Renal Carcinoma Research Articles

The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers

The genetic landscape of urologic cancers has evolved with the identification of actionable mutations that impact diagnosis, prognosis, and therapeutic strategies. This narrative review consolidates existing literature on genetic mutations across key urologic cancers, including bladder, renal, prostate, upper tract urothelial, testicular, and penile. The review highlights mutations in DNA damage repair genes, such as BRCA1/2 and PTEN, as well as pathway alterations like FGFR and PD-L1 overexpression. These mutations influence tumor behavior and therapeutic outcomes, emphasizing the need for precision oncology approaches. Molecular profiling, through tools like next-generation sequencing, has revolutionized patient care by enabling targeted treatment strategies, especially in cancers with distinct molecular subtypes such as luminal or basal bladder cancer and clear cell renal carcinoma. Emerging therapies, including FGFR inhibitors and immune checkpoint blockade, offer new treatment avenues, although resistance mechanisms remain a challenge. We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes.

Composition and Biological Activity of Flavonoid-containing Fractions of an Extract from Gratiola officinalis L.

Gratiola officinalis L. (hedge hyssop), a medicinal plant of the Scrophulariaceae family, has diuretic, purgative, and vermifuge properties. It is used as a herbal tea to treat chronic gastroenteritis, renal colic, jaundice, and intestinal worms. Previously, we have found that an extract from G. officinalis is nontoxic and has antitumor, antioxidant, antimicrobial, antiinflammatory, anticachexic, and other properties. Our aims in this study were to separate the G. officinalis extract into individual fractions, to identify the most biologically active fractions, and to examine the chemical composition of these fractions and their biological activity toward A498 renal carcinoma cells. The G. officinalis extract was fractionated by reversed-phase high-performance liquid chromatography, and each fraction was tested for antitumor activity. The active fractions were characterized by UV-visible electron spectral analysis, circular dichroism analysis, Fourier transform infrared spectroscopy, high-performance liquid chromatography, electrospray ionization tandem mass spectrometry, and nuclear magnetic resonance spectroscopy. Two antitumor-active fractions of a flavonoid nature were isolated and chromatographically purified. On the basis of the nuclear magnetic resonance data, the aglycone fragment of the main component of one fraction was found to be structured as 2-(3,4-dimethoxyphenyl)-7-hydroxychroman-4-one, or 3',4'-dimethoxy-7- hydroxyflavanone. The antitumor effect of the most active fraction containing 7-O-glucoside of apigenin, glycoside 7,3'-di-O-luteolin and trace amounts of eupatilin against renal carcinoma A498 cells was manifested in its cytotoxic, cytostatic, apoptotic and autophagosomal activities. In addition, we found 3-(1-2)-glucoside of soyaspogenol B, which is a pentacyclic triterpenoid in the structure.

Design, synthesis, and cytotoxicity screening of novel pyrazolopyrimidines over renal cell carcinoma (UO-31 cells) as p38α inhibitors, and apoptotic cells inducing activities

A series of novel molecules with pyrazolopyrimidine-4-amine core were designed and synthesized as potential cytotoxic agents over Renal Cell Carcinoma cells (UO-31). Results of cytotoxic activity against UO-31 cells showed that pyrazolopyrimidines 19 and 31 were found to be more cytotoxic than sorafenib (SOR). The cytotoxic activity of these compounds appeared to correlate with their ability to inhibit p38α MAPK which are 2.53- and 2.27- folds more potent than SOR. Moreover, results of the cell cycle analysis as well as the results of annexin-V on the (UO-31) cells showed that pyrazolopyrimidines 19 and 31 had a pro-apoptotic activity higher than SOR by 1.42- and 1.20- folds, respectively. Furthermore, compounds 19 and 31 were found to be effective in arresting the cell cycle throughout the accumulation of the cells at G2/M phase. Finally, the tested compounds decreased the TNF concentration as well as increased the expression of tumor suppressor gene p53, Bax/BCL-2 ratio and caspase 3/7.

