PSA、FPSA检测和骨显像对前列腺癌骨转移的诊断价值

目的：探讨联合应用前列腺特异性抗原（PSA）、游离PSA（FPSA）检测和全身骨显像诊断前列腺癌骨转移的意义。方法：回顾性分析70例经临床确诊的前列腺癌患者，全部行血清PSA、FPSA测定，并作全身骨显像。结果：PSA〈4ng／ml在14例病人中，发生骨转移者7例，诊断阳性率为50％；PSA4ng／ml～20ng／ml共7例，发生骨转移者6例、诊断阳性率为87％；PSA〉20ng／ml组49例，发生骨转移45例，阳性率为92％。结论：PSA、FPSA检测结合全身骨显像，可尽早、全面地发现前列腺癌患者全身骨转移。     

PSA、FPSA检测和骨显像对前列腺癌骨转移的诊断价值

目的:探讨联合应用前列腺特异性抗原(PSA)、游离PSA(FPSA)检测和全身骨显像诊断前列腺癌骨转移的意义.方法:回顾性分析70例经临床确诊的前列腺癌患者,全部行血清PSA、FPSA测定,并作全身骨显像.结果:PSA<4ng/ml在14例病人中,发生骨转移者7例,诊断阳性率为50%;PSA 4ng/ml～20ng/ml共7例,发生骨转移者6例,诊断阳性率为87%;PSA＞20ng/ml组49例,发生骨转移45例,阳性率为92%.结论:PSA、FPSA检测结合全身骨显像,可尽早、全面地发现前列腺癌患者全身骨转移.     

前列腺癌患者骨转移的血清学证据研究进展北大核心CSCD

我国的前列腺癌患者在初次诊断时即有较高比例的骨转移,所以在前列腺癌患者中早期筛查骨转移尤为重要,无论对于制定有效的治疗方案还是预后评估都具有重要的临床价值。放射性核素全身骨显像对前列腺癌早期骨转移有很高的诊断价值,但是具有放射性、特异性低、检查成本高的缺点。很多学者正在探索更加理想的筛查方法,一些研究发现可以用血清指标来早期诊断骨转移,如前列腺特异性抗原(PSA)、碱性磷酸酶(ALP)、骨吸收标志物抗酒石酸酸性磷酸酶5b(TRACP 5b)和血清Ⅰ型胶原吡啶交联终肽(1CTP)等。本文对早期筛查前列腺癌患者骨转移的血清学证据进行综述。     

骨显像剂异常浓聚程度及前列腺癌骨转移预测模型的单中心研究

目的探讨总前列腺特异性抗原(TPSA)、游离前列腺特异性抗原/总前列腺特异性抗原[RAT(F/T)]和Gleason评分等因素与全身骨平面显像评价前列腺癌(PCa)骨转移之间的关系, 以及骨显像剂异常浓聚程度对单发病灶的诊断价值。方法回顾性分析2018年1月至2019年1月, 就诊于山西医科大学第一医院的93例确诊PCa患者的99Tcm-亚甲基二膦酸盐(99Tcm-MDP)全身骨平面显像资料, 以全身骨平面显像诊断骨转移, 采用logistic回归分析PCa骨转移的相关因素, 包括年龄、TPSA、RAT(F/T)和Gleason评分, 采用受试者工作特征(ROC)曲线明确TPSA的最佳临界值。利用感兴趣区域技术于平面图像上重复勾画病灶(T)和骨骼以外的本底区域(NT), 计算骨显像剂异常浓聚程度(T-NT)/NT, 采用ROC曲线明确其诊断价值。结果单因素分析显示, Gleason评分、TPSA和RAT(F/T)均与骨转移有关(均P<0.05);logistic回归分析显示, TPSA和RAT(F/T)与骨转移有关(均P<0.01)。TPSA>92.82 ng/ml时...     

