Clear Cell Research Articles

Targeting ZNF638 activates antiviral immune responses and potentiates immune checkpoint inhibition in glioblastoma.

Viral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression and poor immune cell infiltration (CD8 + T-cells, dendritic cells). ZNF638 knockdown decreased H3K9-trimethylation, increased cytosolic dsRNA and activated intracellular dsRNA-signaling cascades (RIG-I, MDA5 and IRF3). Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in patient-derived GBM neurospheres and diverse murine models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate interferon signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1 and perivascular CD8 cell infiltration, suggesting dsRNA-signaling may mediate response to immunotherapy. Finally, we showed that low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in rGBM patients and melanoma patients. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.

USP7 depletion potentiates HIF2α degradation and inhibits clear cell renal cell carcinoma progression

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib.

Exploring TFE3-Rearranged Renal Cell Carcinoma: A Case Study showing minimal expression of PAX-8

Abstract Introduction/Objective TFE3-rearranged renal cell carcinoma accounts for 1.6-4% of adult renal cell carcinomas (RCC). The histological characteristics of this entity can mimic many other renal cell neoplasms and definite diagnosis is based on immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) analysis. Nonspecific IHC findings can lead to diagnostic challenges delaying confirmatory studies and underdiagnosis. Methods/Case Report A 28-year-old male with sickle cell disease and a right kidney multilocular cystic mass incidentally found during evaluation of splenomegaly underwent partial nephrectomy. The tumor showed papillary, alveolar and sheet-like growth patterns composed of eosinophilic to clear cells with pleomorphic nuclei, including multinucleate forms. Initial ancillary studies showed minimal neoplastic expression (less than 5%) of PAX-8. Repeat PAX-8 yielded similar results and laboratory controls were evaluated successfully. A full work-up showed positivity of AMACR (diffuse), CD10 (diffuse), Cathepsin K (patchy), CK7 (focal), CAIX (focal), and no significant expression of pancytokeratin, HMB-45, Melan-A and SMA. Fumarate hydratase was retained, and the tumor showed a non-specific staining pattern of S (2-succinyl)-cysteine. Controls were appropriate. A high suspicion for a TFE-rearranged RCC was maintained, and a final diagnosis was confirmed with FISH analysis demonstrating a TFE3 (Xp11.23) rearrangement. Results (if a Case Study enter NA) NA Conclusion Reports in the literature detail diffuse PAX-8 expression in TFE3-rearranged RCC. A high index of suspicion based on morphology in our case prompted FISH analysis leading to correct diagnosis. This case highlights the inconsistencies in the reported IHC profile of this entity. More studies are required to elaborate the presentations of this RCC subtype with numerous histologic mimics including the spectrum of immunostaining patterns to better assist patient care for this uncommon variant.

Malignant transformation in mature cystic teratoma of ovary: Series of 4 cases

Mature cystic teratoma is the most common benign ovarian tumour of germ cell origin. Malignant transformation is rare in mature cystic teratoma. Here we present a series of 4 cases showing malignant transformation in the form of squamous cell carcinoma, follicular carcinoma, and clear cell carcinoma in mature cystic teratoma. Our case series suggest that there should be suspicion of malignant transformation in mature cystic teratoma when they are present in perimenopausal and postmenopausal females.

CRTC1::TRIM11-fusion tumor with rare sinonasal presentation and locally aggressive disease course

