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Urological cancers including those of the prostate, bladder, and kidney, are prevalent and often lethal malignancies besides other less common ones like testicular and penile cancers. Current treatments have major limitations like side effects, recurrence, resistance, high costs, and poor quality of life. Nanotechnology offers promising solutions through enhanced diagnostic accuracy, targeted drug delivery, controlled release, and multimodal imaging. This review reflects clinical challenges and nanomedical advances across major urological cancers. In prostate cancer, nanoparticles improve delineation and radiosensitization in radiation therapy, enable fluorescent guidance in surgery, and enhance chemotherapy penetration in metastatic disease. Nanoparticles also overcome bladder permeability barriers to increase the residence time of intravesical therapy and chemotherapy agents. In renal cancer, nanocarriers potentiate tyrosine kinase inhibitors and immunotherapy while gene vectors and zinc oxide nanoparticles demonstrate antiproliferative effects. Across modalities, urological applications of nanomedicine include polymeric, liposomal, and metal nanoparticles for targeted therapy, prodrug delivery, photodynamic therapy, and thermal ablation. Biosafety assessments reveal favorable profiles but clinical translation remains limited, necessitating further trials. In conclusion, nanotechnology holds significant potential for earlier detection, precise intervention, and tailored treatment of urological malignancies, warranting expanded research to transform patient outcomes. [ABSTRACT FROM AUTHOR]

Background: To identify the impact of surgical compliance on survival in patients with kidney cancer and to explore the factors that influence surgical compliance. Methods: Clinical date of kidney cancer patients were identified from the SEER databases, and the patients were divided into surgical compliance group and surgical noncompliance group. Cox survival analysis and Kaplan–Meier curves were used to evaluate the effect of surgical compliance on overall survival (OS) and cancer-specific survival (CSS). A diagnostic nomogram was constructed to quantify individual differences in compliance, and receiver operating characteristics (ROC) curves and calibration curves were used to assess the accuracy of the nomogram. Propensity score matching (PSM) was performed to balance potential baseline confounding factors. Results: Of the 133,950 patients eligible for surgical resection, 2,814 (2.1%) patients did not opt for surgery ultimately. Surgical noncompliance was associated with poor prognosis. In all patients, Cox regression analysis showed that surgical noncompliance was an independent predictor for OS [before: HR = 2.490, 95% CI 2.374–2.612, p < 0.001; after: HR = 2.380, 95% CI 2.202–2.573, p < 0.001] and CSS [before: HR = 2.490, 95% CI 2.318–2.675, p < 0.001; after: HR = 2.035, 95% CI 1.813–2.285, p < 0.001] of kidney cancer patients before and after PSM. Multivariable logistic regression revealed that older age, afro-american origin, lower household income, and advanced tumor grade were associated with surgical noncompliance. The ROC and calibration curves showed that the diagnostic nomogram had high predictive accuracy. Conclusion: Surgical compliance was an independent prognostic factor for OS and CSS in patients with kidney cancer, and surgical noncompliance was associated with poor survival. [ABSTRACT FROM AUTHOR]

Background: Metastatic urothelial carcinoma (mUC) has a poor prognosis, despite recent therapeutic advancements. Prostaglandin Reductase 1 (PTGR1) is essential for activating acylfulvens, a promising class of drugs for treating a subset of urothelial carcinoma (UC) patients. The efficacy of acylfulvens depends on PTGR1 activity and defects in the nucleotide excision repair (NER) pathway, notably ERCC2 mutations present in 10–15% of bladder tumors. This study identifies patients eligible to be included in acylfulven clinical trials based on the presence of PTGR-1 by immunohistochemistry (IHC) staining, RNA expression level and mutations in the NER pathway. Additionally, it evaluates PTGR-1 expression as a prognostic biomarker. Methods: Three PTGR-1 antibodies were tested in a kidney cancer cell line A498 and in tissues with known PTGR1 expression (liver, tonsils, pancreas, small intestine, etc.). Patients with untreated mUC receiving 1st line platinum from Dec. 2019 to Dec. 2021 in the Capital Region, Denmark, were included retrospectively. FFPE tumor samples were collected, and tissue microarrays (TMAs) were constructed. TMAs were stained with the best-performing PTGR1 antibody, RNA expression was analyzed using Nanostring nCounter PanCancer panel and gene mutations were assessed using a targeted genomic panel (TSO-500). Kaplan-Meier and multivariate Cox regression assessed overall survival and covariate impacts. Results: The AB181131 PTGR1 antibody was the most reliable in validation tissues. Tumors from 71 mUC patients were used to construct the TMA, and 40% of tumors scored positive for PTGR1 by IHC staining. A normalized PTGR1 RNA cutoff at 2,550 normalized counts achieved an AUC of 0.9, defining 35 samples as positive with a sensitivity of 96% and specificity of 85% in relation to IHC-positivity. Differential expression showed a significant upregulation of PTGR1 RNA in PTGR1 IHC-positive cases. NER-deficiency and PTGR1 positivity (mutations in ERCC1, ERCC2, ERCC3, ERCC4) was seen in 9 patients (13%). Median overall survival was 16 months in the cohort. Overall survival (OS) analysis indicates that overexpression of PTGR1 RNA was associated with a reduced median OS (12 months vs. 25 months, p = 0.039, log-rank). Conclusion: PTGR1 IHC staining pattern using the Abcam AB181131 antibody is highly correlated with PTGR1 RNA expression. 13% in our cohort were identified as NER deficient and PTGR1 positive. Lower levels of PTGR1 indicates better outcome in this cohort. [ABSTRACT FROM AUTHOR]

Aim Materials and methods Results Conclusions A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone.Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time‐to‐event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes‐related (microvascular) and cancer events over 1–5 years.Analysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all‐cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1–5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all‐cause mortality and several obesity related cancers versus T2D alone.T2D significantly potentiates risk of cardiovascular, malignancy and liver‐related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy). [ABSTRACT FROM AUTHOR]

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short‐term O3 exposure and site‐specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time‐stratified case‐crossover design was applied to assess the O3‐cancer mortality association. Subgroup analyses by age, sex, season, time‐period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non‐threshold exposure‐response relationship was observed for short‐term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%–1.20%) increase in all‐cancer mortality risks for each 10‐μg/m3 increment of three‐day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000–2019, a total of 147,074 (116,690–177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014–28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations. [ABSTRACT FROM AUTHOR]

Objective: To optimize the use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for cancer patients, we characterized and evaluated ONJ related to TKIs and ICIs by analyzing a public database and reviewing the relevant literature. TKIs and ICIs are limited to drugs that treat renal cancer recommended by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Kidney Cancer. Methods: We described a case series of patients experiencing ONJ while on TKIs or ICIs. We also analyzed spontaneous reports submitted to the FAERS in an observational and retrospective manner between January 2004 and December 2022. Selecting ONJ' adverse events to TKIs and ICIs. Associations between TKIs, ICIs and ONJ were assessed using reporting odds ratios (ROR), drug interaction signals based on the Ω shrinkage measure. Results: 29 patients with ONJ events while on TKIs and ICIs were included in our case series. 240 were related to ONJ AEs. Specifically, 32.1% ICSRs were linked to sunitinib, 16.7% to lenvatinib, 12.9% to pazopanib, 12.5% to nivolumab, 10.0% to axitinib, 5.4% to sorafenib, 5.0% to pembrolizumab, 4.2% to cabozantinib, and 1.3% to ipilimumab. More ICSRs were generally seen in male and reported in Europe. The median age was 63 years. Renal cancer and lung cancer was the most common indication for TKIs and ICIs, respectively. Excluding missing data, the prevalence of mortality was highest for sunitinib-related ONJ ICSRs (18.5%), followed by sorafenib-related ONJ ICSRs (15.4%). With the criteria of ROR, sunitinib and lenvatinib were significantly associated with ONJ AEs. With the criteria of Ω, nivolumab + cabozantinib was significantly associated with ONJ AEs. Conclusion: TKIs and ICIs have been reported to have significant ONJ side effects. Patients and physicians need to recognize and monitor these potentially fatal adverse events. [ABSTRACT FROM AUTHOR]

