Incidence Of Renal Cell Carcinoma Research Articles

Construction of an autophagy-related genes risk model as predicting prognosis: BAG1 suppresses growth of clear cell renal cell carcinoma

BackgroundThe incidence of clear cell renal cell carcinoma (ccRCC) is increasing annually. While the cure rate and prognosis of early ccRCC are promising, the 5-year survival rate of patients with metastatic ccRCC is below 12%. Autophagy disfunction is closely related to infection, cancer, neurodegeneration and aging. Nevertheless, there has been limited exploration of the association between autophagy and ccRCC through bioinformatics analysis. MethodsA novel risk model of autophagy-related genes (ARGs) was constructed to predict the prognosis of patients with ccRCC and guide the individualized treatment to some extent. Relevant data samples were obtained from the TCGA database, and ccRCC-related ARGs were identified by Pearson correlation analysis, leading to the establishment of a risk model covering 10 ccRCC-related ARGs. Many indicators were used to assess the accuracy of the risk model. ResultsReceiver operating characteristic (ROC) curve analysis showed that the risk model had high accuracy, indicating that the risk model could predict the prognosis of ccRCC patients. Moreover, the findings revealed significant differences about immune and metabolic features in low- and high-risk groups. The study also found that BAG1 within the risk model was closely related to the prognosis of ccRCC and an independent risk factor. In vitro and in vivo experiments validated for the first time that BAG1 could suppress the proliferation, migration, and invasion of ccRCC. ConclusionThe construction of ARGs risk model, can well predict the prognosis of ccRCC patients, and provide guidance for individual therapy to patients. It was also found that BAG1 has significant prognostic value for ccRCC patients and acts as a tumor suppressor gene in ccRCC. These findings have crucial implications for the prognosis and treatment of ccRCC patients.

Renal cell carcinoma in a transplanted kidney: a retrospective evaluation

IntroductionKidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48–82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10–30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature.ObjectiveTo determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development.Materials and methodsA retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm.ResultsThe incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient.ConclusionLaparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease.

Mapping of Human Polyomavirus in Renal Cell Carcinoma Tissues.

Worldwide, the incidence of renal cell carcinoma (RCC) is rising, accounting for approximately 2% of all cancer diagnoses and deaths. The etiology of RCC is still obscure. Here, we assessed the presence of HPyVs in paraffin-embedded tissue (FFPE) resected tissue from patients with RCC by using different molecular techniques. Fifty-five FFPE tissues from 11 RCC patients were included in this study. Consensus and HPyV-specific primers were used to screen for HPyVs. Both PCR approaches revealed that HPyV is frequently detected in the tissues of RCC kidney resections. A total of 78% (43/55) of the tissues tested were positive for at least one HPyV (i.e., MCPyV, HPyV6, HPyV7, BKPyV, JCPyV, or WUyV). Additionally, 25 tissues (45%) were positive for only one HPyV, 14 (25%) for two HPyVs, 3 (5%) for three HPyVs, and 1 one (1%) tissue specimen was positive for four HPyVs. Eleven (20%) RCC specimens were completely devoid of HPyV sequences. MCPyV was found in 24/55 RCC tissues, HPyV7 in 19, and HPyV6 in 8. The presence of MCPyV and HPyV6 was confirmed by specific FISH or RNA-ISH. In addition, we aimed to confirm HPyV gene expression by IHC. Our results strongly indicate that these HPyVs infect RCC and nontumor tissues, possibly indicating that kidney tissues serve as a reservoir for HPyV latency. Whether HPyVs possibly contribute to the etiopathogenesis of RCC remains to be elucidated.

Renal cell carcinoma in a supernumerary left kidney: A very rare case report

Introduction: The supernumerary kidney, the rarest urinary tract anomaly, typically presents as an asymptomatic third kidney. Renal cell carcinoma constitutes 90% of kidney cancer cases. Supernumerary kidneys are often incidentally discovered via imaging. Management depends on symptoms, with nephrectomy for nonfunctioning kidneys. Only three cases of supernumerary kidney carcinoma are reported. This report aims to report a case of renal cell carcinoma of the left supernumerary kidney discovered intraoperatively. Case report: A 56-year-old woman presented with abdominal enlargement and left flank pain for three months. A palpable lump was found, and a contrast-enhanced CT scan revealed a solid mass at the upper pole of the left kidney with suspected metastasis. During surgery, a large mass was found, leading to a radical nephrectomy. Postoperative recovery was challenging; the patient was moved to intensive care, but her condition worsened, and she died. The pathological diagnosis was clear cell renal cell carcinoma. Conclusion: The incidence of renal cell carcinoma in the supernumerary left kidney is exceedingly rare. Intraoperative findings were different from those observed preoperatively. Radiological assessment is necessary to understand the blood supply, anatomical variations, and associated problems to prevent unnecessary surgery and the associated risk of complications.