89SrCl2治疗前列腺癌骨转移27例疗效分析

目的探讨氯化锶（^89SrCl2）治疗前列腺癌骨转移的疗效。方法采用静脉注射^89SrC2（1．48—2．22MBq/kg体重）治疗27例患者前列腺癌骨转移病灶及疼痛。随访时间6个月。结果^89SrCl2治疗后无效4例（14．8％）；有效16例（59．3％）；显效7例（25．9％）。总有效率为85．2％。部分患者复查骨显像显示，原异常浓聚影明显缩小、减少和／或消失。PSA检查15例（55．5％）较治疗前下降，4例（14．8％）降至20ng／ml以下。70．4％的患者在接受^89SrCl2治疗后，白细胞和血小板计数轻度下降，在3～5个月内恢复到治疗前水平。结论^89SrCl2可以安全、有效地缓解骨转移癌所致疼痛。     

血清PSA、PSAD、ALP联合检测对前列腺癌骨转移的临床诊断价值

目的 探讨血清前列腺特异性抗原(PSA)、前列腺特异性抗原密度(PSAD)、碱性磷酸酶(ALP)联合检测对前列腺癌(PCa)骨转移的诊断价值.方法 回顾性分析98例PCa患者的临床资料,根据是否发生骨转移分为骨转移组(n=56)和非骨转移组(n=42).检测患者的血清PSA、PSAD、ALP水平,分析3项指标单独及联合检测对PCa骨转移的诊断价值.结果 98例PCa患者中,56例患者发生骨转移,骨转移率为57.1％.骨转移组患者的PSA和PSAD值均高于非骨转移组,差异均有统计学意义(P<0.05).ALP+PSA+PSAD联合诊断PCa骨转移的灵敏度(98.34％)、阳性预测值(90.53％)、阴性预测值(92.33％)及约登指数(73.84)均高于PSA、PSAD、ALP单独诊断的结果.结论 血清PSA、PSAD、ALP联合检测对于PCa骨转移具有较高的诊断价值,值得临床推广应用.     

血清BSP水平联合PSADT检测在前列腺癌骨转移早期诊断中的价值

目的探讨骨代谢生化指标骨唾液酸蛋白 ( bone sialoprotein,BSP ) 联合前列腺特异性抗原倍增时间(prostate-specific antigen doubling time,PSADT)检测在前列腺癌骨转移临床诊断中的意义。方法选择 2009年1月-2011年4月我院收治的前列腺癌患者58例,依据诊断分为转移组（28例）和无骨转移组（30例）,取前列腺良性增生患者60例以及60例健康体检人员分别作为增生组和健康对照组。采用视觉模拟疼痛评分( VAS)评价骨痛程度;采用ELISA法检测血清BSP水平;采用电化学免疫发光技术检测血清f-PSA、t-PSA水平,采用倍增公式PSADT=lg(2) [log(PSA2)-log(PSA1)]计算PSADT;采用ROC曲线评价BSP、PSADT及两者联合检测在前列腺癌骨转移诊断中的意义。结果两组患者BSP水平均高于健康对照组和增生组(P<0.05);骨转移组患者血清BSP水平均明显高于无转移组(P<0.05);Pearson’s分析结果显示：前列腺癌骨转移患者的BSP和VAS骨痛评分呈显著正相关（P<0.05）;ROC曲线显示, BSP 诊断骨转移的敏感度和特异性分别为71.12%和72.8%;PSADT诊断骨转移的敏感度和特异性分别为84.15%和82.96%;BSP联合PSADT在前列腺癌骨转移诊断中的敏感度、特异性、AUC面积分别为91.26%,89.54%,0.932。结论BSP可能是前列腺癌骨转移患者的有效诊断指标;BSP和PSADT联合检测能大大提高前列腺癌骨转移的敏感度和准确性,便于前列腺癌骨转移的早期诊断。     

放射性核素全身骨显像诊断肺癌骨转移

本文报告１８４例经病理证实的原发性肺癌骨显像的结果，对不同组织学类型肺癌骨转移的特点和规律进行分析。本组肺癌骨转移性率６６．３％（１２２／１８４），骨转移部位以胸部最多，为３５％，其他依次为脊柱２５．２％，骨盆２２．４％，肢体１５．６％，颅骨１．８％。多发性转移灶占８１．１５％（９９／１２２），孤立性转移灶１８．８５％。肺癌患者应常规行全身骨显像检查，对分期、治疗方案的选择及预后均有重大意义。     