Background: Blood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear. Methods: We performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method. Results: Several blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa. Conclusion: This study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers. [ABSTRACT FROM AUTHOR]

The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm. LncRNAs do not translate to proteins and they have been implicated in the regulation of tumorigenesis. On the other hand, One way cells die is by a process called autophagy, which breaks down proteins and other components in the cytoplasm., while the aberrant activation of autophagy allegedly involved in the pathogenesis of diseases. The autophagy exerts anti-cancer activity in pre-cancerous lesions, while it has oncogenic function in advanced stages of cancers. The current overview focuses on the connection between lncRNAs and autophagy in urological cancers is discussed. Notably, one possible role for lncRNAs is as diagnostic and prognostic variablesin urological cancers. The proliferation, metastasis, apoptosis and therapy response in prostate, bladder and renal cancers are regulated by lncRNAs. The changes in autophagy levels can also influence the apoptosis, proliferation and therapy response in urological tumors. Since lncRNAs have modulatory functions, they can affect autophagy mechanism to determine progression of urological cancers. [ABSTRACT FROM AUTHOR]

This research aims to develop the inclusion complex of 2, 4‐diamino‐6‐hydroxypyrimidine (DHP) with β‐cyclodextrin (β‐CD) using an inclusion process, and to investigate the effect of inclusion on the photo stability and bioactivity of DHP. The formation of DHP‐β‐CD inclusion complex has been examined by means of physicochemical as well as spectroscopic techniques (1H NMR, FT‐IR, PXRD and SEM) suggesting the successful inclusion of the DHP molecule into the β‐CD cavity. The 1 : 1 stoichiometry of the inclusion complex was validated through Job's plot. β‐CD displayed a fairly strong affinity (Ka =889.67 M−1) for DHP, indicating that the binding process is thermodynamically feasible. A molecular docking study speculated the most preferred orientation of DHP molecule within the binding pocket of β‐CD cavity. The photostability of DHP was found to improve on complexation with β‐CD. In vitro antibacterial activity test demonstrated that the DHP‐β‐CD inclusion complex displayed better activity than pure DHP. DHP‐β‐CD inclusion complex (IC50 =240.04 μM) also exhibited relatively significant in vitro cytotoxic activity than pure DHP towards the human kidney cancer cell line (ACHN). These results reveals that the inclusion of DHP using β‐CD could lead to stabilization of DHP and efficient display of its bioactivity. [ABSTRACT FROM AUTHOR]

Fumarate hydratase (FH) mutated papillary renal cell carcinoma is an aggressive variant of kidney cancer that poorly responds to conventional targeted therapies and immunotherapy. Here, we present the 10-year follow-up of a heavily pre-treated patient with several lines of therapy, achieving a remarkable complete response to anti-PD-1 rechallenge. In addition, we highlight a common immune-related adverse event of anti-PD-1, eosinophilia, as a possible biomarker of response and using TCGA data analysis, provide proof-of-concept for tumor expression of the eosinophil-related gene SIGLEC8, as a promising powerful predictor of prognosis for papillary renal cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Small malignant renal tumors can be found in up to 1.3% of kidney donors. Several studies have investigated the use of these kidneys for transplantation, after ex vivo resection of the malignant mass. Methods: We performed a systematic review of the literature on PubMed, Embase, and Web of Science of studies including reports of malignant renal masses excised from kidney grafts prior to transplantation. Articles including benign pathology only were excluded. Results: Our search strategy identified 226 patients over 32 studies. Pathology included 107 clear cell carcinomas, 27 papillary renal cell carcinomas (RCCs), 84 other types of RCCs, and 8 transitional cell carcinomas. The majority of cancers were grade 1 or 2 (81.6%). Average tumor size was 12.6 mm. Clavien–Dindo ≥ 3 complication rate was 22%. Mean follow‐up was 39.9 months. The 1‐year, 3‐year, and 5‐year overall survival rate for recipients of living donor grafts was 95.8%, 92.1%, and 75.1%. The 1‐year, 3‐year, and 5‐year living donor death‐censored graft survival rate was 90.8, 85.2%, and 64.8%. Of the 226 patients, 6 (2.7%) experienced a malignant recurrence. The average time to recurrence was 36.1 months. Conclusions: Transplantation of kidney grafts after resection of small cancerous masses is relatively safe and has low rates of recurrent malignancy. In the case of a living donor, appropriate counseling on partial nephrectomy versus donor nephrectomy should be provided, ideally by a surgeon who is not part of the transplant team. Recipients of these grafts should be carefully selected and counseled regarding the additional potential technical and oncological risks. [ABSTRACT FROM AUTHOR]

l‐2‐Hydroxyglutarate (l‐2‐HG) has been regarded as a tumor metabolite, and it plays a crucial role in adaptation of tumor cells to hypoxic conditions. However, the role of l‐2‐HG in tumor radioresistance and the underlying mechanism have not yet been revealed. Here, we found that l‐2‐HG exhibited to have radioresistance effect on U87 human glioblastoma cells, which could reduce DNA damage and apoptosis caused by irradiation, promote cell proliferation and migration, and impair G2/M phase arrest. Mechanistically, l‐2‐HG upregulated the protein level of hypoxia‐inducible factor‐1α (HIF‐1α) and the expression levels of HIF‐1α downstream target genes. The knockdown of l‐2‐hydroxyglutarate dehydrogenase (L2HGDH) gene promoted the tumor growth and proliferation of U87 cells in nude mice by increasing HIF‐1α expression level in vivo. In addition, the low expression level of L2HGDH gene was correlated with the short survival of patients with glioma or kidney cancer. In conclusion, our study revealed the role and mechanism of l‐2‐HG in tumor radioresistance and may provide a new perspective for overcoming tumor radioresistance and broaden our comprehension of the role of metabolites in tumor microenvironment. [ABSTRACT FROM AUTHOR]

