Search Results (176)

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Currently, there is no standard treatment for renal cell carcinoma (RCC) that is free of side effects and resistance. Additionally, limited information exists on how curcumin affects the gene expression profiles of patients with translocation renal cell carcinoma (tRCC) and papillary renal cell carcinoma (pRCC). The pathways responsible for metastasis in tRCC are still not well understood, and there is no established treatment or reliable biomarker to predict outcomes for metastatic tRCC. Primary clinical data from patients were retrieved from the TCGA database and analyzed using cBioPortal, stitch, string, R and Python. Various analyses were performed, including differential gene expression, protein-protein interaction (PPI) network analysis, drug-targeted gene analysis, gene ontology (GO), enrichment analyses, and systematic searches to assess the impact of curcumin on the transcriptomic profiles of tRCC, pRCC, and clear cell renal cell carcinoma (ccRCC). No significant impact of sensitive genes on survival in KIRC and KIRP was found, though a trend suggested they may delay disease progression. The combination of curcumin with sunitinib showed promise in overcoming drug resistance in ccRCC by inducing ferroptosis, reducing iron, and increasing ADAMTS18 expression. This study, leveraging data from the TCGA database and other databases explored the impact of curcumin on transcriptomic profiles in tRCC, pRCC, and clear cell RCC (ccRCC). Gene analysis revealed immune and metabolic differences, with KIRC showing a stronger immune response. This study is the first to propose that future research into the miR-148/ADAMTS18 genes and the ferroptosis pathway in tRCC and pRCC could lead to the development of new therapies and the identification of novel therapeutic targets, potentially overcoming drug resistance and metastasis. Full article

Renal cell carcinoma (RCC) accounts for about 403,000 new cases and 175,000 deaths worldwide each year. Clear cell RCC (ccRCC), the most prevalent subtype, is often driven by genetic mutations, such as VHL inactivation, leading to angiogenesis and immune escape. Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 have transformed treatment paradigms, yet therapeutic resistance remains a critical challenge. The immunosuppressive nature of the tumor microenvironment (TME) in ccRCC plays a central role in limiting ICI efficacy. Emerging strategies aim to overcome resistance by targeting key components of the TME, including tumor-associated macrophages, regulatory T cells (Tregs), and cytokine signaling. Agents such as nivolumab, pembrolizumab, and ipilimumab have demonstrated the ability to restore T-cell activity and mitigate immune suppression, offering clinical benefit in metastatic ccRCC. However, response rates vary, highlighting the need for rational combination therapies. ICIs combined with VEGF inhibitors have shown promising outcomes in clinical trials, and novel regimens continue to be explored. Risk stratification and personalized treatment selection are increasingly important as the therapeutic landscape evolves. This review synthesizes current advances in immunotherapy for ccRCC, with a focus on mechanisms of resistance and innovative strategies to enhance immune responsiveness. A deeper understanding of TME modulation and strategic combination approaches is essential to improve survival and quality of life for patients with advanced ccRCC. Full article

Objective: Early diagnosis and treatment of metastatic pericardial disease are crucial to prevent the life-threatening complication of cardiac tamponade. Thin Layer Cytology (TLC), a widely adopted technique in cytology, has gained significant acceptance for most specimens. Our study aimed to assess the utility of TLC in diagnosing metastatic neoplasms and their origins in pericardial effusions, as well as monitoring response to chemotherapy. Methods: We examined 184 pericardial fluids collected by pericardiocentesis and processed using the ThinPrep liquid-based technique. Various immunocytochemical markers were used to determine the site of metastatic neoplasms. We also evaluated the response to therapy in 53 patients with lung and breast cancer. Results: Out of 184 specimens, 113 pericardial fluids were diagnosed as positive for malignancy, while 71 were negative. Twenty-three cases of unknown primary site were included in the total positive cases. Ninety cases positive for malignancy had a known primary site of origin, including 31 lung carcinomas, 22 breast carcinomas, 10 ovarian carcinomas, 6 T-cell lymphomas, 3 urinary bladder carcinomas, 4 renal carcinomas, 5 adenocarcinomas of the colon, 5 prostate carcinomas, 2 parotid adenocarcinomas, and 2 melanomas. Regarding the 53 cases with chemotherapy treatment, the cytologic examination of pericardial fluid showed a remarkable reduction in neoplastic burden after the third dose of cisplatin or thiotepa instilled into the pericardial cavity. ThinPrep provided excellent preservation of cytomorphological features, high cellularity per slide, and a clear background. This comprehensive analysis provides crucial information about the types and distribution of cancerous cells present in the samples. Conclusions: Thin Layer Cytology (TLC) is a valuable diagnostic tool for detecting metastatic pericardial malignancy. It allows the examination of exfoliated cells from the pericardial fluid, providing crucial information for diagnosis, management, and monitoring the acute responsiveness to intrapericardial chemotherapy. Immunocytochemistry (IHC) can identify specific markers for various types of cancer, enabling a more accurate diagnosis and guiding further treatment decisions. Full article

