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Historically, papillary renal cell carcinoma (PRCC) was divided into two types, type 1 and type 2, based solely on morphology. However, it is apparent that PRCC is far more complex and represents a histological, clinical, and molecular spectrum. There has been a significant evolution in our understanding of PRCC, highlighted by the recognition of new and molecularly defined entities that were previously included in PRCC type 2. This contemporary review addresses the evolving concepts regarding the PRCC, including why it is no longer needed to subtype PRCC, the current molecular landscape, prognostic parameters, and PRCC variants, including biphasic PRCC, papillary renal neoplasm with reverse polarity, and Warthin-like PRCC. Pathologists should also be aware of the potential mimickers of both low-grade and high-grade PRCCs as well as some new and emerging entities that may show papillary growth that should be excluded in the diagnostic workup. The evolving knowledge of PRCC biomarkers, morphologic patterns, and PRCC variants could also have important implications for clinical management. Lastly, the heterogeneity within the PRCC spectrum needs to be further studied, aiming to better stratify PRCC for appropriate clinical management and systemic therapy. [ABSTRACT FROM AUTHOR]

Objectives: Renal cell carcinoma (RCC) is the most common cancer of the kidney. This study aims to evaluate the potential predictive value of E-cadherin, a marker of the epithelial mesenchymal transit (EMT) process that has been associated with tumor metastasis. Methods: We searched PubMed, Embase, and Cochrane Library to identify prospective studies. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were summarized to validate the relationship between E-cadherin and survival and clinical characteristics. The quality of the included studies was assessed using the NOS table. Then, we analyzed genetic data and clinical characteristics from The Cancer Genome Atlas Program (TCGA) database using R language with the dplyr package for validation. Results: Including 21 articles. The analysis revealed a strong link between high E-cadherin expression and favorable prognosis (for OS, HR = 0.35, 95% CI: 0.19–0.62; for PFS, HR = 0.19, 95% CI: 0.03–0.53; for DSS, HR = 0.25, 95% CI: 0.08–0.76; for RFS, HR = 0.71, 95% CI: 0.44–1.16; for DFS, HR = 0.28, 95% CI: 0.13-0.61; for T stage, OR = 0.21, 95% CI: 0.11–0.41; for N stage, OR = 0.07, 95%CI: 0.02-0.25; for M stage, OR = 0.12, 95% CI: 0.02–0.60; for clinical stage, OR = 0.29, 95% CI: 0.18–0.47; for nuclear grade, OR = 0.23, 95% CI: 0.13–0.41; for tumor size, OR = 0.49, 95% CI: 0.26–0.92). The findings were supported by bioinformatic analysis which used TCGA RCC patient's cohort (P < 0.01). Conclusion: Based on the current data, E-cadherin may predict a better prognosis in RCC patients. [ABSTRACT FROM AUTHOR]

Approximatively 80% of kidney cancers globally are clear cell kidney cancers (ccRCCs), with 80% of these malignancies featuring an inactivating mutation of the Von Hippel-Lindau gene. This genetic alteration leads to the stabilization of hypoxia inducible factors 1 and 2 alpha (HIF 1 and 2a), resulting in the over-expression of target genes such as vascular endothelial growth factor (VEGF), which is crucial for angiogenesis. As a result, ccRCCs are highly vascularized and serve as models for anti-angiogenic treatments (AAT). Current AAT therapies comprise antibodies targeting VEGFs, tyrosine kinase inhibitors (TKi) (Sunitinib) that target neo-angiogenesis receptors, and competitive inhibitor receptors (Aflibercept) that trap VEGFA and PlGF. The over-expression of VEGF and related members such as VEGFC significantly influences angiogenesis, lymphangiogenesis, and immune tolerance. This has resulted in the approval of various immune checkpoint inhibitors (known as anti-PD-1, anti-PD-L1, and anti-CTLA-4) as viable treatment options for kidney cancer. Despite these advances, ccRCC remains challenging to treat adequately. Thus, future research is imperative to better understand the biology and pathophysiology of RCC, the tumor microenvironment, and mechanisms of resistance, with the aim of developing new therapies. [ABSTRACT FROM AUTHOR]

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Background and objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs). Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB–V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB–V CKD, and OCM. Key findings and limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65–74 vs 61 yr, IQR 50–69; p

Early recognition of hereditary urological cancers may influence diagnostic and therapeutic decision-making, and potentially alter the fate of patients and family members. Here, we introduce readers to the current knowledge on germline genetic testing and clinical practice in prostate, bladder, renal, and testicular carcinoma. Considering all urological cancer patients, routine inquiries about familial cancer history should become a standard practice in clinical settings. If suspicion arises, patients can opt for two avenues: referral to genetic counseling or undergoing genetic tests after consultation with the treating urologist. Patient summary: Tumors of the urogenital tract (prostate, kidney, bladder, and testes) can sometimes be related to genetic mutations that are present in all the cells of the body. Such mutations can be inherited and run in families. Therefore, it is relevant to obtain information on the incidence of all cancers in the family history. The information obtained may initiate genetic testing, leading to the identification of mutations that are related to cancer in the current or next generation. In addition, these mutations may offer alternative treatment options for patients.

