatment of RCC.

Moshe C Ornstein,1 Lisa C Rosenblatt,2 Xin Yin,2 Viviana Del Tejo,2 Sarah B Guttenplan,2 Flavia Ejzykowicz,2 Kathleen Beusterien,3 Oliver Will,3 deMauri S Mackie,3 Grace Skiles,3 Marc DeCongelio3 1Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA; 2Global HEOR Oncology, Bristol Myers Squibb, Princeton, NJ, USA; 3Real World Evidence, Oracle Life Sciences, Austin, TX, USACorrespondence: Marc DeCongelio, Oracle Life Sciences, 2800 Rock Creek Parkway, North Kansas City, MO, 64117, USA, Tel +18162011975, Email marc.decongelio@oracle.comIntroduction: The treatment landscape for advanced/metastatic renal cell carcinoma (aRCC) has evolved quickly with the introduction of immunotherapies as a first-line treatment option. This study examined the preferences of patients with aRCC to better understand the characteristics of preferred treatments and the tradeoffs patients are willing to make when choosing treatment.Methods and Materials: An online, cross-sectional survey was conducted in the US from May to August 2022 with adult patients with aRCC. A discrete-choice experiment assessed treatment preferences for aRCC. Attributes were identified through literature review and qualitative interviews and included progression-free survival, survival time, objective response rate, duration of response, risk of serious side effects, quality of life (QoL), and treatment regimen.Results: Survey results from 299 patients with aRCC were analyzed. Patients had a mean age of 55.7 years, were primarily White (50.5%) and were evenly representative of males (49.8%) and females (48.8%). Improvements in all attributes influenced treatment choice. On average, increasing survival time from 10% to 55% was most important, followed by improvements in QoL (ie, from worsens a lot to improves) and improvements to treatment regimen convenience (ie, less frequent infusions). Risk of serious adverse events and increased progression-free time, objective response rate (ORR), and duration of response (DOR) were of lesser importance.Conclusion: In this study, patients highlighted that improving survival time was the most important and that QoL is also an important consideration. Discussions during treatment decision-making may benefit from broader conversations around treatment characteristics, including impacts on QoL and convenience of the regimen.Keywords: discrete choice experiment, patient preference, treatment preference, renal cell carcinoma

Abstract Objective The objective of this study is to independently assess skeletal muscle index (SMI) and body mass index (BMI) as prognostic determinants for renal cell carcinoma (RCC) and investigate their correlation with surgical outcomes. Patients and methods A retrospective cohort study of 524 RCC patients diagnosed between August 2010 and July 2018 was conducted using data from the Zealand University Hospital Renal Cancer Database in Denmark. Patient information was extracted from electronic patient records and the National Cancer Registry and encompassed demographics, clinical factors, tumour characteristics and surgical details. SMI was calculated from a single third lumbar vertebra (L3) axial computed tomography (CT) image via CoreSlicer software and classified into high using gender‐specific thresholds. Primary outcomes focused on complications within 90 days as well as survival outcomes, and their relation with both SMI and BMI. Multivariable analysis assessed SMI's independent prognostic significance in RCC. Results Among 524 patients, 18.5% experienced complications, with high SMI correlating significantly (p = 0.018) with a 72% higher complication risk. High SMI patients had a 22.7% complication rate compared to 14.5% in the low SMI group. High SMI was also linked to prolonged survival (110.95 vs. 94.87 months; p = 0.001), whereas BMI showed no significant survival differences (p = 0.326). Multivariable analysis (n = 522) revealed high SMI associated with improved survival (hazard ratio [HR] = 0.738; 95% CI, 0.548–0.994; p = 0.046). Advanced T‐stage significantly impacted mortality (T2: HR = 2.057; T3: HR = 4.361; p

Abstract Background Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. Methods Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. Results Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. Conclusion Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Abstract Background Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. Methods Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. Results TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. Conclusions Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