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogenous group of malignancies with varying degrees of clinical aggressiveness and response to different systemic therapies. As the characterization of subtypes of nccRCC continues to evolve, it is important to understand the evidence around systemic treatments used in advanced or metastatic stages of specific subtypes. Here, we review the literature on systemic therapies in nccRCC, with a focus on prospective trials that included patients with papillary renal cell carcinoma (RCC), chromophobe RCC, RCC not further classified/unclassified RCC, translocation RCC, collecting duct RCC, and renal medullary carcinoma. We also review emerging treatments for other molecularly defined subtypes of this disease. Full article

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear cell RCC. The patient initially presented with right lower back pain, weight loss, and a loss of appetite. Following systemic immunotherapy with nivolumab and ipilimumab, and right radical nephrectomy, the patient was diagnosed with metastatic clear cell RCC, with new metastatic lesions detected in the liver, and on the chest wall on follow-up imaging. Second-line systemic treatment with pazopanib was initiated. Shortly thereafter, the patient developed severe systemic inflammatory syndrome, resulting in a mental stupor and acute kidney failure. Intensive care, including continuous renal replacement therapy and high-dose immunosuppressants, was administered. The patient’s condition improved significantly with the intensive care regimen, leading to unintended tumor regression. These potentially fatal side effects occurred without infection, as confirmed by negative blood and urine cultures, and were attributed to the recent introduction of pazopanib. Follow-up imaging showed a significant reduction in hepatic metastatic lesions and the disappearance of chest wall nodules. This is the first reported case of RCC tumor regression following the side effects of pazopanib, underscoring the need for further studies into the immune mechanisms involved in RCC treatment and highlighting potential therapeutic strategies that leverage innate immune responses. Full article

Ankyrin repeat domain 1 (Ankrd1), a transcriptional target of Yes-associated protein (YAP), is linked to cardiomyopathy. However, its role in cancer, particularly in clear cell renal cell carcinoma (ccRCC), remains vague. In this study, we examined the expression, regulation, and function of Ankrd1 in ccRCC. High Ankrd1 expression was related to poor prognosis in patients with ccRCC in The Cancer Genome Atlas cohort. Ankrd1 expression was regulated by YAP in all ccRCC cell lines examined and also by ERK5 in a subset of ccRCC cell lines. Moreover, silencing of Ankrd1 in ccRCC cell lines resulted in decreased cell motility, whereas its overexpression increased the cell motility. Ankrd1 colocalized with F-actin in lamellipodia upon phorbol ester stimulation. Ankrd1 silencing resulted in alterations in the shape of RCC cells and caused a decrease in lamellipodia formation. Ankrd1 also colocalized with talin-1 in lamellipodia. Ankrd1 depletion repressed talin-1-mediated activation of the integrin pathway. Immunohistochemical examination of surgical specimens revealed high expression of Ankrd1 in metastatic RCC tissues compared with that in primary RCC tissues from the same patients. Collectively, these findings suggest that Ankrd1 plays a critical role in the motility of ccRCC cells through lamellipodia formation. Full article