Objective: A recent update of the French cohort of uranium miners added seven years of follow-up data. We use these new data to look for new possible radon-related increased risks and refine the estimation of the potential association between cumulative radon exposure and four cancer sites: lung cancer, kidney cancer, brain and central nervous system (CNS) cancer and leukemia (excluding chronic lymphocytic leukemia, which is not radiation-induced). Methods: Several parametric survival models are proposed, fitted and compared under the Bayesian paradigm, to perform new and original exposure-risk analyses. In line with recent UNSCEAR recommendations, we consider time-related effect modifiers and exposure rate as potential effect modifying factors. We use Bayesian model selection criteria to identify radon-related increased hazard rates. Results: Under the assumption of a linear exposure-risk relationship, we found a substantial evidence for a strictly positive effect of cumulative radon exposure on the hazard rate of death by lung cancer among French uranium miners. Given the current available data under the assumptions of a linear or log-linear exposure-risk relationship, it is not possible to conclude in favour of the absence or the existence of a strictly positive effect of chronic exposure to radon on the hazard rate of death by kidney cancer. Regarding death by brain and CNS cancer, there is a substantial evidence for the absence of radon-related effect. Finally, under the assumption of a log-linear exposure-risk relationship, a small positive radon-related effect appears when looking at the risk of death by leukemia (excluding CLL). Conclusion: This study investigates the existence of radon-related increased risk of death by lung cancer, kidney cancer, brain and CNS cancer and leukemia under a Bayesian framework and assumptions of linear and log-linear exposure-risk relationships. If there is no doubt in the interpretation of the results for lung cancer and brain and CNS cancer, the conclusion is less clear-cut in the case of kidney cancer and leukemia (excluding CLL). A future update of the French cohort, increasing the follow-up time for miners, may help to reach a clearer conclusion for these two cancer sites. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are significant risks for kidney cancer (KC) patients undergoing partial (PN) or radical nephrectomy (RN) and for living kidney donors (LKD). This study compares AKI and CKD incidence in these groups with a pre-operative glomerular filtration rate (GFR) over 60 mL/min/1.73 m2. Methods: This study included 465 KC patients with cT1-2N0M0 kidney mass and 256 LKD who underwent nephrectomy at four Italian institutions from 2014 to 2021. Data on demographics, comorbidities, and therapies were analyzed. Serum creatinine and estimated GFR (eGFR) were measured before and after surgery. Outcomes were AKI (per KDIGO guidelines) and CKD stage progression. Analyses included descriptive statistics, ANOVA, logistic regression, and Kaplan–Meier survival. Results: Among 721 patients, significant age and gender differences were noted. Hypertension (41%) and diabetes (7.1%) were prevalent in RN and PN groups. Post-surgery AKI was more common in donors (84%), while CKD stage progression varied by surgery type (CKD stage G3 after 60 months: RN 48.91%, PN 18.22%, LKD 26.56%). Age, pre-surgery CKD, and surgery type predicted CKD progression. Limitations include retrospective design and bias. Conclusions: Both LKD and KC patients face similar AKI and CKD risks. Surgery type significantly influences AKI and CKD incidence, highlighting the importance of approach. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is the integration of human tasks into machine processes. The role of AI in kidney cancer evaluation, management, and outcome predictions are constantly evolving. We performed a narrative review utilizing PubMed electronic database to query AI as a method of analysis in kidney cancer research. Key search-words included: Artificial Intelligence, Supervised/Unsupervised Machine Learning, Deep Learning, Natural Language Processing, Neural Networks, radiomics, pathomics, and kidney or renal neoplasms or cancer. 72 clinically relevant and impactful studies related to imaging, histopathology, and outcomes were recognized. We anticipate the incorporation of AI tools into future clinical decision-making for kidney cancer. [ABSTRACT FROM AUTHOR]

Nous proposons une sélection non exhaustive des principaux essais cliniques présentés courant 2023–2024 ayant retenu notre attention dans le cadre de l'oncologie-radiothérapie appliquée aux cancers urologiques et incluant la prise en charge du cancer de la prostate (radiothérapie du cancer localisé, radiothérapie après prostatectomie, réirradiation, récidive biochimique après traitement local, radiothérapie du cancer métastatique), du cancer de vessie infiltrant le muscle et du primitif rénal. Herein, we provide a non-exhaustive selection of the main clinical trials presented in 2023–2024 related to radiation-oncology used in the treatment of urological cancers including prostate cancer (radiotherapy of localized prostate cancer, post-prostatectomy irradiation, reirradiation, biochemical recurrence following local treatment, radiotherapy for metastatic cancer), muscle invasive bladder cancer and primary kidney cancer. [ABSTRACT FROM AUTHOR]

Background People with chronic kidney disease (CKD) have increased incidence and mortality of most cancer types. We hypothesized that the odds of presenting with advanced cancer may vary according to differences in estimated glomerular filtration rate (eGFR), that this could contribute to increased all-cause mortality and that sex differences may exist. Methods Data were from Secure Anonymised Information Linkage Databank, including people with de novo cancer diagnosis (2011–17) and two kidney function tests within 2 years prior to diagnosis to determine baseline eGFR (mL/min/1.73 m2). Logistic regression models determined the odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRCr and all-cause mortality. Results eGFR <30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared with eGFR >75–90, eGFR <30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females [female: hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.56–1.88; male versus female comparison: HR 0.88, 95% CI 0.78–0.99]. Conclusions Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger association with all-cause mortality in females compared with males with eGFR <30 is concerning and warrants further scrutiny. [ABSTRACT FROM AUTHOR]

Crotonylation, a crotonyl-CoA-based non-enzymatic protein translational modification, affects diverse biological processes, such as spermatogenesis, tissue injury, inflammation, and neuropsychiatric diseases. Crotonylation is decreased in hepatocellular carcinomas (HCCs), but the mechanism remains unknown. In this study, we aim to describe the role of glutaryl-CoA dehydrogenase (GCDH) in tumor suppression. Three cohorts containing 40, 248 and 17 pairs of samples were used to evaluate the link between GCDH expression levels and clinical characteristics of HCC, as well as responses to anti-programmed cell death protein 1 (PD-1) treatment. Subcutaneous xenograft, orthotopic xenograft, Trp53 Δhep/Δhep ; MYC - and Ctnnb oe ; MET oe -driven mouse models were adopted to validate the effects of GCDH on HCC suppression. GCDH depletion promoted HCC growth and metastasis, whereas its overexpression reversed these processes. As GCDH converts glutaryl-CoA to crotonyl-CoA to increase crotonylation levels, we performed lysine crotonylome analysis and identified the pentose phosphate pathway (PPP) and glycolysis-related proteins PGD, TKT, and ALDOC as GCDH-induced crotonylation targets. Crotonyl-bound targets showed allosteric effects that controlled their enzymatic activities, leading to decreases in ribose 5-phosphate and lactate production, further limiting the Warburg effect. PPP blockade also stimulated peroxidation, synergizing with senescent modulators to induce senescence in GCDHhigh cells. These cells induced the infiltration of immune cells by the SASP (senescence-associated secretory cell phenotype) to shape an anti-tumor immune microenvironment. Meanwhile, the GCDHlow population was sensitized to anti-PD-1 therapy. GCDH inhibits HCC progression via crotonylation-induced suppression of the PPP and glycolysis, resulting in HCC cell senescence. The senescent cell further shapes an anti-tumor microenvironment via the SASP. The GCDHlow population is responsive to anti-PD-1 therapy because of the increased presence of PD-1+CD8+ T cells. Glutaryl-CoA dehydrogenase (GCDH) is a favorable prognostic indicator in liver, lung, and renal cancers. In addition, most GCDH depletion-induced toxic metabolites originate from the liver, accumulate locally, and cannot cross the blood-brain barrier. Herein, we show that GCDH inhibits hepatocellular carcinoma (HCC) progression via crotonylation-induced suppression of the pentose phosphate pathway and glycolysis, resulting in HCC cell senescence. We also found that more PD-1+CD8+ T cells are present in the GCDHlow population, who are thus more responsive to anti-PD-1 therapy. Given that the GCDHlow and GCDHhigh HCC population can be distinguished based on serum glucose and ammonia levels, it will be worthwhile to evaluate the curative effects of pro-senescent and immune-therapeutic strategies based on the expression levels of GCDH. [Display omitted] • Proteomics data and clinical validation link GCDH to HCC suppression. • GCDH depletion promotes HCC initiation, development and metastasis. • GCDH suppresses PPP and glycolysis via crotonylation of PGD, TKT and ALDOC, which further induces cell senescence. • GCDH-driven HCC senescence shapes an anti-tumor microenvironment. [ABSTRACT FROM AUTHOR]

