This study aims to apply ResNet-18 convolutional neural network(CNN)and XGBoost to preoperative computed tomography(CT)images and clinical data for distinguishing Xp11.2 translocation renal cell carcinoma(Xp11.2 tRCC)...This study aims to apply ResNet-18 convolutional neural network(CNN)and XGBoost to preoperative computed tomography(CT)images and clinical data for distinguishing Xp11.2 translocation renal cell carcinoma(Xp11.2 tRCC)from common subtypes of renal cell carcinoma(RCC)in order to provide patients with individualized treatment plans.Data from45 patients with Xp11.2 tRCC fromJanuary 2007 to December 2021 are collected.Clear cell RCC(ccRCC),papillary RCC(pRCC),or chromophobe RCC(chRCC)can be detected from each patient.CT images are acquired in the following three phases:unenhanced,corticomedullary,and nephrographic.A unified framework is proposed for the classification of renal masses.In this framework,ResNet-18 CNN is employed to classify renal cancers with CT images,while XGBoost is adopted with clinical data.Experiments demonstrate that,if applying ResNet-18 CNN or XGBoost singly,the latter outperforms the former,while the framework integrating both technologies performs similarly or better than urologists.Especially,the possibility of misclassifying Xp11.2 tRCC,pRCC,and chRCC as ccRCC by the proposed framework is much lower than urologists.展开更多
Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods...Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods:We used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information.The EMTAB-1980 cohort was used for external validation.The GENECARDS database contains the first 100 solute carrier(SLC)-related genes.The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis.An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC.Patients in each cohort were separated into high-and low-risk groups based on their risk scores.The clinical importance of the signature was assessed through survival,immune microenvironment,drug sensitivity,and nomogram analyses using R software.Results:SLC25A23,SLC25A42,SLC5A1,SLC3A1,SLC25A37,SLC5A6,SLCO5A1,and SCP2 comprised the signatures of the eight SLCrelated genes.Patients with ccRCC were separated into high-and low-risk groups based on the risk value in the training and validation cohorts;the high-risk group had a significantly worse prognosis(p<0.001).The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression(p<0.05).Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups(p<0.05).Drug sensitivity analysis showed that compared to the low-risk group,the high-risk group was more sensitive to sunitinib,nilotinib,JNK-inhibitor-VIII,dasatinib,bosutinib,and bortezomib(p<0.001).Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.Conclusions:SLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu.Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.展开更多
Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype cl...Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype classification task from cancer gene expression data,it is challenging to obtain those significant genes due to the high dimensionality and high noise of data.Moreover,the existing methods always suffer from some issues such as premature convergence.Methods:To address those problems,we propose a new ant colony optimization(ACO)algorithm called DACO to classify the cancer gene expression datasets,identifying the essential genes of different diseases.In DACO,first,we propose the initial pheromone concentration based on the weight ranking vector to accelerate the convergence speed;then,a dynamic pheromone volatility factor is designed to prevent the algorithm from getting stuck in the local optimal solution;finally,the pheromone update rule in the Ant Colony System is employed to update the pheromone globally and locally.To demonstrate the performance of the proposed algorithm in classification,different existing approaches are compared with the proposed algorithm on eight high-dimensional cancer gene expression datasets.Results:The experiment results show that the proposed algorithm performs better than other effective methods in terms of classification accuracy and the number of feature sets.It can be used to address the classification problem effectively.Moreover,a renal cell carcinoma dataset is employed to reveal the biological significance of the proposed algorithm from a number of biological analyses.Conclusion:The results demonstrate that CAPS may play a crucial role in the occurrence and development of renal clear cell carcinoma.展开更多
Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell car...Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.展开更多
BACKGROUND Clear cell renal cell carcinoma(ccRCC)is a common type of tumor that can metastasize to any organs and sites.However,it is extremely rare for ccRCC to metastasize to the iris.Here,we describe a rare case of...BACKGROUND Clear cell renal cell carcinoma(ccRCC)is a common type of tumor that can metastasize to any organs and sites.However,it is extremely rare for ccRCC to metastasize to the iris.Here,we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010.CASE SUMMARY A 62-year-old male was admitted to the hospital due to blurred vision and red eyes,and a mass was found on the iris in the right eye.B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o’clock position.Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye.The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses.The patient was still alive at 9 mo after surgical treatment.Ocular metastasis can be an initial sign with a poor prognosis.Timely detection and treatment may improve survival.Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment oppor-tunities.CONCLUSION This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestation for successful disease diagnosis.展开更多
