Journal of Kidney Cancer and VHL最新文献

{"title":"Cabozantinib-Exposed Renal Cell Carcinoma Organoids Suggest Transcriptomic Associations with Treatment Resistance in Clear Cell and Nonclear Cell Tumors.","authors":"Wesley H Chou, Nicholas H Chakiryan, George V Thomas","doi":"10.15586/jkc.v12i2.386","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.386","url":null,"abstract":"<p><p>While vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) are a mainstay of treatment for advanced renal cell carcinoma (RCC), mechanisms of resistance to VEGF-TKIs remain under ongoing investigation. To assess transcriptomic changes in clear-cell RCC (ccRCC) and non-ccRCC exposed to a VEGF-TKI, we analyzed differential single-cell gene expression in RCC tumor-organoids exposed to cabozantinib versus control solvent. In ccRCC organoid cells, <i>LRRC75A</i> was notably highly associated with cabozantinib exposure (log2 fold-change 2.18, detected proportion 0.52 vs. 0.23, false-detection rate adjusted p<0.001). Importantly, our findings were independently validated in a recent study of advanced ccRCC patients treated with cabozantinib, which demonstrated that higher <i>LRRC75A</i> expression was significantly associated with decreased tumor response and less robust reduction of VEGF expression. <i>LRRC75A</i> has been shown to mediate VEGF secretion in a separate study and may potentiate compensatory angiogenesis after cabozantinib exposure. Gene expression scores were then developed based on transcriptomic changes associated with cabozantinib exposure and applied to stage IV patients in several independent cohorts. Higher scores were significant predictors of worse overall survival in TCGA non-RCC patients and worse progression-free survival in JAVELIN Renal 101 ccRCC patients. Overall, this experiment represents an incremental step in a larger effort to elucidate resistance mechanisms to VEGF-TKIs.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"37-45"},"PeriodicalIF":1.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Ipilimumab with Nivolumab versus Immune Checkpoint Inhibitors with Tyrosine Kinase Inhibitors in Patients with Intermediate- or Poor-Risk Metastatic Clear Cell Renal Cell Carcinoma.","authors":"Micah Ostrowski, Yeonjung Jo, Georges Gebrael, Chadi Hage Chehade, Zeynep Irem Ozay, Blake Nordblad, Ayana Srivastava, Diya Garg, Richard Ji, Gliceida Galarza Fortuna, Vinay Mathew Thomas, Beverly Chigarira, Ethan Anderson, Neeraj Agarwal, Benjamin L Maughan, Umang Swami","doi":"10.15586/jkc.v12i2.387","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.387","url":null,"abstract":"<p><p>Ipilimumab with nivolumab (Ipi + Nivo) and immune checkpoint inhibitors with tyrosine kinase inhibitors (ICI + TKI) are the first-line approved treatments for intermediate- and poor-risk metastatic clear cell renal cell carcinoma (mccRCC); however, they have not been compared head-to-head in prospective trials to guide treatment selection. Thereupon, we sought to compare survival outcomes of patients receiving first-line Ipi + Nivo versus ICI + TKI, using a large, real-world database among patients with intermediate- and poor-risk mccRCC. This retrospective cohort study used a nationwide electronic health record-derived deidentified database, where patients with mccRCC with intermediate- or poor-risk who received first-line Ipi + Nivo or ICI + TKI between 20 June, 2016, and 26 January, 2023, were included. Primary outcomes were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS), summarized via Kaplan-Meier survival estimates with 95% confidence intervals (CIs) and compared in the context of propensity score (PS) matching weighted analysis. Of the 12,707 patients in the dataset, 1,438 with mccRCC met eligibility and were included. After PS matching weighted analysis, no significant difference in rwOS was noted between both groups (HR 1.01, 95% CI 0.86-1.19; p = 0.91); however, rwTTNT was significantly shorter with Ipi + Nivo than with ICI + TKI (HR 0.78, 95% CI 0.68-0.89; p < 0.001). In this large real-world study, there was evidence that rwOS was comparable, while rwTTNT was superior in patients receiving ICI + TKI compared to those receiving Ipi + Nivo. These real-world data offer important guidance for clinicians in choosing between Ipi + Nivo and ICI + TKI as frontline treatment.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"27-36"},"PeriodicalIF":1.