Cancer-Associated Fibroblast-Derived FGF7 Promotes Clear Cell Renal Cell Carcinoma Progression and Macrophage Infiltration

As the predominant stromal cells in the ccRCC surrounding environment, cancer-associated fibroblasts (CAFs) have been established as supportive of tumor growth. However, the detailed molecular mechanisms underlying the supporting role of CAFs in ccRCC have not been well characterized. Evidence from the clustering consensus analysis, single-cell analysis, and the experimental results illustrate that CAF-derived FGF7 plays a crucial role as a signaling mediator between CAFs and ccRCC tumor cells. Mechanistically, CAF-derived FGF7 triggers AKT activation to promote cell growth and cell invasion of ccRCC tumor cells. As a response, ccRCC tumor cells stimulate STAT3-mediated transcriptional regulation, directly increasing FGF7 expression at the chromatin level in CAFs. Moreover, there exists a positive clinical correlation between the abundance of CAFs, FGF7 expression, and the infiltration of M2 type macrophages. The RENCA in vivo mouse model also confirmed that FGF7 depletion could impede RCC development by reducing the recruitment of M2 type macrophages. Overall, this study delineates a key signaling axis governing the crosstalk between CAFs and ccRCC tumor cells, highlighting FGF7 as a promising therapeutic target of ccRCC.

Systematic multiomics analysis and in vitro experiments suggest that ITGA5 could serve as a promising therapeutic target for ccRCC

BackgroundIntegrin alpha 5 (ITGA5) was previously confirmed to be related to prognosis in several cancer types; however, its function in clear cell renal cell carcinoma (ccRCC) and how this molecule regulates tumor progression and the tumor microenvironment (TME) remain to be elucidated.MethodsWe investigated the prognostic implications of ITGA5 with a machine learning model and evaluated biological behaviors of different levels of ITGA5 expression in vitro. Bioinformatic analysis was performed to explain the comprehensive effect of ITGA5 on the TME and drug sensitivity.ResultsWe constructed a machine learning model to elaborate the prognostic implication of ITGA5. As tumorigenesis of ccRCC was tightly relevant with several mutant genes, we investigated the correlation between ITGA5 expression and frequent mutations and found ITGA5 upregulation in VHL mutant ccRCC (P = 0.016). Through overexpressing, silencing, and blocking ITGA5, we verified the role of ITGA5 in promoting ccRCC adverse biological activities; and the potential functions of ITGA5 in ccRCC were bioinformatically demonstrated, summarizing as cell proliferation, migration, and angiogenesis. The localization of ITGA5 primarily in endothelia and macrophages further verified its magnitude in angiogenesis and aroused our excavation in ITGA5 regulation of immune infiltration landscape. Generally, ITGA5-high ccRCC presented an immunosuppressive TME by inducing a lower level of CD8 + T cell infiltration. For the last part we predicted drug sensitivity relevant to ITGA5 and concluded that a joint medication of ITGA5 inhibitors and VEGFR-target drugs (including sunitinib, axitinib, pazopanib, and motesanib) might be a promising therapeutic strategy.ConclusionOur findings clarified the adverse outcome induced by high expression of ITGA5 in ccRCC patients. In vitro experiments and bioinformatical analysis identified ITGA5 function as predominantly cell proliferation, migration, angiogenesis, and macrophage recruitment. Further, we predicted immune infiltration and medication sensitivity regulation by ITGA5 and proposed a joint use of ITGA5 inhibitors and anti-angiogenetic drugs as a potential potent therapeutic strategy.

Using CT images to assist the segmentation of MR images via generalization: Segmentation of the renal parenchyma of renal carcinoma patients.

Developing deep learning models for segmenting medical images in multiple modalities with less data and annotation is an attractive and challenging task, which was previously discussed as being accomplished by complex external frameworks for bridging the gap between different modalities. Exploring the generalization ability of networks in medical images in different modalities could provide more simple and accessible methods, yet comprehensive testing could still be needed. To explore the feasibility and robustness of using computed tomography (CT) images to assist the segmentation of magnetic resonance (MR) images via the generalization, in the segmentation of renal parenchyma of renal cell carcinoma (RCC) patients. Nephrographic CT images and fat-suppressed T2-weighted (fs-T2W) images were retrospectively collected. The pure CT dataset included 116 CT images. Additionally, 240 MR images were randomly divided into subsets A and B. From subset A, three training datasets were constructed, each containing 40, 80, and 120 images, respectively. Similarly, three datasets were constructed from subset B. Subsequently, datasets with mixed modality were created by combining these pure MR datasets with the 116 CT images. The 3D-UNET models for segmenting the renal parenchyma in two steps were trained using these 13 datasets: segmenting kidneys and then the renal parenchyma. These models were evaluated in internal MR (n=120), CT (n=65) validation datasets, and an external validation dataset of CT (n=79), using the mean of the dice similarity coefficient (DSC). To demonstrate the robustness of generalization ability over different proportions of modalities, we compared the models trained with mixed modality in three different proportions and pure MR, using repeated measures analysis of variance (RM-ANOVA). We developed a renal parenchyma volume quantification tool by the trained models. The mean differences and Pearson correlation coefficients between the model segmentation volume and the ground truth segmentation volume were calculated for its evaluation. The mean DSCs of models trained with 116 data in CT in the validation of MR were 0.826, 0.842, and 0.953, respectively, for the predictions of kidney segmentation model on whole image, renal parenchymal segmentation model on kidneys with RCC and without RCC. For all models trained with mixed modality, the means of DSC were above 0.9, in all validations of CT and MR. According to the results of the comparison between models trained with mixed modality and pure MR, the means of DSC of the former were significantly greater or equal to the latter, at all three different proportions of modalities. The differences of volumes were all significantly lower than one-third of the volumetric quantification error of a previous method, and the Pearson correlation coefficients of volumes were all above 0.96 on kidneys with and without RCC of three validations. CT images could be used to assist the segmentation of MR images via the generalization, with or without the supervision of MR data. This ability showed acceptable robustness. A tool for accurately measuring renal parenchymal volume on CT and MR images was established.

