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Background: Small renal masses (SRMs) have been shown to have low malignant potential. Active surveillance (AS), typically characterized by regular follow-up and delayed nephrectomy if necessary, is recommended as an option for frail patients with SRMs. Nevertheless, the impact of tumor size on survival in T1a RCC patients undergoing delayed nephrectomy for SRMs remains unclear. Methods: Patients diagnosed with non-metastatic T1a RCC who underwent nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database and divided into immediate (< 6 months) and delayed nephrectomy (≥ 6 months) groups based on the duration from diagnosis to nephrectomy. After propensity score matching (PSM), overall survival (OS) and cancer-specific survival (CSS) were estimated by K-M curves and compared with log-rank test. Results: A total of 27,502 patients were enrolled, of whom 26,915 (97.9%) received immediate nephrectomy and 587 (2.1%) received delayed nephrectomy. After PSM, 1174 patients who underwent immediate nephrectomy and 587 patients who underwent delayed nephrectomy were included. With a median delay of 7 months, delayed nephrectomy resulted in non-inferior OS for RCC tumors sized 0.1–2.0 cm (HR = 1.12, p = 0.636). However, for RCC tumors sized 2.1–3.0 cm (HR = 1.60, p = 0.008) and 3.1–4.0 cm (HR = 1.89, p < 0.001), delayed nephrectomy showed inferior OS compared to immediate nephrectomy. Delayed nephrectomy did not result in significantly worse CSS than immediate nephrectomy in all tumor size subgroups (all p > 0.05), however this may be due to sample size limiting statistical power. Conclusion: Based on the SEER database, we found that with a median delay of 7 months, 2 cm may be an appropriate cut-off point of delayed nephrectomy for patients diagnosed with non-metastatic T1a RCC. [ABSTRACT FROM AUTHOR]

Natural products are chemical compounds produced by living organisms. They are isolated and purified to determine their function and can potentially be used as therapeutic agents. The ability of some bioactive natural products to modify the course of cancer is fascinating and promising. In the past 50 years, there have been advancements in cancer therapy that have increased survival rates for localized tumors. However, there has been little progress in treating advanced renal cell carcinoma (RCC), which is resistant to radiation and chemotherapy. Oncogenes and tumor suppressors are two roles played by microRNAs (miRNAs). They are involved in important pathogenetic mechanisms like hypoxia and epithelial-mesenchymal transition (EMT); they control apoptosis, cell growth, migration, invasion, angiogenesis, and proliferation through target proteins involved in various signaling pathways. Depending on their expression pattern, miRNAs may identify certain subtypes of RCC or distinguish tumor tissue from healthy renal tissue. As diagnostic biomarkers of RCC, circulating miRNAs show promise. There is a correlation between the expression patterns of several miRNAs and the prognosis and diagnosis of patients with RCC. Potentially high-risk primary tumors may be identified by comparing original tumor tissue with metastases. Variations in miRNA expression between treatment-sensitive and therapy-resistant patients' tissues and serum allow for the estimation of responsiveness to target therapy. Our knowledge of miRNAs' function in RCC etiology has a tremendous uptick. Finding and validating their gene targets could have an immediate effect on creating anticancer treatments based on miRNAs. Several miRNAs have the potential to be used as biomarkers for diagnosis and prognosis. This review provides an in-depth analysis of the current knowledge regarding natural compounds and their modes of action in combating cancer. Also, this study aims to give information about the diagnostic and prognostic value of miRNAs as cancer biomarkers and their involvement in the pathogenesis of RCC. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms' Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 − rho = 0.341, p-value = 0.036; TDs − rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Circular bovine meat and milk factor (BMMF) DNAs have recently been identified in peritumoral tissues of human colon and breast cancers. Here we aimed to test the most common subtypes of renal cell carcinoma (RCC) for the prevalence of BMMF1 and BMMF2 DNA. We directly tested formalin-fixed and paraffin-embedded (FFPE) RCC and peritumoral tissues for BMMF1 and BMMF2 sequences by introducing novel consensus PCR primers. We demonstrate that BMMF1- and BMMF2- like DNA sequences can be reliably detected in FFPE tissues by consensus PCR. Our results demonstrate that BMMF1- and BMMF2- like sequences are frequently present in FFPE tissues of RCC and peritumoral tissues. Of interest, these sequences are more prevalent in peritumoral kidney tissues. These findings are potentially in line with the proposed model for BMMF-induced indirect colon carcinogenesis, which includes the presence of BMMFs in adjacent peritumoral tissues. Previous studies have indicated a potential role of diet in the pathogenesis of renal cell carcinoma (RCC). Recently, circular bovine meat and milk factor (BMMF) DNAs have been identified in peritumoral tissues of human colon and breast cancers. Here, we investigated the prevalence of the DNA of these novel human pathogenic infectious agents in RCC and adjacent peritumoral renal tissues. DNA was extracted from formalin-fixed and paraffin-embedded (FFPE) RCC and peritumoral kidney tissues, including a test (n = 11) and a validation (n = 152) collection. BMMF1 and BMMF2 consensus primers were designed to screen for the presence of BMMF1- and BMMF2-like DNA. In addition, BMMF-specific PCR was performed on selected cases to test for the presence of additional regions of BMMF1 and BMMF2 genomes. A reference collection of hepatocellular carcinomas (HCCs; n = 60) and adjacent peritumoral liver tissues (n = 50) was also included. Our results demonstrated that BMMF1 and BMMF2 DNAs are frequently found in human RCC tissues and are particularly more prevalent in peritumoral kidney tissues. Of note, BMMF1 and BMMF2 genotype heterogeneity was higher in peritumoral kidney tissues compared to RCC tissues. This is the first study to directly test human FFPE tissues for BMMF1- and BMMF2-like DNA using consensus PCR and demonstrate BMMF DNA in neoplastic and peritumoral kidney tissues. The findings are in line with the recently proposed indirect etiopathogenetic role of BMMFs in, e.g., colorectal carcinogenesis. Follow-up studies are needed to explore the potential role of BMMFs in the etiopathogenesis of RCC. [ABSTRACT FROM AUTHOR]

