肿瘤标志物在肺癌引起胸腔积液诊断中的应用进展

胸腔积液是一个常见的临床表现.其良恶性的判断与治疗、预后密切相关.许多方法和指标都曾尝试用于恶性胸腔积液的诊断,各有利弊.随着分子生物学和实验技术的迅速发展,新的诊断指标和检测方法不断涌现.肿瘤标志物包括肿瘤相关抗原,肿瘤相关蛋白等,对于肺癌引起的胸腔积液的鉴别诊断具有重要的意义.     

恶性胸腔积液中EGFR突变和肿瘤标志物的关系探讨

目的 探讨非小细胞肺癌(NSCLC)伴恶性胸腔积液患者胸腔积液中表皮生长因子受体(EGFR)突变和肿瘤标志物的关系.方法 收集2013年1月至2016年8月于重庆医科大学附属第一医院经病理证实的晚期NSCLC患者49例.分别对患者的胸腔积液进行肿瘤标志物和EGFR基因检测,同时应用SPSS 23.0软件分析临床特征、肿瘤标志物表达水平和EGFR突变的关系.结果 在49例NSCLC患者中,EGFR突变率为55.1％,EGFR突变和各临床特征间的关系无统计学意义.同时在EGFR突变和肿瘤标志物的关系方面,EGFR突变率随着癌胚抗原和乳酸脱氢酶的表达水平的升高而升高.结论 恶性胸腔积液中肿瘤标志物水平的高低和EGFR突变状态在一定程度上有关.对于不易获取肿瘤组织标本的恶性胸腔积液患者来说,胸腔积液中肿瘤标志物水平可以指导EGFR-酪氨酸激酶抑制剂的使用.     

老年患者肺癌恶性胸腔积液和肺炎旁胸腔积液中FoxM1基因表达差异分析

目的 分析老年人肺癌恶性胸腔积液和肺炎旁胸腔积液中叉头基因FoxM1的基因表达,寻找对于胸水良恶性的鉴别具有诊断意义的基因标志物.方法 分别收集15例老年肺炎患者旁胸腔积液(A组)和21例老年肺癌患者(15例为腺癌,5例为鳞癌,1例为小细胞肺癌)恶性胸腔积液(B组),分别提取各组标本总RNA,再经过逆转录得到c-DNA,通过荧光定量.聚合酶链反应技术分析各组胸腔积液中叉头基冈FoxMl的基因表达差异.结果 B组FoxM1基因平均相对含量明显高于A组(925.014±103.999) vs(244.354±43.429),P＜0.01).结论 FoxM1的基因表达量在老年肺癌恶性胸腔积液组中明显高于老年肺炎旁胸腔积液组,对胸水良恶性的鉴别具有重要诊断参考价值.     

VEGF、CEA、CA153联合检测在恶性胸腔积液中的诊断价值

目的评价胸腔积液VEGF、CEA、及CA153联合检测对恶性胸腔积液鉴别诊断价值。方法采集胸腔积液患者胸水样本80例,其中恶性胸腔积液患者50例,良性胸腔积液患者30例,应用ELISA方法及化学发光法检测标本中VEGF、CEA和CA153的水平。结果恶性胸腔积液组VEGF、CEA、及CA153水平明显高于良性胸腔积液组（P〈0.01）,VEGF、CEA、及CA153联合检测可使鉴别诊断敏感性明显提高,诊断恶性胸腔积液的敏感度为94.28%,特异度为76.93%。结论肿瘤标志物CEA、CA153和CY211的联合检测,对胸腔积液的鉴别诊断有较好的临床价值,联合方式以VEGF＋CEA为佳。     

肿瘤标志物CEA、CA125在恶性胸腔积液中的诊断价值

目的探讨CEA、CA125在恶性胸腔积液中的诊断价值。方法对42例恶性胸腔积液和38例良性胸腔积液患者分别给予胸水和血清CEA、CE125测定。结果恶性胸腔积液组血清和胸水中CEA、CA125测定值均明显高于良性组。结论 CEA、CA125肿瘤标志物的测定在鉴别良恶性胸腔积液中有价值。     