BACKGROUND Renal cell carcinoma(RCC)is the third most common malignancy in the genitourinary tract.The lungs,bone,lymph nodes,liver,and brain are common metastatic sites of RCC.However,there is limited literature on s...BACKGROUND Renal cell carcinoma(RCC)is the third most common malignancy in the genitourinary tract.The lungs,bone,lymph nodes,liver,and brain are common metastatic sites of RCC.However,there is limited literature on single omental metastasis of RCC.CASE SUMMARY We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy.Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC(Fuhrman grade III).At 6 mo postoperatively,abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum.At 7 mo after initial operation,laparoscopic removal of the left omental nodule was performed.The pathological results indicated metastatic clear cell RCC.Currently,the patient is being treated with adjuvant pembrolizumab.CONCLUSION Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare.Urologists should be aware of the diverse nature of RCC.展开更多
BACKGROUND Warthin-like papillary renal cell carcinoma(WPRCC)has been described as a rare pathological subtype of papillary renal cell carcinoma in the 2022 World Health Organization Classification of the Urinary and ...BACKGROUND Warthin-like papillary renal cell carcinoma(WPRCC)has been described as a rare pathological subtype of papillary renal cell carcinoma in the 2022 World Health Organization Classification of the Urinary and Male Reproductive System.Herein we report a case of WPRCC in the left kidney.CASE SUMMARY Physical examination of a previously healthy 47-year-old woman revealed a lump in her left kidney,4.5 cm×3.5 cm×3.5 cm in size.Based on the clinical information,imaging data,histmorphological features,and immunohistochemistry results,the pathological diagnosis was WPRCC in left kidney.CONCLUSION Resection of the mass in the left kidney was performed and her postoperative course was uneventful.展开更多
Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STA...Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STAT3 signaling in ccRCC.Methods:Eighty patients diagnosed with ccRCC by our oncology department from January 2019 to December 2021 were selected as study subjects,and the control subjects were selected from patients who were receiving health check-up from our hospital(matched according to case group:control group,1:2),with 160 healthy patients.All serum samples collected from the case-control subjects were allowed to stand for 1–2 hours,centrifuged at 3000 rpm for 10 minutes,and stored in a-80°C refrigerator,from which they were removed and thawed to measure 25-hydroxyvitamin D(25(OH)D)and interleukin 6(IL-6)levels.Results:The blood calcium level of patients in the cancer group was significantly lower than that of patients in the non-cancer group,and the difference was statistically significant(P<0.05).The IL-6 level of the cancer group was significantly higher than that of the non-cancer group.In high vitamin D state,the IL-6 level of the non-cancer group was higher than that of the cancer group,and the average concentration of IL-6 in both the cancer group and the non-cancer group was significantly higher in low vitamin D state compared with high vitamin D state(P<0.05);the correlation between hypovitaminosis D status and renal Ki-67 was found to be positive.Conclusion:The results showed that serum IL-6 levels were elevated in the cancer group and circulating serum 25(OH)D levels were negatively correlated with IL-6 levels.In addition,signal transducer and activator of transcription 3(STAT3)signaling in RCC tissues was activated in ccRCC patients and in those with low vitamin D status among the cancer group and was higher than that in those with high vitamin D status.These results suggest that hypovitaminosis D status in ccRCC patients is associated with activated IL-6/STAT3 signaling and the activation of tumor proliferation markers proliferating cell nuclear antigen(PCNA),cyclin D1,and Ki-67.展开更多
BACKGROUND Renal cell carcinomas are usually unilateral.However,they are bilateral in 2%to 4%of sporadic cases and is considerably more common in familial cases.Synchronous sporadic bilateral multiple chromophobe rena...BACKGROUND Renal cell carcinomas are usually unilateral.However,they are bilateral in 2%to 4%of sporadic cases and is considerably more common in familial cases.Synchronous sporadic bilateral multiple chromophobe renal cell carcinoma(CHRCC)with different subtypes is rare.CASE SUMMARY In this case report,we describe a case of synchronous bilateral CHRCC with two histological variants,accompanied by a clear cell carcinoma and a cyst in a 50-year-old male.The patient underwent retroperitoneal laparoscopic bilateral nephron-sparing surgery and there was no serious postoperative renal dysfunction.CONCLUSION We report a rare case of synchronous bilateral CHRCC with two histological variants associated with a clear cell carcinoma and a cyst.展开更多
BACKGROUND There is limited information on ipsilateral synchronous papillary renal cell carcinoma(PRCC)and clear cell renal cell carcinoma(CCRCC).Therefore,these rare tumors are often misdiagnosed preoperatively as a ...BACKGROUND There is limited information on ipsilateral synchronous papillary renal cell carcinoma(PRCC)and clear cell renal cell carcinoma(CCRCC).Therefore,these rare tumors are often misdiagnosed preoperatively as a single tumor with intrarenal metastasis or some other diseases.Effective management and long-term overall survival might be affected because the prognosis of the two tumors differs.CASE SUMMARY We describe a case of ipsilateral synchronous PRCC and CCRCC with two histological variants in a 72-year-old man,whose mass was found incidentally,with no other chief complaints and vital signs were normal.Initial ultrasound revealed a hypoechoic lobular mass with a volume of 7.8 cm×4.8 cm×2.8 cm in the middle to lower pole of the left kidney.A subsequent contrast-enhanced computed tomography scan showed a single endophytic mass of 7.5 cm in diameter.The patient underwent laparoscopic left radical nephrectomy.A final diagnosis of ipsilateral synchronous PRCC and CCRCC was confirmed by pathological examination.There was no recurrence or metastasis after 25 mo follow-up.CONCLUSION We report a case of ipsilateral synchronous PRCC and CCRCC,and review related literature to estimate the prevalence of similar cases.The above descriptions may be expected to help understand the disease,and improve diagnosis in the future.展开更多
BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical cha...BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.展开更多
Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of ...Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of metastasis.We further outline evolving strategies to combat metastasis through adjuvant therapy.Finally,we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.展开更多
Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell ...Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still unclear.Methods:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro.The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib.Results:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells.Mechanistically,nobiletin decreased SKP2 protein expression by reducing its transcriptional level.The downregulated SKP2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model.Conclusions:Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.展开更多
The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC an...The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC and t(6;11)RCC,was newly defined as an RCC subtype.Xp11 and t(6;11)RCC are characterized by the rearrangement of the MiT transcription factors TFE3 and TFEB,respectively.Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC.Furthermore,RCC with TFEB amplification,melanotic MiT family translocation neoplasms,was identified may as a unique subtype of MiT family associated renal neoplasms,along with MITF associated RCC.In this review,we will collect available literature of these newly-described RCCs,analyze their clinicopathological and immunohistochemical features,and summarize their molecular and genetic evidences.We expect this review would be beneficial for the understanding of these rare subtypes of RCCs,and eventually promote clinical management strategies.展开更多
Objective:With today’s modern imaging modalities,patients diagnosed with renal cell carcinoma(RCC)rarely present symptomatically.In some cases,however,they can develop paraneoplastic syndromes with associated symptom...Objective:With today’s modern imaging modalities,patients diagnosed with renal cell carcinoma(RCC)rarely present symptomatically.In some cases,however,they can develop paraneoplastic syndromes with associated symptoms.To date,only three cases of RCC presenting with chronic dry cough have been reported.We describe six patients who presented with cough that improved following radical nephrectomy.Methods:A retrospective review of patients undergoing partial or radical nephrectomy for renal masses between January 2015 and March 2016 was performed,and patients presenting with a cough were examined.Results:Six patients presented with chronic cough and were discovered to have a large renal mass.Postoperative spontaneous resolution of cough was noted in all but one patient,in whom coughing was reduced and limited to the mornings.Cough duration ranged from 3 months to just over a year.All patients were treated with radical nephrectomy,which was cytoreductive in four patients.Average tumor size was 10.9 cm(SD=2.2 cm).Five of the tumors had clear cell pathology,and every tumor was Fuhrman grade IV,unifocal,and demonstrated necrosis.Sarcomatoid features were reported in four of the tumors.Conclusion:Our study presents the largest series of patients with RCC who presented with a chronic cough that was significantly improved following radical nephrectomy.We believe the cause of cough is multifactorial and further investigation is needed to clearly elucidate the etiology.展开更多
Objective:Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma(RCC),however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies.We ...Objective:Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma(RCC),however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies.We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score(RISK)could serve as a rigorous prognostic indicator of overall survival(OS)in patients with clear cell and non-clear cell RCC.Methods:Combination of preoperative C-reactive protein(CRP),albumin,erythrocyte sedimentation rate(ESR),corrected calcium,and aspartate transaminase to alanine transaminase(AST/ALT)ratio was used to develop RISK.RISK was developed using grid-search methodology,receiver-operating-characteristic(ROC)analysis,and sensitivity-specificity trade-off analysis.Prognostic value of RISK was analyzed using the KaplaneMeier method and Cox proportional regression models.Predictive accuracy was compared with RISK to Size,Size,Grade,and Necrosis(SSIGN)score,University of California-LOS Angeles(UCLA)Integrated Staging System(UISS),and Leibovich Prognosis Score(LPS).展开更多