Stereotactic ablative body radiotherapy (SABR) is a novel option to treat primary renal cell carcinoma. However, a high radiation dose may be received by the treated kidney, which may affect its function posttreatment. This study investigates the dose-effect relationship of kidney SABR with posttreatment renal function. This was a prespecified secondary endpoint of the multicenter FASTRACK II (Focal Ablative STereotactic RAdiotherapy for Cancers of the Kidney phase II) clinical trial (National Clinical Trial 02613819). Patients received either 26 Gy in a single fraction (SF) for tumors with a maximal diameter of 4 cm or less or 42 Gy in 3 fractions (multifraction [MF]) for larger tumors. To determine renal function change, 99mTc-dimercaptosuccinic acid (DMSA) single-photon emission computed tomography/computed tomography (SPECT/CT) scans were acquired, and the glomerular filtration rate was estimated at baseline, 12, and 24 months posttreatment. Imaging data sets were rigidly registered to the planning CT where kidneys were segmented to calculate dose-response curves. From 71 enrolled patients, 36 (51%) and 26 (37%) patients were included in this study based on availability of posttreatment data at 12 and 24 months, respectively. The ipsilateral kidney glomerular filtration rate decreased from baseline by 42% and 39% in the SF cohort and by 45% and 62% in the MF cohort, at 12 and 24 months, respectively (P <.03). The loss in renal function was 3.6%/Gy ± 0.8%/Gy and 4.5%/Gy ± 1.0%/Gy in the SF cohort and 1.7%/Gy ± 0.1%/Gy and 1.7%/Gy ± 0.2%/Gy in the MF cohort at 12 and 24 months, respectively. The major loss in renal function occurred in high-dose regions, where dose-response curves converged to a plateau. For the first time in a multicenter study, the dose-effect relationship at 12 and 24 months post-SABR treatment for primary renal cell carcinoma was quantified. Kidney function reduces linearly with dose up to 100 Gy BED 3. [ABSTRACT FROM AUTHOR]

The purpose of this study is to identify if the local institutional shift from routine overnight observation to same-day discharge following percutaneous cryoablation (PCA) of renal tumors increases 30 day re-admission rates or serious adverse events (AEs). This retrospective study included 133 adult patients. PCA patients in calendar years 2018-2019 were routinely observed overnight in the hospital, comprising the control group (Group A). PCA patients in calendar years 2021-2022 were routinely discharged the same day, comprising the test group (Group B). Relevant demographic information, tumor characteristics, technical outcomes, and clinical outcomes were recorded. 15 patients (11.3 %) from the total cohort were re-admitted to the hospital within 30 days of PCA for any reason. Seven patients (10.4 %) and eight patients (12.1 %) were re-admitted for any reason within 30 days in Group A and Group B, respectively, with no difference between the two groups (p = 0.76). Nine patients (6.8 %) from the total cohort were re-admitted to the hospital within 30 days for a diagnosis secondary to the procedure. Four patients (6 %) and five patients (7.6 %) were re-admitted within 30 days for reasons related to PCA in Group A and Group B, respectively, with no significant difference between the groups (p = 0.71). Eight patients (12 %) and four patients (6 %) had major AEs following PCA in Group A and Group B, respectively, with no difference between the two groups (p = 0.43). Overall, the change in post-procedural care after PCA did not have a deleterious effect on 30 day re-admission rates or rates of major AEs. [ABSTRACT FROM AUTHOR]

Many robotic platforms are currently available for urologic surgery, each with its technical characteristics. It can be hypothesised that these characteristics might affect postoperative nursing, as they affect several aspects of surgery. They could, therefore, impact the surgical outcomes and wound characteristics, involving aspects of postoperative care such as mobilization, nutrition and length of stay. Although data are available on surgical technique aspects and intraoperative nursing, studies have yet to offer insights and considerations about the potential effect of having different robotic platforms on postoperative nursing care. We aimed to verify whether the technical features of the available robots could impact postoperative nursing. We conducted an integrative review on PubMed, CINAHL and Scopus, using Medical Subject Headings (MeSH) and free‐text terms; wildcards and boolean operators were also used. Studies of any design were included. Fifteen papers were retrieved; the key themes emerging from the literature regard trocar setup, technical characteristics of the robots (e.g. single or multiple ports), pneumoperitoneum and Trendelenburg degree. According to the literature, none of these characteristics produce differences in postoperative nursing. The fundamental concepts of postoperative care in surgical inpatients stay the same no matter the robotic platform used. Having competing platforms able to ensure reduced complications without impacting postoperative nursing allows health care facilities to adopt the newest technologies without the need for differentiated nursing protocols. This is an advantage in times of global nursing shortage as it avoids the need for additional platform‐based nursing training. [ABSTRACT FROM AUTHOR]

Background/Aim: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75% of kidney cancers. The objective of this study was to identify novel progression markers for ccRCC based on proteomics, with the goal of stage determination and early diagnosis of kidney cancer patients. Materials and Methods: We performed quantitative global proteomics coupled with Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and high-resolution tandem mass spectrometry on kidney-derived cells, including HEK-293, 786-O (primary ccRCC), and Caki-1 (metastatic ccRCC) cells, to investigate the novel progression factors of ccRCC. Results: In this study, a total of 1,106 proteins were quantified. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for differentially expressed proteins (DEPs) that were increased in ccRCC cells compared to HEK-293 cells. Ultimately, 99 DEPs including 75 up-regulated and 24 down-regulated proteins, that were significantly altered in both ccRCC cells, were identified. Among DEPs, vimentin was identified as the most significantly changed protein. Its increased expression in ccRCC was verified through immunoblotting in ccRCC cell lines and immunohistochemistry in kidney tumors. Conclusion: From the global proteomics data detected in ccRCC, we propose 99 DEPs including vimentin as progression factors. [ABSTRACT FROM AUTHOR]

Tumor evasion has recently been associated with a novel member of the B7 family, HERV‐H LTR‐associating 2 (HHLA2), which is mostly overexpressed in PDL‐1neg tumors. HHLA2 can either induce a costimulation signal when bound to CD28H or inhibit it by binding to KIR3DL3 on T‐ and NK cells. Given the broad distribution of CD28H expression on NK cells and its role, we compared two monoclonal antibodies targeting this novel NK‐cell engager in this study. We show that targeting CD28H at a specific epitope not only strongly activates Ca2+ flux but also results in NK‐cell activation. CD28H‐activated NK cells further display increased cytotoxic activity against hematopoietic cell lines and bypass HHLA2 and HLA‐E inhibitory signals. Additionally, scRNA‐seq analysis of clear cell renal cancer cells revealed that HHLA2+ clear cell renal cancer cell tumors were infiltrated with CD28H+ NK cells, which could be targeted by finely chosen anti‐CD28H Abs. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé (BHD) syndrome is a genetic condition caused by pathogenic variants in the FLCN gene resulting in benign skin lesions, spontaneous pneumothorax, and increased risk for a variety of renal tumors. Skin manifestations of BHD include trichodiscoma (TD) and fibrofolliculoma (FF), which may represent the same pathologic entity. These lesions can identify BHD patients, who upon positive genetic testing can be considered for life-long surveillance for renal neoplasms. Objective: To characterize patients diagnosed with TD and FF including rates and outcomes of genetics referral. Methods: Retrospective chart reviews of patients with confirmed or possible diagnosis of TD or FF at the University of Michigan from September 2002 through October 2020 to assess pathologic findings, personal and family history of BHD manifestations, referral for genetic evaluation, and genetic testing results. Results: 64 patients had a pathologic diagnosis of TD or FF, 16 of whom (25%) were referred to cancer genetics. Fourteen patients completed genetic evaluation, 9 of whom were diagnosed with BHD (64%), with 6 unique pathogenic variants in FLCN. Conclusion: Providers should consider referral for genetic evaluation for patients with biopsy-proven TD or FF, as early diagnosis of BHD provides the opportunity for early detection and treatment of other BHD-associated conditions. Capsule Summary: • Birt-Hogg-Dube syndrome includes renal cancer, pneumothorax, and trichodiscomas and fibrofolliculomas and is caused by pathogenic variants in FLCN. • Patients with trichodiscoma or fibrofolliculoma should be considered for referral to cancer genetics to allow identification of pathogenic FLCN variants and thus family cascade testing and surveillance for renal tumors. [ABSTRACT FROM AUTHOR]