Lathyrol reduces the RCC invasion and incidence of EMT via affecting the expression of AR and SPHK2 in RCC mice

ObjectiveTo investigate the effects of Lathyrol on the expression of androgen receptor (AR) and sphingosine kinase 2 (SPHK2) in renal cell carcinoma (RCC) mice and to further explore the mechanism by which Lathyrol inhibits the invasion and incidence of epithelial-mesenchymal transition (EMT).MethodsAn RCC xenograft mouse model was constructed, and the mice were randomly divided into a model group, an experiment group and a negative control group. The experiment group was intragastrically gavaged with Lathyrol solution (20 mg/kg), the model group was intragastrically gavaged with 0.9% NaCl (same volume as that used in the experiment group), and the negative control group was injected intraperitoneally with 2 mg/kg cisplatin aqueous solution. Changes in the body weight and tumor volume of the mice were recorded. Western blot (WB) was used to assess the protein expression levels of AR, p-AR, CYP17A1, PARP1, E-cadherin, N-cadherin, vimentin, α-SMA, β-catenin, and ZO-1. Protein expression levels of SPHK2, metal matrix protease 2 (MMP2), MMP9 and urokinase-type plasminogen activator (uPA) in tumor tissues were assessed by immunohistochemistry (IHC). AR expression in tumor tissues was assessed after immunofluorescence (IF) staining.ResultsAfter 14 days of drug administration, compared with that in the model group, the tumor volumes in the negative control and experiment groups were lower; the difference in tumor volume among the model, control and experiment groups was statistically significant (P < 0.05). The differences in body weight among the three groups were not statistically significant (P > 0.05). In the model group, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively increased, the protein expression levels of E-cadherin and ZO-1 were relatively reduced (P < 0.05), and the protein expression levels of N-cadherin, β-catenin, vimentin, and α-SMA were relatively increased (P < 0.05). In the negative control and experiment groups, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively decreased (P < 0.05), the protein expression levels of E-cadherin and ZO-1 were relatively increased (P < 0.05), and the protein expression levels of N-cadherin, β-catenin, vimentin and α-SMA were relatively decreased (P < 0.05).ConclusionLathyrol and cisplatin inhibit the proliferation of RCC xenografts, reduce the protein expression levels of AR, CYP17A1, SPHK2, PARP1, E-cadherin, and ZO-1 in tumor tissues (P < 0.05), and promote the protein expression levels of N-cadherin, β-catenin, vimentin and α-SMA (P < 0.05). Therefore, Lathyrol reduces RCC invasion and EMT by affecting the expression of AR and SPHK2 in RCC mice.

Racial disparities in incidence and survival in renal cell carcinoma in adolescents and young adults (AYA).