Objective:Novel optical imaging modalities are under development with the goal of obtaining an“optical biopsy”to efficiently provide pathologic details.One such modality is confocal microscopy which allows in situ v...Objective:Novel optical imaging modalities are under development with the goal of obtaining an“optical biopsy”to efficiently provide pathologic details.One such modality is confocal microscopy which allows in situ visualization of cells within a layer of tissue and imaging of cellular-level structures.The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer.Methods:Specimens were obtained from patients who underwent robotic partial nephrectomy for renal mass.Samples of suspected normal and tumor tissue were extracted from the excised portion of the kidney and stained with acridine orange.The stained samples were imaged on a Nikon E600 C1 Confocal Microscope.The samples were then submitted for hematoxylin and eosin processing and read by an expert pathologist to provide a gold-standard diagnosis that can later be compared to the confocal images.Results:This study included 11 patients,17 tissue samples,and 118 confocal images.Of the 17 tissue samples,10 had a gold-standard diagnosis of cancer and seven were benign.Of 118 confocal images,66 had a gold-standard diagnosis of cancer and 52 were benign.Six confocal images were used as a training set to train eight observers.The observers were asked to rate the test images on a six point scale and the results were analyzed using a web based receiver operating characteristic curve calculator.The average accuracy,sensitivity,specificity,and area under the empirical receiver operating characteristic curve for this study were 91%,98%,81%,and 0.94 respectively.Conclusion:This preliminary study suggest that confocal microscopy can be used to distinguish cancer from normal tissue with high sensitivity and specificity.The observers in this study were trained quickly and on only six images.We expect even higher performance as observers become more familiar with the confocal images.展开更多
Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive neph...Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive nephrectomy,but systemic therapy is required for advanced RCC.Single agent targeted therapies are moderately toxic and only somewhat effective,leading to development of immunotherapies and combination therapies.This review identifies limitations of monotherapies for metastatic renal cell carcinoma,discusses recent advances in combination therapies,and highlights therapeutic options under development.The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect.However,combining targeted therapies may cause increased toxicity.The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity.To date,five combination therapies have been approved by the U.S.Food and Drug Administration,with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy.Several other combination therapies are under development,including some in the phase 3 stage.The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles.展开更多
Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal t...Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.展开更多
Objective:To report the outcomes of surgery for a contemporary series of patients with locally advanced non-metastatic renal cell carcinoma(RCC)treated at a referral academic centre,focusing on technical nuances and o...Objective:To report the outcomes of surgery for a contemporary series of patients with locally advanced non-metastatic renal cell carcinoma(RCC)treated at a referral academic centre,focusing on technical nuances and on the value of a multidisciplinary team.Methods:We queried our prospective institutional database to identify patients undergoing surgical treatment for locally advanced(cT3-T4 N0-1 M0)renal masses suspected of RCC at our centre between January 2017 and December 2020.Results:Overall,32 patients were included in the analytic cohort.Of these,12(37.5%)tumours were staged as cT3a,8(25.0%)as cT3b,5(15.6%)as cT3c,and 7(21.9%)as cT4;6(18.8%)patients had preoperative evidence of lymph node involvement.Nine(28.1%)patients underwent nephron-sparing surgery while 23(71.9%)received radical nephrectomy.A template-based lymphadenectomy was performed in 12 cases,with evidence of disease in 3(25.0%)at definitive histopathological analysis.Four cases of RCC with level IV inferior vena cava thrombosis were successfully treated using liver transplant techniques without the need for extracorporeal circulation.While intraoperative complications were recorded in 3(9.4%)patients,no postoperative major complications(Clavien-Dindo3)were observed.At histopathological analysis,2(6.2%)patients who underwent partial nephrectomy harboured oncocytoma,while the most common malignant histotype was clear cell RCC(62.5%),with a median Leibovich score of 6(interquartile range 5e7).Conclusion:Locally advanced RCC is a complex and heterogenous disease posing several challenges to surgical teams.Our experience confirms that provided careful patient selection,surgery in experienced hands can achieve favourable perioperative,oncological,and functional outcomes.展开更多
基金supported by Beijing Ronghe Medical Development Foundation。
文摘This study aims to apply ResNet-18 convolutional neural network(CNN)and XGBoost to preoperative computed tomography(CT)images and clinical data for distinguishing Xp11.2 translocation renal cell carcinoma(Xp11.2 tRCC)from common subtypes of renal cell carcinoma(RCC)in order to provide patients with individualized treatment plans.Data from45 patients with Xp11.2 tRCC fromJanuary 2007 to December 2021 are collected.Clear cell RCC(ccRCC),papillary RCC(pRCC),or chromophobe RCC(chRCC)can be detected from each patient.CT images are acquired in the following three phases:unenhanced,corticomedullary,and nephrographic.A unified framework is proposed for the classification of renal masses.In this framework,ResNet-18 CNN is employed to classify renal cancers with CT images,while XGBoost is adopted with clinical data.Experiments demonstrate that,if applying ResNet-18 CNN or XGBoost singly,the latter outperforms the former,while the framework integrating both technologies performs similarly or better than urologists.Especially,the possibility of misclassifying Xp11.2 tRCC,pRCC,and chRCC as ccRCC by the proposed framework is much lower than urologists.
基金supported by the National Natural Science Foundation of China[Grant Numbers 82170769,81900684,and 81870512].