肺癌并恶性胸腔积液患者血清和胸腔积液肿瘤标志物水平变化及其对良恶性胸腔积液的鉴别诊断价值研究

目的分析肺癌并恶性胸腔积液患者血清和胸腔积液肿瘤标志物水平变化及其对良恶性胸腔积液的鉴别诊断价值。方法选取2016年2月—2017年12月苏州大学附属常熟医院收治的肺癌并恶性胸腔积液患者34例作为试验组,以性别、年龄为匹配条件,按照1:1比例选取同期收治的良性胸腔积液患者34例作为对照组。对照组患者针对原发病给予对症治疗及胸腔积液引流,试验组患者给予化疗及胸腔积液引流。观察试验组患者化疗效果,比较两组患者治疗前血清和胸腔积液肿瘤标志物水平、试验组患者化疗前后及不同化疗效果患者血清肿瘤标志物水平,并绘制ROC曲线以评价治疗前胸腔积液肿瘤标志物水平对良恶性胸腔积液的鉴别诊断价值。结果 (1)试验组患者中完全缓解13例,部分缓解10例,疾病稳定5例,疾病进展6例;化疗有效23例,化疗失败11例。(2)试验组患者治疗前血清和胸腔积液细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、鳞状上皮细胞癌抗原(SCC-Ag)水平高于对照组(P0.05)。(3)绘制ROC曲线发现,治疗前胸腔积液CYFRA21-1、CEA、NSE、SCC-Ag水平鉴别诊断良恶性胸腔积液的曲线下面积分别为0.881[95%CI(0.716,0.928)]、0.963[95%CI(0.683,0.964)]、0.910[95%CI(0.688,0.975)]、0.926[95%CI(0.724,0.972)]。(4)试验组患者化疗后血清CYFRA21-1、CEA、NSE、SCC-Ag水平低于化疗前(P0.05);化疗有效患者血清CYFRA21-1、CEA、NSE、SCC-Ag水平低于化疗失败患者(P0.05)。结论肺癌并恶性胸腔积液患者血清和胸腔积液CYFRA21-1、CEA、NSE、SCC-Ag水平升高,治疗前胸腔积液CEA、NSE、SCC-Ag水平对良恶性胸腔积液的鉴别诊断价值较高,且血清CYFRA21-1、CEA、NSE、SCC-Ag水平可用于评估肺癌并恶性胸腔积液患者近期化疗效果。     

肺癌合并恶性胸腔积液化疗前后CEA、NSE、SCC-Ag的表达及意义

目的探讨肿瘤标志物CEA、NSE和SCC-Ag在肺癌合并恶性胸腔积液的诊断和评估近期疗效的价值。方法用电化学发光法分别检测肺癌合并恶性胸腔积液患者(实验组)和良性胸腔积液患者(对照组)血清及胸水中CEA、NSE和SCC-Ag水平,及实验组化疗后血清上述肿瘤标志物水平。结果实验组血及胸水中CEA、NSE、SCC-Ag水平均高于对照组(P0.05);化疗有效组血中CEA、NSE、SCC-Ag水平均低于化疗前(P0.05);化疗失败组血中CEA水平明显高于化疗前(P0.05),NSE、SCC-Ag水平无明显变化(P0.05)。结论 CEA、NSE、SCC-Ag对肺癌合并恶性胸腔积液的诊断有指导意义,CEA能判断肺癌合并恶性胸腔积液患者化疗的近期疗效。     

