Renal Cancer Research Articles

Comparative Proteomics of ccRCC Cell Lines to Identify Kidney Cancer Progression Factors.

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. 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. 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. From the global proteomics data detected in ccRCC, we propose 99 DEPs including vimentin as progression factors.

Gastric metastasis from renal cell carcinoma with submucosal invasion treated by surgical full-thickness resection: a case report

BackgroundMetastatic 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 presentationThe 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.ConclusionsIn 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.

Association of hypertension and the risk of cancer: a study based on the UK Biobank

Abstract Introduction With the increasing incidence rate of hypertension and carcinoma, there is a growing interest in investigating the potential link between these two diseases. The subdiscipline of hypertension, Onco-hypertension, has been proposed and attracted much attention. However, there are still few researches on this subdiscipline. Purpose This study aims to investigate the relationship between hypertension and the occurrence of cancer. Additionally, we explore whether anti-hypertensive treatment has any impact on the incidence of cancer. Methods This study involved 244,496 participants recruited between 2006-2010 from the UK Biobank, with 21,765 participants were diagnosed with the hypertension according to the ICD10 coding. The Cox regression was used to analyse the the risk of cancer associated with hypertension. The effect of anti-hypertensive treatment on the occur of cancer was also verified according to the Cox regression and the Drug target Mendelian randomization. Results Compared to those participants without hypertension, those people with hypertension have higher risk of the occur of cancer(adjusted hazard ratio(aHR) 1.35, 95% confidence interval(CI)1.3-1.4), especially in breast cancer(aHR 1.43, 95% CI 1.27-1.61), prostate cancer(aHR 1.85, 95% CI 1.7-2.02), lung cancer(aHR 2.15, 95% CI 1.86-2.48), renal cancer(aHR 1.91, 95% CI 1.46-2.49), pancreas cancer(aHR 1.55, 95% CI 1.2-2). Compared to those people with hypertension but without anti-hypertensive treatment, the anti-hypertensive treatment increase the cancer risk(aHR 1.19, 95% CI 1.06-1.33). However, thiazide diuretic have protect effect for hypertension patients on occur of the prostate cancer (aHR 0.74, 95% CI 0.61-0.89) and beta-receptor blocker have protect effect for hypertension patients on occur of the lung cancer (aHR 0.71, 95% CI 0.54-0.93). The result of Drug target Mendelian randomization shows the anti-hypertensive treatment have no significant effect on the risk of cancer. Conclusion The onset of high blood pressure is linked to an elevated risk of several cancers. However, it cannot be conclusively determined whether the use of medications for high blood pressure increases or decreases the overall risk of cancer. This study provides instructive evidences for the further study of Onco-hypertension.The result of main analyseThe analyse of the antihypertensive drug

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Direct annual healthcare costs in survivors of acute pulmonary embolism: estimates based on a prospective multicentre cohort study

Abstract Background Patients surviving acute pulmonary embolism (PE) necessitate long-term care and follow-up. However, the economic impact of PE on healthcare systems after the acute event remains largely unknown. Purpose To estimate the direct cost of PE during the first year after discharge from hospital for the index event, focusing on rehospitalizations, anticoagulant medication, and outpatient follow-up. Methods We analyzed the data from a multicentre cohort study of 1017 unselected patients with confirmed acute symptomatic PE in Germany. After the index episode, the costs of which were not considered, patients prospectively followed an outpatient visit plan at 3, 12 and 24 months. All rehospitalisations were documented with the main and accompanying diagnoses; hospital costs were calculated based on current reimbursement in the German Diagnosis Research Groups (G-DRG) system. The duration and type (central unique drug identifier) of anticoagulant treatment was documented at each visit. Per-patient costs of ambulatory follow-up visits and tests were calculated by multiplying (i) the costs of each visit/test (German ambulatory healthcare services reimbursement catalogue) by (ii) the probability π (0.0≤π≤1.0) of needing that specific service, based on the PE follow-up algorithm of the ESC Guidelines which we populated with the actual results per step in the present study (Figure). The primary analysis was conducted in all patients with ≥3-month follow-up. An additional sensitivity analysis included only the patients completing ≥12-month follow-up. We additionally identified the baseline predictors for the number of rehospitalizations and costs using multivariable zero-inflated Poisson and hurdle regression and accounting for censored data. Results Of 1017 enrolled patients, 958 (94%) were included in the primary analysis. Of them, 24% were rehospitalized, for a marginal mean of 0.34 (bootstrapped 95% CI: 0.30-0.39) readmissions per PE survivor. Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis) cancer, emerged as independent cost predictors by multivariable hurdle gamma regression (Table). Estimated overall rehospitalisation costs were €1138 (95% CI 896-1420) per patient (€1171 [908-1479] in the sensitivity analysis). Mean anticoagulation duration was 330 days, with estimated per-patient costs of €1050 (€1190 in the sensitivity analysis). Per-patient costs of ambulatory follow-up visits and tests were estimated at €182, yielding a total cost of illness per PE survivor of €2370-2543. For the entire country, the annual direct costs after acute PE would thus amount to €202-217 million. Conclusions By estimating per-patient costs and identifying major cost drivers of post-PE care, the present study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved overall cardiovascular prevention.TableFigure