Background and Clinical Significance: Renal cell carcinoma (RCC) is the third most common cancer that metastasizes to the oral and maxillofacial region following breast and lung cancers. Metastatic involvement in the oral cavity is rare and can present as a diagnostic challenge due to non-specific clinical features that mimic other benign or malignant conditions. The limited information available regarding oral metastasis of RCC highlights the importance of recognizing this uncommon presentation. Case Presentation: A 50-year-old female presented with a painful swelling in the buccal and palatal mucosa of the right maxilla that progressively enlarged over several months. Initially, this lesion was diagnosed clinically as a pyogenic granuloma. However, given the lesion’s continued growth and unusual presentation, a biopsy was performed. Histopathological examination confirmed the lesion as metastatic renal clear-cell carcinoma (ccRCC), with immunohistochemical analysis verifying the renal origin. Further diagnostic tests, including a computed tomography (CT) urogram, chest CT, and bone scintigraphy, revealed additional metastases in the left adrenal gland, lungs, and bone. Conclusions: This case is notable because the oral lesion was the first visible sign of RCC, making it a rare presentation of metastatic RCC. This underscores the importance of thorough history taking, detailed clinical evaluations, and considering rare metastatic conditions in the differential diagnosis of oral swellings. Additionally, this case reinforces the significance of routine cancer screenings for early detection of undiagnosed cancer. We also updated a previous literature review of metastatic RCC to the head and neck region, covering cases until 2023. Full article

Despite advances in the management of advanced clear cell renal cell carcinoma (ccRCC), robust biomarkers for prognosis and therapeutic response prediction remain elusive. Dysregulation of the intrarenal renin–angiotensin system (RAS) has been implicated in renal carcinogenesis but little explored, particularly regarding biomarker discovery and therapeutic innovation. Consequently, this study investigates the immunohistochemical expression and clinical relevance of the Mas-related G-protein-coupled receptor D (MrgD) in patients with ccRCC who developed metastatic disease (mccRCC). A cohort of 132 patients treated between 2008 and 2018 with nephrectomy and tyrosine kinase inhibitor (TKI)-based sequential therapy was analyzed. Treatment response was assessed using both the MASS and RECIST scoring systems. High MrgD expression in primary tumors was significantly associated with larger size, advanced stage, higher histological grade, and worse overall survival. Among 81 patients with metachronous metastases, high MrgD expression independently predicted shorter disease-free survival. High MrgD staining intensity correlated with poorer TKI responses in first-line therapy but improved outcomes with second-line mTORC1 inhibitors. These findings suggest that MrgD may be a useful biomarker of RAS linked to tumor aggressiveness in ccRCC. MrgD holds potential for identifying high-risk patients and guiding treatment selection in advanced disease. Further research is needed to unlock its clinical potential. Full article

Background: Immunotherapy based on checkpoint inhibition is widely used in the treatment of metastatic renal cell carcinoma (RCC); however, predictive and prognostic biomarkers are yet to be explored. The objective of this study was to evaluate the prognostic value of the hemoglobin, albumin, lymphocyte, platelet (HALP) score in metastatic RCC patients receiving nivolumab. Methods: We enrolled 149 individuals (including 38 females) with a median age of 62 years, who were treated with nivolumab (at a dosage of 240 mg biweekly or 480 mg every 28 days) following progression on at least one tyrosine kinase inhibitor (TKI) between 2016 and 2024. The study population was dichotomized by the median HALP score (27.53), which was calculated as hemoglobin (g/L) × albumin (g/L) × absolute lymphocyte count/platelets (g/L) at immunotherapy initiation. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, with differences analyzed via a log-rank test. A multivariate Cox proportional hazards model was utilized for evaluation of the prognostic value of performance status, lactate dehydrogenase (LDH) levels, and HALP score. Results: At a median follow-up of 31.1 months, 122 patients had progressed on nivolumab and 87 had died. Poor performance status was associated with significantly worse PFS and OS (HR 0.20 and 0.14, respectively). Survival was worse in individuals with an LDH level higher than 1.5 times the normal range compared to those with lower LDH values (HR 0.45 for PFS and HR 0.41 for OS). Patients with low HALP scores had shorter PFS (HR 0.69) and OS (HR 0.58) versus patients with high HALP scores. In the multivariate analysis, the independent prognostic value of the HALP index for OS was revealed in a metastatic clear-cell RCC (ccRCC) population. Conclusions: The HALP score determined before nivolumab initiation as the second or third line of treatment is an independent prognostic factor of OS in metastatic ccRCC patients. Prospective validation could lead to the incorporation of this index into prognostic models for patients with RCC. Full article