Abstract Background Renal cell carcinoma (RCC), one of the most fatal urologic tumors, accounts for approximately 3% of all adult cancers and exhibits a high metastatic index at diagnosis and a high rate of relapse. Radical or partial nephrectomy is a curative option for nonmetastatic RCCs. Targeted therapy has been shown to improve the survival of patients with metastatic RCCs. However, the underlying cellular and molecular events associated with RCC pathogenesis are not well known. Methods To investigate the clinical role of the transcription factor activator protein (AP)-2α in RCC, methylated CpG island recovery assays and microarray analysis were employed. COBRA and RT‒qPCR assays were performed to assess AP-2α expression in RCC. Results A negative correlation was noted between AP-2α mRNA expression levels and methylation status. Multivariate analyses showed that AP-2α mRNA was a major risk factor not only for overall and disease-free survival in RCC but also for disease-free survival in clear cell RCC. Conclusions Our results indicated that AP-2α expression was deregulated in RCC and associated with overall patient survival and disease-free survival. Such findings suggest that AP-2α might play an important role in the pathogenesis of RCC.

In this research, we investigated the role of PIK3R6, a regulatory subunit of PI3Kγ, known for its tumor-promoting properties, in clear cell renal cell carcinoma (CCRCC). Utilizing the UALCAN website, we found PIK3R6 upregulated in CCRCC, correlating with lower survival rates. We compared PIK3R6 expression in CCRCC tumor tissues and adjacent normal tissues using immunohistochemistry. Post RNA interference-induced knockdown of PIK3R6 in 786-O and ACHN cell lines, we performed CCK-8, colony formation, Edu staining, flow cytometry, wound healing, and transwell assays. Results showed that PIK3R6 silencing reduced cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis. Molecular analysis revealed decreased CDK4, Cyclin D1, N-cadherin, Vimentin, Bcl-2, p-PI3K and p-AKT, with increased cleaved caspase-3, Bax, and E-cadherin levels in CCRCC cells. Moreover, inhibiting PIK3R6 hindered tumor growth. These findings suggest a significant role for PIK3R6 in CCRCC cell proliferation and metastasis, presenting it as a potential therapeutic target.

Desmoid fibromatosis (DF) is an extremely rare tumor, which is locally aggressive in nature with no metastatic potential. Presenting symptoms depend on tumor size, site and progression speed. Most commonly occur sporadically, or associated with familial adenomatous polyposis (FAP). Factors may contribute to develop DF are trauma or surgical incision. In this article, we report a 41-years old male, which had partial upper pole nephrectomy, and developed lower pole desmoid fibrosis proven by histopathology.To our best knowledge, there are no article discussed the 2 different tumors occur in the same kidney at 2 different locations.

Tubulocystic renal cell carcinoma (RCC) is a rare renal cancer first recognized by the WHO in 2016 as independent disease category, characterized by its typically indolent features and low rates of metastasis. We present a 35-year-old male with tubulocystic RCC diagnosed incidentally on evaluation of flank pain. Magnetic resonance imaging showed Bosniak class 4 renal cyst, although initial computed topography showed a hypodense nonenhancing lesion classified as Bosniak 1 cyst. Patient underwent robotic assisted partial nephrectomy, histopathology confirmed as tubulocystic RCC. This case highlights the importance of considering tubulocystic RCC in the differential diagnoses of renal cysts and other solid renal masses to ensure timely and effective treatment plan.

Over the last decade, immune checkpoint inhibitors (ICIs) have dramatically improved the systemic treatment of multiple solid tumour types. However, they can also induce inflammation in an extensive range of normal tissues types. The entity of ICI-induced cholangitis is rare and has not been widely described. We present three cases of ICI-induced cholangitis which illustrate the difficulties associated with its diagnosis and management. We also present associated radiological findings that include intrahepatic duct abnormalities consistent with sclerosing cholangitis-progressive worsening of intrahepatic duct dilatation and pericholecystic haziness suggesting inflammation characteristic of this rare, but severe, toxicity.