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decade of Surgical Management of Renal Cell Carcinoma with IVC Thrombus and Bilateral Renal Tumors: Emphasis on Auto-transplantation.","authors":"Abdul Rouf Khwaja, Aamir Mushtaq, Younis Mushtaq, Arif Hamid, Sajad Mali, Sajad Parra, Saqib Mehdi, Faheem Ul Islam, Akil Lateif","doi":"10.15586/jkc.v12i2.367","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.367","url":null,"abstract":"<p><p>To assess the surgical outcomes and techniques in managing renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus and bilateral renal tumors with a focus on the role of autotransplantation in complex cases, this retrospective study analyzed 58 patients treated at our center between 2013 and 2023 for RCC with tumor thrombus extending into the IVC and, in some cases, the right atrium (RA). Surgical management included radical nephrectomy and thrombectomy with techniques adapted to thrombus level. For level I and II thrombi, innovative occluding maneuvers were used to control the contralateral renal vein. For level IV thrombi, a beating heart technique combined with cardiopulmonary bypass (CPB) was employed. Of the 10 patients with bilateral renal tumors, 2 underwent autotransplantation and 8 underwent bilateral partial nephrectomy. In this 10-year retrospective study of 58 patients with either RCC with venous tumor extension or bilateral RCC, 40 males and 18 females, with a mean age of 66 ± 8 years. Tumor involvement was predominantly right-sided (72.4%). Thrombus levels included 53.44% Level I, 25.9% Level II, and 3.4% Level IV. Intraoperative and postoperative complications were minimal, affecting 10 patients; patients with Level I thrombus had a better survival rate; and one patient with Level IV thrombus died postoperatively. The mean blood loss was 360 mL and the mean operative time was 195 minutes. Histopathology revealed clear cell carcinoma in 65.5% of cases. Among the 10 patients with bilateral renal tumors, autotransplantation and partial nephrectomies resulted in excellent renal preservation and favorable outcomes. This study demonstrates the effectiveness of radical nephrectomy and thrombectomy for RCC with venous tumor extension. Tailored surgical techniques, including autotransplantation for bilateral tumors, resulted in excellent outcomes with minimal complications. Personalized surgical strategies were key to preserving renal function and improving survival in complex RCC cases.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"19-26"},"PeriodicalIF":1.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reno-Gonadal Venous Anastomosis for Right Renal Venous Drainage Following Juxtarenal Cavectomy for Renal Cell Carcinoma.","authors":"Jabrina Simmons, Tae-Hee Kim, Tasha Posid, Shawn Dason","doi":"10.15586/jkc.v12i2.390","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.390","url":null,"abstract":"<p><p>This article is a case report of a 62-year-old male with a left-sided renal cell carcinoma (RCC) with a level II inferior vena cava (IVC) thrombus and caval occlusion. He was managed with open left radical nephrectomy and juxtarenal cavectomy. To preserve right renal venous drainage, the right renal vein was anastomosed to the right gonadal vein. He has not had any renal functional decline or disease recurrence with 3 years of follow-up. The focus of this article is to discuss this distinctive method for vascular reconstruction as an option for right renal venous drainage following left nephrectomy and juxtarenal cavectomy.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"14-18"},"PeriodicalIF":1.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Perspective on Medical Conditions Post Immune Checkpoint Therapy in Advanced Renal Carcinoma.","authors":"Ulka Vaishampayan, Sumanta Pal, Sephora Dafinescu, Neha Shah, Dena Battle, Michael Staehler","doi":"10.15586/jkc.v12i2.383","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.383","url":null,"abstract":"<p><p>Immune checkpoint therapy (ICI) has enabled induction of remission in advanced renal cell carcinoma RCC. ICI toxicities can persist as chronic health conditions. We developed a patient survey to assess changes in medical comorbidities after ICI. The survey was developed by the Kidney Cancer Research Alliance (KCCure), with multidisciplinary representation from urologic surgeons, medical oncologists, and patient advocates. The survey was broadcast between July 2022 and September 2022 to patients via website, mailing lists, and social media platforms. Patient perspective on changes to any medical