Incidental findings of renal masses are increasing. However, a substantial portion of surgically treated renal masses turn out to be benign on histopathological examination. Thus, there is a clear need for improved pre-surgical assessment to minimize unnecessary invasive procedures. The challenge intensifies when distinguishing between renal cell carcinoma (RCC) and angiomyolipoma (AML) in renal lesions smaller than 4 cm with minimal adipose tissue. In such cases, contrast-enhanced ultrasound (CEUS) has emerged as a valuable diagnostic tool, by utilizing both qualitative and quantitative parameters. Quantitative measures offer objectivity, reliability, and reproducibility compared to qualitative parameters, enabling the characterization of RCC subtypes and differentiation from AML. Qualitative features as enhancement pattern, degree, and peak were less helpful in distinguishing triphasic minimal fat AML (TAML) from epithelioid AML (EAML), with the pseudocapsule sign potentially being the only distinguishing qualitative feature. The pseudocapsule sign was more frequently observed in ccRCCs (38.0%) than in AMLs (15.6%). Moreover, it was detected in 40.0% of EAMLs and 34.5% of ccRCCs but not in TAMLs due to similar growth patterns between EAMLs and low-grade ccRCCs. Quantitative measures such as the time-to-peak (TTP) ratio can further enhance diagnostic accuracy and also TOC ratio should be considered, as it was higher in clear cell RCCs (ccRCCs) and in EAMLs compared to TAMLs, indicating behavior similar to ccRCCs. However, CEUS remains an operator-dependent exam. [ABSTRACT FROM AUTHOR]

Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder’s group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Kidney renal carcinoma is a type of cancer that originates in the renal cortex, the outer part of the kidney. It includes various subtypes, such as clear cell, papillary and chromophobe renal cell carcinomas, which are characterized by different cellular structures and behaviours. This cancer is often detected through imaging techniques and poses significant challenges due to its potential to metastasize and vary in treatment response. To address these challenges, we developed a novel computational framework named Kidney Ensemble-Net, designed to enhance the accuracy of renal carcinoma classification. Our approach begins by acquiring spatial features from contrast-enhanced images using a Convolutional Neural Network (CNN) effectively capturing intricate patterns and structures characteristic of different carcinoma subtypes. These extracted features are then transferred into a refined probabilistic feature set, upon which we construct an ensemble model leveraging the strengths of Logistic Regression (LR), Random Forest (RF), and Gaussian Naive Bayes (GNB) classifiers. The integration of these models within the Kidney Ensemble-Net architecture resulted in an outstanding performance, with our Kidney Ensemble-Net + LR model achieving a 99.72% accuracy score significantly surpassing existing state-of-the-art methodologies. Furthermore, we rigorously evaluated our model using k-fold validation analysis, ensuring its robustness and generalizability across diverse datasets. This comprehensive comparison with current leading approaches highlights the potential of Kidney Ensemble-Net as a powerful tool for the precise and reliable classification of kidney renal carcinoma, paving the way for improved diagnostic and treatment strategies.

Abstract Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a “living drug” has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allogeneic hematopoietic stem cell transplantation, T cell receptor gene-modified T cells, chimeric antigen receptor (CAR) T cells, CAR natural killer (NK) cells, lymphokine-activated killer (LAK) cells, γδ T cells, and dendritic cell vaccination. We have also included perspectives for using other recent approaches, such as CAR macrophages, dendritic cell-cytokine induced killer cells and regulatory CAR-T cells to shed light on preclinical development of cell therapy and advancing cell therapy into clinic to achieve cures for RCC.