Abstract Background Sunitinib is a multikinase inhibitor used to treat patients with advanced renal cell carcinoma (RCC). However, sunitinib toxicity makes it a double-edged sword. Potent immune modulation by sunitinib extends to nuclear interactions. To address these issues, there is an urgent need for delivery vectors suitable for sunitinib treatment. Methods We developed PEGylated liposomes as delivery vectors to precisely target sunitinib (lipo-sunitinib) to RCC tumors. Further investigations, including RNA sequencing (RNA-seq), were performed to evaluate transcriptomic changes in these pathways. DiI/DiR-labeled lipo-sunitinib was used for the biodistribution analysis. Flow cytometry and immunofluorescence (IF) were used to examine immune modulation in orthotopic RCC models. Results The evaluation of results indicated that lipo-sunitinib precisely targeted the tumor site to induce autophagy and was readily taken up by RCC tumor cells. In addition, transcriptomic assays revealed that following lipo-sunitinib treatment, autophagy, antigen presentation, cytokine, and chemokine production pathways were upregulated, whereas the epithelial-mesenchymal transition (EMT) pathway was downregulated. In vivo data provided evidence supporting the inhibitory effect of lipo-sunitinib on RCC tumor progression and metastasis. Flow cytometry further demonstrated that liposunitinib increased the infiltration of effector T cells (Teffs) and conventional type 1 dendritic cells (cDC1s) into the tumor. Furthermore, systemic immune organs such as the tumor-draining lymph nodes, spleen, and bone marrow exhibited upregulated anticancer immunity following lipo-sunitinib treatment. Conclusion Our findings demonstrated that lipo-sunitinib is distributed at the RCC tumor site, concurrently inducing potent autophagy, elevating antigen presentation, activating cytokine and chemokine production pathways, and downregulating EMT in RCC cells. This comprehensive approach significantly enhanced tumor inhibition and promoted anticancer immune modulation. Graphical Abstract

Abstract Background Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. Methods KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. Results One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2–14.3) and 10.3 months (2.7–13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2–44.1] and sunitinib/pazopanib (29.2% [18.6–41.8]). Grade 3–5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. Conclusions ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab. Clinical trial registration ClinicalTrials.gov; NCT03260894 .

Abstract Background Renal cell carcinoma (RCC) is presently recognized as the most prevalent kidney tumor. However, the role and underlying mechanism of action of the conversion factor-inducible protein (TGFBI), an extracellular matrix protein, in RCC remain poorly understood. Methods In this study, we employed Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry techniques to assess the expression of TGFBI in RCC tissues or cells. Furthermore, we analyzed the proliferation and migration of RCC cells using CCK8, cloning, scratching, and migration assays. Additionally, we examined apoptosis and cell cycle progression through flow cytometry, analysis. Lastly, we employed gene set enrichment analysis (GSEA) to investigate the biological processes associated with TGFBI, which were subsequently validated. Results The findings indicate that TGFBI exhibits significantly elevated expression levels in both renal cell carcinoma (RCC) tissues and cells. Furthermore, the knockdown of TGFBI in SiRNA transfected cells resulted in the inhibition of RCC cell proliferation, migration, invasiveness, apoptosis, and alteration of the cell cycle. Additionally, TGFBI was found to impede the epithelial-mesenchymal transition (EMT) process in RCC cells. Bioinformatics analysis suggests that TGFBI may exert its influence on various biological processes in RCC through the tumor immune microenvironment. Moreover, our study demonstrates that TGFBI promotes RCC progression by activating the PI3K/AKT/mTOR/HIF-1α. Conclusions Our research indicates that TGFBI exhibits high expression in RCC and facilitate RCC progression and metastasis through various molecular mechanisms. Hence, TGFBI has the potential to be a novel therapeutic target for the diagnosis and treatment of RCC in the future.