Abstract Introduction/Objective Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a rare dermatological neoplasm that has not yet been formally recognized by the World Health Organization. At present, our knowledge of this disease is limited to single reports and a series 41 cases with limited follow-up information. It is typically described as a skin lesion expressing melanocytic makers, often leading to its misdiagnosis as melanoma or clear cell sarcoma. CMTCT is regarded as an indolent tumor with infrequent recurrence after complete surgical excision. However, we present a case with uncommon sinonasal presentation and metastasis after multiple resections. Methods/Case Report A 23-year-old woman presented with a right nasal vestibule mass, requiring partial rhinectomy in a foreign country, where she subsequently received chemoradiation. Her tumor at the time was diagnosed as a mucosal melanoma. Eleven years following initial presentation, she demonstrated a recurrent right nasal tumor, as well as neck mass, cervical lymphadenopathy, and lung nodules. The patient then underwent a nasal endoscopic resection and modified neck dissection, which demonstrated a high-grade neoplasm with intersecting fascicles of medium-to-large monomorphic cells; whole exome and whole transcriptome sequencing performed on the resected neck mass identified a pathogenic TERT c.-146C>T alteration and CRTC1 exon 1::TRIM11 exon 2 fusion. The patient is currently alive and undergoing post-surgical chemoradiation. Results (if a Case Study enter NA) NA Conclusion This case expands our understanding of CMTCT and emphasizes its potentially aggressive behavior. The sinonasal presentation contrasts the tumor’s typical appearance on the skin and could mimic mucosal melanoma. Of note, our patient developed recurrent disease and distant metastases, thereby emphasizing the possible role of systemic therapy and suggesting that simple surgical excision may not be curative in all cases. Our case illustrates that CMTCT is an uncommon and potentially misidentified neoplasm, but that its proper diagnosis is essential for treatment selection and follow up.

Surgical Treatment and Clinical Evaluation of Calvarial Metastases.

The aim of this study is to explore surgical treatment techniques and clinical attributes associated with calvarial metastases, while providing a comprehensive review of the treatment experiences relevant to this particular type of tumor. This study involves a retrospective analysis of clinical data from 12 patients diagnosed with calvarial metastatic tumors who underwent surgical intervention. Among these patients, 5 had a history of previous malignant tumor resections, while 7 presented with calvarial metastatic tumors as their initial symptom. In all cases, the surgical approach consisted of calvarial tumor resection followed by titanium mesh repair. Following the surgical intervention, all patients underwent a comprehensive course of treatment, encompassing both local radiotherapy and systemic chemotherapy. In 1 instance, a patient presented with multiple tumors located in the central area of the frontal bone and the right temporal bone. The larger tumor situated in the middle of the frontal bone was surgically excised, while the tumor in the right temporal bone was treated using radiotherapy. In 2 cases characterized by multiple metastases within the skull, a comprehensive excision of all tumors was accomplished in a single surgical procedure. In the remaining cases featuring a solitary metastatic growth, the respective tumors were surgically removed. There were 10 instances of dura mater invasion and 3 cases involving the invasion of brain tissue. Pathologic examinations revealed 1 case of metastatic lung adenocarcinoma, 1 case of metastatic paraganglioma, 1 case of metastatic hepatocellular carcinoma, 2 cases of metastatic thyroid carcinoma, and 7 cases of metastatic clear cell renal cell carcinoma. Throughout the follow-up period, spanning from 14 to 90 months, various outcomes were noted. These included three occurrences of in situ recurrence. In addition, 1 patient required 3 distinct surgical interventions, while 2 other patients underwent 2 separate surgical procedures each. Notably, 1 of these cases involved the exposure of the titanium mesh on the scalp, necessitating the removal of the titanium mesh. Regrettably, there have been 9 recorded fatalities among the patients, while 3 individuals have survived. Solitary metastasis of calvarium region is rare, and surgical resection is effective. However, it is necessary to extend the resection range and combine with local radiotherapy to avoid local recurrence. Surgical intervention can significantly enhance the quality of life for affected patients. The prognosis of the patients mainly depends on the treatment of the primary disease and the situation of important organ dissemination and treatment.

Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report

Abstract Introduction/Objective The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis. Methods/Case Report A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established. Results (if a Case Study enter NA) NA Conclusion Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.

Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma.

Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

Value of Contrast-Enhanced Ultrasound in the Diagnosis of Clear Cell Renal Cell Carcinoma: A Meta-Analysis.