文摘Background:Clear-cell renal cell carcinoma(ccRCC)is the most common malignant kidney cancer.However,the tumor microenvironment and crosstalk involved in metabolic reprogramming in ccRCC are not well-understood.Methods:We used The Cancer Genome Atlas to obtain ccRCC transcriptome data and clinical information.The EMTAB-1980 cohort was used for external validation.The GENECARDS database contains the first 100 solute carrier(SLC)-related genes.The predictive value of SLC-related genes for ccRCC prognosis and treatment was assessed using univariate Cox regression analysis.An SLC-related predictive signature was developed through Lasso regression analysis and used to determine the risk profiles of patients with ccRCC.Patients in each cohort were separated into high-and low-risk groups based on their risk scores.The clinical importance of the signature was assessed through survival,immune microenvironment,drug sensitivity,and nomogram analyses using R software.Results:SLC25A23,SLC25A42,SLC5A1,SLC3A1,SLC25A37,SLC5A6,SLCO5A1,and SCP2 comprised the signatures of the eight SLCrelated genes.Patients with ccRCC were separated into high-and low-risk groups based on the risk value in the training and validation cohorts;the high-risk group had a significantly worse prognosis(p<0.001).The risk score was an independent predictive indicator of ccRCC in the two cohorts according to univariate and multivariate Cox regression(p<0.05).Analysis of the immune microenvironment showed that immune cell infiltration and immune checkpoint gene expression differed between the two groups(p<0.05).Drug sensitivity analysis showed that compared to the low-risk group,the high-risk group was more sensitive to sunitinib,nilotinib,JNK-inhibitor-VIII,dasatinib,bosutinib,and bortezomib(p<0.001).Survival analysis and receiver operating characteristic curves were validated using the E-MTAB-1980 cohort.Conclusions:SLC-related genes have predictive relevance in ccRCC and play roles in the immunological milieu.Our results provide insight into metabolic reprogramming in ccRCC and identify promising treatment targets for ccRCC.
基金supported by the Langfang Science and Technology Plan Project(No.2018013151)from Hebei Petro China Central Hospital.
文摘Background:Recently,researchers have been attracted in identifying the crucial genes related to cancer,which plays important role in cancer diagnosis and treatment.However,in performing the cancer molecular subtype classification task from cancer gene expression data,it is challenging to obtain those significant genes due to the high dimensionality and high noise of data.Moreover,the existing methods always suffer from some issues such as premature convergence.Methods:To address those problems,we propose a new ant colony optimization(ACO)algorithm called DACO to classify the cancer gene expression datasets,identifying the essential genes of different diseases.In DACO,first,we propose the initial pheromone concentration based on the weight ranking vector to accelerate the convergence speed;then,a dynamic pheromone volatility factor is designed to prevent the algorithm from getting stuck in the local optimal solution;finally,the pheromone update rule in the Ant Colony System is employed to update the pheromone globally and locally.To demonstrate the performance of the proposed algorithm in classification,different existing approaches are compared with the proposed algorithm on eight high-dimensional cancer gene expression datasets.Results:The experiment results show that the proposed algorithm performs better than other effective methods in terms of classification accuracy and the number of feature sets.It can be used to address the classification problem effectively.Moreover,a renal cell carcinoma dataset is employed to reveal the biological significance of the proposed algorithm from a number of biological analyses.Conclusion:The results demonstrate that CAPS may play a crucial role in the occurrence and development of renal clear cell carcinoma.
基金funded by the Shenzhen Longhua District Medical and Health Institutions Research Fund(Project No.2022102).
文摘Background:In many cancer types,aryl hydrocarbon receptor nuclear translocator 2(ARNT2)has been found to be associated with tumor cell proliferation and prognosis.However,the role of ARNT2 in clear cell renal cell carcinoma(ccRCC)has not been completely elucidated.In this study,the potential role of ARNT2 in ccRCC development was characterized.Methods:A pan-cancer dataset(TCGA-TARGET-GTEx)was accessed from UCSC Xena Data Browser.ARNT2 expression in normal and tumor samples was compared.Univariate Cox regression was performed to evaluate the prognostic value of ARNT2.Single sample gene set enrichment analysis(ssGSEA)was used to estimate the enrichment of functional pathways and gene signatures.CIBERSORT and ESTIMATE methods evaluated the immune infiltration.The ARNT2 expression was determined in ccRCC tissue and cell lines using RT-qPCR and Western blot.Results:ARNT2 expression was significantly dysregulated in 23 out of 30 cancer types.Pan-cancer data revealed a strong correlation between ARNT2 expression and immune modulators,immune cell infiltration,and genomic alternations.In ccRCC patients,the low-ARNT2 expression group had higher immune infiltration,CD8 T cells,and programmed cell death ligand 1 expression,as well as higher enrichment score of immunotherapeutic predictors than those in the high-ARNT2 expression group.Low-ARNT2 expression group was more responsive to immunotherapy.Moreover,low ARNT2 expression was observed in ccRCC tissue and cell lines.Conclusions:Dysregulated ARNT2 expression is involved in cancer development and the modulation of the immune microenvironment.ARNT2 can be potentially used as a prognostic indicator and an immunotherapeutic indicator for ccRCC.