The objectives of this study were to investigate the diagnostic efficacy of dynamic contrast-enhanced Computed Tomography (CT) and tumor markers and their combined evaluation in renal cancer patients. A total of eighty male patients with solid renal lesions were selected from our hospital and categorized into two groups based on pathological examination findings: renal cancer group and benign lesion group. A comparison was made between the findings of dynamic contrast-enhanced CT and tumor markers and the diagnostic efficacy of either mono or combined evaluation were compared. Receiver operating characteristic curves were plotted to better analyze and compare different diagnostic techniques. The serum concentrations of carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), midkine (MK) and matrix metalloproteinase 9 (MMP-9) in renal cancer patients were significantly higher than those with benign lesions (p < 0.05). The Receiver Operating Characteristic (ROC) curve analysis demonstrated that the combination of dynamic contrast-enhanced CT and tumor markers had the highest area under the curve. This difference was statistically significant (p < 0.05). The analysis of the overall model quality results revealed that the model values for both single and combination indicators exceeded 0.5, with the combined indicators having the highest value of (0.84). The diagnostic efficacy of dynamic contrast-enhanced CT combined with tumor markers for renal cancer is significantly higher than either the dynamic contrast-enhanced CT or tumor markers alone. The combination of dynamic contrast-enhanced CT and tumor markers has a significant therapeutic benefit in diagnosing renal cancer. We envisage that, this approach can offer valuable guidance for the clinical diagnosis and treatment of renal cancer.

The purpose of this study was to examine the factors influencing the efficacy and safety of the ultrasound-guided radiofrequency ablation of renal tumors. Between January 2010 and December 2018, 159 patients with renal tumors treated with ultrasound-guided percutaneous radiofrequency ablation at our institution were included in this study. Biopsies were performed for histopathological analysis prior to each ablation. Patients underwent computed tomography follow-ups at 3, 6, and 12 months and were subsequently observed on an annual basis. The primary efficacy rate (i.e., residual tumor), local tumor progression, morbidity and mortality, and possible outcome predictors (age, body mass index, gender, tumor size, tumor location, tumor characteristics, ablation temperature, and reported technical problems) were analyzed using binary logistic regression. At the first follow-up, 3 months after ablation, the primary efficacy rate was 79%. Two percent of the tumors showed local tumor progression during the whole follow-up. Tumor proximity to the collecting system and the final temperature in the ablation region were associated with the occurrence of residual tumor (OR = 2.85, p = 0.019 and OR = 4.23, p = 0.006, respectively). A similar trend was shown for tumors larger than 3 cm (p = 0.066). A short distance to the collecting system and the ablation temperature were significantly related to the occurrence of residual tumors after the radiofrequency ablation of small renal masses. The ultrasound guidance used in our study has a lower primary efficacy rate than the computed tomography guidance used in comparable studies.

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

Abstract Background Circulating tumor cells (CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear. Methods This study investigated C–C motif chemokine ligand 5 (CCL5)'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients' CTCs prognostic value through Lasso regression and Kaplan–Meier survival curves. Results Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various CTCs, correlating with poor prognosis in renal cancer. In 786-O-CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed CTCs, with mesenchymal CTCs having the highest value. Conclusions In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.

The long‐term incidence trends of 32 cancers in China remained unclear. Cancer statistics for young population were often presented in aggregate, masking important heterogeneity. We aimed to assess the incidence trends of 32 cancers in China from 1983 to 2032, stratified by sex and age groups. Data on cancer incidence from 1983 to 2017 were extracted from Cancer Incidence in Five Continents Volumes VI–XII. The age‐period‐cohort model was utilized to assess age and birth cohort effects on the temporal trends of 32 cancers in China, while the Bayesian age‐period‐cohort model was utilized to project future trends from 2018 to 2032. An increase in cohort effects is observed in some cancers such as thyroid and kidney cancers. Eight of the 12 obesity‐related cancers may rise in the 0–14 age group, and nine in the 15–39 age group from 2013 to 2032. Liver and stomach cancers show an increasing trend among the younger population, contrasting with the observed declining trend in the middle‐aged population. There has been a significant rise in the proportions of cervical cancer among females aged 40–64 (4.3%–19.1%), and prostate cancer among males aged 65+ (1.1%–11.8%) from 1983 to 2032. Cancer spectrum in China is shifting toward that in developed countries. Incidence rates of most cancers across different age groups may increase in recent cohorts. It is essential to insist effective preventive interventions, and promote healthier lifestyles, such as reducing obesity, especially among younger population. [ABSTRACT FROM AUTHOR]