conditions were evaluated in the survey questionnaire. Of 1062 patients that responded, 399 were self-identified as being metastatic and 289 reported to be treated with ICI. Eighty-five percent of respondents were from the United States. The most common conditions noted were thyroid dysfunction in 80 patients, hypertension in 50 patients, chronic kidney disease in 23 patients, heart disease in 10 patients, and diabetes mellitus (DM) in 13 patients. Immune disorders developed in 26 (9%) patients. The limitations are the survey had minimal participation from minority populations. Multiple medical conditions were noted to either emerge or worsen as a result of ICI-based therapies in RCC. Awareness of this information as a starting point should stimulate the development of survivorship programs for renal cancer. A survey of patients with advanced kidney cancer showed that some medical conditions such as thyroid dysfunction, hypertension, heart and kidney disease, DM, and immune conditions were newly diagnosed and/or persisted after immune therapy.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Cell Carcinoma Masquerading as Pyonephrosis - A Case Report of A Rare Presentation.","authors":"Vishnu Pratap, Prakash Pawar, Ajit Sawant","doi":"10.15586/jkc.v12i2.330","DOIUrl":"https://doi.org/10.15586/jkc.v12i2.330","url":null,"abstract":"<p><p>We describe here an atypical case of pyonephrosis which on further evaluation turned out to be a renal cell carcinoma (RCC). The clinical presentation of the patient was that of an infective etiology. However, the renal mass associated with renal vein thrombus and lung metastasis was later diagnosed based on the clinical deterioration of the patient even after insertion of percutaneous nephrostomy. In this case, an underlying renal cancer was probably complicated secondarily leading to pyonephrosis which was the initial presenting manifestation which led to a delay in diagnosis. Pyonephrosis is usually associated with Xanthogranulomatous pyelonephritis. Association of RCC with pyonephrosis is extremely rare and hence seldom reported. Our patient later on underwent radical nephrectomy and the histopathology report was suggestive of RCC. We have described here the clinical manifestations and diagnostic issues of such a case. This case provides evidence that RCC should be kept as one of the differentials in such patients.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 2","pages":"1-4"},"PeriodicalIF":1.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11976670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine: Seeing the Tree in the Forest!","authors":"Ulka Vaishampayan","doi":"10.15586/jkc.v12i1.395","DOIUrl":"10.15586/jkc.v12i1.395","url":null,"abstract":"","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 1","pages":"27-28"},"PeriodicalIF":1.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review of Robotic Nephrectomy for Kidney Cancer.","authors":"Danilo Coco, Silvana Leanza, Massimo Giuseppe Viola, Desideria Coco","doi":"10.15586/jkc.v12i1.372","DOIUrl":"https://doi.org/10.15586/jkc.v12i1.372","url":null,"abstract":"<p><p>Robotic nephrectomy has become an increasingly preferred surgical technique for managing renal cell carcinoma (RCC). This review aims to systematically evaluate existing literature on the safety, efficacy, clinical outcomes, and associated costs of robotic nephrectomy, especially in relation to tumor dimensions and other pertinent patient factors. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed an extensive literature search across major databases (PubMed, Scopus, and Cochrane Library) from inception to October 2023. The inclusion criteria encompassed randomized controlled trials (RCTs), cohort studies, and case-control studies that compared robotic nephrectomy with open or laparoscopic nephrectomy. Outcomes analyzed included operative time, intraoperative blood loss, complication rates, length of hospital stay, oncological outcomes, and cost-effectiveness. The Egger test was used to assess publication bias. The review incorporated 30 studies involving 5,432 patients who underwent robotic nephrectomy. Key findings indicated that robotic nephrectomy resulted in significantly reduced intraoperative blood loss (mean difference of -85 mL; p < 0.001) and shorter hospital stays (mean difference of -1.3 days). Tumor size had a notable impact on surgical outcomes, with larger tumors (≥7 cm) being associated with prolonged operative times and slightly higher complication rates. Robotic nephrectomy was also associated with higher costs compared to conventional surgical techniques; however, reduced readmission rates offset some of these costs. Oncological outcomes for robotic nephrectomy were comparable to those of open nephrectomy. Robotic nephrectomy is a safe and effective approach for kidney cancer that demonstrates advantages in perioperative recovery and surgical precision, particularly for smaller tumors. While costs may be higher, the clinical benefits and potential long-term savings from decreased postoperative complications recommend its use. Further high-quality RCTs are essential to validate these findings.