e23153 Background: Renal cell carcinoma (RCC) has doubled in incidence over the past 50 years. Most cases are incidentally discovered. AYA cancer is defined as cancer in individuals 15 to 39 years. There is paucity of data in the literature on racial disparities in the incidence and survival outcomes of RCC in AYA. We aim to determine the influence of race on incidence and survival outcomes in AYA. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) 17 program were utilized to obtain annual percentage change (APC) of RCC from 2000-2020 for patients aged 15-39 years. Patient characteristics were expressed in proportions. Relative survival rate (RSR) was used to determine survival outcomes. The 5-year RSR was defined as the percentage of patients alive 5 years after the diagnosis of cancer. SEER*Stat software was used to determine the RSR. Results: We identified 8751 patients with RCC. A higher proportion of cases were males (57.9%) vs females (52.1%). Patients were predominantly non-hispanic whites (NHW, 54.7%), hispanics (24.9%), non-hispanic blacks (NHB, 11.4%), non-hispanic asian or pacific islander (NHAPI, 0.06%) &amp; non-hispanic american indian/alaska native (NHAIAN, 0.01%). There was significant increase in RCC incidence (APC: 4.0%, CI: 3.0, 4.9). Incidence was higher in males (APC: 4.0, CI: 3.1, 5.0) vs females (APC: 3.9, CI: 2.8, 5.0). Incidence was highest in Hispanics (APC: 5.6%, CI: 4.4, 6.8), followed by NHW (APC: 4.1 % CI: 3.1, 5.2, -2.3), NHAPI (APC: 3.3%, CI: 1.2, 5.5) and NHB (APC: 1.5%, CI: 1.1, 2.0). The 5-year RSR was 79.7% (CI: 77.7, 81.6). Survival was greatest in females (RSR: 82.8, CI: 79.8, 85.4) vs males (RSR: 77.3%, CI: 74.4, 79.9). NHB had the lowest survival (RSR: 65.9%, CI: 60.2, 71.0) compared to NHW (RSR: 83.9%, CI: 81.3-86.2). Conclusions: In AYA, RCC incidence has increased; consistent with global trends. Significant racial disparity in incidence and survival exists. Survival in NHB remained poorer than other racial groups despite minimal increase in incidence. More studies are needed to explore the reasons for these racial differences to improve the outcomes among AYA patients. [Table: see text]

Clinical characteristics and treatment outcomes in Hispanic/Latino patients with advanced renal cell carcinoma at a single institution.

e13738 Background: The incidence of renal cell carcinoma (RCC) is increasing, with an expected 81,610 new cases and 14,390 deaths in 2024. While clinical characteristics in patients with RCC have been well described, studies focusing on minority patients, such as Hispanic and Latino (HL), are limited. The objectives of the current study are to analyze differences in clinical, pathological, and outcome characteristics between HL and non-Hispanic Latino (NHL) pts. with advanced RCC (aRCC) in South Florida. Methods: We retrospectively reviewed clinical and pathological data from pts. with aRCC treated at Sylvester Comprehensive Cancer Center (SCCC) from 2010 to 2023. Descriptive statistics were used to summarize demographic and baseline characteristics. HL vs. NHL groups were compared using chi-square or Fisher’s exact test for categorical variables, and Wilcoxon rank-sum test for continuous variables. Time-to-event outcomes including metastasis-free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method, and two groups were compared using the log rank rest. Results: A total of 417 patients diagnosed with aRCC who received care at SCCC were analyzed. HLs comprised 45% while NHLs represented 55% of patients with aRCC. A higher proportion of HLs presented at an earlier age (&lt; 60y.o, 53% vs. 44%), were female (31% vs. 24%), and had a higher proportion of ISUP grade 4 tumors (47% vs. 34.8%). HLs had a significantly shorter metastasis-free survival (HR 1.48 [95% CI: 1.06-2.05]) compared to NHLs. There were no differences in the frequency of AEs from TKI, IO or IO-TKI based therapies between HLs and NHLs. HLs were less likely to achieve an objective response (CR/PR) to 1st-line therapy compared to NHLs (OR 0.54 (95% [CI: 0.31-0.94]), including HLs with non-ccRCC (OR 0.24 [95% CI: 0.07-0.81]). There was no significant correlation between ethnicity and overall survival in pts. treated with systemic therapy. HLs were less likely to achieve CR/PR to 1st-line therapy compared to NHLs (OR 0.54 [95% CI: 0.31-0.94, p=0.030]) in 217 pts. treated with 1st-line therapy, and in 55 with non-cc RCC (OR 0.24 [95% CI: 0.07-0.81, p=0.021]). There was no significant correlation between ethnicity and overall survival in pts. treated with systemic therapy. Conclusions: In our cohort, patients with aRCC presented at an earlier age and we had a higher proportion of females in HLs compared to NHLs. HLs had a higher risk of developing metastases after nephrectomy compared to NHLs and were less likely to achieve an objective response to 1st-line systemic therapy. Our results, suggesting a potentially more aggressive clinical course of aRCC in HLs in our patients, need further validation in a larger cohort. Future studies will incorporate analysis of molecular tumor characteristics, to further understand biological differences explaining outcomes observed in HL vs NHL populations with aRCC.

Effect of Acridine Orange and Zoledronic Acid on Bone Metastasis in Renal Cell Carcinoma.

The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC. RENCA cells (1.0×106 cells/10 μl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively. The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05). AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU

IntroductionThe incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. Material and methodsWe conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. ResultsStudies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately −5 to −17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. ConclusionStereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. Level of evidence5.