The benefit of the delivery of the right form of cancer care, tailored to the right patient, at the right time is increasingly being recognized in the global oncology community. Information on the role and feasible potential of precision oncology during the management of genitourinary cancer in Nigeria, the most populous country in Africa, is limited. This article, therefore, describes the present application of personalized medicine in Nigeria and its barriers and facilitators. It provided granular details on manpower distribution and epidemiological disparities. It also explored the use of clinical and biological markers for screening and early diagnosis, the application of team science to support genomic profiling, cost-effective approaches for image-based phenotypic precision oncology, the emerging role of molecular imaging, access to clinical trials; and their potential to support data driven diagnosis, treatment decision and care availability in order to address gaps in genitourinary cancer management in the country. [ABSTRACT FROM AUTHOR]

Kidney cancer is a significant health concern worldwide, with early detection crucial for successful treatment outcomes. Recently, there has been an increasing focus on investigating affordable and non-intrusive methods for detecting cancer at its early stages. This proposed approach delves into the utilization of antenna arrays to identify kidney cancer. Specifically, antenna array with circular polarization has been crafted to identify tumors in the human kidney. This array design has been implemented using CST software, operating at 2.4 GHz. The antenna array having a dimension of 150 mm x 150 mm. The array consists of four-square patches each having a length of 30 mm and the spacing between the patches is preferred to be 20 mm for ensuring the mutual coupling. FR4 substrate is used with the relative permittivity 4.3 and 1.6 mm thickness. The axial ratio of the circularly polarized antenna is 0.9 dB at 2.4 GHz. The reflection coefficient S 11 = –30dB. The renal phantom in humans has been built with the kidney, adrenal gland, ureter, skin, fat, and muscle components to allow for precise simulation. Following that, four stages of cancer tumors were built employing all of the necessary qualities. For every stage of the cancer tumor, the reflection coefficient growth and resonance frequency shift are calculated. For the initial stages, the resonance frequency shift is very low. Consequently, the primary determinant of detection is the rise in S 11 . For 3rd and 4th stages of the tumor, there is a significant change in resonance frequency and increase S 11 , which facilitates identification. The calculated specific absorption rate (SAR) is a smaller amount than the safety thresholds, indicating that using this method is safe. Overall, this research points to a novel, easy-to-use method for kidney cancer screening. This method has the following benefits: it is non-invasive, safe, quick, affordable, and comfortable, and it emits no ionizing radiation during the measurement process. Furthermore, a range of output parameters such as gain, directivity, and polar radiation have been accurately computed. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma, the most prominent kind of adult kidney cancer, lacks early warning symptoms, leading to metastases at the time of diagnosis. Renal cell carcinoma begins with N -diethylnitrosamine (DEN) and is accelerated by ferric nitrilotriacetate (Fe-NTA), which may be a good research model for renal cell carcinoma. Purpose: This study was designed to unveil the protective potential of punicalagin against renal cell tumors induced by Fe-NTA in male mice. Materials and Methods: Renal cancer initiation was achieved through a single intraperitoneal injection of DEN (200 mg/kg body weight (b.wt.)), followed by promotion using Fe-NTA (9 mg Fe/kg b.wt. intraperitoneally) administered twice weekly over 16 weeks. Simultaneously, mice were subjected to punicalagin (10 mg/kg b.wt.) for an uninterrupted 16-week duration. The chemopreventive efficacy of punicalagin was assessed by evaluating antioxidant activities, oxidative stress markers, renal function parameters, histopathological examinations, and immunohistochemical analyses. Results: Results showed a significant reduction in DEN and Fe-NTA-mediated lipid peroxidation, concurrent with the amelioration of renal function, as reflected by diminished levels of blood urea nitrogen, creatinine, and kidney injury molecule-1 in punicalagin-treated mice. Furthermore, punicalagin restored the renal antioxidant parameters like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione in DEN and Fe-NTA-treated mice. Further, it was observed that punicalagin reduces the expression of 8-hydroxy-2′-deoxyguanosine (levels and 4-hydroxy-2-nonenal-modified protein adducts within the kidney tissue. Conclusion: These findings were further substantiated by histological examinations. Our current findings indicate that punicalagin might be a potential contender for preventing renal cancer, likely due to its capacity to reduce oxidative stress in laboratory animals. [ABSTRACT FROM AUTHOR]

This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN). First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3–5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy. We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9–17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer. Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki‐1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p‐ERK/Sp1 and p‐PKCα/Sp1‐mediated MMP1 expression in RCC. [ABSTRACT FROM AUTHOR]

