An evaluation of current prostate cancer diagnostic approaches with emphasis on liquid biopsies and prostate cancer

ABSTRACT

Introduction: Knowledge of the complex biology of prostate cancer is constantly growing, opening the field up to new therapeutic advances. The selection of patients on the basis of prognostic and predictive biomarkers is a challenging and emerging clinical need, not yet completely fulfilled. In this scenario, liquid biopsy offers a noninvasive and attractive approach to give important information about tumor biology and eventual resistance to treatments.

Areas covered: The aim of this review of the literature is to evaluate the current knowledge and the promising value of liquid biopsy in prostate cancer. Circulating tumor cells and circulating tumor DNA identified by liquid biopsies are currently under evaluation to guide therapeutic decisions in prostate cancer management, even though practical applications of these approaches are still very limited. We examined the current areas of interest in which circulating tumor cells and circulating tumor DNA are being investigated, such as their prognostic and predictive role in response to chemotherapy or androgen receptor signaling inhibition, especially in the castration-resistant setting.

Expert opinion: As the body of knowledge on liquid biopsy rapidly grows, we need to identify which can be the real applications of this technique in clinical practice and to overcome the problems that are limiting its routinely use.     

Sonographic patterns of renal cell carcinoma with emphasis on relation to tumor size

The sonographic appearance of 37 renal cell carcinomas was reviewed with particular emphasis on the relationship between the echo pattern of tumor and tumor size. Small carcinomas tended to be solid and hypoechoic; seven lesions less than 5 cm in the largest dimension were either hypo- or isoechoic . The echogenicity level of the solid parts within the lesion, whether it was solid or mixed, tended to increase as the tumor grew. It is important to recognize that the sonographic appearance of renal cell carcinomas varies with the size of the tumor.     

透明质酸测定鉴别诊断肾细胞癌和移行细胞癌

目的:探讨并评价血、尿透明质酸的测定在肾癌、肾盂癌鉴别诊断中的价值。方法:采集41份血液和尿液样本,其中肾癌17例,肾盂癌14例,正常人10例;采用酶联免疫法(ELISA)测定尿液和血液样本中透明质酸的浓度;采用化学发光法测定尿液中蛋白浓度,用SPSS 11.0分析血液、校正尿液的透明质酸浓度及其比值。结果:在41份血液样本中,各组数据间差异无统计学意义;41份尿液样本中,比较经尿蛋白浓度校正后的尿透明质酸浓度,肾癌组与肾盂癌组差异有统计学意义(P<0.01);比较41例样本的血尿透明质酸浓度比值,肾癌组与肾盂癌组差异有统计学意义(P<0.01)。结论:肾盂癌患者尿液中校正透明质酸浓度明显高于正常人和肾癌患者。尿液透明质酸浓度可作为移行细胞癌的肿瘤标志物,用于肾盂癌的诊断及其与肾癌的鉴别诊断。     

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies

ABSTRACT

Introduction: Prostate cancer (PCa) is one of the most common malignancies in men and a major cause of cancer deaths among men worldwide. Prostate specific antigen (PSA) monitoring and histopathological examination of tumor biopsies remain gold standards in PCa diagnostics. These clinical parameters are not well suited for patient stratification, predicting and monitoring treatment response. On the other hand, liquid biopsies offer a unique opportunity to easily isolate tumor-derived material for longitudinal clinical assessment.

Areas covered: In this review we focus on the clinical application of novel liquid biomarkers that have the potential to monitor and stratify patients in order to achieve better therapeutic effects and improve clinical outcomes. Enumeration and characterization of circulating tumor cells (CTCs), tumor-educated platelets, exosomes, and cell-free nucleic acids have been studied for their clinical utility in PCa diagnostics, prognostics, monitoring treatment response and guiding treatment choice.

Expert opinion: Liquid biomarkers have high potential to be used for prognosis, monitoring treatment response and guiding treatment selection. Although there is a remarkable progress in PCa biomarker discovery, their clinical validation is very limited. Research should be focused on biomarker validation and the incorporation of these biomarkers in clinical practice.     