Background: Hypoxia inducible factors, HIF‐1α and HIF‐2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. Patients and Methods: In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence‐free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue‐microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow‐up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. Results: Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT‐stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. Conclusions: The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies. [ABSTRACT FROM AUTHOR]

Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a "living drug" has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allogeneic hematopoietic stem cell transplantation, T cell receptor gene-modified T cells, chimeric antigen receptor (CAR) T cells, CAR natural killer (NK) cells, lymphokine-activated killer (LAK) cells, γδ T cells, and dendritic cell vaccination. We have also included perspectives for using other recent approaches, such as CAR macrophages, dendritic cell-cytokine induced killer cells and regulatory CAR-T cells to shed light on preclinical development of cell therapy and advancing cell therapy into clinic to achieve cures for RCC. [ABSTRACT FROM AUTHOR]

Objective: The coronavirus disease-2019 pandemic has shown us that postponing elective surgeries that include nephrectomy due to renal cell carcinomas (RCC) was undertaken by the physicians to use hospital facilities in a balanced way. However, both urologists and patients were concerned about postponements that may increase the risk of progression. To determine the optimal threshold of postponement time-period for surgery (PTP) and according to the clinical T stages in patients who underwent nephrectomy due to RCC, we used the Urologic Cancer Database-Kidney. Materials and Methods: Patients who underwent detailed clinical T stage analysis with admission and surgery dates were included in the study. PTP was calculated using the dates of definitive preoperative diagnosis and surgery date. Recurrence, overall mortality (OM), recurrence-free survival, and overall survival (OS) were evaluated. The effects of PTP on oncological outcome according to tumor diameter and clinical T stages were also evaluated. We also analyzed the optimal cut-offs of PTP based on clinical T stages. Results: Among 3.258 patients, in the evaluation of 2.946 clinically localized patients, PTP and tumor diameter were found to be important predictors of recurrence (p=0.037 and p<0.001). The optimal PTP of 30 days was found to be an important significant threshold time for the T1 stage and 20 days for T2-4 stage tumors. Patients with longer PTP according to the thresholds shown in this study had higher upstaging for clinical T1a, T2a, and T3 stages; higher recurrence rates for T1b and T2b stages; and higher OM for T2a and T3 tumors. The survival have also shown that more than 20 days of PTP affected OSs for clinical-stage T1 (p=0.019), T2 (p=0.021) and T3 (p=0.007) tumors. Conclusions: All patients with tumors, including clinical T1 tumors, had worsening oncological results as the PTP increased (>20-30 days). [ABSTRACT FROM AUTHOR]

Introduction: Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy. Methods: We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression. Results: A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia. Conclusions: Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy. Low creatinine to cystatin-C ratio (Cr/Cys-C) is associated with decreased overall survival (OS) but, to date, has not been examined in patients with renal cell carcinoma (RCC). This article evaluates associations between low Cr/Cys-C ratio and OS and recurrence-free survival in patients with RCC treated with nephrectomy. [ABSTRACT FROM AUTHOR]

Abstract Background Radiofrequency ablation (RFA) has an established role in effective treatment of renal cell carcinomas (RCCs), as most of RCCs are diagnosed incidentally in early stages. Long-term follow-up is however important to consolidate the technique. Most of the literature contains series of short-term follow-ups of periods shorter than 2 years. This study in hand demonstrates the results of longer-term follow-up than the previously published series. Results Data analysis of 31 patient records involved in this study demonstrated the high clinical efficacy of RFA for long term, 12-year follow-up, by following the absence of tumor recurrences, as shown on regular interval contrast enhanced computed tomography (CT) and or magnetic resonance imaging (MRI). Conclusions RFA continues to prove its competent role in treating RCCs on longer-term follow-ups; the smaller the size of a tumor and the more peripheral the tumor is, the more effective the therapy. Even in larger early stages tumors, repeating the ablative sessions results in complete ablation without the need for more invasive surgical interventions.

Abstract Background Hypoxia inducible factors, HIF‐1α and HIF‐2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. Patients and Methods In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence‐free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue‐microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow‐up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. Results Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT‐stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. Conclusions The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies.