Strategies for tackling cancer involve surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors (ICB). However, the effectiveness of ICB remains constrained, prompting the need for a proactive strategy to foresee treatment responses and resistances. This study undertook an analysis across diverse cancer patient cohorts (including melanoma, clear cell renal carcinoma, glioblastoma, bladder, and stomach cancers) subjected to various immune checkpoint blockade treatments. Surprisingly, our findings unveiled that over 38% of patients demonstrated resistance and persistent disease progression despite undergoing ICB intervention. To unravel the intricacies of resistance, we scrutinized the immune profiles of cancer patients experiencing ongoing disease progression and resistance post-ICB therapy. These profiles delineated multifaceted defects, including compromised macrophage, monocyte, and T cell responses, impaired antigen presentation, aberrant regulatory T cell (Tregs) responses, and an elevated expression of immunosuppressive and G protein-coupled receptor molecules (TGFB1, IL2RA, IL1B, EDNRB, ADORA2A, SELP, and CD276). Building upon these insights into resistance profiles, we harnessed machine learning algorithms to construct models predicting the response and resistance to ICB and developed the accompanying software. While previous work on glioblastoma with only one type of algorithm had an accuracy of 0.82, we managed to develop 20 models that provided estimates of future events of resistance or response in five cancer types, with accuracies ranging between 0.79 and 1, based on their distinct immune characteristics. In conclusion, our approach advocates for the personalized application of immunotherapy in cancer patients based on patient-specific attributes and computational models.

Abstract A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.

Abstract Background Understanding sex‐specific factors contributing to advanced‐stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. Method We used linked primary care and cancer registry data to examine associations between symptoms and advanced‐stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Results Female sex (OR vs. men 1.89 [1.28–2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34–3.69]) and abdominal symptoms (OR 2.19 [1.30–3.70]) were associated with increased odds of advanced‐stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced‐stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Conclusion Non‐haematuria symptoms are associated with higher risk of advanced‐stage bladder cancer. Greater risk of advanced‐stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

Introduction Secondary eosinophilia due to solid tumors is a rare case. This is the first study to report secondary eosinophilia due to renal cancer in a patient on dialysis. Case presentation A 70‐year‐old man, on long‐term hemodialysis was incidentally detected with right renal cancer, and workup performed revealed eosinophilia. Allergic symptoms caused by hemodialysis were initially considered; however, treatment did not lead to any improvement in eosinophilia. Therefore, nephrectomy for renal cancer was performed. The resolution of symptoms and eosinophilia after surgery suggested renal cancer as the cause of eosinophilia. Conclusion As demonstrated in this patient with dialysis‐related renal cancer, eosinophilia associated with solid tumors may be addressed by treating the tumor.

Abstract Backgrounds A growing number of expression quantitative trait loci (eQTLs) have been found to be linked with tumorigenesis. In this article, we employed integrated Mendelian randomization (MR) analyses to identify novel susceptibility genes in renal cancer (RC) and reveal their potential mechanisms. Methods Two-sample MR analyses were performed to infer causal relationships between eQTLs, metabolites, and RC risks through the “TwoSampleMR” R package. Sensitivity analyses, such as heterogeneity, pleiotropy, and leave-one-out analysis, were used to assess the stability of our outcomes. Summary-data-based MR (SMR) analyses were used to verify the causal relationships among cis-eQTLs and RC risks via the SMR 1.3.1 software. Results Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001–1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397). Further SMR analysis validated the causal relationships among AFF3 cis-eQTLs and RC risks (P

Abstract Background Renal neuroendocrine neoplasms (R‐NEN) are exceptionally rare tumours characterized by high mortality rates. Objective The objective of this study is to analyse prognostic factors and treatment impact on overall survival in patients with R‐NEN. Design, setting and participants We identified all patients with R‐NEN in the National Cancer Database (NCDB) from 2004 to 2019 and identified prognostic factors for improved survival. Results and limitations Of 542 R‐NEN cases, 166 (31%) were neuroendocrine tumour grade 1 (NET‐G1), 14 (3%) were neuroendocrine tumour grade 2 (NET‐G2), 169 (31%) were neuroendocrine carcinoma (NEC‐NOS), 18 (3%) were large cell neuroendocrine carcinoma (LC‐NEC) and 175 (32%) were small cell neuroendocrine carcinoma (SC‐NEC). Median overall survival for all patients in the study was 44.88 months (SE, 4.265; 95% CI, 27.57–62.19). Median overall survival was 7.89 months (SE 0.67; 95% CI, 6.58–9.20) for patients without surgical intervention and 136.61 months (SE 16.44; 95% CI, 104.38–168.84, p