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

BackgroundTuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations.Case presentationA 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5’UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient’s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified.ConclusionsTo our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

#2918 Genetic background of kidney graft cancer

Abstract Background and Aims Renal cell carcinoma (RCC) is one of the most prevalent cancer in kidney transplant recipient (KTR). Majority of RCC occurs in native kidney as opposed to kidney graft. The genetic background of RCC in native kidneys has been determined implicating the clinical importance. Method This single-center cohort study aimed to identify genetic background of kidney graft RCC and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested kidney graft RCC. Genetic analysis (NGS) from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using cancer-predisposition panel CZECANCA (CZEch CAncer paNel for Clinical Application). Results The calculated incidence of kidney graft RCC was 0.43%. Of the eighteen KTR with manifested kidney graft RCC, fifteen KTR and donors underwent NGS. The average patient age at transplantation was 50.3 years (median 54; 5-67 years) and 66 years (median 66; 24-79 years) at the diagnosis of kidney graft RCC. The mean donor age at transplantation was 39.7 years (median 42; 7-68 years) and graft age at kidney graft RCC diagnosis 50.2 years (median 46; 20-83 years). The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0-112 months). The most prevalent was papillary RCC (n=8) followed by clear cell RCC (n=6) and renal pelvis urothelial RCC (n=1). Thirteen RCC were low stage (pT1a/b) disease, one was pT3 and one was unknown stage. Majority of RCC were higher graded. No cancer-predisposition gene was found in KTR or his donor. Conclusion Kidney graft RCC is very rare. NGS cancer-predisposition panel CZECANCA has not detected any genetic predisposition for kidney graft RCC. Further research is needed to assess clinical relevance of genetic testing for cancer risk in KTR.

Percutaneous Ablation of T1b Renal Cell Carcinoma: An Overview.

There is increasing incidence of renal cell carcinoma (RCC) with multiple treatment options currently available. The purpose of this review is to outline patient selection and technical approaches and present the current literature for percutaneous ablation of T1b (4.1-7cm) RCC. An increasing number of retrospective studies and meta-analyses have evaluated the use of percutaneous ablation for T1b RCC. Overall, these studies tend to show that percutaneous ablation in this patient population is feasible. However, rates of major adverse events and local recurrence after percutaneous ablation for T1b RCC are both higher than when ablation is used for smaller tumors. As such, a multi-disciplinary, patient-centered approach is required. Due to the increasing literature in this area, the most recent National Comprehensive Cancer Network (NCCN) guidelines include percutaneous ablation as an option for non-surgical patients with T1b RCC.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma– results from a nation-wide study covering 50 years in Iceland

IntroductionPapillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10–15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period.Materials and methodsA Population based retrospective study including consecutive cases of RCC in Iceland from 1971–2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan–Meier method and Cox regression were used for outcome analysis.ResultsA total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading.ConclusionspRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

Decreased risk of renal cell carcinoma in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors.

Patients with type 2 diabetes (T2D) are at a higher risk of developing renal cell carcinoma (RCC) than the general population. Invitro and invivo investigations of the effects of sodium glucose cotransporter-2 inhibitors (SGLT2I) have shown a significantly reduced risk of RCC. However, the impact of these drugs on the incidence of RCC in the human population is unclear. This study aimed to examine the association between SGLT2I use and RCC risk in patients with T2D. We undertook a nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2020). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was applied to analyze the association between SGLT2I use and RCC risk in patients with T2D. In a cohort of 241,772 patients with T2D who were using SGLT2Is and 483,544 participants who were not, 220 and 609 RCC cases, respectively, were recorded. The mean follow-up period of the study subjects was 2 years. There was a decreased risk of RCC for SGLT2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68; 95% CI, 0.58-0.81). The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.67; 95% CI, 0.55-0.81). The subgroup analysis revealed consistent results for sex, age (<70 years), and comorbidity with chronic kidney disease. The present study indicates that SGLT2I therapy significantly decreases RCC risk in patients with T2D. This finding was also consistent among the sensitivity test and subgroup analysis for those with or without chronic kidney disease/hypertension.