Oncoguía de cáncer renal 2023

Renal cell carcinoma (RCC) stands for 2-3 % of all neoplasms worldwide. The most important risk factors identified for RCC are obesity, hypertension, type 2 diabetes mellitus, and tobacco use. Nowadays, more than 50 % of RCCs are detected incidentally. There are multiple therapeutic strategies to treat RCC, ranging from active surveillance or nephrectomy for localized disease to combinations of targeted therapies and immunotherapy for patients with advanced disease.

Integrated pan-cancer analysis and experimental verification of the roles of ZBED3 in kidney renal clear cell carcinoma

The present study investigated the Zinc finger BED-type containing 3 (ZBED3) mRNA expression levels, diagnostic and prognostic values, co-expressed and differentially expressed genes, immune infiltration, and functional enrichment analysis in patients with kidney renal clear cell carcinoma (KIRC) using various public databases such as The Cancer Genome Atlas, Genotype-Tissue Expression Project, LinkedOmics, Gene Set Enrichment Analysis databases, and the Xiantao academic tool. Through extensive data mining, our study revealed differential expression of ZBED3 in various tumor and paired normal tissues. Specifically, ZBED3 expression was found to be significantly decreased in KIRC, particularly in advanced pathologic stages and histologic grades, when compared to corresponding control tissues. Our analysis revealed that the overexpression of ZBED3 is associated with a favorable overall survival outcome in KIRC patients. Moreover, functional enrichment analysis identified key pathways related to inflammation response and DNA methylation of ZBED3 in KIRC. Additionally, our findings suggest that the upregulation of ZBED3 leads to the inhibition of cell proliferation by modulating cell-cycle progression in KIRC cell lines. Taken together, these results suggest that ZBED3 may serve as a promising biomarker and prognostic indicator for individuals diagnosed with KIRC.

Thyroid cancer in a child with Cowden syndrome

Cowden disease (Cowden syndrome) refers to PTEN-associated hamartoma tumor syndromes. It arises due to a mutation in the phosphatase and tensin homolog gene, one of the main functions of which is cell cycle regulation. The presence of a mutation in the gene leads to uncontrolled cell growth, and patients have a lifelong increased risk of neoplasms of various degrees of malignancy. This article presents a clinical case of Cowden syndrome with an early debut at the age of 7 years. The combination of macrocephaly (SDS of head circumference >2) with various skin manifestations (facial trichilemmomas, acral keratosis, papillomatous papules) and the presence of benign and/or malignant neoplasms are pathognomonic for Cowden syndrome. Of the malignancies, breast and thyroid cancer, colorectal cancer, renal cell carcinoma, and endometrial cancer are the most common. Thyroid carcinoma has been shown to have an earlier age of manifestation and often occurs already in childhood. This determines the need to screen patients with a proven mutation in the PTEN gene for nodal neoplasms from an early age. If surgical treatment is necessary, thyroidectomy remains preferable due to the frequent recurrence of nodules, as well as the uncertain potential for malignancy due to the low study of thyroid nodules in patients with mutations in the PTEN gene.