Abstract Background Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi-fraction stereotactic ablative radiotherapy (SABR) have led to better outcomes and reduced treatment-related toxicities, sparking renewed interest in using RT to treat RCC. Moreover, numerous studies have revealed that certain therapeutic agents including chemotherapies can increase the sensitivity of tumors to RT, leading to a growing interest in combining these treatments. Here, we developed a rational combination of two radiosensitizers in a tumor-targeted liposomal formulation for augmenting RT in RCC. The objective of this study is to assess the efficacy of a tumor-targeted liposomal formulation combining the mTOR inhibitor everolimus (E) with the survivin inhibitor YM155 (Y) in enhancing the sensitivity of RCC tumors to radiation. Experimental design We slightly modified our previously published tumor-targeted liposomal formulation to develop a rational combination of E and Y in a single liposomal formulation (EY-L) and assessed its efficacy in RCC cell lines in vitro and in RCC tumors in vivo. We further investigated how well EY-L sensitizes RCC cell lines and tumors toward radiation and explored the underlying mechanism of radiosensitization. Results EY-L outperformed the corresponding single drug-loaded formulations E-L and Y-L in terms of containing primary tumor growth and improving survival in an immunocompetent syngeneic mouse model of RCC. EY-L also exhibited significantly higher sensitization of RCC cells towards radiation in vitro than E-L and Y-L. Additionally, EY-L sensitized RCC tumors towards radiation therapy in xenograft and murine RCC models. EY-L mediated induction of mitotic catastrophe via downregulation of multiple cell cycle checkpoints and DNA damage repair pathways could be responsible for the augmentation of radiation therapy. Conclusion Taken together, our study demonstrated the efficacy of a strategic combination therapy in sensitizing RCC to radiation therapy via inhibition of DNA damage repair and a substantial increase in mitotic catastrophe. This combination therapy may find its use in the augmentation of radiation therapy during the treatment of RCC patients.

Laparoscopic partial nephrectomy (LPN) is a standard surgical treatment option for renal tumors. Prior to LPN, it is necessary to evaluate the tumor condition and develop a surgical plan using precise imaging. To explore the clinical application value of 3D virtual model (3DVM) in LPN. A total of 80 patients with renal tumor who underwent LPN were measured. Patients were divided into three cohorts (A, B, C) according to the difficulty of surgery. Each group was further divided into the test and control groups based on the application of preoperative 3DVM. Surgical safety and efficacy were assessed, and a questionnaire was developed to investigate the opinions of patients and physicians on 3DVM. The duration of LPN and intraoperative renal artery occlusion were significantly different between the test and control groups in both cohorts A and B (P< 0.05). In cohort C, the surgical duration, duration of intraoperative renal artery occlusion, length of stay, time to postoperative ambulation, intraoperative bleeding, incidence of postoperative bleeding were significantly between the two groups (P< 0.05). The analysis both of patients and physicians questionnaire scores were statistically significant (P< 0.05). 3DVM contributes to safer and more effective LPN. It benefits both doctors and patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA).This study was a multi‐institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer‐specific survival (CSS), overall survival (OS), treatment‐related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan–Meier method was used to estimate freedom from local and distant failure, CSS and OS.Seventeen patients with 18 biopsy‐confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6–68.7) years, a median (IQR) tumour size of 3.5 (1.9–4.1) cm and follow‐up (reverse Kaplan–Meier method) of 3.36 (95% confidence interval [CI] 1.6–4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5–5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression‐free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%–100%), 92.3% (95% CI 78.9%–100%) and 82.1% (95% CI 62.1%–100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40–71) mL/min, and at last follow‐up, it was 48 (33–57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end‐stage renal disease.The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA. [ABSTRACT FROM AUTHOR]

Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment, but their use is linked to immune-related adverse events (irAEs), including the rare ICI-associated myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome. This systematic review aims to highlight MMM's clinical implications in emergency departments. PubMed and Embase were searched using a specific search strategy. Reports were eligible for inclusion if all three conditions were present and associated with the use of an ICI. Data were extracted by independent reviewers using the Rayyan web application for systematic reviews. Descriptive statistics and qualitative synthesis were used to summarize demographic, clinical, and treatment data for the reported cases. Among 50 cases, predominantly associated with melanoma, lung cancer, and renal cancer, the in-hospital mortality rate was 38.0%. The most commonly presenting symptoms were ptosis (58%), dyspnea (48%), diplopia (42%), or myalgia (36%). The median time from ICI initiation to MMM presentation was 21 days (interquartile range: 15–28 days). Corticosteroids were the primary treatment for the irAEs. MMM, a rare but potentially fatal complication of ICI therapy, requires prompt recognition in emergency settings. Corticosteroids should be initiated if suspected, without waiting for confirmation. Multidisciplinary collaboration is vital for diagnosis and treatment planning. Research on MMM's link to specific cancers and ICIs is imperative for better risk assessment and interventions. [ABSTRACT FROM AUTHOR]