乳头状肾细胞癌伴砂粒体形成─附3例报告

本文报告了３例乳头状肾细胞癌伴砂粒体形成的病理变化和砂粒体的形态特征，探讨了砂粒体的形成机制，提出了在肾细胞癌中出现砂粒体，预示此类肿瘤生长缓慢，可能与预后有关。     

内皮抑素基因对ACHN RCC细胞增殖和凋亡的影响

目的利用已构建的带有内皮抑素基因真核表达载体质粒导入裸鼠ACHN肾细胞癌（renal cell carcinoma,RCC）细胞中,研究内皮抑素基因对RCC细胞增殖和凋亡的影响。方法ACHN细胞浓度1×10^7个/L,经裸鼠右侧背部皮下注射0.2 ml,共注射24只裸鼠。荷瘤裸鼠随机分为3组,每组8只。治疗组：每只裸鼠瘤内3点注射复合物100μl（内含30μl梭华-SofastTM和30μg pSecES质粒）;对照组：每只裸鼠瘤内3点注射复合物100μl（内含30μl梭华-SofastTM和30μg pcDNA3.1质粒）;空白组：每只裸鼠瘤内3点注射生理盐水100μl。各组每只裸鼠间隔3 d注射1次,连续注射3次。以增殖细胞核抗原（PCNA）作为细胞增殖状态,按链霉亲和素生物素法（SABC）进行免疫组化染色。细胞凋亡检测用TUNEL法。结果内皮抑素真核表达质粒能显著抑制裸鼠ACHN RCC肿瘤体积增长,pSecES治疗组平均瘤重明显小于空白组和对照组（P〈0.01）,与空白组的肿瘤生长抑制率为34.48%,与对照组的肿瘤生长抑制率为40.68%。治疗组肿瘤细胞的凋亡指数（AI）明显高于对照组和空白组（P〈0.01）。pSecES治疗组肿瘤组织的AI/PI比值明显高于对照组和空白组（F=189.27,P〈0.05）。Spearman相关分析表明,肿瘤体积与细胞增殖之间无明显相关性（r=-0.041 2,P〉0.05）,肿瘤体积与细胞凋亡呈负相关（r=-0.734 6,P〈0.01）。结论内皮抑素基因治疗可使裸鼠ACHN RCC肿瘤细胞凋亡增加,肿瘤细胞的数量减少,在总体上表现为肿瘤的生长变慢、体积变小。     

An update on liquid biopsy analysis for diagnostic and monitoring applications in non-small cell lung cancer

Introduction: Collection of tumor samples is not always feasible in non-small cell lung cancer (NSCLC) patients, and circulating free DNA (cfDNA) extracted from blood represents a viable alternative. Different sensitive platforms have been developed for genetic cfDNA testing, some of which are already in clinical use. However, several difficulties remain, particularly the lack of standardization of these methodologies.

Areas covered: Here, the authors present a review of the literature to update the applicability of cfDNA for diagnosis and monitoring of NSCLC patients.

Expert commentary: Detection of somatic alterations in cfDNA is already in use in clinical practice and provides valuable information for patient management. Monitoring baseline alterations and emergence of resistance mutations is one of the most important clinical applications and can be used to non-invasively track disease evolution. Today, different technologies are available for cfDNA analysis, including whole-genome or exome sequencing and targeted methods that focus on a selection of genes of interest in a specific disease. In the case of Next Generation Sequencing (NGS) approaches, in depth coverage of candidate mutation loci can be achieved by selecting a limited number of targeted genes.     

不易确诊的小肾癌的临床诊断与治疗

目的 探讨小肾癌的诊断与治疗方法。方法回顾性分析12例小肾癌的临床资料及影像学特征,初步诊断与术后病理学检查结果进行对照。结果术前诊断正确率：B超为28．2％、CT为89．6％。8例行肾癌根治术,4例行保留肾单位手术。结论小肾癌临床分期低,预后较好。影像学及病理学检查对于小肾癌的诊断具有重要意义,保留肾单位手术为其治疗的最佳选择。     

Challenges for CTC-based liquid biopsies: low CTC frequency and diagnostic leukapheresis as a potential solution

Circulating tumor cells (CTCs) are very attractive surrogate markers for systemic cancer. Currently, major efforts are being made to use these rare cells in the sense of a liquid biopsy to gain molecular information for rational therapeutic decision-making. The advancements in molecular analyses of CTCs down to the single-cell level have been significant in recent years and some applications are ready to be used in clinical studies. As discussed in this review, a major challenge for translating such molecular CTC-based assays into the clinic is the extremely low frequency of CTCs and the associated problems of their reliable detection and isolation. A potential solution to overcome the low CTC frequency is the recently introduced diagnostic leukapheresis that permits screening of liters of blood. Discussed here are the challenges as well as the current efforts implementing this method into clinical workflows to realize more reliable liquid biopsies.     