Purpose: To investigate the biological function and mechanisms of circPDSS1 in triggering malignant progression of renal cell carcinoma (RCC). Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine circPDSS1 levels in 50 pairs of RCC and para-cancerous tissues. The relationship between circPDSS1 level and pathological indices in RCC patients was analyzed, while the in vitro effect of circPDSS1 in regulating RCC proliferation was assessed using cell counting kit-8 (CCK-8), colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assay. The sponge effect of circPDSS1 on miR-182-5p was examined by bioinformatics analysis and dual-luciferase reporter assay, while their involvement in mediating malignant progression of RCC was analyzed using rescue experiments. In vivo, the influence of circPDSS1 on RCC growth was determined by establishing a xenograft model in nude mice. Thereafter, RCC tissues were harvested from mice to assess relative levels of miR-182-5p and Ki-67. Results: CircPDSS1 was highly expressed in RCC tissues (p < 0.05). A high level of circPDSS1 correlated with advanced tumor staging and low overall survival. Knockdown of circPDSS1 inhibited RCC cell proliferation, and CircPDSS1 sponged and negatively regulated miR-182-5p (p < 0.05). MiR-182-5p was able to abolish regulatory effect of circPDSS1 on malignant proliferative potential in RCC cells. In nude mice bearing RCC, in vivo knockdown of circPDSS1 slowed down tumor growth and decreased positive expression of Ki-67 in tumor tissues (p < 0.05). Conclusion: CircPDSS1 predicts tumor stage and prognosis in RCC patients. It triggers malignant progression of RCC through sponging of miR-182-5p. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is often diagnosed in advanced stages and a third of patients have distant metastasis at diagnosis. Metastasis may be the first evidence of clear cell RCC in many cases. RCC most often metastasises to the lung, liver, bone, brain and thyroid; however, metastatic disease to the oral cavity, especially the mandible, is rare. The purpose of this study is to report a case of clear cell RCC metastatic to the mandible and review the literature. The mandible lesion underwent radical excision in this case. Notably, no metastatic lesions were detected in the lungs and liver in this patient until 15 months after the mandibulectomy. The patient lived for around 2.5 years after the diagnosis of RCC. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) has an established role in effective treatment of renal cell carcinomas (RCCs), as most of RCCs are diagnosed incidentally in early stages. Long-term follow-up is however important to consolidate the technique. Most of the literature contains series of short-term follow-ups of periods shorter than 2 years. This study in hand demonstrates the results of longer-term follow-up than the previously published series. Results: Data analysis of 31 patient records involved in this study demonstrated the high clinical efficacy of RFA for long term, 12-year follow-up, by following the absence of tumor recurrences, as shown on regular interval contrast enhanced computed tomography (CT) and or magnetic resonance imaging (MRI). Conclusions: RFA continues to prove its competent role in treating RCCs on longer-term follow-ups; the smaller the size of a tumor and the more peripheral the tumor is, the more effective the therapy. Even in larger early stages tumors, repeating the ablative sessions results in complete ablation without the need for more invasive surgical interventions. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care. [ABSTRACT FROM AUTHOR]

This study investigated the utility of histogram parameters derived from diffusion-weighted imaging (DWI) for evaluating renal cell carcinoma (RCC) grading prior to surgery. This retrospective study included 88 patients who were histopathologically diagnosed with RCC and underwent magnetic resonance imaging (MRI) examinations. The patients were divided into two groups as well-differentiated (Group 1) and poorly differentiated (Group 2). Demographic data, preoperative MRI findings, MRI apparent diffusion coefficient (ADC) histogram analyzes, operation types, postoperative histopathological data and cancer stages of the patients were recorded. The histogram parameters of ADC values, comprising the mean, minimum, maximum, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, as well as skewness, kurtosis, and variance, were calculated. The study included 59 males and 29 women with an average age of 56.21 ± 1.33 years. There were 52 patients in Group 1 and 36 patients in Group 2. The ADCmin, ADCmean, ADCmax, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values of the poorly differentiated group were all lower than those of the well-differentiated group. ADCmin and the 5th percentile of ADC values, as well as ADCmean and the 10th, 25th, 50th, and 75th percentiles of ADC values, showed a statistically significant difference (p < 0.05). The AUC, sensitivity, and specificity of the ADCmin value were 0.703, 56.3%, and 75.7%, respectively. The present study indicated that histogram parameters generated from DWI were capable of differentiating between high-grade and low-grade RCC. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract, particularly the colon, represents a rare site of metastatic carcinoma. It is difficult to diagnose because of its nonspecific clinical and imaging features. Herein, we reported the case of a 64-year-old Asian male who presented with a solitary mass on his right colon. We successively performed contrast-enhanced ultrasonography, computed tomography (CT) and colonoscopy. Colonoscopy-guided biopsy revealed inflammatory granulomatous and necrotic tissue. The mass was resected and identified as a metastatic carcinoma of renal cell carcinoma (RCC). The details of the case and review of related articles are presented.

Many current microRNA (miRNA) expression datasets for renal cell carcinoma (RCC) often show inconsistent analysis results, so a shift to comprehensive analysis of multiple datasets can effectively accelerate molecular screening for precision medicine and translational medicine research. MicroRNA (miR)‐188‐5p is a clinically noteworthy miRNA whose aberrant expression was previously observed in a variety of cancers, but its role in RCC is unclear. In this study, we undertook a comprehensive analysis of four RCC miRNA expression datasets and validated the results using The Cancer Genome Atlas (TCGA) dataset and a cohort of collected clinical samples. Fifteen miRNAs were identified as potential diagnostic markers by the analysis of four RCC miRNAs datasets. Analysis of the TCGA kidney renal clear cell carcinoma dataset showed significantly shorter survival in RCC patients with reduced miR‐188‐5p expression levels, and our collection of RCC clinical samples showed low miR‐188‐5p expression in the tumors. Overexpression of miR‐188‐5p in Caki‐1 and 786‐O cells inhibited cell growth, colony formation, invasion, and migration. In contrast, miR‐188‐5p inhibitors reversed these cell phenotypes. We identified a binding site for miR‐188‐5p in the 3′‐UTR region of myristoylated alanine‐rich C‐kinase substrate (MARCKS) mRNA and demonstrated an interaction between these two molecules. Quantitative RT‐PCR and western blot analysis revealed that miR‐188‐5p could regulate the AKT/mTOR signaling pathway through MARCKS. Mouse transplantation tumor assay indicated that miR‐188‐5p reduced the tumorigenicity of RCC in vivo. MicroRNA‐188‐5p could be a valuable new molecule for RCC diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Materials and methods: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. Results: the most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Conclusion: Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions. [ABSTRACT FROM AUTHOR]