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 1","pages":"29-35"},"PeriodicalIF":1.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Case of Bilateral Adrenal Tumors Confirms Pathogenicity of Previously Described c.463+4C>G Variant in the von-Hippel Lindau Gene.","authors":"Samuel Morriss, Victoria Beshay, Huei San Leong, Ingrid Winship","doi":"10.15586/jkc.v12i1.381","DOIUrl":"10.15586/jkc.v12i1.381","url":null,"abstract":"<p><p>We report a case of a pathogenic variant c.463+4C>G in the von Hippel-Lindau (VHL) gene identified in a patient presenting with bilateral adrenal tumors, including a histologically confirmed pheochromocytoma with no significant family history of VHL-associated tumors. This same variant was first reported as having pathogenic significance in an unrelated proband with a hemangioblastoma and a family history of pheochromocytoma. In our patient, next-generation sequencing and subsequent RNA (ribonucleic acid) analysis confirmed this mutation to be a pathogenic (class 4) variant in intron 2. The lack of family history of VHL-associated tumors correlated with the proband further suggests that this mutation may have reduced penetrance. This case confirms the pathogenicity of the same previously described variant in the VHL gene and underscores the utility of genetic testing in patients with atypical presentations of adrenal tumors, even in the absence of a relevant family history.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 1","pages":"23-26"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of BCL11A, NTN5, and OGN as Diagnosis Biomarker of Papillary Renal Cell Carcinomas by Bioinformatic Analysis.","authors":"Zahra Haghshenas, Sina Fathi, Alireza Ahmadzadeh, Elham Nazari","doi":"10.15586/jkc.v12i1.366","DOIUrl":"10.15586/jkc.v12i1.366","url":null,"abstract":"<p><p>The prevalence of papillary renal cell carcinomas (PRCCs) is estimated to be between 10% and 15%. At present, there is no effective therapeutic approach available for patients with advanced PRCCs. The molecular biomarkers associated with PRCC diagnoses have been rarely studied compared to renal clear cell carcinomas; therefore, the necessity for the identification of novel molecular biomarkers to aid in the early identification of this disease. Bioinformatics and artificial intelligence technologies have become increasingly important in the search for diagnostic biomarkers for early cancer detection. In this study, three genes-BCL11A, NTN5, and OGN-were identified as diagnostic biomarkers using the Cancer Genome Atlas (TCGA) database and deep learning techniques. To identify the differential expression genes (DEGs), ribonucleic acid (RNA) expression profiles of PRCC patients were analyzed using a machine learning approach. A number of molecular pathways and coexpressions of DEGs have been analyzed and a correlation between DEGs and clinical data has been determined. Diagnostic markers were then determined via machine learning analysis. The 10 genes selected with the highest variable importance value (more than 0.9) were further investigated, with six upregulated (BCL11A, NTN5, SEL1L3, SKA3, TAPBP, SEMA6A) and four downregulated (OGN, ADCY4, SMOC2, CCL23). A combined receiver operating characteristic (ROC) curve analysis revealed that the BCL11A-NTN5-OGN genes, which have specificity and sensitivity values of 0.968 and 0.901, respectively, can be used as a diagnostic biomarker for PRCC. In general, the genes introduced in this study may be used as diagnostic biomarkers for the early diagnosis of PRCC, thus providing the possibility of early treatment and preventing the progression of the disease.</p>","PeriodicalId":44291,"journal":{"name":"Journal of Kidney Cancer and VHL","volume":"12 1","pages":"12-22"},"PeriodicalIF":1.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}