Abstract 4358: Genomic profiling of residual kidney structures in dialysis patients

Abstract Background: Chronic kidney disease is frequently associated with persistent inflammation, which results in fibrosis in the stroma, a reduced number of renal tubules, the formation of multiple cystic lesions, ultimately terminating in renal failure and hemodialysis. The high incidence of renal cell carcinoma (RCC) in hemodialysis patients suggests a relationship between tissue remodeling by chronic inflammation and carcinogenesis. However, little is known about the genetic background of cancer development from remaining tubules and cystic lesions in hemodialysis patients. Methods: We enrolled 5 patients under hemodialysis who were accompanied by acquired cystic kidney disease and who underwent total nephrectomy for renal cancer. Surgical specimens were fixed with alcohol-based solution and paraffin-embedded, and after H&amp;E staining, subjected to laser capture microdissection (LCM) to collect remaining tubules and cysts containing approximately 200 cells. DNA was extracted and analyzed for somatic mutations and copy number alteration by whole-exome sequencing. Results: In total, we collected 161 LCM samples, including 118 from proximal tubules, 17 from collecting ducts, and 26 from cysts. The median variant allele frequencies of detected mutations were 0.237 in proximal tubules, 0.133 in collecting duct, and 0.381 in cysts, indicating larger clonal expansion in proximal tubules and cysts than in collecting ducts. Proximal tubules and cysts contained recurrent mutations in FAT1 (11% and 8%, respectively), STAG2 (5% and 8%), and PTEN (3% and 4%), whereas no recurrent driver mutations were identified in collecting ducts. In copy number analysis, 26% of proximal tubules, 35% of collecting ducts, and 80% of cysts had copy number alterations. Of note, samples from cysts had more copy number alterations compared to remaining tubules (on average, 2.3 vs. 1.1). Proximal tubules had recurrent copy number gains of chromosomes 3, 7, 10, 18, and 20, and loss of chromosome 22 and samples from collecting ducts showed gains of chromosome 7 and loss of chromosome 18. In cysts, gains of chromosomes 2, 3, 7, 10, 12, and 16 and loss of chromosomes 15, 16, 21, and 22 were frequently observed. Copy number profile in cysts was similar to that of papillary RCC and acquired cystic disease-associated RCC. Conclusion: In the end-stage cystic kidney, both proximal tubules and cysts exhibited an enrichment of driver mutations commonly found in papillary RCC and RCC with acquired cystic disease, reflecting the fact that the incidence of these two types of RCC increases as the duration of dialysis becomes longer. In addition, clear cell RCC drivers, such as VHL mutation and loss of chromosome 3, were not observed, possibly explaining the rare occurrence of clear cell RCC in hemodialysis patients. Since cysts had more frequent copy number alterations than remaining tubules, cysts in the end-stage kidney might be precursor lesions of RCC. Citation Format: Kosuke Ieiri, Nobuyuki Kakiuchi, Tomonori Hirano, Koichi Watanabe, Hirona Maeda, Hiroko Tanaka, Satoru Miyano, Dai Takamatsu, Takashi Matsumoto, Keisuke Monji, Masaki Shiota, Junichi Inokuchi, Hideki Makishima, Masatoshi Eto, Seishi Ogawa. Genomic profiling of residual kidney structures in dialysis patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4358.

Association between thymectomy and incidence of renal cell carcinoma (RCC).

Association between thymectomy and incidence of renal cell carcinoma (RCC).

Anemia in patients ≥ 75 years with metastatic clear cell renal cell carcinoma: an important poor prognostic factor in the international metastatic renal cell carcinoma database consortium model

BackgroundDue to an increase in life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years has been increasing. In this study we investigated the characteristics before treatment and the outcomes of systemic therapies for patients aged ≥75 years with mRCC and compared the results with those for patients aged < 75 years in order to determine whether differences in age influenced survival.MethodsA total of 206 consecutive Japanese patients with mRCC, including 47 patients aged ≥75 years, who received systemic therapy were included. Clinical data from medical records were retrieved and analyzed retrospectively. Survival analyses were determined using a Kaplan–Meier method, and analyzed with a log-rank test.ResultsElderly patients categorized as favorable risk group based on the International Metastatic RCC Database Consortium (IMDC) stratification system were significantly lower. Among IMDC risk factors, the rate of anemia was significantly higher in elderly patients. No statistically significant benefit in progression free survival for first and second line treatment was observed, whereas improvements in overall survival as well as cancer specific survival were seen in patients aged < 75 years.ConclusionsFor mRCC patients aged ≥75 years, a higher proportion of base line anemia, which resulted in higher rates of IMDC intermediate/poor risk, would be responsible for shorter OS/CSS. Furthermore, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. Overcoming under-treatment in elderly patients might help to prolong survival in mRCC.