肿瘤标志检测联合胸腔镜在恶性胸腔积液诊断中的应用

目的探讨肿瘤标志检测联合胸腔镜在恶性胸腔积液诊断中的应用。方法选取恶性胸腔积液患者120例,根据检查方法不同分为两组,对照组采用肿瘤标志物检测诊断恶性胸腔积液,实验组采用肿瘤标志检测联合胸腔镜,比较两种方法的恶性胸腔积液阳性检出率。结果实验组患者经胸腔镜检查的阳性检出率为96.67%;与对照组相比,实验组行联合检测,恶性胸腔积液的阳性检出率明显升高(P0.05)。结论肿瘤标志检测联合胸腔镜对恶性胸腔积液诊断的检出率高于单纯使用一种检测手段,对临床恶性胸腔积液的早期诊断和早期治疗有重要意义。     

血清及胸腔积液CEA检测联合细胞染色体分析在老年患者恶性胸腔积液诊断中的应用

目的 探讨血清及胸腔积液癌胚抗原（CEA）检测联合细胞染色体分析在老年患者恶性胸腔积液诊断中的应用价值.方法 收集不明原因胸腔积液老年患者48例,按组织病理学诊断结果分为恶性胸腔积液组28例和良性胸腔积液组20例.检测两组患者血清、胸腔积液中的CEA,并对其胸腔积液中的细胞染色体进行分析.结果 单纯采用细胞染色体分析确诊恶性胸腔积液的灵敏度为61％、特异度为95％,血清及胸腔积液CEA检测联合细胞染色体分析确诊恶性胸腔积液的灵敏度为86％、特异度为100％,两者相比,P均＜0.05.结论 血清及胸腔积液中CEA的检测对诊断恶性胸腔积液具有一定价值,尤其胸腔积液CEA,联合细胞染色体分析对诊断恶性胸腔积液的灵敏度和特异度升高.     

力尔凡治疗恶性胸腔积液88例

胸部恶性肿瘤常见的并发症之一是恶性胸腔积液.胸腔积液常压迫心脏和肺脏,产生胸闷、呼吸困难、憋气等临床症状,还引起低蛋白血症、电解质紊乱、严重脱水等并发症,若不及时处理,会严重影响患者的生活质量及生命健康.临床上常见的治疗恶性胸腔积液的措施是局部使用相关药物减少积液产生、促进积液的排出.目前治疗恶性胸腔积液的药物主要包括化疗药物、生物制剂、免疫药物及中药.顺铂是临床上治疗肺癌常见的药物,而力尔凡是常见的治疗胸腔积液的一种生物制剂.为探讨力尔凡治疗恶性胸腔积液的临床效果和不良反应,本研究总结并分析了2012年1月至2014年2月来我院采用力尔凡联合顺铂治疗恶性胸腔积液患者的临床资料及,报道如下.     

Identification of differentially expressed proteins in human malignant pleural effusions.

A high protein concentration in a pleural effusion makes it more likely to be a malignant than a transudative effusion. However, the variability in protein composition between these two forms of pleural effusion is not well understood. In order to compare their protein compositions, the proteomic profiles of 14 malignant and 13 transudative pleural effusions were studied using two-dimensional gel electrophoresis. Protein spots with differential expression were identified by matrix-assisted laser desorption/ionisation quadrupole time-of-flight mass spectrometry and liquid chromatography/tandem mass spectrometry. Targeted proteins were further examined by ELISA and Western immunoassay in all samples. Two-dimensional gel electrophoresis revealed seven spots whose expression was reduced in malignant pleural effusions. Four of the abnormal spots were identified as fibrinogen gamma-chain precursor, two as fibrinogen beta-chain precursor and one as pigment epithelium-derived factor. ELISA and Western immunoassay showed that pigment epithelium-derived factor levels were significantly lower in malignant than in transudative pleural effusions. It has been demonstrated that proteomic technologies may help in the elucidation of variable expression of proteins with particular functions. By applying these technologies, the level of pigment epithelium-derived factor, a potent anti-angiogenic factor, was found to be significantly lower in malignant than in transudative pleural effusions. This finding allows for further exploration regarding how underexpression of pigment epithelium-derived factor may relate to the pathogenesis of malignant pleural effusions.     