This meta-analysis aims to evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in diagnosing clear cell renal cell carcinoma (ccRCC). Literature published in five databases was searched. Twelve studies were included. The pooled results showed sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS were 79% (95% CI: 75%-83%), 84% (95% CI: 80%-88%), 4.97 (95% CI: 3.86-6.39), 0.24 (95% CI: 0.20-0.30), and 20.32 (95% CI: 13.84-29.84), respectively. The area under the summary receiver operating characteristic curve was 0.86. In conclusion, CEUS demonstrates high sensitivity and specificity in diagnosing ccRCC, showing good diagnostic accuracy.

Fatal Case of Immune-Related Myocarditis and Myositis Due to Treatment with Immune Checkpoint and Tyrosine Kinase Inhibitors.

Immune checkpoint inhibitor and tyrosine kinase inhibitor combinations have become the new standard of care in the first-line treatment of metastatic clear cell renal cell carcinoma. However, there is a growing concern regarding severe immune-related adverse events. A 78-year-old man with metastatic clear cell renal cell carcinoma, treated with pembrolizumab and axitinib, was admitted to the emergency department 30 days after initiating treatment due to rapidly progressive myositis. Myocarditis with severe ventricular dysfunction was identified. Muscular biopsy findings were compatible with inflammatory myopathy associated with immune checkpoint inhibitors. Initial treatment with high-dose corticosteroids showed an insufficient response. Therapeutic escalation on the third day with methylprednisolone, immunoglobulin, and abatacept resulted in clinical improvement. On the eleventh day, a sudden malignant arrhythmia occurred, followed by cardiac arrest. This represents one of the first case reports describing myocarditis and myositis during treatment with pembrolizumab-axitinib. While immune checkpoint inhibitor may play a major role, it is also possible that the tyrosine kinase inhibitor, while attempting to promote immune modulation, also increases severe toxicities.

Clear Cell Carcinoma Arising From Adenomyotic Cyst: A Case Report

Clear Cell Carcinoma Arising From Adenomyotic Cyst: A Case Report

Detection and Validation of Organic Metabolites in Urine for Clear Cell Renal Cell Carcinoma Diagnosis.

Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70-80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model. This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers. The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity. This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study's capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise.

The prognostic value and immunological role of calcium/calmodulin dependent protein kinase kinase 2 (CAMKK2) in pan-cancer study.

A thorough assessment of calcium/calmodulin dependent protein kinase kinase 2 (CAMKK2) in pan-cancer studies is currently absent. We integrate multi-omics and clinical data to conduct a molecular landscape of CAMKK2. Gene variation results revealed abnormal high frequency mutations of CAMKK2 in uterine corpus endometrial carcinoma, while expression level analysis demonstrated relatively high expression of CAMKK2 in prostate adenocarcinoma. The aberrant expression of CAMKK2 was found to be predictive of survival outcomes in several cancer types. Additionally, we identified potential regulators of CAMKK2 expression, including miRNAs such as miR.129.1.3p, as well as small-molecule drugs such as EPZ004777, which significantly correlated with CAMKK2 expression. Single-cell transcriptome analysis of kidney renal clear cell carcinoma further revealed a significantly higher expression of CAMKK2 in and monocyte and macrophage M1. Furthermore, in the kidney renal clear cell carcinoma IMvigor210 cohort, patients ongoing immunotherapy with higher CAMKK2 expression experienced a significantly longer median overall survival, but it was observed that in bladder urothelial carcinoma GSE176307 and skin cutaneous melanoma GSE78220 cohorts, CAMKK2 might significantly prolong overall survival. Briefly, CAMKK2 emerges as a promising molecular biomarker that holds potential implications for prognostic evaluation and predicting the effectiveness of immunotherapy across cancers.