血清FPSA/TPSA与核素骨显像在前列腺癌骨转移诊断中的应用

前列腺癌 (PCa)是欧美国家男性最常见的恶性肿瘤 ,其发病率在我国亦有上升趋势[1 ] 。而且骨转移发生率相当高 ,国外文献报道可达 50 %～ 80 % [2 ] 。我们对本院 1 999年 1月～ 2 0 0 2年 5月期间既接受核素全身骨显像 ,又有血清TPSA和FPSA测定资料的 61例前列腺癌患者 ,进行了回顾分析 ,旨在探讨上述检查方法联合应用诊断前列腺癌骨转移的临床意义。材料和方法一研究对象 61例PCa患者均经病理和 (或 )穿刺细胞学检查证实 ,年龄 43～ 88岁 ,平均 70 .6岁。按骨显像结果分为两组 :骨显像阳性组 47例 ;骨显像阴性组 1 4例。按治疗情况分…     

SPECT全身骨显像对多发性骨髓瘤和前列腺癌骨转移瘤的鉴别诊断价值

目的:探究多发性骨髓瘤和前列腺癌在单光子发射计算机断层成像术(SPECT)骨显像上的区别与联系.方法:对2013年6月至2015年12月收治的SPECT图像表现为全身广泛骨质代谢活跃灶的多发性骨髓瘤和前列腺癌患者进行回顾性研究,分析两者病灶部位、数目、形态以及各自典型影像表现.结果:25例多发性骨髓瘤患者共检出327个病灶,病灶最常累及部位分别为肋骨、脊柱、骨盆、颅骨、肩关节和股骨;33例前列腺癌患者共检出851个病灶,转移病灶最常累及部位分别为脊柱、肋骨、骨盆、股骨和肩关节、胸骨、颅骨、肱骨.多发性骨髓瘤在图像上表现为多发点状或类圆形浓聚,颅骨"帽状"浓集、肋骨"串珠样"浓集是其特征性表现;前列腺癌骨显像表现为放射性核素异常浓聚,大小、形态不一,多为点状、条状、片状或不规则浓集灶,全身骨骼"超级影像"为其特征性表现.结论:SPECT骨显像对多发性骨髓瘤和前列腺癌骨转移瘤有一定的鉴别诊断价值.     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的:探讨前列腺特异抗原(PSA)、发射型计算机断层扫描(ECT)99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法:对80例(骨转移组31例,非骨转移组49例)前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果:骨转移组与非骨转移组的PSA值差异有显著性(139.36μg/Lvs37.58μg/L,P<0.01);PSA与骨转移的程度正相关,PSA<10μg/L,骨转移率为15.38%;PSA<20μg/L,骨转移率为19.35%;PSA>20μg/L,骨转移率为51.02%;PSA>100μg/L,骨转移率为78.95%。结论:ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA<10μg/L,前列腺癌骨转移的可能性极小;PSA>100μg/L者,骨转移的可能性极大。PSA>20μg/L,建议行ECT骨扫描。     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的：探讨前列腺特异抗原（PSA）、发射型计算机断层扫描（ECT）99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法：对80例（骨转移组31例,非骨转移组49例）前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果：骨转移组与非骨转移组的PSA值差异有显著性（139.36μg/Lvs37.58μg/L,P〈0.01）;PSA与骨转移的程度正相关,PSA〈10μg/L,骨转移率为15.38%;PSA〈20μg/L,骨转移率为19.35%;PSA〉20μg/L,骨转移率为51.02%;PSA〉100μg/L,骨转移率为78.95%。结论：ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA〈10μg/L,前列腺癌骨转移的可能性极小;PSA〉100μg/L者,骨转移的可能性极大。PSA〉20μg/L,建议行ECT骨扫描。     

Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis

The development of effective therapies inhibiting prostate cancer progression and metastasis may substantially impact prostate cancer mortality and potentially reduce the rates of invasive treatments by enhancing the safety of active surveillance strategies. Hepsin (HPN) is a cell surface serine protease amplified in a subset of human sarcomas (7.2%), as well as in ovarian (10%), lung adeno (5.4%), lung squamous cell (4.5%), adenoid cystic (5%), breast (2.6%), uterine (1.7%) and colon (1.4%) carcinomas. While HPN is not amplified in prostate cancer, it is one of the most prominently overexpressed genes in the majority of human prostate tumors and genetic experiments in mice indicate that Hepsin promotes prostate cancer metastasis, particularly metastasis to the bone marrow. We report here the development, analysis and animal trial of the small-molecule Hepsin inhibitor HepIn-13. Long-term exposure to HepIn-13 inhibited bone, liver and lung metastasis in a murine model of metastatic prostate cancer. These findings indicate that inhibition of Hepsin with small-molecule compounds could provide an effective tool for attenuation of prostate cancer progression and metastasis.     