Incidence of renal cell carcinoma after solid organ transplantation: a systematic review and meta-analysis

BackgroundThe incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk.MethodsPubMed, Embase and the Cochrane Library from their inception until August 16,2023. Retrospective and cohort studies which focus on the statistical data of standardized incidence ratios (SIRs) of RCC after solid organ transplantation (SOT) more than one year have been included and extracted. The study was registered with PROSPERO, CRD4202022343633.ResultsSixteen original studies have been included for meta-analysis. Liver transplantation could increase the risk of RCC (SIR = 0.73, 95%CI: 0.53 to 0.93) with no heterogeneity(P = 0.594, I2 = 0.0%). And kidney transplantation could increase the risk of RCC(8.54, 6.68 to 10.40; 0.000,90.0%). Besides, heart and lung transplantation also could increase the risk of RCC(SIR = 0.73, 95%CI: 0.53 to 0.93; SIR = 1.61, 95%CI:0.50 to 2.71). Moreover, significance could also be found in most subgroups, especially the European group and retrospective study group. What’s more, after removing studies which have a greater impact on the overall outcome in RCC rate after kidney transplantation, heterogeneity did not solve and significant different was also observed in the European group (7.15, 5.49 to 8.81; 0.000, 78.6%).ConclusionLiver, kidney, heart and lung transplantation patients have an increased risk of processing RCC compared to the general population and most subgroups, especially in geographic location of European subgroup, which suggested that patients should be screened frequently after transplantation.

The incidence, pathogenesis, and management of non-clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and is divided into two distinct subtypes, clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC). Although many treatments exist for RCC, these are largely based on clinical trials performed in ccRCC and there are limited studies on the management of nccRCC. Non-clear cell RCC consists of multiple histological subtypes: papillary, chromophobe, translocation, medullary, collecting duct, unclassified, and other rare histologies. Due to variations in pathogenesis and therapeutic response, therapy should be tailored to specific variant histologies. For patients with localized nccRCC, surgical resection remains the gold standard. In the metastatic setting, the standard of care has yet to be clearly defined, and most guidelines recommend clinical trial participation. General therapeutic options include immunotherapy, either as monotherapy or in combination, targeted therapies such as vascular endothelial growth factor tyrosine kinase inhibitors and MET inhibitors, and chemotherapy in certain subtypes. Here we present a review of the incidence and pathogenesis of the various subtypes, as well as available clinical data to support therapeutic recommendations for these subtypes. We also highlight currently available clinical trials in nccRCC and future directions in investigating novel treatment modalities tailored to patients with variant histology.

Benefits of Routine Screening for Renal Cell Carcinoma of Native Kidney in Renal Transplant Recipients

Renal-cell carcinoma (RCC) is the most common solid organ cancer in kidney transplantation recipients (KTRs). Analyze the incidence, prognosis, and evolution of primitive kidney RCC in KTRs at our institution. Observational descriptive retrospective study in which all KTRs from January 2000 to December 2022 were included. We performed an annual abdominal ultrasound in all KTRs. Demographic and clinical data were collected. The surgical approach, location, size, histologic type, and tumor grade were analyzed. We assessed the coexistence of risk factors. We reported the appearance of tumors in other locations, changes in immunosuppressants (IS) after the diagnosis, and survival and recurrence rates observed during follow-up. Eighteen RCCs of native kidneys were diagnosed with an incidence in our population of 1.08%. The majority were men (77.8%), with a mean age of 59.9 years. The pathologic analysis revealed 11 clear cell carcinomas, 6 papillary carcinomas, and 1 chromophobe cell carcinoma. The median tumor size was 2.7 cm. TNM stage was T1aN0M0 in 15 cases. Laparoscopy was performed to remove the tumor in most cases. All our patients underwent changes in IS therapy, with conversion to mammalian target of rapamycin inhibitors when possible and reduction of IS in all of them. After a mean follow-up of 78.6 months, survival was 100% without tumor recurrence. Seven of the patients were diagnosed with a new tumor in another location. In our experience, annual abdominal ultrasound in KTRs may be an option for the early detection of RCC in native kidneys.