Aim: We conducted a bibliometric analysis to quantitatively study the development pathway, research hotspots and evolutionary trends of nano-drug delivery systems (NDDS) in treating urological tumors. Materials & methods: We used the Web of Science Core Collection to retrieve the literature related to NDDS in the urological tumors up to November 1, 2023. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer and R-Bibliometrix. The major aspects of analysis included contributions from different countries/regions, authors' contributions, keywords identification, citation frequencies and overall research trends. Results: We included 3,220 articles. The analysis of annual publication trends revealed significant growth in this field since 2010, which has continued to the present day. The United States and China have far exceeded other countries/regions in the publication volume of papers in this field. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Mucoadhesive NDDS for intravesical drug delivery is a hotspot and a potential research material for bladder cancer. Conclusion: The field of NDDS in urological tumors has emerged as a research hotspot. Future research should focus on synergistic effects of NDDS with other treatment modalities. Article highlights NDDS studies for prostate, kidney and bladder cancers began to increase around 2010 and the number of studies has subsequently shown a steady increase. The United States and China have made major contributions to NDDS research in urologic tumors, including prostate, kidney, bladder, testicular and penile cancers. In the field of prostate cancer NDDS research, the largest research cluster was magnetic nanoparticles, while drug delivery represented an ongoing theme of research. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Early research in this field of renal cancer NDDS focused on cancer chemotherapy, cells, cytotoxicity, apoptosis and tissue distribution, whereas more recent studies have primarily concentrated on kidney microenvironment and survival benefits. Bladder cancer-related NDDS studies have focused on their penetration of the urinary epithelium and the retention time of therapeutic agents in the bladder. The evolution of NDDS is a significant hallmark of the continuous progress and optimization in the field of drug delivery, providing novel insights and directions for future drug development and therapy. A combination of multimodal synergistic therapy of NDDS with dynamic therapies or with radiotherapy, chemotherapy, immunotherapy and other treatment modalities could bring breakthroughs to treating urological tumors. [ABSTRACT FROM AUTHOR]

Introduction: With the advancement of surgical technology, the opportunity to integrate novel surgical preparation is imperative to improve patient outcomes and enhance safety. Methods: Patient specific perfused kidney phantoms including the tumor, parenchyma, artery, vein, and calyx were fabricated using 3D-printing and hydrogel injection molding from scans of 25 patients scheduled for robotic partial-nephrectomy (RAPN). Models are validated for anatomical accuracy, mechanical, functional properties and surrounded by the other models of relevant anatomy in a body cast for a simulated surgical rehearsal. We investigated the impact of these preoperative rehearsals preceding complex RAPN by analyzing changes in surgeons' decisions following review of both axial-imaging and following rehearsal simulation. Predictive ability of these rehearsal platforms was compared to live surgery outcomes and trifecta of cases as an outcome was calculated. Results: 25 patients with complex renal tumors, average 9.8 nephrometry score and 4.9 cm mean tumor diameter were consented. Mean blood loss and WIT were 193.2 ml and 19.8 min. Two Clavien 2 complications were reported at 30-day postoperative. Trifecta was achieved in 17 (68%) of surgical cases. Surgeons' confidence in their ability to complete a partial nephrectomy and ability to predict WIT significantly increased from initial viewing the axial imaging to after the rehearsal. The correlation coefficient between the procedural clinical data collected during the rehearsals and live surgery were calculated. Conclusion: The application of this versatile method for creating authentic perfused kidney phantoms can result in increased confidence in surgical plan and thus improved surgical performance and outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to investigate the intrafractional movement of the spinal cord and spinal canal during MR-guided online adaptive radiotherapy (MRgART) for kidney cancer. Materials and methods: All patients who received stereotactic MRgART for kidney cancer between February 2022 and February 2024 were included in this study. Patients received 30–42 Gy in 3-fraction MRgART for kidney cancer using the Elekta Unity, which is equipped with a linear accelerator and a 1.5 Tesla MRI. MRI scans were performed at three points during each fraction: for online planning, position verification, and posttreatment assessment. The spinal cord was contoured from the upper edge of Th12 to the medullary cone, and the spinal canal was contoured from Th12 to L3, using the first MRI. These contours were adjusted to the second and third MR images via deformable image registration, and movements were measured. Margins were determined via the formula "1.3×Σ+0.5×σ" and 95% prediction intervals. Results: A total of 22 patients (66 fractions) were analyzed. The median interval between the first and third MRI scans were 38 minutes. The mean ± standard deviation of the spinal cord movements after this interval were −0.01 ± 0.06 for the x-axis (right–left), 0.01 ± 0.14 for the y-axis (caudal–cranial), 0.07 ± 0.05 for the z-axis (posterior–anterior), and 0.15 ± 0.08 for the 3D distance, respectively. The correlation coefficients of the 3D distance between the spinal cord and the spinal canal was high (0.92). The calculated planning organ at risk volume margin for all directions was 0.11 cm for spinal cord. The 95% prediction intervals for the x-axis, y-axis, and z-axis were −0.11–0.09 cm, −0.23–0.25 cm and −0.14–0.03 cm, respectively. Conclusions: Margins are necessary in MRgART to compensate for intrafractional movement and ensure safe treatment delivery. [ABSTRACT FROM AUTHOR]

Purpose: Wilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT. Methods: Our study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations. Results: The in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies. Conclusion: This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma. [ABSTRACT FROM AUTHOR]

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated according to baseline levels and early dynamic changes of ALAT, ASAT, GGT and LDH. Multivariate Cox proportional hazard regression models were generated to identify independent prognosticators for PFS and OS. High baseline levels and non-normalized kinetics of ALAT, ASAT, GGT and LDH were significantly associated with shorter PFS and OS (p < 0.05), which was also reflected by lower response rates. Combining the four parameters at baseline into a 4-Risk-Score resulted in an enhanced prognostic power, as indicated by a higher C-index of 0.693 for OS compared to the individual parameters (≤ 0.663). Patients with all four risk factors present showed the worst PFS and OS. Overall, baseline levels and early kinetics of the four parameters as well as the 4-Risk-Score were identified as independent prognosticators for PFS and OS by multivariate analysis. As standard laboratory parameters, ALAT, ASAT, GGT and LDH are cost-effective and could be easily used either alone or in combination for therapy monitoring of CPI-treated mRCC patients. [ABSTRACT FROM AUTHOR]

Some special therapeutic responses may appear during immunotherapy, such as hyperprogression, pseudoprogression and so on. Dissociated response of immunotherapy has been clinically reported in recent years mainly in lung cancer and kidney cancer. Since there were poor prognosis and simple treatment of advanced head and neck cancer, the application of immunotherapy in head and neck cancer has risen in recent years. But the dissociated response of immunotherapy in head and neck cancer is rarely reported. We reported two series of cases of advanced head and neck cancer that showed dissociated response after immunotherapy, tumor progression was assessed by imaging methods such as PET-CT, enhanced CT and enhanced MR, and reviewed the literature related to dissociated response in immunotherapy. We propose that the dissociated response of immunotherapy may affect the treatment strategy of advanced head and neck cancer, but more clinical analyses and researches are needed to confirm it. [ABSTRACT FROM AUTHOR]