The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to provide an up-to-date understanding regarding the literature on sarcopenia and inflammation as prognostic factors in the context of renal cell carcinoma (RCC). Recent Findings: Sarcopenia is increasingly recognized as a prognostic factor in RCC. Emerging literature suggests monitoring quantity of muscle on successive imaging and examining muscle density may be additionally informative. Inflammation has prognostic ability in RCC and is also considered a key contributor to development and progression of both RCC and sarcopenia. Recent studies suggest these two prognostic factors together may provide additional prognostic ability when used in combination. Ongoing developments include quality control regarding sarcopenia research and imaging, improving understanding of muscle loss mechanisms, and enhancing clinical incorporation of sarcopenia via improving imaging analysis practicality (i.e., artificial intelligence) and feasible biomarkers. Summary: Sarcopenia and systemic inflammation are complementary prognostic factors for adverse outcomes in patients with RCC. Further study on high-quality sarcopenia assessment standardization and expedited sarcopenia assessment is desired for eventual routine clinical incorporation of these prognostic factors. [ABSTRACT FROM AUTHOR]

Simple Summary: The advent of immune checkpoint inhibitors has dramatically changed the history of advanced renal cell carcinoma treatment. Their use in first-line therapy provides an undeniable advantage in terms of survival; nevertheless, a considerable proportion of patients undergo disease progression. Similarly to other advanced solid tumors, even in renal cell carcinoma, preliminary data are beginning to emerge concerning the activity and the efficacy of a rechallenge of an immune checkpoint inhibitor-based treatment. In this mini-review, we summarize available data about immunotherapy rechallenge in renal carcinoma and its future perspectives. Immune checkpoint inhibitor-based therapies represent the current standard of care in the first-line treatment of advanced renal cell carcinoma. Despite a clear benefit in survival outcomes, a considerable proportion of patients experience disease progression; prospective data about second-line therapy after first-line treatment with immune checkpoint inhibitors are limited to small phase II studies. As with other solid tumors (such as melanoma and non-small cell lung cancer), preliminary data about the clinical efficacy of rechallenge of immunotherapy (alone or in combination with other drugs) in renal cell carcinoma are beginning to emerge. Nevertheless, the role of rechallenge in immunotherapy in this setting of disease remains unclear and cannot be considered a standard of care; currently some randomized trials are exploring this approach in patients with metastatic renal cell carcinoma. The aim of our review is to summarize main evidence available in the literature concerning immunotherapy rechallenge in renal carcinoma, especially focusing on biological rationale of resistance to immune checkpoint inhibitors, on the published data of clinical efficacy and on future perspectives. [ABSTRACT FROM AUTHOR]

The feasibility and efficacy of particle beam therapy (PBT) using protons or carbon ions were compared with those of photon-based stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC) via a systematic review and nationwide registry for PBT (Japanese Society for Radiation Oncology [JASTRO] particle therapy committee). Between July 2016 and May 2019, 20 patients with non-metastatic RCC who were treated at six Japanese institutes (using protons at three, using carbon ions at the other three) were registered in the nationwide database and followed up prospectively. The 20 patients comprised 15 men and had a median age of 67 (range: 57–88) years. The total radiation dose was 66–79.6 Gy (relative biological effectiveness [RBE]). Over a median follow up of 31 months, the 3-year rates of overall survival (OS) and local control (LC) were 100% and 94.4%, respectively. No grade ≥ 3 toxicities were observed. Based on a random effects model, a meta-analysis including the present results revealed 3-year OS rates after SBRT and PBT of 75.3% (95% CI: 57.3–86.6) and 94.3% (95% CI: 86.8–97.6), respectively (P  = 0.005), but the difference in LC rates between the two methods was not observed (P  = 0.63). PBT is expected to have similar if not better treatment results compared with SBRT for primary renal cancer. In particular, PBT was shown to be effective even for large RCC and could provide a therapeutic option when SBRT is not indicated. [ABSTRACT FROM AUTHOR]