Pembrolizumab Induced Recall Dermatitis Occurring 5 Years After Radiotherapy

Background and Clinical Significance: Radiation recall dermatitis (RRD) following immune checkpoint inhibitor (ICI) therapy has been infrequently reported. Case Presentation: We present a 47-year-old female patient who developed RRD of the breast following three doses of pembrolizumab administered as an adjuvant treatment post-nephrectomy for Stage III renal cell carcinoma (RCC). Notably, the affected breast had previously undergone external beam radiotherapy 247 weeks earlier for Stage IA invasive ductal carcinoma. She had received no prior chemotherapy at any point. RRD manifested as breast induration, erythema, and peau d’orange, and contraction of breast volume was noted following three cycles of pembrolizumab on week 17 (400 mg dose every 6 weeks). The dermatitis responded rapidly to systemic corticosteroids and no treatment interruption was needed. Conclusion: To date, this is the longest reported interval from completion of radiotherapy to RRD. A literature search underscores the variability in presentation and management of ICI-associated RRD.

Complete response to fifth-line anti-PD-1 rechallenge in fumarate hydratase-mutated papillary renal cell carcinoma

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.

C-reactive Protein-albumin-lymphocyte Index as a Novel Biomarker for Progression in Patients Undergoing Surgery for Renal Cancer.

Some patients with renal cell carcinoma (RCC) develop early or late recurrence after surgery. However, there is no clear consensus on which patients with postoperative RCC should be treated. This study aimed to establish a biomarker for selecting patients who are at a higher risk of relapse following renal cancer surgery. A total of 378 patients who underwent nephrectomy or partial nephrectomy for a diagnosis of RCC at our hospital were included, with a focus on pT3 cases at high risk of recurrence. Factors associated with postoperative progression, including pathological and hematological parameters, were examined. Sarcomatoid features, Fuhrman grade 4, and C-reactive protein-albumin-lymphocyte (CALLY) index were statistically significant predictive factors for progression-free survival after surgery (p<0.0011, p=0.0047, and p<0.0001, respectively). In the multivariate Cox proportional regression analysis, the CALLY index was the most statistically significant predictor of the risk of postoperative recurrence (p=0.0002). In addition to the existing risk factors for RCC recurrence, such as sarcomatoid features and Fuhrman grade, we propose that the CALLY index is a predictor of postoperative recurrence and that patients with a low CALLY index are good candidates for postoperative treatment. Our study may help select patients with pT3 disease with a high risk of recurrence who require postoperative treatment.

Diagnostic and Prognostic Potential of FBXO8 Expression in Kidney Renal Clear Cell Carcinoma and Its Regulation of Renal Adenocarcinoma Cells

BackgroundThe F-box protein 8 Gene (FBXO8) has been shown to suppress invasion and metastasis in various cancer types. Recurrence and drug resistance pose significant challenges in renal cell carcinoma (RCC). Identifying novel biomarkers is crucial for addressing these issues. MethodsData on RNA sequencing and patient survival for KIRC was obtained from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. We confirmed FBXO8 gene expression and its impact on survival. Clinical characteristics were classified, and FBXO8 expression differences among various categories were observed. We conducted biofunctional predictions and analyzed the tumor microenvironment (TME), immune cell infiltration, and immune checkpoints in relation to FBXO8 expression. FBXO8 was overexpressed using a plasmid, and we assessed Kidney renal clear cell carcinoma (KIRC) cell proliferation, migration, and apoptosis through CCK8, wound healing tests, and western blot analysis. ResultsOur findings revealed decreased FBXO8 expression in KIRC, with patients exhibiting low FBXO8 expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that FBXO8 expression was notably linked to drug metabolism cytochrome P450, nutrition disease, receptor-ligand activity, and neuroactive ligand-receptor interaction. Furthermore, we discovered significant correlations between FBXO8 expression and immune cell infiltration, as well as checkpoints such as CD274. Overexpression (OE) of FBXO8 led to a marked reduction in cell proliferation and migration, along with increased apoptosis, as evidenced by apoptosis-related protein expression. ConclusionThis study demonstrates that FBXO8 serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.

Metastatic renal cell carcinoma presenting as gastrointestinal bleeding.

A 73-year-old female with metastatic renal cell carcinoma (RCC) presented with melena and lethargy. She was found to be iron deficient with a hemoglobin of 101 g/L. Her gastroscopy found six irregular pedunculated non-bleeding polyps, 10-20 mm in diameter. Histopathology of the resected polyp returned as metastatic clear cell renal cell carcinoma. Gastric metastases from any primary malignancy are rare and metastatic RCC accounts for only 7% of these tumors. Furthermore, while RCC commonly metastasises to the lung, bone and lymph nodes, metastasis to the gastrointestinal tract is extremely rare, occurring in <1% of patients. Presentation of RCC as a gastric polyp is usually a late event, and on average occurs 6.7 years after initial diagnosis of RCC. Therefore, this case highlights a rare but important late complication of RCC, presenting as gastrointestinal bleeding secondary to gastric metastases.