Abstract Objectives This study aimed to assess the predictive value of radiomics derived from intratumoral and peritumoral regions and to develop a radiomics nomogram to predict preoperative nuclear grade and overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC). Methods The study included 395 patients with ccRCC from our institution. The patients in Center A (anonymous) institution were randomly divided into a training cohort (n = 284) and an internal validation cohort (n = 71). An external validation cohort comprising 40 patients from Center B also was included. Computed tomography (CT) radiomics features were extracted from the internal area of the tumor (IAT) and IAT combined peritumoral areas of the tumor at 3 mm (PAT 3 mm) and 5 mm (PAT 5 mm). Independent predictors from both clinical and radiomics scores (Radscore) were used to construct a radiomics nomogram. Kaplan–Meier analysis with a log-rank test was performed to evaluate the correlation between factors and OS. Results The PAT 5-mm radiomics model (RM) exhibited exceptional predictive capability for grading, achieving an area under the curves of 0.80, 0.80, and 0.90 in the training, internal validation, and external validation cohorts. The nomogram and RM gained from the PAT 5-mm region were more clinically useful than the clinical model. The association between OS and predicted nuclear grade derived from the PAT 5-mm Radscore and the nomogram-predicted score was statistically significant (p

Abstract Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described. The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group. We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months. Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

Xu Yang,1,* Jianwei Wu,1,* Longlong Fan,2 Binghua Chen,3 Shiqiang Zhang,4 Wenzhong Zheng1 1Department of Urology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Urology, Pingtan Branch of Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenzhong Zheng, Department of Urology, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian Province, 200001, People’s Republic of China, Email wenzhong_zheng@yeah.net Shiqiang Zhang, Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 628, Zhenyuan Road, Guangming Dist, Shenzhen, 518107, People’s Republic of China, Email zhangshq55@mail.sysu.edu.cnBackground: The involvement of cytotoxic CD4+ T cells (CD4+ CTLs) and their potential role in dictating the response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC) remains an unexplored area of research.Methods: Utilizing single-cell RNA sequencing, we analyzed the immunophenotype and expression patterns of CD4+ T lymphocyte subtypes in mRCC patients, followed by preliminary validation via multi-immunofluorescent staining. In addition, we obtained a comprehensive immunotherapy dataset encompassing single-cell RNA sequencing datasets and bulk RNA-seq cohorts from the European Genome-Phenome Archive and ArrayExpress database. Utilizing the CIBERSORTx deconvolution algorithms, we derived a signature score for CD4+ CTLs from the bulk-RNA-seq datasets of the CheckMate 009/025 clinical trials.Results: Single-cell analysis of CD4+ T lymphocytes in mRCC reveals several cancer-specific states, including diverse phenotypes of regulatory T cells. Remarkably, we observe that CD4+ CTLs cells constitute a substantial proportion of all CD4+ T lymphocyte sub-clusters in mRCC patients, highlighting their potential significance in the disease. Furthermore, within mRCC patients, we identify two distinct cytotoxic states of CD4+ T cells: CD4+GZMK+ T cells, which exhibit a weaker cytotoxic potential, and CD4+GZMB+ T cells, which demonstrate robust cytotoxic activity. Both regulatory T cells and CD4+ CTLs originate from proliferating CD4+ T cells within mRCC tissues. Intriguingly, our trajectory analysis indicates that the weakly cytotoxic CD4+GZMK+ T cells differentiate from their more cytotoxic CD4+GZMB+ counterparts. In comparing patients with lower CD4+ CTLs levels to those with higher CD4+ CTLs abundance in the CheckMate 009 and 25 immunotherapy cohorts, the latter group exhibited significantly improved OS and PFS probability.Conclusion: Our study underscores the pivotal role that intratumoral CD4+ CTLs may play in bolstering anti-tumor immunity, suggesting their potential as a promising biomarker for predicting response to ICIs in patients with mRCC.Keywords: single-cell analysis, granzyme K and granzyme B, cytotoxic CD4+ T cells, immune checkpoint inhibitors, renal cell carcinoma

Introduction. Partial nephrectomy is the treatment of choice for small renal tumors. There are other indications include tumors in a solitary kidney, multiple and bilateral tumors.Сase presentation. A 67-year-old male presented with left flank pain and lower urinary tract symptoms. Computed tomography for abdominal and pelvis showed bilateral renal masses. After doing the essential laboratory tests and investigations, he underwent bilateral open simultaneous partial nephrectomies. After two days, he was discharged with no complains. Follow-up after three months showed no recurrence and acceptable renal function.Discussion. Partial nephrectomy is increasingly used for the management of renal masses. The preservation of renal function with reduced morbidity and equivalent oncologic outcomes led to a paradigm shift away from radical nephrectomy.Conclusion. Bilateral partial nephrectomy is feasible with both clinical and oncological good results.