The Interplay between von Hippel-Lindau Tumor Suppressor Gene, Lon Protease, ROS Accumulation, and Inflammation in Clear Cell Renal Cell Carcinoma.

This study explores the role of the von Hippel-Lindau (VHL) tumor suppressor gene and Lon protease in the development of clear cell renal carcinoma (ccRCC) through mechanisms involving inflammation and reactive oxygen species (ROS) accumulation in kidney cells. By examining the impact of VHL on the early stages of kidney cancer development, this research highlights the contributions of inflammation and ROS, as well as the involvement of Lon protease. The findings reveal increased Lon expression and ROS levels in VHL-knockdown HK-2 cells, along with elevated phospho-c-Jun N-terminal kinase (JNK) levels, emphasizing the complex interplay between VHL, Lon protease, inflammation, and ROS in kidney cell models. These insights point to potential therapeutic pathways for ccRCC.

Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis: A Multi-institutional Clinicopathologic and Molecular Study of Five Patients.

Clear cell adenocarcinoma (CCA) of the urinary tract is a rare malignancy and tumors involving the renal pelvis are notably sparse in the literature, with only 5 other patients reported. We present 5 patients, 4 women, and 1 man, with CCA of the renal pelvis. The age at presentation ranged from 29 to 81 years. The tumor size ranged from 4.5 to 8.0 cm. Tumors exhibited shared morphologic and immunohistochemical features with CCA of the female genital tract and those originating in the bladder and urethra, including cells with large nuclei, prominent nucleoli, nuclear hobnailing, and scant clear cytoplasm. Common immunohistochemical findings included reactivity for PAX8, CK7, HNF1β, and Napsin-A. One of the tumors arose in the background of a mixed epithelial and stromal tumor. Another tumor occurred in a renal allograft and tumor cells were positive for the BK virus, demonstrated by SV40 immunohistochemistry. All tumors were negative for TFE3 and TFEB rearrangement and lacked TERT alterations. Follow-up was limited with no recurrence in 4 patients at a maximum of 20 months follow-up and 1 patient died of an unrelated cause at 25 months of follow-up. Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.

Inhibition of primary cilia-hedgehog signaling axis triggers autophagic cell death and suppresses malignant progression of VHL wild-type ccRCC

Primary cilia are present on renal tubules and are implicated to play a pivotal role in transducing signals during development; however, the oncogenic role of cilia in clear cell renal cell carcinoma (ccRCC) has not been examined. Here we show that VHL wild-type ccRCC cell lines have a high incidence of primary cilia, and a high frequency of primary cilia is positively correlated with VHL expression and poor prognosis. Besides, the depletion of KIF3A and IFT88, genes required for ciliogenesis, significantly inhibited tumor proliferation and metastasis in vitro and in vivo. Further analysis found that mutations of key genes in hedgehog signaling are enriched in VHL wild ccRCC, its downstream signaling activation depends on ciliogenesis. Moreover, depletion of primary cilia or suppression of hedgehog pathway activation with inhibitor-induced robust autophagic cell death. Collectively, our findings revealed that primary cilia could serve as a diagnostic tool and provide new insights into the mechanism of VHL wild-type ccRCC progression. Targeting the primary cilia-hedgehog pathway may represent an effective therapeutic strategy for VHL wild-type ccRCC.

Application of artificial intelligence model in pathological staging and prognosis of clear cell renal cell carcinoma