Human fucosyltransferase 6 enables prostate cancer metastasis to bone

Background:

The interaction between human prostate cancer (PCa) cells and bone marrow (BM) endothelium follows a rolling-and-adhesion cascade mediated by E-selectin ligand (ESL): E-selectin. This adhesion is enabled by elevated expression of α-1,3-fucosyltransferases (FTs), enzymes responsible for ESL-mediated bone metastasis in humans. In contrast, the incidence of bone metastasis in mice is rare.

Methods:

FT 3, 6 and 7 were overexpressed in mouse PCa cells. The rolling cell number, cell-rolling velocity and transendothelial migration were characterised in vitro. Fucosyltransferases-transduced mouse PCa cells expressing luciferase were inoculated into mice via left ventricle to compare the capability of bone metastasis. Mass spectrometry and immunoprecipitation were utilised for identification of ESLs.

Results:

Overexpression of FT3, FT6 or FT7 restored ESLs and enabled mouse PCa cells to roll and adhere in E-selectin-functionalised microtubes, similar to trafficking of circulating PCa cells in BM vessels. Following intracardiac inoculation, FT6-transduced cells induced robust bone metastasis in mice. Inhibition of FT6 by a fucose mimetic significantly reduced bone metastasis. Importantly, comparison of FT3, FT6 and FT7 gene expression in existing clinical samples showed significant upregulation of FT6 in PCa-distant metastases.

Conclusion:

FT6 is a key mediator of PCa cells trafficking to the BM. It may serve as a viable drug target in preclinical tests of therapeutics for reduction of PCa bone metastasis.     

Evaluation of the current incidence of nodal metastasis from prostate cancer

To determine the influences of transrectal ultrasonography, prostate-specific antigen (PSA), and heightened public awarencess of prostate cancer stage at diagnosis, we prospectively evaluated our most recent 173 patients who had a pelvic lymphadenectomy from 1987 to 1991. All patients had clinically localized prostate cancer and underwent bilateral limited pelvic lymph node dissections (N = 173); 19 (10.7%) were found to have nodal metastasis. Pathologic tumor stage and grade information was available for 168 patients who had a simultaneous radical prostatectomy. Clinical T-stage data revealed that only one patient had a T3 lesion. Pathologic T stage showed 7.1% to be T1a (12/168), 4.1% to be T1b (7/168), 13.7% to be T2a (23/168), 34.5% to be T2b (58/168), and 40.5% to be T3 lesions (68/168). Metastatic nodal involvement was not seen in any T1a, T1b, or T2a lesions. A Gleason's score of less than 5 lesions was predictive of no nodal metastasis. The clinical stage was upstaged pathologically in none of the T1a, 16.7% of the clinical T1b, 75% of the T2a, and 73% of the T2b, lesions. With regard to serum PSA, 27% of those patients with a level > 20 ng/ml had nodal metastasis (6/22) in this series. Although an elevated PSA was not predictive of tumor nodal metastasis, no patient with a normal PSA had nodal metastasis. Although the distribution of pathologic T stages is similar to that reported in the literature, our low incidence of nodal metastasis may suggest that prostate cancer is being diagnosed earlier. © 1993 Wiley-Liss, Inc.     

Percentage of the positive area of bone metastasis is an independent predictor of disease death in advanced prostate cancer

We addressed in this study whether quantifying the extent of disease on bone scans can predict the disease death of patients with advanced prostate cancer using computer-assisted image analysis. Pretreatment radionuclide bone scans were reviewed in 56 patients with bone metastases from prostate cancer, and the percentage of the positive area on a bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program for estimation of the accurate extent of metastatic bone lesions on a bone scan. The significance of the %PABS as well as the other known prognostic factors was evaluated using univariate and multivariate Cox proportional hazards analysis. In univariate regression analysis, the %PABS (P=0.0155), serum alkaline phosphatase (P=0.0272), the tumour grade based on biopsy (P=0.044) and the number of bone lesions on bone scans (P=0.0388) were well associated with disease-specific survival. In multivariate analysis, the %PABS (P=0.0155, relative risk ratio 2.603), but not the other factors, was the independent predictor of the disease death. These results suggest that the %PABS is a novel parameter for predicting the prognosis of patients with advanced prostatic cancer.     