文摘BACKGROUND Clear cell renal cell carcinoma(ccRCC)is a common type of tumor that can metastasize to any organs and sites.However,it is extremely rare for ccRCC to metastasize to the iris.Here,we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010.CASE SUMMARY A 62-year-old male was admitted to the hospital due to blurred vision and red eyes,and a mass was found on the iris in the right eye.B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o’clock position.Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye.The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses.The patient was still alive at 9 mo after surgical treatment.Ocular metastasis can be an initial sign with a poor prognosis.Timely detection and treatment may improve survival.Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment oppor-tunities.CONCLUSION This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestation for successful disease diagnosis.
文摘BACKGROUND Renal cell carcinoma(RCC)is the third most common malignancy in the genitourinary tract.The lungs,bone,lymph nodes,liver,and brain are common metastatic sites of RCC.However,there is limited literature on single omental metastasis of RCC.CASE SUMMARY We present the case of a 44-year-old man with single omental metastasis of RCC after laparoscopic radical nephrectomy.Pathological diagnosis of the resected left kidney revealed pT3a clear cell RCC(Fuhrman grade III).At 6 mo postoperatively,abdominal computed tomography revealed a 12-mm enhancing nodule in the left lower peritoneum.At 7 mo after initial operation,laparoscopic removal of the left omental nodule was performed.The pathological results indicated metastatic clear cell RCC.Currently,the patient is being treated with adjuvant pembrolizumab.CONCLUSION Omental metastasis of RCC owing to laparoscopic radical nephrectomy is rare.Urologists should be aware of the diverse nature of RCC.
基金Supported by the Natural Science Foundation of Shandong Province,No.ZR2021MH261.
文摘BACKGROUND Warthin-like papillary renal cell carcinoma(WPRCC)has been described as a rare pathological subtype of papillary renal cell carcinoma in the 2022 World Health Organization Classification of the Urinary and Male Reproductive System.Herein we report a case of WPRCC in the left kidney.CASE SUMMARY Physical examination of a previously healthy 47-year-old woman revealed a lump in her left kidney,4.5 cm×3.5 cm×3.5 cm in size.Based on the clinical information,imaging data,histmorphological features,and immunohistochemistry results,the pathological diagnosis was WPRCC in left kidney.CONCLUSION Resection of the mass in the left kidney was performed and her postoperative course was uneventful.
基金funded by the Health Commission of Hebei Province under the project Chuanxiong Extract Improves Inflammatory Response in Rats with Pyelonephritis Through IL-6/STAT3 Signaling Pathway(Project Number:20231486).
文摘Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STAT3 signaling in ccRCC.Methods:Eighty patients diagnosed with ccRCC by our oncology department from January 2019 to December 2021 were selected as study subjects,and the control subjects were selected from patients who were receiving health check-up from our hospital(matched according to case group:control group,1:2),with 160 healthy patients.All serum samples collected from the case-control subjects were allowed to stand for 1–2 hours,centrifuged at 3000 rpm for 10 minutes,and stored in a-80°C refrigerator,from which they were removed and thawed to measure 25-hydroxyvitamin D(25(OH)D)and interleukin 6(IL-6)levels.Results:The blood calcium level of patients in the cancer group was significantly lower than that of patients in the non-cancer group,and the difference was statistically significant(P<0.05).The IL-6 level of the cancer group was significantly higher than that of the non-cancer group.In high vitamin D state,the IL-6 level of the non-cancer group was higher than that of the cancer group,and the average concentration of IL-6 in both the cancer group and the non-cancer group was significantly higher in low vitamin D state compared with high vitamin D state(P<0.05);the correlation between hypovitaminosis D status and renal Ki-67 was found to be positive.Conclusion:The results showed that serum IL-6 levels were elevated in the cancer group and circulating serum 25(OH)D levels were negatively correlated with IL-6 levels.In addition,signal transducer and activator of transcription 3(STAT3)signaling in RCC tissues was activated in ccRCC patients and in those with low vitamin D status among the cancer group and was higher than that in those with high vitamin D status.These results suggest that hypovitaminosis D status in ccRCC patients is associated with activated IL-6/STAT3 signaling and the activation of tumor proliferation markers proliferating cell nuclear antigen(PCNA),cyclin D1,and Ki-67.