磁共振成像对肾癌分期的价值

目的评价磁共振成像对肾癌分期的诊断价值.方法 49例经手术病理证实的肾癌患者,术前行MR检查,并根据影像表现分期.术后根据手术病理结果,用Robson分期法将其分为Ⅰ～Ⅳ期,将MR分期与术后病理分期进行对照研究.结果 49例患者术后病理分期:Ⅰ期12例,Ⅱ期10例,Ⅲ期20例,Ⅳ期7例.MR诊断正确率为Ⅰ期75%(9/12)例,Ⅱ期70%(7/10),Ⅲ期85%(17/20),Ⅳ期100%(7/7),总的诊断正确率为81.6%(40/49).MR对Ⅰ期患者分期错误的主要原因是病灶较小,在图像上有部分容积效应而显示边界不清楚;对Ⅱ期患者是病灶周围有微小的肾周浸润,在MR图像上未能显示;对Ⅲ期患者的主要原因是肾静脉内的微瘤栓在MR图像不能显示.结论 MR可用于肾癌的分期,对于Ⅲ、Ⅳ期肾癌的分期诊断准确性较高,而对于Ⅰ、Ⅱ期肾癌的分期准确性有待提高.     

经皮射频消融治疗肾癌

射频消融技术是一种安全的微创介入技术,但该技术在治疗肾脏肿瘤方面仍处于起步期,本文简要介绍了该技术的发展历史、原理及其基本设备,并主要回顾了该技术在肾癌治疗方面的基础研究和临床应用、潜在的并发症、影像监测及疗效评价等有关问题。     

Portal venous tumor thrombus associated with hepatic metastasis of renal cell carcinoma: case report

We report a case of liver metastasis of renal cell carcinoma with portal venous tumor thrombus. Abdominal computed tomographic images showed a large hepatic mass that enhanced slightly during arterial phase. Multiple hypoattenuating lesions were seen in the intrahepatic portal venous branches and were traced directly from the mass. The histologic specimen confirmed metastatic liver tumor of renal cell carcinoma with portal venous tumor thrombus.     

胃黏膜活检中黏液细胞癌的临床病理特点

目的：分析胃黏膜活检中黏液细胞癌的病变特点，总结其临床病理特征，避免误诊漏诊。方法：通过组织病理学和组织化学PAS，AB染色法，对93例胃黏液细胞癌黏膜活检标本进行病理观察。结果：根据组织学特点，将癌组织分布形式分为黏膜固有层浅层，黏膜固有层深层，弥漫分布，黏膜边缘及坏死组织周围5种病变类型，其在93例标本中分别占8．6％，31．2％，30．1％，11．8％和18．3％，每种黏液细胞癌类型的细胞形态，排列方式及细胞周围的组织变化均有所不同，其癌细胞也具有不同的形态特征和黏液分泌特点，结论：胃黏液细胞癌的形态特征与组织分布具有相对的特殊性，掌握其特点可以在外科病理检查中减少误诊漏诊。     

超声造影在肾细胞癌分型中的应用价值

目的 探讨超声造影在肾细胞癌分型中的应用价值.方法 对经手术病理证实的70个肾细胞癌(包括58个肾透明细胞癌,7个乳头状细胞癌,5个嫌色细胞癌)的超声造影图像进行分析,对比观察肿瘤及瘤旁肾皮质显影过程,检测指标包括开始增强方式、消退方式、到达时间、达峰时间、达峰强度及消退强度(后4项由时间-强度曲线得到).结果 53个透明细胞癌表现为肿瘤开始增强较肾皮质早或同时,消退较慢,肿瘤内造影剂灌注量多于肾皮质,即富血供表现.以富血供表现诊断透明细胞癌的特异性及敏感性为100%和91%.其余肾细胞癌为乏血供表现,其中嫌色细胞癌全部以均匀增强、消退期肿瘤周边出现高增强晕环,达峰强度稍低于肾皮质为特征性表现;乳头状细胞癌及乏血供透明细胞癌造影表现有交叉.结论 超声造影有助于肾细胞癌的分型诊断.     