FGF-8 is involved in bone metastasis of prostate cancer

Prostate cancer is the most common malignancy of men in Western countries. Patients with advanced prostate cancer suffer from incurable bone metastases. Recent data indicate that interactions between prostate cancer cells, osteoblasts, osteoclasts and the bone matrix are essential in the formation of bone metastases. FGF-8 is widely overexpressed in prostate cancer. Recently, FGF-8 has been found to affect both osteoblast and osteoclast differentiation. The aim of this study was to examine the role of FGF-8 in bone metastasis of prostate cancer. Immunohistochemistry was used to analyse FGF-8 expression in clinical samples of prostate cancer bone metastases. The functional significance of FGF-8 in growth of bone metastasis and formation of bone lesions was verified by using intratibial inoculations of FGF-8 or mock transfected PC-3 prostate cancer cells in nude mice. Intratibial tumors and bone lesions were analysed with X-ray, micro-CT and detailed histomorphometry using image analysis software and with immunostaining for osteocalcin and cathepsin K. Immunohistochemical analysis of tissue microarray of bone metastases of human prostate cancer showed that 76% of human bone metastasis samples (n = 25 from 11 patients) were positive for FGF-8. FGF-8 increased the growth of intratibial tumors and local formation of lytic and sclerotic lesions of bone. These results demonstrate that FGF-8 is expressed at a high frequency in bone metastases of human prostate cancer and that expression of FGF-8 in PC-3 prostate cancer cells increases their growth as intratibial tumors and modulates formation of bone lesions in an in vivo model of prostate cancer bone metastasis.     

Steps in prostate cancer progression that lead to bone metastasis

Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone are not completely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bidirectional interactions between the tumor and the bone microenvironment. In this review, we discuss the current understanding of the biologic processes and regulatory factors involved in the metastasis of prostate cancer cells, and their specific properties that promote growth in bone. Although many of these processes still need to be fully elucidated, a better understanding of the complex tumor/microenvironment interplay is slowly leading to more effective therapies for patients with prostate cancer bone metastases.     

以骨转移癌为首发表现的前列腺癌诊治分析

目的:对以骨转移癌为首发表现的前列腺癌患者进行分析,提高对晚期前列腺癌的认识。方法:对32例以骨转移癌为首发表现的前列腺癌患者症状与体征、实验室检查、影像学检查、病理学检查结果等资料进行回顾分析。结果:32例患者表现为骨痛25例(78.13%),凝血功能障碍、贫血10例(31.25%),发热2例(6.25%),伴有泌尿系统症状8例(25%),血清前列腺特异性抗原(PSA):PSA>50ng/ml者15例,PSA>100ng/ml者8例,碱性磷酸酶升高(超过150U/L)13例(72%)。进一步行骨核素扫描见多发、散在、无规律的放射性增高或浓聚灶,骨转移瘤见于腰骶椎体、髋骨占30例（93.75%）,其次为肋骨和胸骨,伴一处或以上的脏器转移占6例(18.75%)。追问病史发现前列腺癌诊断线索8例。经前列腺穿刺活组织检查确诊前列腺癌22例,临床诊断10例。结论:对于临床上出现不明原因骨痛、凝血功能障碍、贫血、发热等症状的老年男性患者,应考虑到前列腺癌伴骨转移可能,应常规查血PSA,据情行骨扫描及骨髓活检等检查。     

Significant addition to treatment options for bone metastasis in prostate cancer

Pathologic fractures, spinal compression, and pain take a great toll on the healthcare costs and well-being of men with prostate cancer metastatic to the bone. For almost 10 years, the only drug proven to prevent these skeletal-related adverse events was the bisphosphonate zoledronic acid. In a study published by Fizazi et al. in The Lancet, the monoclonal antibody to RANKL, denosumab, is shown to be superior to zoledronic acid in the prevention of these events. The only notable adverse event more frequent in either arm was increased hypocalcemia in the denosumab arm. There was a greater frequency of osteonecrosis of the jaw in the denosumab treatment group that did not reach statistical significance, but is of great concern. While further analysis is needed to determine the value of denosumab in preventing adverse events and improving quality of life, this new therapy is a significant addition to the treatment of men living with metastatic prostate cancer.