What does routinely-collected electronic health record data tell us about the use of heart failure medication among older people in Wales? Making progress but could do better

Abstract Background European Society of Cardiology 2021 guidelines recommend 4 pillars of treatment to reduce mortality for those with heart failure (HF) and reduced ejection fraction (HFrEF): pillar 1) angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), pillar 2) beta-blocker (BB), pillar 3) mineralocorticoid receptor antagonist (MRA), pillar 4) sodium-glucose co-transporter 2 inhibitor (SGLT2i). When there is heart failure with preserved ejection fraction (HFpEF), guidelines recommend diuretics to alleviate congestion and treatment of risk factors such as hypertension and diabetes. Prior to 2021, United Kingdom guidelines did not include SGLT2i. Purpose To examine how HF treatment is recorded in routinely-collected electronic health record (EHR) data for older people in Wales, and to explore how that has changed since 2015. Methods We conducted a retrospective, population-level, observational study using linked anonymised EHR data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period (21.5% of population in 2022). Of these, 65,010 had a code for heart failure in their primary or secondary care records. We excluded 13,990 individuals with fewer than 12 months data pre- or post-diagnosis. We looked forward, from HF diagnosis, for codes associated with specific medications. Results The final cohort comprised 51,020 individuals aged 65y and over with a diagnosis of heart failure between 2015-2022. Incidence and prevalence of heart failure increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Preceding cardiovascular diagnoses included hypertension (69.5%), atrial fibrillation (36.7%), myocardial infarction (30.5%), coronary artery disease (25.7%), and valve disease (17.7%). Diabetes (41.7%), chronic kidney disease (30.9%) and cancer (26.4%) were the most common comorbidities. The subtype of HF (HFrEF or HFpEF) was only evident in 5,850. Treatments recorded most often were loop diuretics, ACE-I, and BB (Table 1). SGLT2i codes increased in 2020/2021(Figure 1). At 10-12 months post diagnosis, the proportion with simultaneous pillar combinations was; 27.4% 1 + 2, 12.5% 1, 2 + 3, and only 2% 1, 2, 3 + 4. Conclusions In Wales, there is a need to improve the coding of HF subtype in primary care records. We suggest interpreting data with the assumption that approximately half of the cohort are likely to have HFrEF. While the cohort proportion on ACE-I or beta-blockers may be appropriate, the proportion with more than 1 simultaneous pillar of treatment recorded appears low. The use of SGLT2i in codes is increasing. These results are important in evaluating health service delivery and in establishing baseline data from which to monitor improvements.

Cancer incidence associations with drinking water arsenic levels and disinfection methods in Maine, USA

ABSTRACT Maine is a largely rural state where nearly half of the population uses drinking water from private wells. Arsenic (As) is present in some groundwater in the state and has been linked to cancer, and a lack of testing and treatment may expose people with private wells to elevated As levels. Disinfection byproducts (DBPs) include known and suspected carcinogens that form when chlorine or chloramines are added to water. People served by public water systems may be exposed to elevated levels of regulated DBPs such as trihalomethanes and haloacetic acids associated with chlorine and/or unregulated nitrogenous DBPs, or N-DBPs, such as nitrite and N-nitrosodimethylamine associated with chloramines. Contrary to initial expectations, there were no significant associations between median town As in well water and bladder, lung, kidney, or skin cancer incidence. Furthermore, bladder, melanoma, and other skin cancer incidence rates were negatively correlated with the percent of the town population using private wells. Analysis of cancer incidence associated with chlorine and chloramine disinfection showed elevated melanoma, and other skin cancer with chloramine use and elevated bladder and non-melanoma skin cancer with chlorine use compared to the no disinfectant case. We recommend more research on the links between disinfectant use and cancer.

Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors: a prospective multimodal cardiovascular assessment (AMICI study)

Abstract Background Immune checkpoint inhibitors (ICIs) are transformative treatments in oncology, yet they are also associated with a range of cardiovascular (CV) events. Purpose To identify the incidence of CV events (including subclinical) in patients receiving ICIs for solid cancer, either alone or in association with other cancer therapies (e.g., chemotherapies, target therapies). Objectives and methods The Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors(AMICI) study prospectively assessed the incidence of CV changes by means of a thorough multimodal assessment. This included repeated CV imaging (transthoracic echocardiograms (TTE), cardiac magnetic resonance imaging (CMR)), serum biomarkers (troponin, brain natriuretic peptides in a single laboratory), and ambulatory ECG monitoring, before and during (at 6 weeks and at 6 months) ICI therapy (Figure). Cardiovascular events included myocarditis, pericarditis, acute coronary syndrome, heart failure (HF), high degree conduction abnormalities (defined as new grade 2 or 3 atrioventricular block) or sustained ventricular arrhythmias (defined as 3 or more ventricular beats at a rate ≥ 120/min), CV death as a composite endpoint, validated by an independent expert panel Results Out of 130 solid cancer patients considered for ICI therapy, 49 patients (38 (77.6%) male; mean age 64.3 (­SD 11.0) years old) were included (June 2020 -December 2021). 22 (55.1%) suffered from kidney or bladder cancer; 7 (14.3%) had CV disease prior to cancer diagnosis; 4 (8.2%) received PD1 and CTLA4 inhibitors. Early CV events were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P=0.035) predicted early CV events at 6 weeks (Table). At 6 months follow-up, 18 CV events were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias or conduction disorders and 4 (8.2%) AF. There was a significant decline in LVEF (P<0.001) in patients even in the absence of CV event (P=0.003) or HF (P=0.003). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P=0.006) predicted HF. Conclusions Cardiovascular complications arising during cancer treatment with ICIs are primarily due to the exacerbation of pre-existing HF or the onset of non-inflammatory heart rhythm disorders. The majority of these CV changes manifest shortly after starting ICIs and do not need hospital admission. Our results suggest that more close follow-up may be needed in patients with underlying CV conditions when starting ICI therapy, by means of CMR and ambulatory ECG holter monitoring.

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

ZSTK474 targeting PIK3R3 inhibits the Wilms' tumor through G0 / G1 phase arrest.

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. 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. 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. This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.

Application of irreversible electroporation ablation in oncology - a narrative review

Irreversible electroporation-IRE is an innovative cancer treatment method that can selectively destroy cancer cells without damaging surrounding tissues. It is a safe and effective alternative to traditional methods, with the patient faster recover potential and spare critical body structures such as blood vessels and nerves.In surgical oncology, the IRE treatment technique is used especially in cases where other methods are not possible or have limited effectiveness. The method is proving to be seen as an effective local treatment with good clinical results and limited side effects in prostate, biliary, pancreatic, kidney and liver cancers.

Clinical characteristics of renal anastomotic hemangioma.

In this editorial, we comment on the article by Chen and Cai. We focus on renal anastomotic hemangioma, which is a rare benign hemangiomatous disease. This disease has unique clinical characteristics. Its biological behavior is benign, but its imaging results are similar to those of renal cancer. Renal anastomotic hemangioma is easy to misdiagnose and can lead to unnecessary radical nephrectomy. Therefore, urologists need a better understanding of this disease. We believe that patients with renal anastomotic hemangioma should receive individualized diagnosis and treatment to avoid overtreatment.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy

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.

Update on Tumor Genetics and Molecular Biology of Selected Renal Cell Carcinomas: Implications on Diagnosis and Management

Recent advances in genetics, molecular pathology and oncology have led to discovery of specific genetic changes and distinctive metabolic pathways that contribute to tumorigenesis as well as determine the biological behavior and imaging findings of a multitude of renal cell carcinomas. Multiphase CT and multiparametric MRI play major roles in the detection, localization, characterization, staging, surveillance, and follow-up of kidney cancers. While some imaging features are characteristic enough to suggest a tissue diagnosis, histopathology is required for definitive diagnosis, treatment, and prognostication.