Anorexia protocolis

BACKGROUND: We sought a marker to differentiate malignant from nonmalignant pleural effusions. METHODS: We studied 41 patients presenting with pleural effusions to the National Sanyo Hospital between April 2000 and January 2002 (33 men and 8 women; mean age, 68 years). Twenty patients (49%) were proven to have malignant pleural effusions, while 21 patients (51%) had nonmalignant pleural effusions. Thoracentesis was performed. RESULTS: The mean (+/- SD) concentration of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in malignant pleural effusions, measured by enzyme-linked immunosorbent assay, was significantly higher than that in nonmalignant pleural effusions (15.1 +/- 33.6 vs 1.4 +/- 0.81 U/mL, respectively; p < 0.05). CONCLUSION: The determination of the RCAS1 concentration in pleural fluid is informative in the diagnosis of malignant pleural effusions.     

Macrophage-derived chemokine in malignant and tuberculous pleural effusions

BACKGROUND AND OBJECTIVES: Macrophage-derived chemokine (MDC/CCL22) is recognized as a T-helper (Th) 2-type chemokine. Both malignant and tuberculous pleural effusions are typically lymphocytic pleural effusions. Tuberculous pleural effusions have a more polarized Th1 reaction than malignant effusions, which are predominantly Th2 in nature. The aim of this study was to compare the levels of MDC in malignant pleural effusions with those in tuberculous pleural effusions to help delineate the role of MDC in Th2 versus Th1 effusions. METHODS: Forty-three patients with pleural effusions (32 malignant, 11 tuberculous) were studied. The concentration of MDC in the pleural effusion was measured by ELISA. RESULTS: The median concentration of MDC was lower in malignant pleural effusions than in tuberculous pleural effusions (P < 0.005). CONCLUSIONS: MDC has been reported to both promote and suppress antitumour immunity. The low concentration of MDC in malignant effusions is likely to minimise its antitumour activity but the precise role of MDC in malignant and tuberculous effusions needs to be investigated further.     

Th1 and th2 cytokine profiles in malignant pleural effusion

Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analyzed using enzyme-linked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.     

Role of pleural viscosity in the differential diagnosis of exudative pleural effusion

OBJECTIVE AND BACKGROUND: Determining the aetiology of an effusion involves assessing if it is an exudate or a transudate. However, a reliable test for determining the aetiology of a pleural effusion is lacking. Pleural viscosity has a high sensitivity and specificity and a high positive and negative predictive value for discriminating exudative and transudative pleural effusions. The aim of this study was to use pleural fluid viscosity to discriminate between various aetiologies of exudative effusions, namely malignant, parapneumonic and tuberculous. METHODS: Seventy consecutive patients (24 women, 46 men, mean age = 67 years) with exudative pleural effusion due to pneumoniae in 24 patients, tuberculous pleurisy in 21 and lung cancer in 25 were studied prospectively. Measurements of pleural fluid and plasma viscosity were performed using Brookfield DV-II viscometer. RESULTS: Pleural viscosity and pleural LDH were highest in the tuberculous pleurisy patients and lowest in the lung cancer patients. Pleural viscosity > or = 1.57 was found to be indicative of tuberculous pleurisy with a sensitivity of 100% and specificity of 95%. Pleural viscosity < 1.39 was found to be indicative of lung cancer with a sensitivity of 100% and specificity of 94%. Pleural viscosity was significantly correlated with pleural albumin (r = 0.34, P = 0.004), protein (r = 0.40, P = 0.001), LDH (r = 0.70, P < 0.001) and plasma viscosity (r = 0.44, P < 0.001), having the most significant value with pleural LDH. CONCLUSION: The pleural fluid viscosity of patients with parapneumonic, tuberculous and malignant effusions are significantly different from each other. Among these groups, tuberculous effusions had the highest viscosity, and malignant effusions from lung cancer the lowest.     