文摘BACKGROUND Renal cell carcinomas are usually unilateral.However,they are bilateral in 2%to 4%of sporadic cases and is considerably more common in familial cases.Synchronous sporadic bilateral multiple chromophobe renal cell carcinoma(CHRCC)with different subtypes is rare.CASE SUMMARY In this case report,we describe a case of synchronous bilateral CHRCC with two histological variants,accompanied by a clear cell carcinoma and a cyst in a 50-year-old male.The patient underwent retroperitoneal laparoscopic bilateral nephron-sparing surgery and there was no serious postoperative renal dysfunction.CONCLUSION We report a rare case of synchronous bilateral CHRCC with two histological variants associated with a clear cell carcinoma and a cyst.
文摘BACKGROUND There is limited information on ipsilateral synchronous papillary renal cell carcinoma(PRCC)and clear cell renal cell carcinoma(CCRCC).Therefore,these rare tumors are often misdiagnosed preoperatively as a single tumor with intrarenal metastasis or some other diseases.Effective management and long-term overall survival might be affected because the prognosis of the two tumors differs.CASE SUMMARY We describe a case of ipsilateral synchronous PRCC and CCRCC with two histological variants in a 72-year-old man,whose mass was found incidentally,with no other chief complaints and vital signs were normal.Initial ultrasound revealed a hypoechoic lobular mass with a volume of 7.8 cm×4.8 cm×2.8 cm in the middle to lower pole of the left kidney.A subsequent contrast-enhanced computed tomography scan showed a single endophytic mass of 7.5 cm in diameter.The patient underwent laparoscopic left radical nephrectomy.A final diagnosis of ipsilateral synchronous PRCC and CCRCC was confirmed by pathological examination.There was no recurrence or metastasis after 25 mo follow-up.CONCLUSION We report a case of ipsilateral synchronous PRCC and CCRCC,and review related literature to estimate the prevalence of similar cases.The above descriptions may be expected to help understand the disease,and improve diagnosis in the future.
基金Supported by Natural Science Foundation of Jiangxi Province,No.2010GZY0806。
文摘BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.
文摘Although multiple advances have been made in systemic therapy for renal cell carcinoma(RCC),metastatic RCC remains incurable.In the current review,we focus on the underlying biology of RCC and plausible mechanisms of metastasis.We further outline evolving strategies to combat metastasis through adjuvant therapy.Finally,we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.
基金supported by the National Natural Science Foundation of China(Grant Nos.81772702 and 81502214)。
文摘Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still unclear.Methods:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro.The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib.Results:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells.Mechanistically,nobiletin decreased SKP2 protein expression by reducing its transcriptional level.The downregulated SKP2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model.Conclusions:Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.
文摘The microphthalmia(MiT)subfamily of transcription factors includes TFE3,TFEB,TFEC,and MITF.In the 2016 World Health Organization classification,MiT family translocation renal cell carcinoma(tRCC)including Xp11 tRCC and t(6;11)RCC,was newly defined as an RCC subtype.Xp11 and t(6;11)RCC are characterized by the rearrangement of the MiT transcription factors TFE3 and TFEB,respectively.Recent studies identified the fusion partner-dependent clinicopathological and immunohistochemical features in TFE3-rearranged RCC.Furthermore,RCC with TFEB amplification,melanotic MiT family translocation neoplasms,was identified may as a unique subtype of MiT family associated renal neoplasms,along with MITF associated RCC.In this review,we will collect available literature of these newly-described RCCs,analyze their clinicopathological and immunohistochemical features,and summarize their molecular and genetic evidences.We expect this review would be beneficial for the understanding of these rare subtypes of RCCs,and eventually promote clinical management strategies.
文摘Objective:With today’s modern imaging modalities,patients diagnosed with renal cell carcinoma(RCC)rarely present symptomatically.In some cases,however,they can develop paraneoplastic syndromes with associated symptoms.To date,only three cases of RCC presenting with chronic dry cough have been reported.We describe six patients who presented with cough that improved following radical nephrectomy.Methods:A retrospective review of patients undergoing partial or radical nephrectomy for renal masses between January 2015 and March 2016 was performed,and patients presenting with a cough were examined.Results:Six patients presented with chronic cough and were discovered to have a large renal mass.Postoperative spontaneous resolution of cough was noted in all but one patient,in whom coughing was reduced and limited to the mornings.Cough duration ranged from 3 months to just over a year.All patients were treated with radical nephrectomy,which was cytoreductive in four patients.Average tumor size was 10.9 cm(SD=2.2 cm).Five of the tumors had clear cell pathology,and every tumor was Fuhrman grade IV,unifocal,and demonstrated necrosis.Sarcomatoid features were reported in four of the tumors.Conclusion:Our study presents the largest series of patients with RCC who presented with a chronic cough that was significantly improved following radical nephrectomy.We believe the cause of cough is multifactorial and further investigation is needed to clearly elucidate the etiology.