This study aims to develop a deep learning (DL) model based on whole-slide images (WSIs) to predict the pathological stage of clear cell renal cell carcinoma (ccRCC). The histopathological images of 513 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training set and validation set according to the ratio of 8∶2. The CLAM algorithm was used to establish the DL model, and the stability of the model was evaluated in the external validation set. DL features were extracted from the model to construct a prognostic risk model, which was validated in an external dataset. The results showed that the DL model showed excellent prediction ability with an area under the curve (AUC) of 0.875 and an average accuracy score of 0.809, indicating that the model could reliably distinguish ccRCC patients at different stages from histopathological images. In addition, the prognostic risk model constructed by DL characteristics showed that the overall survival rate of patients in the high-risk group was significantly lower than that in the low-risk group (P = 0.003), and AUC values for predicting 1-, 3- and 5-year overall survival rates were 0.68, 0.69 and 0.69, respectively, indicating that the prediction model had high sensitivity and specificity. The results of the validation set are consistent with the above results. Therefore, DL model can accurately predict the pathological stage and prognosis of ccRCC patients, and provide certain reference value for clinical diagnosis.

Prognostic factors and prognostic model of non-metastatic clear cell renal cell carcinoma

IntroductionAlthough there are some established prognostic evaluation models for clear cell renal cell carcinoma (ccRCC), more robust postoperative prognostic evaluation model is urgently needed. Our study intends to explore new clinical and pathological prognostic factors related to non-metastatic ccRCC, which help to establish a better prognostic risk evaluation model in non-metastatic ccRCC.Patients and methodsA retrospective cohort study was conducted in non-metastatic ccRCC patients spanning from 2010 to 2018. Clinical and pathological factors of these patients were collected. Cox regression analysis was employed to assess the relationship between these factors and disease-free survival (DFS), and a nomogram risk prediction model was also constructed.ResultsA total of 1467 patients were ultimately included, comprising 994 men (67.8%), with 800 patients aged between 40 and 60 years old (54.5%), and 80 patients (5.5%) experiencing relapse or metastasis of ccRCC within three years after operation. The follow-up duration ranged from 39 to 146 months. Univariate and multivariate Cox regression analysis identified five independent prognostic factors of DFS (P < 0.05) including sex, tumor maximum diameter, T stage, lactate dehydrogenase (LDH), and basophils. Leveraging these five factors, we established a prognostic evaluation model demonstrating good predictive efficacy.ConclusionMale, tumor maximum diameter, T stage, LDH, and basophils serve as prognostic indicators for DFS in patients with non-metastatic ccRCC. Patients with high scores based on our model exhibit an elevated likelihood of recurrence or metastasis, thereby potentially selecting postoperative patients with high risk for adjuvant therapy.

Radiomics-based machine learning role in differential diagnosis between small renal oncocytoma and clear cells carcinoma on contrast-enhanced CT: A pilot study

PurposeTo investigate the potential role of radiomics-based machine learning in differentiating small renal oncocytoma (RO) from clear cells carcinoma (ccRCC) on contrast-enhanced CT (CECT). Material and methodsFifty-two patients with small renal masses who underwent CECT before surgery between January 2016 and December 2020 were retrospectively included in the study. At pathology examination 39 ccRCC and 13 RO were identified. All lesions were manually delineated unenhanced (B), arterial (A) and venous (V) phases. Radiomics features were extracted using three different fixed bin widths (bw) of 25 HU, 10 HU, and 5 HU from each phase (B, A, V), and with different combinations (B+A, B+V, B+A+V, A+V), leading to 21 different datasets. Montecarlo Cross Validation technique was used to quantify the estimator performance. The final model built using the hyperparameter selected with Optuna was trained again on the training set and the final performance evaluation was made on the test set. ResultsThe A+V bw 10 achieved the greater median (IQR) balanced accuracy considering all the models of 0.70 (0.64–0.75), while A bw 10 considering only the monophasic ones. The A bw 10 model achieved a median (IQR) sensitivity of 0.60 (0.40–0.60), specificity of 0.80 (0.73–0.87), AUC-ROC of 0.77 (0.66–0.84), accuracy of 0.75 (0.70–0.80), and a Phi Coefficient of 0.38 (0.20–0.47). None of the nine models with the lowest mean balanced accuracy values implemented features from A. ConclusionThe A bw 10 model was identified as the most efficient mono-phasic model in differentiating small RO from ccRCC.