Abstract Background The detection of small renal masses has significantly increased due to the widespread use of cross-sectional imaging in recent years. Among these masses, clear cell renal cell carcinoma (ccRCC) is the most common subtype and progresses quickly, resulting in the advancement of the disease and the development of metastases. In this prospective study, our goal is to assess the effectiveness of multiparametric MRI clear cell Likelihood Score in small solid renal masses and its utility in predicting tumor grade. Results In total, 103 patients (mean age 52.5 ± 13.16 years) with small solid renal masses of stage T1a (≤ 4 cm) were identified. Mean tumor size was 3.4 ± 0.6 cm. According to our study results, the clear cell Likelihood Score (ccLS) had sensitivity of 75.6%, specificity of 93.5%, PPV of 88.6%, NPV of 85.3% and accuracy of 86.4% in diagnosing ccRCC using a ccLS threshold of 4 and 5. As regard the assessment of ccLS threshold of 1 or 2 in excluding ccRCC pathological subtype, our study found that out of 29 patients with ccLS 1 or 2, there was only 1 ccRCC case with false result (3% false positive). It was also noted that there is significant relation between Arterial-to-delayed-enhancement-ratio (ADER) value and the grade of the ccRCC. The median interquartile range (IQR) of ADER parameter was statistically significant higher in grade II compared to grade I (Median was 1.6 and 0.9 respectively) and much higher in grade III compared to grades I and II (Median was 2.9) with P value

Abstract Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.

Abstract Objective To investigate the effects of Lathyrol on the expression of androgen receptor (AR) and sphingosine kinase 2 (SPHK2) in renal cell carcinoma (RCC) mice and to further explore the mechanism by which Lathyrol inhibits the invasion and incidence of epithelial-mesenchymal transition (EMT). Methods An RCC xenograft mouse model was constructed, and the mice were randomly divided into a model group, an experiment group and a negative control group. The experiment group was intragastrically gavaged with Lathyrol solution (20 mg/kg), the model group was intragastrically gavaged with 0.9% NaCl (same volume as that used in the experiment group), and the negative control group was injected intraperitoneally with 2 mg/kg cisplatin aqueous solution. Changes in the body weight and tumor volume of the mice were recorded. Western blot (WB) was used to assess the protein expression levels of AR, p-AR, CYP17A1, PARP1, E-cadherin, N-cadherin, vimentin, α-SMA, β-catenin, and ZO-1. Protein expression levels of SPHK2, metal matrix protease 2 (MMP2), MMP9 and urokinase-type plasminogen activator (uPA) in tumor tissues were assessed by immunohistochemistry (IHC). AR expression in tumor tissues was assessed after immunofluorescence (IF) staining. Results After 14 days of drug administration, compared with that in the model group, the tumor volumes in the negative control and experiment groups were lower; the difference in tumor volume among the model, control and experiment groups was statistically significant (P 0.05). In the model group, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively increased, the protein expression levels of E-cadherin and ZO-1 were relatively reduced (P

Abstract Background Collecting duct carcinoma (CDC) is a rare histological type of renal cell carcinoma that lacks a prognostic prediction model. In this study, we developed a nomogram to predict the prognosis of CDC patients. Methods Data for patients (n = 247) diagnosed with CDC from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were randomized into training (n = 165) and validation (n = 82) cohorts. Survival outcomes were evaluated by the Kaplan–Meier method. Significant variables determined by univariate and multivariate Cox regression analyses were used to construct the nomogram. C-indexes and calibration plots were applied to evaluate the performance of the nomogram. Results CDC patients had a median overall survival (OS) of 18.0 months (95% confidence interval: 13.7–22.3); 1-year, 3-year, and 5-year OS rates were 58.7%, 34.2%, and 29.4%, respectively. Independent prognostic factors, including age at diagnosis, tumor size, tumor grade, T stage, N stage, M stage, and surgery information, were identified by multivariate analysis. The nomogram was constructed based on significant factors in the training cohort. The C-indexes were 0.769 (training cohort) and 0.767 (validation cohort). The calibration curves for survival rates showed that the predicted and observed values were consistent. Conclusions This study constructed a nomogram to predict prognosis in patients with CDC. The nomogram performed well in predicting the 1-year, 3-year, and 5-year OS, which can help doctors actively monitor and follow up patients.