Malignant Pleural Effusion: Presentation,Diagnosis, and Management

Malignant pleural effusions are common in patients with cancer. Most malignant pleural effusions are secondary to metastases to the pleura, most often from lung or breast cancer. The presence of malignant effusion indicates advanced disease and poor survival; in lung cancer, the presence of malignant effusion upstages the cancer to stage 4. Usually presenting as a large, unilateral exudative effusion, most patients with malignant pleural effusion experience dyspnea. Prior to intervention, diagnosis of malignant pleural effusion and exclusion of infection should be made. Thoracic imaging is typically performed, with computed tomography considered by many to be the gold standard. Thoracic ultrasound is also useful, particularly if diaphragmatic or pleural thickening and nodularity can be identified. Cytology should then be obtained; this is typically done via pleural fluid aspiration or pleural biopsy. Treatment focuses on palliation and relief of symptoms. Numerous interventions are available, ranging from drainage with thoracentesis or indwelling pleural catheter to more definitive, invasive options such as pleurodesis. There is no clear best approach, and a patient-centered approach should be taken.     

基因重组白细胞介素2联合杀伤细胞治疗晚期肺癌癌性胸腔积液

采用异体淋巴因子激活的杀伤细胞（ＬＡＫ）联合基因重组白细胞介素２胸腔内注射治疗晚期肺癌癌性胸腔只液３３例。结果表明本疗法治疗晚期肺癌癌性胸液是有效的，能提高患者的生活质量。     

重组IL2联合LAK和TIL细胞治疗癌性胸腔积液

采用自体淋巴因子激活的杀伤细胞(LAK)和重组白细胞介素2_rIL_2静脉滴注,同时将胸液中的肿瘤浸润淋巴细胞(TIL)体外培养、扩增后联同_rIL_2注入胸腔治疗肺癌癌性胸腔积液30例。结果显示完全缓解(CR)16例(53％),部分缓解(PR)12例(40％),无效(NC)2例(7％)。治疗后多数患者闷喘减轻,精神好转,食欲增加,体力增强,外周血白细胞增加,PR、NC病例胸液中淋巴细胞增多,癌胚抗原(CEA)下降。除12例(40％)出现一过性发热,4例(13％)出现荨麻疹,未作处理好转。表明本疗法治疗肺癌癌性胸腔积液是有效的,能提高患者的生存时间及生活质量。     

Causes of pleural exudates in a region with a high incidence of tuberculosis

OBJECTIVE: To define the causes of exudative pleural effusions in our region. METHODOLOGY: A retrospective study was performed on consecutive patients with exudative pleural effusion seen in our hospital during a 4-year period. RESULTS: Of 186 patients with a mean age (+/- SD) of 51.2 (+/- 19.2) years with exudative pleural effusions, 131 (70.4%) were males and 55 (29.6%) were females. The most frequent cause of exudative pleural effusions was tuberculosis (44.1%), followed by malignancy (29.6%). The majority (94.5%) of malignant pleural effusions were due to lung cancer. Apart from a patient with bilateral pleural effusions due to cryptococcosis, patients with tuberculous pleural effusion (mean age (+/- SD), 39.7 (+/- 17.5)) were significantly younger than the rest (P < 0.05). Tuberculous effusions were most frequent in the first five decades (60/82, 73.2%) and were the most common type of pleural effusion, accounting for 60 (69.8%) of 86 cases, in this age range. Malignant effusions were more frequent among the older age groups, 74.5% (41/55) of patients with malignant effusions being older than 50 years. Most types of pleural effusions showed a preference for the right side. Of the 44 cases of large effusions, 28 (63.6%) were caused by malignancy. CONCLUSIONS: In our region with a high incidence of tuberculosis, the most frequent cause of pleural exudates is tuberculosis followed by malignancy, particularly lung cancer.