Abstract Objective Systematic evaluation of the effectiveness and safety of laparoscopic radical nephrectomy (LRN) for renal tumor (>7 cm). Methods The databases PubMed, Scopus, SinoMed, ScienceDirect, and Google Scholar were systematically searched for trials up to November 2022. The pooled results were evaluated by weighted mean difference (WMD), odds ratio (OR), and hazard ratio (HR). Results This meta-analysis (18 trials) demonstrated that compared to open radical nephrectomy (ORN), LRN had a longer operative time (OT) (WMD=15.99, 95% CI: 6.74 to 25.24, p = 0.0007), lower estimated blood loss (EBL) (WMD = −237.07, 95% CI: −300.02 to −174.12, p < 0.00001), lower transfusion rates (OR = 0.37, 95% CI: 0.24 to 0.55, p < 0.00001), and shorter length of stay (LOS) (WMD = −2.95, 95% CI: −3.86 to −2.03, p < 0.00001). No statistically relevant differences were found in overall survival (OS) (HR = 1.04, 95% CI: 0.81 to 1.35, p = 0.76), cancer-specific survival (CSS) (HR = 1.28, 95% CI: 0.97 to 1.68, p = 0.08), progression-free survival (PFS) (HR = 1.20, 95% CI 0.97 to 1.48, p = 0.1), recurrence-free survival (RFS) (OR = 1.27, 95% CI: 0.89 to 1.81, p = 0.56), local recurrence rate (OR = 0.85, 95% CI: 0.42 to 1.71, p = 0.65), and intraoperative and postoperative complications. Conclusion For patients with renal tumors (> 7 cm), LRN has specific perioperative advantages over ORN (LOS, EBL, and transfusion rates). However, the OT was prolonged in the LRN group. In addition, no differences in complication or oncological outcomes (OS, CSS, PFS, RFS, and local recurrence rate) were reported. Trial registration PROSPERO CRD42022367114

Abstract Background Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. Results We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues. Conclusions We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.

Abstract Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy has become a game-changing therapeutic approach revolutionizing the treatment setting of human malignancies, such as renal cell carcinoma (RCC). Despite the remarkable clinical activity of anti-PD-1 or anti-PD-L1 monoclonal antibodies, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might ultimately favor cancer development in patients with clinical responses. In light of this, recent reports have signified that the addition of other therapeutic modalities to PD-1/PD-L1 blockade therapy might improve clinical responses in advanced RCC patients. Until, combination therapy with PD-1/PD-L1 blockade therapy plus cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor (ipilimumab) or various vascular endothelial growth factor receptors (VEGFRs) inhibitors axitinib, such as axitinib and cabozantinib, has been approved by the United States Food and Drug Administration (FDA) as first-line treatment for metastatic RCC. In the present review, we have focused on the therapeutic benefits of the PD-1/PD-L1 blockade therapy as a single agent or in combination with other conventional or innovative targeted therapies in RCC patients. We also offer a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy.

Abstract Background To observe the diagnostic efficacy of preoperative fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) upon venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC), and investigate the prognostic value of imaging parameters integrated with clinicopathological characteristics in patients with VTT after nephrectomy with tumor thrombectomy. Methods Patients with newly diagnosed RCC who underwent 18F-FDG PET/CT were reviewed retrospectively. The diagnostic efficacy of 18F-FDG PET/CT in VTT was analyzed. Logistic regression analysis was carried out to identify the clinical variables and PET/CT variables (including maximum standardized uptake value (SUVmax) of primary tumor, VTT SUVmax and primary tumor size) for differentiating early VTT (Mayo 0-II) from advanced VTT (Mayo III-IV). Cox proportional hazard analyses were used to evaluate clinicopathological factors and PET/CT factors (including distant metastasis, primary tumor SUVmax, VTT SUVmax and primary tumor size) for disease-free survival (DFS) in patients with VTT after operation. Results A total of 174 eligible patients were included in this study, including 114 men (65.5%) and 60 women (34.5%), with a median age of 58 years (range, 16–81 years). The distribution of pathological tumor stage (T stage) was 56 (T1), 17 (T2), 95 (T3), and 6 cases (T4), respectively. According to WHO/ISUP grade, except for 4 cases of chromophobe cell RCC, there were 14 patients (8.0%) of grade 1, 59 patients (33.9%) of grade 2, 74 patients (42.5%) of grade 3 and 23 patients (13.2%) of grade 4. The median maximum diameter of the primary tumor on PET/CT was 7.3 cm (5.0–9.5 cm). The distal metastasis was observed in 46 patients (26.4%). Sixty-one cases (35.1%) were confirmed with VTT by pathology. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT imaging were 96.7, 99.1, 98.3, 98.3, and 98.2%, in detecting VTT, respectively, and 70.0, 100.0, 94.9, 100.0, and 94.2%, in evaluating the level of VTT, respectively. Elevated VTT SUVmax (≥5.20) could significantly distinguish the early VTT group and advanced VTT group (P = 0.010). In the prognosis analysis, elevated VTT SUVmax (≥4.30) (P = 0.018, HR 3.123, 95% CI 1.212–8.044) and distant metastasis (P = 0.013, HR 3.344, 95% CI 1.293–8.649) were significantly independent predictors for DFS. Conclusion Preoperative 18F-FDG PET/CT has a high diagnostic efficacy in detecting VTT and evaluating its level in RCC patients. Those patients with elevated VTT SUVmax should be carefully monitored to detect the possibility of disease progression after operation.