Abstract Background The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. Methods This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. Discussion This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. Trial registration ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

Introduction The pathologic evaluation and clinical course of cytoreductive nephrectomy after combined immuno‐oncology therapy were reviewed to understand the benefits of cytoreductive nephrectomy. Case presentation Three patients with clear cell carcinoma underwent tumor biopsy before combined immuno‐oncology therapy. Case 1 was found to have a sarcomatoid component upon nephrectomy and continued with combined immuno‐oncology therapy. Case 2 discontinued combined immuno‐oncology therapy due to adverse events but maintained tumor shrinkage. The patient was found to have viable cells in most nephrectomy specimens but has had no recurrence after combined immuno‐oncology therapy was discontinued. In case 3, the residual tumor was deemed resectable with combined immuno‐oncology therapy, and nephrectomy and metastasectomy were performed. No viable cells were observed in either specimen, and the patient has had no recurrence. Conclusion Cytoreductive nephrectomy after combined immuno‐oncology therapy may be useful to allow pathologic evaluation of treatment and provide an indicator for subsequent treatment.

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75–80% of all patients with renal cell carcinoma. Despite its prevalence, little is known regarding the key components involved in ccRCC metastasis. In this study, scRNA‐seq analysis was employed to classify CD8+ T cells into four sub‐clusters based on their genetic profiles and immunofluorescence experiments were used to validate two key clusters. Through gene set enrichment analysis, these newly identified sub‐clusters were found to exhibit distinct biological characteristics. Notably, TYMP, TOP2A, CHI3L2, CDKN3, CENPM, and RZH2 were highly expressed in these sub‐clusters, indicating a correlation with poor prognosis. Among these sub‐clusters, CD8+ T cells (MT‐ND4) were identified as potentially playing a critical role in mediating ccRCC metastasis. These results contribute to our understanding of CD8+ T cell heterogeneity in ccRCC and shed light on the mechanisms underlying the loss of immune response against cancer.

Renal cell carcinoma (RCC) is an extremely rare cancer in pediatric, accounting for 0.1% to 0.3% of all pediatric malignancies. Due to its low incidence in this age group, literature on pediatric RCC is limited. We present a case of localized RCC in pediatric patient treated with nephroureterectomy and lymphadenectomy. A 14-year-old girl with a 2-year history of red urine, blood clots, and left flank pain underwent physical examination, revealing left flank tenderness. Laboratory results showed anemia, leukocytosis, elevated LDH, and erythrocytes in urine. Imaging revealed a hyperechoic area in the left kidney's lower pole (4.0 × 2.8 cm). Contrast abdominal CT scan indicated a solid mass (5.4 × 3.8 × 3.2 cm) in left renal pelvis extending to the minor calyx and severe hydronephrosis. The patient was diagnosed with suspected cT3N0M0 left upper tract urothelial carcinoma and underwent cystoscopy, bladder cuff excision, and left radical nephroureterectomy with paraaortic lymph node dissection. Pathological analysis revealed clear cell type renal cell carcinoma, WHO ISUP grade IV, extending to the perirenal fat, with tumor-free ureteral resection margins, and no paraaortic lymph node metastasis. Follow-up on postoperative period showed a satisfactory outcome. In cases of pediatric localized RCC, surgical therapy, including radical nephrectomy or nephron-sparing surgery (NSS), can be a preferred treatment for small tumor volumes. This approach preserves kidney function and is generally considered safe for achieving tumor-free margins.