Kidney cancer is a malignant tumor with a high mortality rate. The accurate segmentation of tumors from computed tomography (CT) scans can assist physicians in clinical diagnosis. We introduced a new segmentation network called DWR-SegFormer to address the challenge of accurately segmenting kidney tumors in CT images. The method involved binarizing the label maps of clear cell renal cell carcinoma and papillary renal cell carcinoma CT images for identification, and the cancer lesion area was obtained by the label so that the model could accurately identify the area and enhance the feature extraction ability. Secondly, an optimized segmentation model combining a DWR attention mechanism and SegFormer network was constructed. MiT-B0 was used as the encoder of the model to establish long-distance feature dependencies and effectively extract feature information at different resolutions. The decoder with a multi-branch DWR module was implemented to utilize multi-scale feature information effectively and enhance segmentation accuracy. Comparing the experimental results with other existing models shows that the model significantly outperformed the comparison methods in all evaluation metrics on the CT image dataset of clear cell renal cancer. Furthermore, the experimental findings highlight the robustness of the proposed model across other datasets. [ABSTRACT FROM AUTHOR]

Purpose: Epigenetic modifications play a crucial role in cancer development, and our study utilized public data to analyze which leads to the discovery of significant epigenetic abnormalities in lncRNAs, offering valuable insights into prognosis and treatment strategies for renal carcinoma. Methods: Public data were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) database. The analysis of the online public data was all completed in R software. Results: We discovered a great number of epigenetic abnormalities of lncRNA in renal cancer, which is achieved by comparing the following modification and methylation of histone region changes on the promoter and enhancer of lncRNA: H3K27ac, H3K4me1, H3K4me3. As a result, 12 specific epigenetic disorders of lncRNA genes in renal cancer were identified. Finally, based on this lncRNA, we investigated the prognosis of renal cancer samples, among which 8 lncRNA can be seen as markers of prognosis in renal cancer, which had great prediction ability for ccRCC prognosis. Meanwhile, high risk score may pose response better to axitinib and nilotinib, but not sorafenib or sunitinib. Beyond, we observed an elevated level of risk score in immunotherapy non-responders. Further, biological enrichment and immuno-infiltration analysis was conducted to investigate the fundamental differences between patients categorized as high or low risk. Conclusion: Our research improves the understanding in the function of epigenetic dysregulated long non-coding RNAs in renal carcinoma. [ABSTRACT FROM AUTHOR]

Early diagnosis is crucial for enhancing the survival rate of renal cell cancer patients, and exosomes present potential advantages in this area. Their small size, high mobility, and lipid bilayer structure enable exosomes to cross biological membranes easily, protecting the bioactive cargo within from degradation. Exosomes significantly influence the invasion and metastasis of RCC, and they also contribute to tumor drug resistance and immune evasion. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), amember of the CNCbZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Schwannomas are usually benign tumors typically found in the head, neck, and extremities, with approximately 3% originating in the retroperitoneum. In this case, a young male presented with incidental masses in the left kidney and retroperitoneum. Abdominal pelvic enhanced computerized tomography (CT) revealed a tumor apparently originating from the left kidney, along with a retroperitoneal mass suspected to be a metastatic lymph node. Subsequently, a radical nephrectomy of the left kidney and retroperitoneal mass resection was performed. Pathological examination confirmed the left kidney mass as renal clear cell carcinoma and the retroperitoneal mass as schwannoma. The patient recovered uneventfully and was discharged from the hospital. A 6-month postoperative follow-up showed no evidence of recurrence. Preoperative diagnosis of schwannomas concurrent with other concurrent malignancies in rare sites, such as the retroperitoneum, is challenging due to their rare and nonspecific radiological features. Although retroperitoneal schwannomas are rare, they should be considered in the differential diagnosis during CT examinations for renal cancer. Additionally, the advantages of a multidisciplinary team approach should be utilized in tumor management. [ABSTRACT FROM AUTHOR]

Emerging Industry 5.0 designs promote artificial intelligence services and data-driven applications across multiple places with varying ownership that need special data protection and privacy considerations to prevent the disclosure of private information to outsiders. Due to this, federated learning offers a method for improving machine-learning models without accessing the train data at a single manufacturing facility. We provide a self-adaptive framework for federated machine learning of healthcare intelligent systems in this research. Our method takes into account the participating parties at various levels of healthcare ecosystem abstraction. Each hospital trains its local model internally in a self-adaptive style and transmits it to the centralized server for universal model optimization and communication cycle reduction. To represent a multi-task optimization issue, we split the dataset into as many subsets as devices. Each device selects the most advantageous subset for every local iteration of the model. On a training dataset, our initial study demonstrates the algorithm's ability to converge various hospital and device counts. By merging a federated machine-learning approach with advanced deep machine-learning models, we can simply and accurately predict multidisciplinary cancer diseases in the human body. Furthermore, in the smart healthcare industry 5.0, the results of federated machine learning approaches are used to validate multidisciplinary cancer disease prediction. The proposed adaptive federated machine learning methodology achieved 90.0%, while the conventional federated learning approach achieved 87.30%, both of which were higher than the previous state-of-the-art methodologies for cancer disease prediction in the smart healthcare industry 5.0. [ABSTRACT FROM AUTHOR]