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Background: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. Methods: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. Results: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H2O2. Conclusions: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future. [ABSTRACT FROM AUTHOR]

Introduction: Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. Materials and methods: We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Results: Treatment ofmice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. Conclusion: EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum is an organelle exerting crucial functions in protein production, metabolism homeostasis and cell signaling. Endoplasmic reticulum stress occurs when cells are damaged and the capacity of this organelle to perform its normal functions is reduced. Subsequently, specific signaling cascades, together forming the so-called unfolded protein response, are activated and deeply impact cell fate. In normal renal cells, these molecular pathways strive to either resolve cell injury or activate cell death, depending on the extent of cell damage. Therefore, the activation of the endoplasmic reticulum stress pathway was suggested as an interesting therapeutic strategy for pathologies such as cancer. However, renal cancer cells are known to hijack these stress mechanisms and exploit them to their advantage in order to promote their survival through rewiring of their metabolism, activation of oxidative stress responses, autophagy, inhibition of apoptosis and senescence. Recent data strongly suggest that a certain threshold of endoplasmic reticulum stress activation needs to be attained in cancer cells in order to shift endoplasmic reticulum stress responses from a pro-survival to a pro-apoptotic outcome. Several endoplasmic reticulum stress pharmacological modulators of interest for therapeutic purposes are already available, but only a handful were tested in the case of renal carcinoma, and their effects in an in vivo setting remain poorly known. This review discusses the relevance of endoplasmic reticulum stress activation or suppression in renal cancer cell progression and the therapeutic potential of targeting this cellular process for this cancer. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is associated with high mortality rates worldwide and survival among RCC patients has not improved significantly in the past few years. A better understanding of the pathogenesis of RCC can enable the development of more effective therapeutic strategies against RCC. Hyaluronan (HA) is a glycosaminoglycan located in the extracellular matrix (ECM) that has several roles in biology, medicine, and physiological processes, such as tissue homeostasis and angiogenesis. Dysregulated HA and its receptors play important roles in fundamental cellular and molecular biology processes such as cell signaling, immune modulation, tumor progression and angiogenesis. There is emerging evidence that alterations in the production of HA regulate RCC development, thereby acting as important biomarkers as well as specific therapeutic targets. Therefore, targeting HA or combining it with other therapies are promising therapeutic strategies. In this Review, we summarize the available data on the role of abnormal regulation of HA and speculate on its potential as a therapeutic target against RCC. [ABSTRACT FROM AUTHOR]

Abstract Background Lymph node metastasis is one of the major factors that decide the prognosis of renal cell carcinoma. Presently, lymphadenectomy is only accepted as the most precise and dependable staging method to detect lymph node invasion; still, its therapeutic value for renal cell carcinoma is controversial. Diffusion-weighted magnetic resonance imaging along with its apparent diffusion coefficient value has already shown great value as a non-invasive modality to detect early microstructural changes in various human tumours. The present study is done to know the role of DWMRI in determining regional lymph node positivity in radiologically organ-confined renal cell carcinoma. Methods In this prospective study, we measured the ADC value of renal mass and regional lymph node in patient of RCC. ADC value

Objective: Systematic evaluation of the effectiveness and safety of laparoscopic radical nephrectomy (LRN) for renal tumor (>7 cm). Methods: The databases PubMed, Scopus, SinoMed, ScienceDirect, and Google Scholar were systematically searched for trials up to November 2022. The pooled results were evaluated by weighted mean difference (WMD), odds ratio (OR), and hazard ratio (HR). Results: This meta-analysis (18 trials) demonstrated that compared to open radical nephrectomy (ORN), LRN had a longer operative time (OT) (WMD=15.99, 95% CI: 6.74 to 25.24, p = 0.0007), lower estimated blood loss (EBL) (WMD = −237.07, 95% CI: −300.02 to −174.12, p < 0.00001), lower transfusion rates (OR = 0.37, 95% CI: 0.24 to 0.55, p < 0.00001), and shorter length of stay (LOS) (WMD = −2.95, 95% CI: −3.86 to −2.03, p < 0.00001). No statistically relevant differences were found in overall survival (OS) (HR = 1.04, 95% CI: 0.81 to 1.35, p = 0.76), cancer-specific survival (CSS) (HR = 1.28, 95% CI: 0.97 to 1.68, p = 0.08), progression-free survival (PFS) (HR = 1.20, 95% CI 0.97 to 1.48, p = 0.1), recurrence-free survival (RFS) (OR = 1.27, 95% CI: 0.89 to 1.81, p = 0.56), local recurrence rate (OR = 0.85, 95% CI: 0.42 to 1.71, p = 0.65), and intraoperative and postoperative complications. Conclusion: For patients with renal tumors (> 7 cm), LRN has specific perioperative advantages over ORN (LOS, EBL, and transfusion rates). However, the OT was prolonged in the LRN group. In addition, no differences in complication or oncological outcomes (OS, CSS, PFS, RFS, and local recurrence rate) were reported. Trial registration: PROSPERO CRD42022367114 [ABSTRACT FROM AUTHOR]