Synchronous pancreatic neuroendocrine tumors and renal cell cancer are extremely rare. Von-Hipple-Landau syndrome is a major association. A 43-year-old male patient with left upper quadrant pain and significant weight loss was diagnosed with a synchronous pancreatic tail neuroendocrine tumor with solitary splenic metastasis and a clear-cell renal cell carcinoma of the left kidney. Sonography and a computed tomography scan of the abdomen showed a complex exophytic left renal mass and a necrotic lesion limited to the spleen. Although not apparent on preoperative imaging, distal pancreatic mass was also discovered intraoperatively. Subsequently, left radical nephrectomy, splenectomy, and distal pancreatectomy were performed, and the synchronous primaries and splenic metastasis were confirmed histopathologically. This case is unique in that it demonstrates multiple extremely rare events occurring simultaneously, namely pancreatic and kidney primaries, as well as solitary splenic metastasis.

Primary multiple malignancies (PMMs) are defined as two or more malignant tumors of various pathogenic origin detected simultaneously or sequentially in one patient. Despite the successes of modern medicine, the incidence of PMMs is steadily increasing. According to worldwide statistics, the incidence of PMMs in the oncological population has increased from 2.4 to 8.0 % over the course of the 20 year span. The number of patients with PMMs is also increasing in the Russian Federation. Total of 58,217 PMMs were detected for the first time in our country in 2021, which constitutes 10.0 % of all newly diagnosed malignant neoplasms. Two tumors are usually observed among patients with PMMs (in 84–100 % of patients), three tumors occur in 9.9–16.0 % of these patients, four in 1.62 %, and five or more occur in only 0.095 %.Currently, the pathogenesis of this condition has not yet been fully studied. There are hypotheses that endogenous, exogenous, hereditary, and therapeutic factors are involved in the occurrence of PMMs. Endogenous factors include immunologic status, endocrine factors, and hereditary predisposition. Exogenous factors are represented by lifestyle and environmental factors such as smoking and alcohol, low physical activity, as well as prolonged exposure to ultraviolet radiation and industrial pollution. Iatrogenic factors, including radiation therapy and chemotherapy, can also increase the risk of developing PMMs.This article represents a clinical case of a patient born in 1942, in whom, during 11 years of follow-up care, primary multiple synchronous metachronous cancers of 5 localizations and 4 histological types were verified and treated. The presented clinical case is interesting for a very rare number of neoplasms and a relatively high duration of follow-up period. The authors describe in detail each stage, the choice of diagnostic methods and the definition of treatment tactics with an assessment of the accuracy of clinical decision-making.

Introduction: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. The aim of this study is to investigate the effects of the buforin II gene on the expression of lncRNAs PVT1, EGOT and LINC00312 in ACHN kidney cancer cells. Material & Methods: Recombinant plasmid pcDNA3.1(+) containing buforin II gene and empty plasmid pcDNA3.1(+) were introduced into E. coli strain TOP10 by heat shock method and then purified. Then both mentioned plasmids were introduced into ACHN cells by lipofection method and screening was done by neomycin antibiotic. Finally, real time RT-PCR reaction was performed in order to investigate the expression change of EGOT, PVT1 and LINC00312 lncRNAs. Results: After lipofection, the transfected cells grew in the culture medium containing neomycin antibiotic. The real time RT-PCR reaction showed that the expression of buforin II gene in ACHN kidney cancer cells caused a significant increase in the expression of lncRNAs EGOT (P=0.0033) and LINC00312 (P=0.0272) and a significant decrease in the expression of PVT1 (P=0.0278). Discussion & Conclusion: Considering that the presence of buforin II gene causes a significant change in the expression of lncRNAs EGOT, PVT1 and LINC00312, it is possible that it can activate cell pathways including apoptosis.

Renal cell carcinoma (RCC) with TFE3 gene fusion caused by Xp11.2 translocations is a rare RCC subtype. This tumor is typically seen in children, comprising 20‒40% of overall RCC cases compared to 1‒1.6% observed in adults. Xp11.2 RCC is associated with a poor prognosis due to both the progression of local lesions and early distant and lymphatic metastasis.