A thorough study of Clear Cell Renal Cell Carcinoma (ccRCC) shows that combining tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICI) shows promising results in addressing the tumor-promoting influences of abnormal immunological and molecular biomarkers in metastatic Clear Cell Renal Cell Carcinoma (ccRCC). These abnormal biomarkers enhance drug resistance, support tumor growth, and trigger cancer-related genes. Ongoing clinical trials are testing new treatment options that appear more effective than earlier ones. However, more research is needed to confirm their long-term safety use and potential side effects. This study highlights vital molecular and immunological biomarkers associated with drug resistance in Clear Cell Renal Cell Carcinoma (ccRCC). Furthermore, this study identifies a number of promising drug candidates and biomarkers that serve as significant contributors to the enhancement of the overall survival of ccRCC patients. Consequently, this article offers pertinent insights on both recently completed and ongoing clinical trials, recommending further toxicity study for the prolonged use of this treatment strategy for patients with metastatic ccRCC, while equipping researchers with invaluable information for the progression of current treatment strategies. Full article

Mutations of the von Hippel–Lindau (VHL) tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of VHL lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes. Belzutifan, an HIF-2α inhibitor, has been recently indicated for metastatic RCC and other antiangiogenic drugs directed against HIF-2α are currently under investigation. Further, clinical and preclinical studies of combination approaches for metastatic RCC including belzutifan with cyclin-dependent kinase 4–6 inhibitors, tyrosine kinase inhibitors, or immune checkpoint inhibitors achieved promising results or are ongoing. This review aims to summarize the existing evidence regarding the VHL/HIF pathway, and the approved and emerging treatment strategies that target this pivotal molecular axis and their mechanisms of resistance. Full article

Purpose of Review: This review aims to describe the role of limbic system-associated membrane protein (LSAMP) in normal- and pathophysiology, and its potential implications in oncogenesis. We have summarized research articles reporting the role of LSAMP in the development of a variety of malignancies, such as clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. We also examine the current understanding of how defects in LSAMP gene function may contribute to oncogenesis. Finally, this review discusses the implications of future LSAMP research and clinical applications. Recent Findings: LSAMP has been originally described as a surface adhesion glycoprotein expressed on cortical and subcortical neuronal somas and dendrites during the development of the limbic system. It is categorized as part of the IgLON immunoglobulin superfamily of cell-adhesion molecules and is involved in regulating neurite outgrowth and neural synapse generation. LSAMP is both aberrantly expressed and implicated in the development of neuropsychiatric disorders due to its role in the formation of specific neuronal connections within the brain. Additionally, LSAMP has been shown to support brain plasticity via the formation of neuronal synapses and is involved in modulating the hypothalamus in anxiogenic environments. In murine studies, the loss of LSAMP expression was associated with decreased sensitivity to amphetamine, increased sensitivity to benzodiazepines, increased hyperactivity in new environments, abnormal social behavior, decreased aggressive behavior, and decreased anxiety. Findings have suggested that LSAMP plays a role in attuning serotonergic activity as well as GABA activity. Given its importance to limbic system development, LSAMP has also been studied in the context of suicide. In malignancies, LSAMP may play a significant role as a putative tumor suppressor, the loss of which leads to more aggressive phenotypes and mortality from metastatic disease. Loss of the LSAMP gene facilitates epithelial-mesenchymal transition, or EMT, where epithelial cells lose adhesion and gain the motile properties associated with mesenchymal cells. Additionally, LSAMP and the function of the RTK pathway have been implicated in tumorigenesis through the modulation of RTK expression in cell membranes and the activation of second messenger pathways and β-catenin. Summary: Beyond its many roles in the limbic system, LSAMP functions as a putative tumor suppressor protein. Loss of the LSAMP gene is thought to facilitate epithelial-mesenchymal transition, or EMT, where cells lose adhesion and migrate to distant organs. LSAMP’s role in modulating RTK activity and downstream ERK and Akt pathways adds to a large body of data investigating RTK expression in oncogenesis. The characteristics of LSAMP defects and their association with aggressive and metastatic disease are evident in reports on clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. Full article

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. Full article

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim, suggestive of an inflammatory appearance. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient’s stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. The primary presumptive diagnosis was of cutaneous metastasis, considering the patient’s history of metastatic ccRC. However, given the recent initiation of new pharmacological agents, the rapid progression of the cutaneous lesions, and their clinical presentation, alternative differential diagnoses were considered, including drug-induced reactions such as erythema multiforme or fixed drug eruption. A biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the potential for extremely rapidly evolving cutaneous metastases from ccRC and their capacity to occasionally mimic atypical drug eruptions. Additionally, it reaffirms the poor prognosis of such metastases, as evidenced by the patient’s death within two months. Full article