Over the last two decades the detection rate of small renal masses has increased, due to improving diagnostic accuracy, and nephron-sparing treatments have become the first-choice curative option for small renal masses. As a minimally invasive alternative, thermal ablation has increased in popularity, offering a good clinical outcome and low recurrence rate. Radiofrequency ablation, Cryoablation, and Microwave ablation are the main ablative techniques. All of them are mostly overlapping in term of cancer specific free survival and outcomes. These techniques require imaging study to assess lesions features and to plan the procedure: US, CT, and both of them together are the leading guidance alternatives. Imaging findings guide the interventional radiologist in assessing the risk of complication and possible residual disease after procedure. The purpose of this review is to compare different ablative modalities and different imaging guides, underlining the effectiveness, outcomes, and complications related to each of them, in order to assist the interventional radiologist in choosing the best option for the patient. [ABSTRACT FROM AUTHOR]

Small renal masses (SRM) are increasingly detected incidentally during imaging. They vary widely in histology and aggressiveness, and include benign renal tumors and renal cell carcinomas that can be either indolent or aggressive. Imaging plays a key role in the characterization of these small renal masses. While a confident diagnosis can be made in many cases, some renal masses are indeterminate at imaging and can present as diagnostic dilemmas for both the radiologists and the referring clinicians. This review focuses on CT characterization of small renal masses, perhaps helping us understand small renal masses. The following aspects were considered for the review: (a) assessing the presence of fat, (b) assessing the enhancement, (c) differentiating renal tumor subtype, and (d) identifying valuable CT signs. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. Results: We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues. Conclusions: We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: The kidneys are affected by various tumors amongst which, majority of renal neoplasms are reported as malignant, with renal cell carcinoma and wilms tumor being the most commonly diagnosed entities. Material and Methods: The study comprises of 65 patients who were diagnosed as having renal tumors and were registered in the department of Pathology from 1st July 2018 to 30th September 2021. The demographic and clinicopathological data was collected and analysed carefully. Results: Of the 65 renal tumors studied, 6 (9.23%) were reported as benign and 59 (90.77%) were reported as malignant tumors, with Renal Cell Carcinoma and Wilms tumor being the most common ones. In our study, clear cell variant of renal cell carcinoma was the most common variant reported in 39 cases (60%). Majority of cases were reported in 51-60 years age group (25 cases, 38.5%) with mean age for RCC being 53 years and for wilms tumor being 2 years. Conclusion: A wide array of renal tumors are encountered day to day on the histopathology of nephrectomy specimens, many of which may be misdiagnosed clinically, so it is very important that each and every nephrectomy specimen be subjected to a meticulous and detailed histopathological examination for a clinico-pathological correlation to ensure proper post operative management. [ABSTRACT FROM AUTHOR]

The kidney plays a crucial role in regulating homeostasis within the human body. Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for nearly 90 % of all renal malignancies. Despite the availability of various therapeutic strategies, RCC remains a challenging disease due to its resistance to conventional treatments. Nanotechnology has emerged as a promising field, offering new opportunities in cancer therapeutics. It presents several advantages over traditional methods, enabling diverse biomedical applications, including drug delivery, prevention, diagnosis, and treatment. Lipid nanoparticles (LNPs), approximately 100 nm in size, are derived from a range of lipids and other biochemical compounds. these particulates are designed to overcome biological barriers, allowing them to selectively accumulate at diseased target sites for effective therapeutic action. Many pharmaceutically important compounds face challenges such as poor solubility in aqueous solutions, chemical and physiological instability, or toxicity. LNP technology stands out as a promising drug delivery system for bioactive organic compounds. This article reviews the applications of LNPs in RCC treatment and explores their potential clinical translation, identifying the most viable LNPs for medical use. With ongoing advancement in LNP-based anticancer strategies, there is a growing potential to improve the management and treatment of renal cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • ATR-FTIR is a promising technology for characterizing the RCC state and recovery. • The spectra show a significant difference between pre and post-operative RCC patients. • Samples collected from the same patient can identify specific RCC optical biomarkers. • Plasma and urine samples exhibit almost equal performance for classification. • The XGBoost method outperformed other machine learning algorithms. Renal cell carcinoma (RCC) is the most common malignant tumor in the urinary system, accounting for 80 % to 90 % for all renal malignancies. Traditional diagnostic methods like magnetic resonance imaging (MRI) and computed tomography (CT) lack the sensitivity and specificity as they lack specific biomarkers. These limitations impede effective monitoring of tumor recurrence. This study aims to employ Attenuated Total Reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, an optical technology sensitive to molecular groups, to analyze the potential optical biomarkers in urine and plasma samples from RCC patients pre- and post-surgery. The results reveal distinctive spectral information from both plasma and urine samples. Post-surgery urine spectra exhibit complexity compared to plasma, showing reduced content at 1072 cm−1, 1347 cm−1 and 1654 cm−1 bands, while increased content at 1112 cm−1, 1143 cm−1, 1447 cm−1, 3334 cm−1 and 3420 cm−1 bands. Utilizing machine learning models such as eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), and artificial neural network (ANN), the study evaluated plasma and urine samples pre- and post-surgery. Remarkably, the XGBoost method excelled in distinguishing between tumor conditions and recovery, achieving an impressive AUC value of 0.99. These results underscore the potential of ATR-FTIR technology in identifying RCC optical biomarkers, with XGBoost showing promise as a valuable screening tool for RCC recurrence diagnosis. [ABSTRACT FROM AUTHOR]