嗜酸性实性和囊性肾细胞癌2例临床病理观察

目的探讨嗜酸性实性和囊性肾细胞癌的诊断及鉴别诊断。方法分析2例嗜酸性实性和囊性肾细胞癌的临床病理特征及免疫表型,并复习相关文献。结果例1肿瘤以实性区为主,局灶形成囊腔,肿瘤细胞强嗜酸性,有胞质内彩斑、空泡,可见多核化,囊壁被覆鞋钉样排列的强嗜酸性细胞。例2以囊性区(巨囊)为主,局灶实性,囊壁被覆强嗜酸性肿瘤细胞,呈鞋钉样排列,胞质内彩斑及空泡不明显。2例免疫组化表型均为局灶CK20(+)。结论嗜酸性实性和囊性肾细胞癌是新近认识的一种以实性和囊性结构及大的嗜酸性细胞为主型的惰性肾肿瘤,具有独特的病理特征,免疫表型表现为独特的CK20局灶阳性。通过其特征性的组织学形态和独特的免疫表型表现比较容易与其他嗜酸性肾细胞肿瘤鉴别。     

肾细胞癌和肾血管平滑肌脂肪瘤冷冻切片误诊分析

目的 分析肾细胞癌和肾血管平滑肌脂肪瘤冷冻切片误诊原因以及提高诊断准确率的方法。方法 分析术中肾冷冻切片112例，根据最后诊断结果分为两组，第一组24例，为肾血管平滑肌脂肪瘤；第二组88例，为肾细胞癌。将患者的临床资料、冷冻切片及术后常规石蜡切片诊断结果作对照。结果 第一组中1例术中诊断为肉瘤样癌，2例良恶性难定，21例诊断正确；第二组中6例术中诊断为肾血管平滑肌脂肪瘤，1例黄色肉芽肿性肾盂肾炎，2例良恶性难定，79例诊断正确。结论 提高冷冻切片准确率的关键在于详尽了解临床资料、正确而全面地取材以及丰富的经验。     

超声造影在肾细胞癌与肾血管平滑肌脂肪瘤鉴别诊断中的价值

目的:探讨超声造影(CEUS)在肾细胞癌(RCC)与肾血管平滑肌脂肪瘤(RAML)鉴别诊断中的价值。方法:回顾性分析经手术病理证实的53例RCC患者和17例RAML患者的二维灰阶超声、彩色多普勒血流显像(CDFI)和CEUS特征。结果:RCC的二维灰阶超声特征以低回声为主,RAML则以高回声为主(P0.05);RCC的CDFI检查分级以Ⅱ～Ⅲ级为主,而RAML以0～Ⅱ级为主,但两者间差异尚无统计学意义(P>0.05);CEUS特征比较,RCC组与RAML组间患者病灶检查所显示的灌注程度、灌注均匀性和有无环状灌注的差异有统计学意义(P<0.01)。结论:CEUS在RCC与RAML的鉴别诊断中具有重要的临床价值。     

尾加压素Ⅱ在肾癌患者血液和孵育组织中的表达

目的测定肾癌患者和正常对照人群血液和孵育组织中尾加压素Ⅱ(Urotensin Ⅱ,UⅡ)的表达量,以期探讨UⅡ表达在肾透明细胞癌发生中的临床意义。方法对20例肾透明细胞癌患者及20例对照人群通过放免方法检测血液和孵育组织UII的表达。结果肾癌患者和正常对照人群血液和孵育组织中均有UⅡ表达。放免结果显示肾透明细胞癌组患者血浆UII水平(50.08±4.77 pg/ml)与正常对照组血浆UⅡ(45.55±6.05 pg/ml)相比差异无统计学意义(P>0.05)。肾透明细胞癌组织孵育后UII水平(30.83±8.51 pg/mg pro)明显高于正常肾组织(16.09±3.13 pg/mgpro)(P<0.01)。结论肾透明细胞癌组织可分泌UⅡ,且较正常肾组织高,提示UⅡ可能与肾透明细胞癌的发生、发展有关,UⅡ可能通过自分泌或旁分泌的方式发挥作用。     

肾细胞癌的MRI影像分析

目的分析肾细胞癌亚型MRI信号平扫特点及增强表现,提高对肾细胞癌的诊断水平。方法收集有完整临床资料及病理证实肾细胞癌48例,均做T_1WI、T_2WI、TRUFI序列平扫及增强扫描,其中15例行MRI动态增强扫描。结果本组48命名透明细胞型41例,嫌色细胞型4例,乳头状细胞型3例。T_1WI均匀等或低信号33例,混杂信号15例;T2WI均匀高信号14例,等信号6例,混杂信号28例。显示假包膜者10例。增强扫描6例病灶均匀强化,34例不均匀强化,5例内壁不规则环状强化,3例均匀环状强化(假包膜强化)。结论 MRI能够准确诊断肾细胞癌,并有助于判断细胞亚型。