文摘Objective:Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma(RCC),however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies.We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score(RISK)could serve as a rigorous prognostic indicator of overall survival(OS)in patients with clear cell and non-clear cell RCC.Methods:Combination of preoperative C-reactive protein(CRP),albumin,erythrocyte sedimentation rate(ESR),corrected calcium,and aspartate transaminase to alanine transaminase(AST/ALT)ratio was used to develop RISK.RISK was developed using grid-search methodology,receiver-operating-characteristic(ROC)analysis,and sensitivity-specificity trade-off analysis.Prognostic value of RISK was analyzed using the KaplaneMeier method and Cox proportional regression models.Predictive accuracy was compared with RISK to Size,Size,Grade,and Necrosis(SSIGN)score,University of California-LOS Angeles(UCLA)Integrated Staging System(UISS),and Leibovich Prognosis Score(LPS).
基金Research reported in this publication was supported by the National Cancer Institute Cancer Center Support Grant(P30 CA023074)and used the Tissue Acquisition and Cellular/Molecular Analysis Shared Resource at the University of Arizona.
文摘Objective:Novel optical imaging modalities are under development with the goal of obtaining an“optical biopsy”to efficiently provide pathologic details.One such modality is confocal microscopy which allows in situ visualization of cells within a layer of tissue and imaging of cellular-level structures.The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer.Methods:Specimens were obtained from patients who underwent robotic partial nephrectomy for renal mass.Samples of suspected normal and tumor tissue were extracted from the excised portion of the kidney and stained with acridine orange.The stained samples were imaged on a Nikon E600 C1 Confocal Microscope.The samples were then submitted for hematoxylin and eosin processing and read by an expert pathologist to provide a gold-standard diagnosis that can later be compared to the confocal images.Results:This study included 11 patients,17 tissue samples,and 118 confocal images.Of the 17 tissue samples,10 had a gold-standard diagnosis of cancer and seven were benign.Of 118 confocal images,66 had a gold-standard diagnosis of cancer and 52 were benign.Six confocal images were used as a training set to train eight observers.The observers were asked to rate the test images on a six point scale and the results were analyzed using a web based receiver operating characteristic curve calculator.The average accuracy,sensitivity,specificity,and area under the empirical receiver operating characteristic curve for this study were 91%,98%,81%,and 0.94 respectively.Conclusion:This preliminary study suggest that confocal microscopy can be used to distinguish cancer from normal tissue with high sensitivity and specificity.The observers in this study were trained quickly and on only six images.We expect even higher performance as observers become more familiar with the confocal images.
文摘Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive nephrectomy,but systemic therapy is required for advanced RCC.Single agent targeted therapies are moderately toxic and only somewhat effective,leading to development of immunotherapies and combination therapies.This review identifies limitations of monotherapies for metastatic renal cell carcinoma,discusses recent advances in combination therapies,and highlights therapeutic options under development.The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect.However,combining targeted therapies may cause increased toxicity.The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity.To date,five combination therapies have been approved by the U.S.Food and Drug Administration,with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy.Several other combination therapies are under development,including some in the phase 3 stage.The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles.
文摘Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.
文摘Objective:To report the outcomes of surgery for a contemporary series of patients with locally advanced non-metastatic renal cell carcinoma(RCC)treated at a referral academic centre,focusing on technical nuances and on the value of a multidisciplinary team.Methods:We queried our prospective institutional database to identify patients undergoing surgical treatment for locally advanced(cT3-T4 N0-1 M0)renal masses suspected of RCC at our centre between January 2017 and December 2020.Results:Overall,32 patients were included in the analytic cohort.Of these,12(37.5%)tumours were staged as cT3a,8(25.0%)as cT3b,5(15.6%)as cT3c,and 7(21.9%)as cT4;6(18.8%)patients had preoperative evidence of lymph node involvement.Nine(28.1%)patients underwent nephron-sparing surgery while 23(71.9%)received radical nephrectomy.A template-based lymphadenectomy was performed in 12 cases,with evidence of disease in 3(25.0%)at definitive histopathological analysis.Four cases of RCC with level IV inferior vena cava thrombosis were successfully treated using liver transplant techniques without the need for extracorporeal circulation.While intraoperative complications were recorded in 3(9.4%)patients,no postoperative major complications(Clavien-Dindo3)were observed.At histopathological analysis,2(6.2%)patients who underwent partial nephrectomy harboured oncocytoma,while the most common malignant histotype was clear cell RCC(62.5%),with a median Leibovich score of 6(interquartile range 5e7).Conclusion:Locally advanced RCC is a complex and heterogenous disease posing several challenges to surgical teams.Our experience confirms that provided careful patient selection,surgery in experienced hands can achieve favourable perioperative,oncological,and functional outcomes.