Purpose: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). Methods: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005–2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. Results: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. Conclusion: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients. [ABSTRACT FROM AUTHOR]

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) and gout are risk factors for renal cancer. We analysed the effects of comorbid diabetic kidney disease and gout on renal cancer. Methods This retrospective cohort study enrolled 847 884 patients with type 2 diabetes mellitus (T2DM) who underwent health assessments provided by the Korean National Health Insurance Service in 2009. Based on CKD occurrence (glomerular filtration rate <60 ml/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD−Gout− (87.5%), CKD−Gout+ (2.5%), CKD+Gout− (9.3%) and CKD+Gout+ (0.7%). Patients with incident renal cancer (International Classification of Diseases code C64) were followed up until December 2018. Results Renal cancer was diagnosed in 2376 patients (0.3%). Renal cancer incidence increased in sequential order of CKD−Gout− [0.29/1000 person-years (PY), CKD+Gout− and CKD−Gout+ (0.44 and 0.48/1000 PY, respectively) and CKD+Gout+ (1.14/1000 PY). Comorbid gout increased renal cancer risk depending on CKD occurrence {hazard ratio [HR] 1.28 [95% confidence interval (CI) 1.04–1.58 among those without CKD; HR 1.95 [95% CI 1.45–2.63] among those with CKD; P -value for interaction = 0.024}. The interaction was significant, particularly in men and patients with a shorter diabetes duration (<5 years) and lesser medication use (no insulin or fewer than three classes of oral hypoglycaemic agents). Conclusions CKD and gout individually contributed to renal cancer incidence, and the risk is further increased when gout coexists with CKD. Screening for gout and appropriate management of CKD at an early T2DM stage may be beneficial. [ABSTRACT FROM AUTHOR]

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase (FH) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal cell carcinoma (RCC). HLRCC-associated RCC is aggressive and diagnosed at a much earlier age than sporadic RCC. It is essential for carriers of HLRCC to undergo annual renal screening by magnetic resonance imaging to detect early stage RCCs. Metastatic HLRCC-associated RCC must be treated by systemic therapy; however, it is unclear which medicines are most effective in treating this cancer owing to its low incidence rate. Immune checkpoint inhibitor (ICI) combinations or ICIs plus tyrosine kinase inhibitors are administered as systemic therapy for clear cell RCC. Here, we report a patient with HLRCC-associated RCC treated with sequential therapy, including ipilimumab plus nivolumab combination and cabozantinib, after diagnosis of HLRCC-associated RCC using FoundationOne Liquid CDx and single-site analysis. We also investigated familial FH mutations and describe a new family pedigree for HLRCC. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)–deficient RCC. FH‐deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH‐deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo‐cytoplasmic expression of S‐(2‐succino)‐cysteine (2‐SC), with loss of FH in seven cases. FH‐deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2‐SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review is to assess the clinical implications of employing various Extended Reality (XR) tools for image guidance in urological surgery. Methods: In June 2023, a systematic electronic literature search was conducted using the Medline database (via PubMed), Embase (via Ovid), Scopus, and Web of Science. The search strategy was designed based on the PICO (Patients, Intervention, Comparison, Outcome) criteria. Study protocol was registered on PROSPERO (registry number CRD42023449025). We incorporated retrospective and prospective comparative studies, along with single-arm studies, which provided information on the use of XR, Mixed Reality (MR), Augmented Reality (AR), and Virtual Reality (VR) in urological surgical procedures. Studies that were not written in English, non-original investigations, and those involving experimental research on animals or cadavers were excluded from our analysis. The quality assessment of comparative and cohort studies was conducted utilizing the Newcastle-Ottawa scale, whilst for randomized controlled trials (RCTs), the Jadad scale was adopted. The level of evidence for each study was determined based on the guidelines provided by the Oxford Centre for Evidence-Based Medicine. Results: The initial electronic search yielded 1,803 papers after removing duplicates. Among these, 58 publications underwent a comprehensive review, leading to the inclusion of 40 studies that met the specified criteria for analysis. 11, 20 and 9 studies tested XR on prostate cancer, kidney cancer and miscellaneous, including bladder cancer and lithiasis surgeries, respectively. Focusing on the different technologies 20, 15 and 5 explored the potential of VR, AR and MR. The majority of the included studies (i.e., 22) were prospective non-randomized, whilst 7 and 11 were RCT and retrospective studies respectively. The included studies that revealed how these new tools can be useful both in preoperative and intraoperative setting for a tailored surgical approach. Conclusions: AR, VR and MR techniques have emerged as highly effective new tools for image-guided surgery, especially for urologic oncology. Nevertheless, the complete clinical advantages of these innovations are still in the process of evaluation. [ABSTRACT FROM AUTHOR]