Background: Metastatic gastric tumors are rare and malignant melanoma, breast cancer, lung cancer, and esophageal cancer are common as primary lesions. On the other hand, renal cell carcinoma is easy to metastasize hematogenously to the whole body. However, metastasis to the stomach is rare and the detailed treatment of gastric metastasis is not mentioned. In this study, we report an uncommon case of gastric metastasis from renal cell carcinoma that underwent surgical full-thickness resection and reviewed the literature for treatment options. Case presentation: The patient was a female in her 60s and in January 2007, she underwent a transabdominal left nephrectomy for clear cell carcinoma of the left kidney. The pathological diagnosis was pT2N0M0 stage II. In October 2017, a total pancreatectomy with D2 dissection was performed for multiple pancreatic masses, in which the pathological diagnosis was pancreatic metastasis of renal cell cancer. In May 2019, an esophagogastroduodenoscopy for heartburn revealed redness and erosion in the greater curvature of the residual gastric body. The pathological diagnosis was gastric metastasis from renal cell carcinoma. No metastatic findings were observed and gastric wedge resection was performed. Pathological diagnosis of the resected specimen showed a 4-mm tumor, mainly within the mucosa and partly extended to the submucosal layer in 500 µm. The resected specimen had a clear resection margin. Conclusions: In this study, we report a case in which a full-thickness resection was performed for gastric metastasis 12 years after renal cancer surgery and 2 years after pancreatic metastasis surgery. The patient survived 4 years and 8 months after gastric wedge resection. Although gastric metastasis often takes the form of submucosal tumors, it is necessary to select full-thickness resection for R0 resection, even in small and flat lesions. [ABSTRACT FROM AUTHOR]

Urinary tumors pose a significant health threat because of their high prevalence and recurrence rates. Despite the availability of various treatment options, many patients poorly respond to traditional therapies, highlighting the urgent need for alternative approaches. Oncolytic viruses are promising therapeutic agents. These viruses exploit the unique characteristics of cancer cells to specifically target and destroy them, thereby triggering potent antitumor immune responses. This review delves into recent advancements and future prospects of oncolytic viruses, focusing on their application in renal, bladder, and prostate cancers. By discussing practical implications and the potential of different viruses, including the cowpox virus, adenovirus, measles virus, coxsackievirus, and reovirus, we pave the way for further exploration and refinement of this exciting field. [ABSTRACT FROM AUTHOR]

Purpose: Evaluation of a kidney-adjusted enhanced recovery after surgery (ERAS®) protocol (kERAS) in patients undergoing nephron-sparing surgery (PN). Methods: The kERAS protocol is a multidimensional protocol focusing on optimized perioperative fluid and nutrition management as well as strict intraoperative and postoperative blood pressure limits. It was applied in a prospective cohort (n = 147) of patients undergoing open or robotic PN. Patients were analyzed for the development of acute postoperative renal failure (AKI), achievement of TRIFECTA criteria, upstaging or new onset of chronic kidney disease (CKD) and length of hospital stay (LOS) and compared to a retrospective cohort (n = 162) without application of the protocol. Results: Cox regression analyses could not confirm a protective effect of kERAS on the development of AKI post-surgery. A positive effect was observed on TRIFECTA achievement (OR 2.2, 95% CI 1.0-4.5, p = 0.0374). Patients treated with the kERAS protocol showed less long-term CKD upstaging compared to those treated with the standard protocol (p = 0.0033). There was no significant effect on LOS and new onset of CKD. Conclusion: The implementation of a kERAS protocol can have a positive influence on long-term renal function in patients undergoing PN. It can be used safely without promoting AKI. Furthermore, it can be realized with a manageable amount of additional effort. [ABSTRACT FROM AUTHOR]

Background and aims: The effects of metabolic obesity (MO) phenotypes status and their dynamic changes on urologic cancer (UC) is ignored. We aimed to investigate the association between metabolic syndrome (MetS) and MO status at baseline, their dynamic changes and UC risk. Methods: This paper studied 97,897 subjects who were free of cancers at baseline (2006−2007). Individuals were classified into four MO phenotypes by MetS and obesity at baseline. Transitions in MetS and MO status from 2006–2007 to 2008–2009 were considered. The hazard ratios (HRs) and 95% confidence intervals (CIs) for UC were assessed by multifactorial Cox proportional risk regression models. The main limitations of this study are as follows: the ratio of men to women in the cohort is unbalanced; the impacts of MetS and MO on each cancer type (kidney cancer, prostate cancer, bladder cancer) have not been analyzed separately; the transition intervals of MetS and MO phenotypes are relatively short. Results: From baseline (2006–2007) survey to December 31, 2020, during a median follow-up of 14.02 years, 554 cases of UC were diagnosed. Participants with MetS [HRs (95% CI) = 1.26 (1.06–1.49)] and metabolically unhealthy obesity (MUO) [HRs (95% CI) = 1.49 (1.17–1.89)] had significantly higher risk of UC than those with non-MetS and metabolically healthy normal weight (MHN). Transitions in MetS and MO phenotypes over time were studied. Compared with non-MetS to non-MetS, the risks for UC in MetS to MetS [HRs (95% CI) = 1.45 (1.11–1.88)] was increased. Compared with MHN to MHN, both MUO to metabolically healthy obesity (MHO) [HRs (95% CI) = 2.65 (1.43–4.92)] and MUO to MUO [HRs (95% CI) = 1.60 (1.06–2.42)] had significantly higher UC risk. Conclusions: MetS and MUO increased the UC risk at baseline. Transitions of MetS to MetS, MUO to MUO and even MUO to MHO over time significantly increased the risk of UC development. [ABSTRACT FROM AUTHOR]

Evaluating the risk factors for the conversion from robotic-assisted partial nephrectomy (RAPN) to radical nephrectomy (RN). Through a comprehensive database search encompassing PubMed, Web of Science, Embase, and the Cochrane Library, we identified pertinent English-language research published by June 2024. We utilized the NOS scale for quality assessment. The aggregate effect was quantified via the odds ratio (OR), alongside a 95% confidence interval (CI). Sensitivity analyses were conducted using both fixed-effects and random-effects models to evaluate reliability. The meta-analytical process was facilitated by the Stata 18 software suite. Our meta-analysis encompassed a total of 8 retrospective studies and 3 prospective studies, totaling 4056 patients. We found that increasing patient age (OR: 1.04; 95% CI 1.00–1.08; P = 0.005), higher American Society of Anesthesiologists (ASA) scores (3 or above) (OR: 2.74; 95% CI 1.52–4.93; P = 0.001), elevated R.E.N.A.L. scores (7 or above) (OR: 2.49; 95% CI 1.57–3.95; P < 0.001), and the use of off-clamp RAPN (OR: 7.21; 95% CI 2.60–19.93; P < 0.001) significantly raised the odds of surgical conversion. On the other hand, male sex (OR: 1.04; 95% CI 0.67–1.62; P = 0.858), the side of the tumor (OR: 0.97; 95% CI 0.48–1.95; P = 0.936), tumor size (OR: 3.43; 95% CI 0.57–20.55; P = 0.177), body mass index (BMI) (OR: 1.03; 95% CI 0.96–1.11; P = 0.426), clinical stage (OR: 3.78; 95% CI 0.46–30.70; P = 0.214), and the use of single-port RAPN (OR: 0.54; 95% CI 0.16–1.78; P = 0.31) did not show a statistically significant link to an increased conversion risk. This meta-analysis elucidates the critical risk factors for the conversion from robotic-assisted partial nephrectomy to radical nephrectomy, providing significant guidance for preoperative risk assessment and clinical decision-making. However, our findings necessitate validation through studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