Updated Survival Follow-Up for Phase Ib Trial of the Histone Deacetylase Inhibitor Abexinostat With Pazopanib in Patients With Solid Tumor Malignancies.

Histone deacetylase (HDAC) inhibition downregulates hypoxia-inducible factor-1α and modulates multiple metabolomic pathways relevant in cancer. Here we report a potential novel biomarker to predict exceptional responders (>3 years) in patients receiving HDAC and vascular endothelial growth factor (VEGF) inhibition. Patients with solid tumor malignancies were enrolled in this phase Ib trial of abexinostat (4/7 ×21 days) and pazopanib (28/28 days), with a dose expansion in renal cell carcinoma (RCC). Plasma was analyzed for metabolomics and peripheral blood mononuclear cells (PBMCs) for VEGF and HDAC2 expression levels. Fifty-one patients were enrolled: n = 36 patients in dose escalation and n = 15 in dose expansion. After the initial report in 2017, six patients had remained on study: four with RCC and one each with medullary thyroid and thymic neuroendocrine carcinoma. One patient with RCC remains on treatment for >11 years after progression on five systemic therapies. Overall, the median duration of therapy measured 5.6 (1-133) months. The median duration of therapy in exceptional responders measured 44.1 (39.8-133+) months. The median overall survival in patients with high PBMC HDAC2 expression versus low HDAC2 was 32.3 versus 9.2 months (P = .004) for all patients and 43.3 versus 25.1 months for patients with RCC (P = .09). Exceptional responders had lower kynurenine levels both pre- and post-treatment (P = .002, P < .001, respectively). HDAC2 and kynurenine expression levels were inversely correlated (P = .02). Abexinostat added to pazopanib shows extended tolerability and long-term responses and survival. PBMC HDAC2 levels, the abexinostat target, are relevant predictors of response. In addition, metabolomic assessment points to kynurenine as a predictor for exceptional response to combined VEGF plus HDAC inhibition.

Development and Validation of a Comprehensive Predictive Model for Surgical Planning in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus

ObjectiveTo investigate preoperative predictors for selecting different surgical approaches in patients with renal cell carcinoma with inferior vena cava (IVC) tumor thrombus (RCC-IVCTT), and to establish and validate corresponding predictive models. MethodsClinical data of 583 RCC-IVCTT patients were retrospectively analyzed. Of these, 465 cases were used to construct predictive models, and 118 cases were used for validation. Univariate and multivariate analyses identified independent predictors for surgical strategies. Two nomogram prediction models were established based on relevant independent factors to predict surgical approach. ResultsIn the development cohort, 342 patients underwent IVC thrombectomy (IVCT), 91 underwent IVC cavectomy (IVCC), and 32 underwent IVC reconstruction (IVCR). Multivariate logistic regression analysis identified the following predictors for inability to perform IVCT: higher Mayo classification of tumor thrombus (TT), IVC wall invasion, presence of bland thrombus, pan-immune-inflammation value (PIV) > 358×109, and maximum anteroposterior (AP) diameter of IVC at renal vein ostium (RVo) > 24mm. Platelet > 170×109/L and inadequate collateral circulation were predictors for IVCR. The developed model predicted capacity of the nomogram was evaluated in terms of its calibration, discrimination, and clinical utility. The validation set confirmed these findings. ConclusionThe comprehensive preoperative predictive model for RCC-IVCTT patients aids in preoperative determination of the required surgical approach and necessity for IVC angiography, facilitating perioperative preparation and reducing unnecessary invasive examinations.

Multinucleated tumor cells and micropapillary morphology appear to be predictors of poor prognosis in renal cell carcinoma with papillary and oncocytic features

Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for “RCC” and “papillary,” and tumors with >50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36–93) years, and a mean tumor size of 5.2 (range: 1–21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2–3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3–4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for FLCN and MET gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01–19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p < 0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p = 0.005); micropapillary features (HR: 18.42; p = 0.017) and MTC (HR: 180.22; p = 0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p = 0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors.