Purpose: To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) for highly-complex renal masses (PADUA ⩾ 10) with versus without the use of 3DVMs. Materials and Methods: We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Only PADUA ⩾ 10 cases were considered eligible for analysis. Propensity score matching (PSM) analysis was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary outcomes were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. Results: Thirty seven patients for each group were analyzed after PSM. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32.5% vs 16.2%, p = 0.03) and a higher enucleation rate (43.2% vs 29.8%, p = 0.04). Twelve-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1–1.4] vs 1.6 [IQR 1.1–1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2–74.1] vs 52.3 [IQR 49.2–74.1], p = 0.03). MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop in this subgroup of patients. Conclusions: RAPN performed with the use of 3DVM assistance for PADUA ⩾ 10 cases resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month follow-up. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency, and new approaches should be explored. In this study, we studied the possible role of hemoadsorption to achieve a fast, safe, and effective removal of PFAS from blood in patients with high blood levels. Methods: We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 L) through a sorbent cartridge (Jafron Medical, Zhuhai, China) for 120 min at a flow of 150 mL/min. We collected samples at different time points and analyzed 39 different PFAS compounds. Results: For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 min of circulation leading to almost complete elimination of all pollutants at 120 min. Conclusions: The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution. [ABSTRACT FROM AUTHOR]

Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity—both actual and specific—was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Pyrroline-5-carboxylate reductase (PYCR) is pivotal in converting pyrroline-5-carboxylate (P5C) to proline, the final step in proline synthesis. Three isoforms, PYCR1, PYCR2, and PYCR3, existed and played significant regulatory roles in tumor initiation and progression. In this study, we first assessed the molecular and immune characteristics of PYCRs by a pan-cancer analysis, especially focusing on their prognostic relevance. Then, a kidney renal clear cell carcinoma (KIRC)-specific prognostic model was established, incorporating pathomics features to enhance predictive capabilities. The biological functions and regulatory mechanisms of PYCR1 and PYCR2 were investigated by in vitro experiments in renal cancer cells. The PYCRs' expressions were elevated in diverse tumors, correlating with unfavorable clinical outcomes. PYCRs were enriched in cancer signaling pathways, significantly correlating with immune cell infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI). In KIRC, a prognostic model based on PYCR1 and PYCR2 was independently validated statistically. Leveraging features from H&E-stained images, a pathomics feature model reliably predicted patient prognosis. In vitro experiments demonstrated that PYCR1 and PYCR2 enhanced the proliferation and migration of renal carcinoma cells by activating the mTOR pathway, at least in part. This study underscores PYCRs' pivotal role in various tumors, positioning them as potential prognostic biomarkers and therapeutic targets, particularly in malignancies like KIRC. The findings emphasize the need for a broader exploration of PYCRs' implications in pan-cancer contexts. [ABSTRACT FROM AUTHOR]

Background: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. Methods: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. Results: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. Conclusions: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future. [ABSTRACT FROM AUTHOR]

The landscape of the management of renal cell carcinoma has evolved substantially in the last decade, leading to improved survival in localised and advanced disease. We review the epidemiology, pathology, and diagnosis of renal cell carcinoma and discuss the evidence for current management strategies from localised to metastatic disease. Developments in adjuvant therapies are discussed, including use of pembrolizumab—the first therapy to achieve overall survival benefit in the adjuvant setting. The treatment of advanced disease, including landmark trials that have established immune checkpoint inhibition as a standard of care, are also reviewed. We also discuss the current controversies that exist surrounding the management of metastatic renal cell carcinoma, including the use of risk assessment models for disease stratification and treatment selection for frontline therapy. Management of non-clear cell renal cell carcinoma subtypes is also reviewed. Future directions of research, including a discussion of ongoing clinical trials and the need for reliable biomarkers to guide treatment in kidney cancer, are also highlighted. [ABSTRACT FROM AUTHOR]

In patients with advanced or metastatic non–clear cell renal cell carcinoma, cabozantinib plus nivolumab demonstrated promising efficacy, with an objective response rate of 48%, and potential for sustained responses, with a median duration of response of 17 mo. The toxicity profile was as expected for the two agents. Treatment options are limited for patients with non–clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5–63.9%). Median PFS was 13 mo (95% CI 7–16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34–65%) and 23% (95% CI 11–37%), respectively. Median OS was 28 mo (95% CI 23–43); the 18-mo and 36-mo OS rates were 70% (95% CI 53–82%) and 44% (95% CI 28–60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC. [ABSTRACT FROM AUTHOR]