Background: Synchronous occurrence of prostate cancer (PCa) and renal cell carcinoma (RCC) is uncommon. RCC has a higher tendency to metastasize to the adrenal glands, renal hilar, and retroperitoneal lymph nodes compared to PCa. To date, there are no documented cases existing where metastatic tumors in these regions, observed in patients concurrently with PCa and RCC, have originated from the PCa rather than the RCC. Case presentation: In this case report, we described a 67-year-old male presented with dysuria for two months and left lower extremity edema for three days. Percutaneous biopsies revealed synchronous primary RCC and PCa. However, the origin of the metastatic tumors, especially those involving the adrenal glands, renal hilum, and retroperitoneal regions, remained undetermined. Subsequent surgical procedures identified that the metastatic lesions originated from the PCa, while the RCC was localized. Ultimately, the patient with metastatic hormone-sensitive prostate cancer (mHSPC) received combination therapy with rezvilutamide and goserelin, which resulted in a satisfactory treatment response. Conclusion: In patients with concurrent PCa and RCC, metastatic lesions in the adrenal glands, renal hilar, and retroperitoneal lymph nodes may also originate from the PCa. Accurate identification of the primary tumor and proper staging are critical for the appropriate management of patients with multiple primary malignancies with concurrent metastases. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive. Methods: By leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays. Results: Our investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth. Conclusion: Our findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment. [ABSTRACT FROM AUTHOR]

Recent progress in elucidating the role of specific antidiuretic hormones in Drosophila models has provided valuable insights into the mechanisms underlying tumor-induced renal dysfunction. Xu et al. identified the mammalian neurokinin 3 receptor (TACR3), a homolog of the G protein-coupled receptor TkR99D in fruit flies, as a potential therapeutic target for alleviating renal tubular dysfunction in mice with malignant neoplasms. Here, we commented on these findings by emphasizing the structural and evolutionary significance of TACR3 and provided an in-depth analysis of cell type specific expression of TACR3 in response to renal injury and expressional dynamics during renal carcinoma progression. The implications of these findings for transforming the therapeutic approaches to renal complications associated with oncological disorders were highlighted. We also acknowledged the limitations of current experimental models in this study and emphasized the necessary clinical validation in the future. These insights could contribute to the advancement of diagnostic and therapeutic strategies for treating tumor-related renal pathologies. Take home message: Recently, the neurokinin 3 receptor (TACR3) has emerged as a crucial factor of renal dysfunction among cancer patients, suggesting its potential as a target for innovative therapeutic intervention. Our analysis delves into the evolutionary insights of TACR3 from multiple studies on both Drosophila and mammals. We elucidate the role of TACR3 in renal pathologies by integrating multi-omics datasets and conducting a thorough phylogenetic and structural analyses. [ABSTRACT FROM AUTHOR]

Purpose: To clarify specific factors associated with surgical outcomes in robot-assisted partial nephrectomy (RAPN) that require extended warm ischemia time (WIT), which may have a negative impact, but cannot always be avoided. Methods: We included 1,182 patients who had RAPN performed between January 2016 and December 2022 from a prospectively generated multi-institutional RAPN database, divided into normal WIT (nWIT) (≤ 20 min; 843 patients) and extended WIT (eWIT) (> 20 min; 339 patients) groups. Primary outcome measures were WIT and the Surface-Intermediate-Base (SIB) margin score, which contribute to postoperative trifecta achievement. Results were compared between the two groups using logistic regression. Results: Patients in the eWIT group had larger tumors, higher RENAL nephrometry scores, and lower SIB scores than those of the nWIT group. The trifecta achievement rate was significantly different between the two groups (nWIT: 70.1 vs. 49.0%, p < 0.001). In the nWIT group, WIT (coefficient: -0.105 [standard error 0.020], p < 0.001) and SIB score (coefficient: -0.107 [0.053], p = 0.045) were significant predictors of trifecta achievement. In the eWIT group, the SIB score (coefficient − 0.216 [0.082], p = 0.008) was significantly associated with trifecta attainment, whereas WIT only showed a trend toward significance. Limitations included a lack of long-term survival, renal function, and chronic complications data. Conclusions: For patients with eWIT during RAPN, the tumor dissection technique may be more important than WIT in predicting postoperative outcomes. Further prospective studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Methods: Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Results: Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. Conclusions: During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common. [ABSTRACT FROM AUTHOR]

The mTOR inhibitor everolimus has been approved as a sequential or second‐line therapy for renal cell carcinoma (RCC). However, the development of drug resistance limits its clinical applications. This study aims to address the challenge of everolimus resistance and provide new insights into the treatment of advanced RCC. Here, the cytotoxicity of the DNA methyltransferase 1 (DNMT1) inhibitor SGI‐1027 in inducing cell vacuolation and methuosis is discovered and demonstrated for the first time. Additionally, SGI‐1027 exerts synergistic effects with everolimus, as their combination suppresses the growth, migration, and invasion of renal cancer cells. Mechanistically, apoptosis and GSDME‐dependent pyroptosis triggered by lysosomal membrane permeability (LMP) are observed. The upregulation of GSDME expression and increased lysosomal activity in renal cancer cells provide a therapeutic window for the combination of these two drugs to treat renal cancer. The combination treatment exhibits effective anti‐tumor activity and is well tolerated in a subcutaneous tumor model. Overall, this study validates and reveals the specific cytotoxicity property of SGI‐1027 and its potent synergistic effect with everolimus, offering new insights into advanced RCC therapy and everolimus‐resistance overcoming. [ABSTRACT FROM AUTHOR]

Background: Growing evidence shows that ultra-processed food consumption is associated with the risk of cancer. However, prospective evidence is limited on renal cell carcinoma (RCC) incidence and mortality. In this study, we aimed to examine the association of ultra-processed food consumption and RCC incidence and mortality in a large cohort of US adults. Methods: A population-based cohort of 101,688 participants were included from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed food items were confirmed by using the NOVA food classification system. The consumption of ultra-processed food was expressed as a percentage of total food intake (g/day). Prospective associations were calculated using Cox regression. Restricted cubic spline regression was used to assess nonlinearity. Subgroup analyses were performed to investigate the potential effect modifiers on the incidence and mortality of RCC. Results: A total of 410 participants developed RCC during a total of 899,731 person-years of follow-up (median 9.41 years) and 230 RCC deaths during 1,533,930 person-years of follow-up (median 16.85 years). In the fully adjusted model, participants in the highest compared with the lowest quintiles of ultra-processed food consumption had a higher risk of RCC (HR quartile 4 vs 1:1.42; 95% CI: 1.06–1.91; Ptrend = 0.004) and mortality (HR quartile 4 vs. quartile 1: 1.64; 95% CI: 1.10–2.43; Ptrend = 0.027). Linear dose–response associations with RCC incidence and mortality were observed for ultra-processed food consumption (all Pnonlinearity > 0.05). The reliability of these results was supported by sensitivity and subgroup analyses. Conclusion: In conclusion, higher consumption of ultra-processed food is associated with an increased risk of RCC incidence and mortality. Limiting ultra-processed food consumption might be a primary prevention method of RCC. [ABSTRACT FROM AUTHOR]

Tumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic "bloating" of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6- like oncokines that perturb renal water-transporting cells and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units. [ABSTRACT FROM AUTHOR]