Impact of neoadjuvant therapy on prognosis in renal cell carcinoma with inferior vena cava thrombus

BackgroundThe standard treatment for non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is complete surgical resection; however, this procedure is complex and carries high complication rates and perioperative mortality. Previous studies have explored preoperative multimodal therapy to reduce surgical difficulty, but limited evidence prevents guideline recommendations. This study aimed to investigate the impact of neoadjuvant therapy on the prognosis of patients with RCC and IVC thrombus without distant metastasis. MethodsData from 2006 to 2024 on RCC patients with IVC thrombus undergoing radical nephrectomy plus IVC thrombus resection were collected. Patients received neoadjuvant therapy, including tyrosine kinase inhibitors or immune checkpoint inhibitors, followed by surgery. Tumor size and thrombus height were assessed by computed tomography. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier curves. Multivariate analysis was used to identify factors predicting DFS. ResultsThirty-one patients who did not receive neoadjuvant chemotherapy therapy (NAC-Naive group) and 19 patients who received neoadjuvant chemotherapy therapy (NAC group) were analyzed. The NAC group showed significant reductions in primary renal tumor size and neutrophil-to-lymphocyte ratio compared to the NAC-Naive group just before nephrectomy. The NAC group had significantly improved DFS and OS. Median DFS and OS were not reached in the NAC group compared to 26.3 months and 73.5 months, respectively, in the NAC-Naive group. The NAC group had a 2-year recurrence-free survival rate of 70.9% compared to 50.6% in the NAC-Naive group. Multivariate analysis identified a preoperative tumor size of 10 cm or larger and lack of neoadjuvant therapy as poor prognostic factors for DFS. ConclusionNeoadjuvant therapy significantly improves the prognosis of RCC patients with IVC thrombus. This therapy reduces surgical invasiveness and has a mid- to long-term preventive effect on recurrence. These findings support the potential benefit of neoadjuvant systemic therapy in improving outcomes for this patient population.

Surgical and Oncological Outcomes of Level III-IV Versus Level I-II Inferior Vena Cava Thrombectomy: A Decennial Experience of a High-Volume European Referral Center.

In patients with renal cell carcinoma (RCC) the role of the extent of tumor thrombus into the inferior vena cava (IVC) has never been addressed from a surgical and oncologic standpoint. This study aims to evaluate differences between level III-IV versus level I-II patients concerning peri- and postoperative morbidity, additional treatments and long-term oncological outcomes. Overall, 40 patients with RCC underwent radical nephrectomy (RN) with IVC thrombectomy at a single European institution between 2010 and 2023. Complications were reported according to the European Union (EAU) guidelines recommendations. Spider chart served as graphical depiction of surgical and oncologic outcomes. Overall, 22 (55%) and 18 (45%) patients harbored level III-IV and I-II IVC thrombus. Level III-IV patients experienced significantly higher rates of intraoperative transfusions (68 vs 39%), but not significantly higher rates of intraoperative complications (32% vs 28%). Level III-IV patients had significantly higher rates of postoperative transfusions (82% vs 33%) and Clavien Dindo ≥3 complications (41% vs 15%). In level III-IV versus level I-II patients, median follow up was 482 and 1070 days, the rate of distant recurrence was 59% and 50%, the rate of systemic progression was 27% and 13%, and the rate of additional treatment/s was 64% and 61%, respectively (all p values > 0.05). Overall survival was 36% in level III-IV patients and 67% in level I-II (p = 0.001). Our findings suggest that patients with level III-IV RCC who are candidates for IVC thrombectomy should be counselled about the higher likelihood of postoperative severe adverse events and worse overall survival relative to level I-II counterparts.

Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma

Sunitinib is a first-line treatment for renal cell carcinoma (RCC), but suffers from drug resistance, causing therapy failure. Therefore, nano-scale delivery systems should be introduced for targeted delivery. Metal-organic frameworks (MOFs) are attractive drug carriers that not only enable multidrug combination therapies but also exert photodynamic effects by incorporating photosensitizers as components. Here, a Zr-based porphyrinic nanoscale MOF, PCN224, was prepared as the carrier for the co-delivery of sunitinib and the siRNA against vascular endothelial growth factor receptor-2 (VEGFR-2). Drug-loaded PCN-224 is coated with hyaluronic acid (HA) to prevent drug molecular leakage and to exert tumor-targeting effects (CD44 in tumor cells). Photodynamic therapy was conducted under 660 nm laser (50 mW·cm−2, 10 min) irradiation. Compared with St/siVEGFR-2@PCN-224@HA without the HA coating, St/siVEGFR-2@PCN-224@HA significantly suppressed cell viability and promoted cell apoptosis. Laser irradiation further increased the anti-cancer effect of St/siVEGFR-2@PCN-224@HA by generating cytotoxic ROS. H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.