EFFICACY OF NEOADJUVANT TARGETED THERAPY IN TREATMENT OF PATIENTS WITH LOCALISED CLEAR-CELL RENAL CELL CARCINOMA

Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, accounting for approximately 75-80% of all renal malignancies. Objectives: The main objective of the study is to find the efficacy of neoadjuvant targeted therapy in the treatment of patients with localised clear-cell renal cell carcinoma. Methods: This prospective study was conducted at Mardan Medical Complex from June 2023 to January 2024. Data were collected from 85 patients. Patients aged&gt;18 years and have a histologically confirmed diagnosis of localized ccRCC were included in the study. Tumor size was required to be 4 cm or larger, but confined to the kidney, corresponding to Stage I to III disease. Results: Data were collected from 85 patients with an average baseline tumour size for the entire cohort was 7.5 cm, and after 12 weeks of treatment, tumours shrank to an average of 5.6 cm, resulting in a mean tumour reduction of 25%. In the sunitinib group, the tumour size decreased from 7.5 cm to 5.55 cm, reflecting a 26% reduction. Similarly, in the pazopanib group, the tumour size was reduced from 7.5 cm to 5.65 cm, with an average reduction of 24%. Conclusion: It is concluded that neoadjuvant targeted therapy, using agents such as sunitinib and pazopanib, effectively reduces tumour size and improves surgical outcomes in patients with localized clear-cell renal cell carcinoma.

Meta-analysis and systematic review of factors predicting conversion to radical nephrectomy following robotic-assisted partial nephrectomy in renal cancer patients.

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.

Increased risk of genitourinary cancer in kidney transplant recipients: a large-scale national cohort study and its clinical implications.

To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications. Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia. We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population. This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field.

Differentiation fate of a stem-like CD4 T cell controls immunity to cancer.

The T cell response to cancer controls disease progression and response to immunotherapy1-3. Despite extensive knowledge regarding CD8 T cells, how CD4 T cells contribute to this process is less well understood. Here we identified a population of PD1+TCF1+ CD4 T cells with stem-like properties that are capable of self-renewal and differentiation into canonical CD4 effector cells. Primarily residing in tumour-draining lymph nodes (TDLNs), these tumour-specific CD4 T cells are restricted by T regulatory (Treg) cells to a stem-like fate that predominantly generated induced Treg (iTreg) cells, limiting effector CD8 T cell responses to the tumour. By contrast, upon Treg depletion, stem-like CD4 T cells differentiated into T helper 1 (TH1) cells, and via IFNγ production induced robust effector differentiation from TCF1+ CD8 T cells in TDLNs, a state we defined as 'active'. Notably, enforcing TBET expression in transferred stem-like CD4 T cells was sufficient to overcome the established restricted T cell state. Despite the presence of Treg cells, endogenous stem-like CD4 T cells actively generated TH1 cells, which were required to restore TDLN effector CD8 T cell differentiation, enhance tumour control and rescue response to immunotherapy. In agreement, TH1 differentiation in patients with kidney cancer predicted successful immunotherapy responses and improved progression-free survival. Together, these findings identify a stem-like CD4 T cell population that through alternative differentiation fates controls the switch between restricted and active T cell states with implications for cancer immunotherapies.

Source free domain adaptation for kidney and tumor image segmentation with wavelet style mining

Kidney cancer is a serious malignant disease, and early diagnosis along with precise segmentation are crucial for effective treatment. However, due to the scarcity of labelled medical image data, the development of the intelligent diagnosis of kidney cancer is restricted. To address this challenge, we propose a novel unsupervised domain adaptation (UDA) framework specifically designed for kidney and tumor CT image segmentation. Our framework consists of a generation phase and an adaptation phase. In the generation phase, we employ a wavelet-based style mining generator to create class-specific source-like images, facilitating domain alignment. In the adaptation phase, we introduce contrastive domain extraction and compact-aware domain consistency modules, enhancing feature-level and output-level adaptability through data augmentation techniques. Experimental results demonstrate that our method performs better in kidney and tumor segmentation tasks, exhibiting higher accuracy and generalization capability than state-of-the-art domain adaptation methods. This indicates that our approach has significant advantages in medical image segmentation for kidneys and tumors.

Striving for Equity: Examining Health Disparities in Urologic Oncology

Health disparities in urologic oncology, particularly in prostate, bladder, kidney, and testicular cancers, significantly impact patient outcomes across different demographic groups. This narrative review aims to investigate the extent and drivers of these disparities, focusing on the influence of race, socioeconomic status, and geographic location on diagnosis, treatment, and survival outcomes. We conducted a comprehensive review of the existing literature and analyzed data from national cancer databases to identify patterns of inequity. Our findings reveal that minority populations, individuals with lower socioeconomic status, and those residing in underserved areas are less likely to receive timely and guideline-based care, leading to worse outcomes. This review underscores the urgent need for targeted interventions, including policy reforms, health system restructuring, enhanced community outreach, and increased funding for disparity-focused research, to ensure equitable access to high-quality oncologic care. Addressing these disparities is crucial for improving cancer outcomes and achieving health equity in urologic oncology.