Giant cell glioblastoma often exhibits genome instability and is frequently associated with mutations in genes involved in DNA repair pathways including TP53 and DNA mismatch repair genes. Several germline mutations have been identified in giant cell glioblastoma, including mutations of MSH1 and MSH2, TP53, and POLE. We have documented a case of a germline mutation in CHEK2, another gene crucial to DNA repair, in a patient with giant cell glioblastoma. The CHEK2 mutation was inherited from the patient's father, who had a history of gastric cancer and renal cell carcinoma. In addition to the germline CHEK2 mutation, the giant cell glioblastoma exhibited a genome-wide loss of heterozygosity, a characteristic observed in a subset of giant cell glioblastomas. Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease. [ABSTRACT FROM AUTHOR]

Introduction: To assess differences in referral and pathologic outcomes for uro-oncology cases prior to, during, and after the COVID-19 pandemic, comparing clinical and pathological data from cancer surgeries performed at a university medical center between 2018 and 2023. Methods: We collected data of 212 patients with radical prostatectomy (RP) for prostate cancer, 157 patients with radical cystectomies (RCs) for bladder cancer, 36 patients with radical nephroureterectomies (RNUs) for upper tract urothelial carcinoma, 133 patients with partial nephrectomies (PNs), and 160 patients with radical nephrectomies (RNs) for renal cancer, 93 patients with orchifunicolectomy for testicular cancer, 39 patients with newly diagnosed penile cancer. Data from patients treated between 2018 and February 2020 (before the COVID-19 pandemic) were compared with data from patients treated between March 2020 and March 2022 (during the COVID-19 pandemic) and between April 2022 and February 2023 (after the COVID-19 pandemic). Results: No differences in terms of main pathologic features were observed in patients undergoing RP, RNU, orchifunicolectomy, or circumcision and/or penectomy. Further, a lower pathological tumor stage was diagnosed for RN after the COVID-19 pandemic (p < 0.05). A higher age at diagnosis for penile cancer was observed during the pandemic cohort in comparison to the pre-COVID-19 pandemic cohort (p < 0.05), but this did not translate into a worse pathological stage or lymph node involvement. Another notable change was the shortening of the length of stay (LOS) for orchifunicolectomy over the pandemic (p < 0.05). Conclusion: Neither decline in uro-oncologic activity nor pathological features were observed at our institution before, during, and after the COVID-19 pandemic. A significantly lower pathological tumor stage for RN after the COVID-19 pandemic was seen. Penile cancer was diagnosed at a significantly higher age during the COVID-19 pandemic, and a decrease in LOS for orchifunicolectomy was observed. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers. Methods: We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy. Results: After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10−4 ≤ P < 0.05). Conclusion: Our study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies. [ABSTRACT FROM AUTHOR]

Introduction: Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer in adults, presents significant challenges owing to its resistance to conventional therapies. Standard treatment primarily revolves around surgical methods, particularly nephrectomy, which is critical for managing localized diseases. Despite recent advancements, the metastatic potential of ccRCC necessitates ongoing vigilance in postoperative monitoring to manage and detect disease recurrence. Recent shifts in treatment paradigms, especially with the integration of molecular patterns in ccRCC, have enabled the development of targeted therapies. Immune checkpoint and tyrosine kinase inhibitors (TKIs) have become central to managing metastatic ccRCC, offering new hope through improved survival outcomes. Recent studies have corroborated this by demonstrating the benefits of combining these therapies. Case Presentation: This report discusses a case study of a patient with high-grade ccRCC and thyroid metastases initially deemed non-resectable. The combination of immunotherapy and TKIs reduced tumor size, transforming the thyroid metastasis to a resectable state. Conclusion: This case highlights significant advancements in treatment approaches and the critical in the management of ccRCC, underscoring the necessity for continuous adaptation of clinical practices to incorporate new therapeutic developments. [ABSTRACT FROM AUTHOR]

Background: We report two cases of fungal endophthalmitis induced by Candida species identified based on internal transcribed spacer 1 (ITS1) sequencing. Case presentation: In two cases, endophthalmitis was suspected, and the patients underwent pars plana vitrectomy. Case 1 was a 64-year-old woman with a history of cataract surgery 10 days prior. She had a history of anal primary melanoma, which metastasized throughout the body and subsequently relapsed. Vitreous culture and ITS-1 deep sequencing revealed the presence of the rare fungus, Candida dubliniensis. Case 2 was a 54-year-old man with a history of liver cancer and kidney failure. Culture methods and ITS1 deep sequencing both revealed the presence of Candida albicans. Both patients exhibited good visual prognoses after treatment with topical and systemic antibiotics. Conclusions: We present two cases of fungal endophthalmitis caused by two Candida species identified by both the culture method and ITS1 deep sequencing. The fungal pathogen was identified by ITS deep sequencing three days after sample submission; the culture method yielded results after 1 week. These findings support the applicability of ITS1 sequencing for timely pathogen identification for cases of fungal endophthalmitis and provide detailed taxonomic information at the species level. [ABSTRACT FROM AUTHOR]

CRISPR is revolutionizing the ability to do somatic gene editing in mice for the purpose of creating new cancer models. Inactivation of the VHL tumor suppressor gene is the signature initiating event in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). Such tumors are usually driven by the excessive HIF2 activity that arises when the VHL gene product, pVHL, is defective. Given the pressing need for a robust immunocompetent mouse model of human ccRCC, we directly injected adenovirus-associated viruses (AAVs) encoding sgRNAs against VHL and other known/suspected ccRCC tumor suppressor genes into the kidneys of C57BL/6 mice under conditions where Cas9 was under the control of one of two different kidney-specific promoters (Cdh16 or Pax8) to induce kidney tumors. An AAV targeting Vhl, Pbrm1, Keap1, and Tsc1 reproducibly caused macroscopic ccRCCs that partially resembled human ccRCC tumors with respect to transcriptome and cell of origin and responded to a ccRCC standard-of-care agent, axitinib. Unfortunately, these tumors, like those produced by earlier genetically engineered mouse ccRCCs, are HIF2 independent. [ABSTRACT FROM AUTHOR]

Background The population with kidney failure is at increased risk of cancer and associated mortality. Relative survival can provide insight into the excess mortality, directly or indirectly, attributed to cancer in the population with kidney failure. Methods We estimated relative survival for people all ages receiving dialysis (n  = 4089) and kidney transplant recipients (n  = 3253) with de novo cancer, and for the general population with cancer in Australia and New Zealand (n  = 3 043 166) over the years 1980–2019. The entire general population was the reference group for background mortality, adjusted for sex, age, calendar year and country. We used Poisson regression to quantify excess mortality ratios. Results Five-year relative survival for all-site cancer was markedly lower than that for the general population for people receiving dialysis [0.25, 95% confidence interval (CI) 0.23–0.26] and kidney transplant recipients (0.55, 95% CI 0.53–0.57). In dialysis, excess mortality was more than double (2.16, 95% CI 2.08–2.25) that of the general population with cancer and for kidney transplant recipients 1.34 times higher (95% CI 1.27–2.41). There was no difference in excess mortality from lung cancer between people with kidney failure and the general population with cancer. Comparatively, there was a significant survival deficit for people with kidney failure, compared with the general population with cancer, for melanoma, breast cancer and prostate cancers. Conclusion Decreased cancer survival in kidney failure may reflect differences in multi-morbidity burden, reduced access to treatment, or greater harm from or reduced efficacy of treatments. Our findings support research aimed at investigating these hypotheses. [ABSTRACT FROM AUTHOR]