The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted ...The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib with minimal lasting toxicity.展开更多
Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 ...Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 computerized tomography(cT)images from four independent patient cohorts were included for analysis in this study.We propose a V Bottieneck multi-resolution and focus-organ network(VB-MrFo-Net)using a cascade framework for deep learning analysis.The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation,with a Dice score of 0.87.The nuclear-grade prediction model performed best in the logistic regression classifier,with area under curve values from 0.782 to 0.746.Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk,with a hazard ratio(HR)of 2.49[95%confidence interval(CI):1.13-5.45,P=0.023]in the General cohort.Excellent performance had also been verified in the Cancer Genome Atlas cohort,the Clinical Proteomic Tumor Analysis Consortium cohort,and the Kidney Tumor Segmentation Challenge cohort,with HRs of 2.77(95%CI:1.58-4.84,P=0.0019),3.83(95%CI:1.22-11.96,P=0.029),and 2.80(95%CI:1.05-7.47,P=0.025),respectively.In conclusion,we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRcc.The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments,which couid provide practical advicefordecidingtreatmentoptions.展开更多
Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resist...Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.展开更多
目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,...目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,并评估肿瘤微血管密度。结果16例肿瘤中CD31和CD34免疫组化染色显示,肉瘤样肾细胞癌区域微血管密度明显高于不伴肉瘤样分化的区域,微血管密度计数分别为68.6±25.8 vs 38.7±16.0(t=3.931,P=0.0005)和69.5±28.1 vs 40.1±18.4(t=3.506,P=0.0015),差异有统计学意义。肉瘤样区域PD-L1表达水平高于非肉瘤样区域,CPS分别为34.7±26.9和25.9±27.6,但差异无统计学意义。结论在肉瘤样肾细胞癌中,肉瘤样区域微血管密度和PD-L1表达水平明显高于非肉瘤样区域,提示靶向治疗联合免疫治疗可能为此类肿瘤提供一种有效的治疗方法。展开更多
文摘The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib with minimal lasting toxicity.
基金supported by the National Natural Science Foundation of China(Grants No.81972393 and 82002665).
文摘Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma(ccRcC),non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment.A total of 126345 computerized tomography(cT)images from four independent patient cohorts were included for analysis in this study.We propose a V Bottieneck multi-resolution and focus-organ network(VB-MrFo-Net)using a cascade framework for deep learning analysis.The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation,with a Dice score of 0.87.The nuclear-grade prediction model performed best in the logistic regression classifier,with area under curve values from 0.782 to 0.746.Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk,with a hazard ratio(HR)of 2.49[95%confidence interval(CI):1.13-5.45,P=0.023]in the General cohort.Excellent performance had also been verified in the Cancer Genome Atlas cohort,the Clinical Proteomic Tumor Analysis Consortium cohort,and the Kidney Tumor Segmentation Challenge cohort,with HRs of 2.77(95%CI:1.58-4.84,P=0.0019),3.83(95%CI:1.22-11.96,P=0.029),and 2.80(95%CI:1.05-7.47,P=0.025),respectively.In conclusion,we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRcc.The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments,which couid provide practical advicefordecidingtreatmentoptions.
文摘Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality worldwide.Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term control.Mechanisms of resistance have been explored in a variety of solid tumors,including RCC.Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in combination.Nevertheless,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease.In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.
文摘目的探讨肉瘤样肾细胞癌组织中PD-L1的表达及肿瘤内微血管密度情况,为肉瘤样肾细胞癌免疫治疗及靶向治疗方案的选择提供理论依据。方法通过免疫组化法检测PD-L1、CD31及CD34在16例肉瘤样肾细胞癌(癌成分均为透明细胞肾细胞癌)中的表达,并评估肿瘤微血管密度。结果16例肿瘤中CD31和CD34免疫组化染色显示,肉瘤样肾细胞癌区域微血管密度明显高于不伴肉瘤样分化的区域,微血管密度计数分别为68.6±25.8 vs 38.7±16.0(t=3.931,P=0.0005)和69.5±28.1 vs 40.1±18.4(t=3.506,P=0.0015),差异有统计学意义。肉瘤样区域PD-L1表达水平高于非肉瘤样区域,CPS分别为34.7±26.9和25.9±27.6,但差异无统计学意义。结论在肉瘤样肾细胞癌中,肉瘤样区域微血管密度和PD-L1表达水平明显高于非肉瘤样区域,提示靶向治疗联合免疫治疗可能为此类肿瘤提供一种有效的治疗方法。
文摘目的:透明细胞乳头状肾细胞肿瘤(clear cell papillary renal cell tumor,CCPRCT)是一种少见但重要的肾肿瘤类型,与其他肾细胞肿瘤具有类似的形态学特征,易导致误诊。本研究旨在探讨CCPRCT的临床病理特征、诊断及鉴别诊断要点,以提高其病理诊断的准确性。方法:收集15例CCPRCT患者,观察其临床及影像学特点,分析其镜下形态、免疫表型,并复习相关文献。结果:15例患者中,男10例,女5例,年龄为(54±17)岁,10例患者肿瘤位于左肾,5例患者肿瘤位于右肾。组织学上肿瘤均由增厚的纤维囊包裹,并局限于肾实质内;肿瘤细胞排列成乳头状、管状、囊状、腺泡及实性等结构;乳头由小到中等大小、透明细胞质的单层细胞组成,肿瘤均为世界卫生组织/国际泌尿病理学会(World Health Organization/International Society of Urological Pathology,WHO/ISUP)1级或2级;细胞核反极性分布,即核上移,靠近腔面,远离基底,类似鲨鱼牙齿排列。免疫组织化学染色显示:细胞角蛋白7、碳酸酐酶9(carbonic anhydrase 9,CA9)和高分子量细胞角蛋白(34βE12)均为阳性表达;α甲基酰基辅酶A消旋酶、CD117、转录因子E3均为阴性表达;CCPRCT中典型的CA9表现方式是“U型”着色,即腔缘不表达,基底和侧面表达。患者术后随访均未见复发或转移。结论:CCPRCT是一种惰性肾细胞肿瘤,预后好,临床可能存在过诊断,其形态学为特征性的核朝向腔缘的线性排列,特殊的免疫表型CA9呈“U型”阳性,可以与其他肾细胞肿瘤区分开来,但仍然需要积累更多患者来阐释其预后。
