Treatment of malignant pleural effusion

A malignant pleural effusion in the patients with cancer is one of the common complications that make the patients critically ill condition without the adequate treatment. The present paper reviewed the literature concerning the clinical results of all techniques designed to treat this problem. We would like to recommend intrapleural administration of several sclerosing agents with tube thoracostomy as the technique of choice. We also showed the results obtained in our hospital using intra pleural IL-2 instillation.     

Management of malignant pleural effusion

Malignant pleural effusion (MPE) often presents in patients with cancer at an advanced stage and thus carries a poor prognosis. This review updates the current knowledge on the management of MPE, focusing on recent literature about the efficacy and safety of the most common methods, including pleurodesis by either thoracoscopy with talc insufflation or thoracostomy with talc slurry, use of an indwelling pleural catheter, and intrapleural chemotherapy. Talc remains the agent of choice in pleurodesis, although the use of alternative agents continues to be explored. The choice of procedure to achieve pleurodesis depends on careful patient selection based on predictive factors and individual characteristics. Talc pleurodesis is relatively well tolerated and safe, as is an indwelling pleural catheter, in an appropriate patient population. Because MPE is a common problem in cancer patients, future research with more randomized, prospective designs and innovative interventions is needed.     

良恶性胸腔积液的临床特征及预测因素分析

目的:对比分析良恶性胸腔积液的临床特征,筛选恶性胸腔积液可能的预测因素。方法:收集良性胸腔积液患者30人和恶性胸腔积液患者32人的临床资料,分析胸腔积液及血液学相关指标（胸腔积液物理性状、胸腔积液和血液学生化、肿瘤标志物）。结果:恶性胸腔积液患者的年龄明显高于良性胸腔积液患者,但二者在性别分布上无差异。恶性胸腔积液的乳酸脱氢酶（LDH）、腺苷脱氨酶（ADA）、γ-干扰素（γ-IFN）显著低于良性胸腔积液,而癌胚抗原（CEA）、糖类抗原（CA19-9）、神经特异性烯醇化酶（NSE）显著高于良性胸腔积液（P均<0.05）。两组患者血液LDH、ADA、CEA、CA19-9的差异也具有统计学意义。条件Logistic回归分析发现CEA>10ng/ml、血性胸腔积液、ADA<15U/ml、CA19-9>20U/ml为恶性胸腔积液的预测因素。结论:非肿瘤标志物（如胸水颜色、ADA值）也有助于胸腔积液性质的判断。恶性胸腔积液的预测作用由大到小依次为CEA、血性胸腔积液、ADA、CA19-9。     

Efficacy of intrapleural treatment with aclacinomycin combined with closed tube thoracostomy for malignant pleural effusion

Intrapleural treatment with aclacinomycin combined with closed tube thoracostomy was used in 7 patients with malignant pleural effusion. Five patients had no recurrence of effusion 3 months after the treatment. Aclacinomycin levels were much higher in blood cells than in plasma, and metabolites were present as the active form. We posit that the local instillation of aclacinomycin is indicated in the management of malignant pleural effusion.     

恶性胸腔积液肿瘤标志物

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。现根据近年来相关的临床研究结果,对各种肿瘤标志物进行客观评价。     

Management of malignant pleural effusion.

A pleural effusion is a frequent complication of malignant disease. Essential to the care of oncology patients is a fundamental knowledge of the pathophysiology and treatment of such effusions. This article discusses the current thoughts concerning the occurrence of malignant effusions, outlines the current available methods and agents employed for control, and presents a modification of the thoracostomy procedure that appears to be more effective than the standard procedure.     

Multidisciplinary management of malignant pleural effusion

Approximately 50% of patients with metastatic disease develop a malignant pleural effusion (MPE). Prompt clinical evaluation and treatment to achieve successful palliation are the main goals of management of MPE. Optimal treatment is still controversial and there is no universal standard approach. Management options include observation, thoracentesis, indwelling pleural catheter (IPC) or chest tube placement, pleurodesis, and surgical pleurectomy. The treatment for each patient should be based on symptoms, general condition, and life expectancy.     

恶性胸腔积液肿瘤标志物

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。现根据近年来相关的临床研究结果,对各种肿瘤标志物进行客观评价。     

Small bore catheter drainage and sclerotherapy for malignant pleural effusions

The accumulation of large amounts of fluid in the pleural space is a common sequela of disseminated carcinomatosis. Traditional management has included therapeutic thoracentesis or the placement of a large bore chest tube for drainage with the subsequent installation of a sclerosing agent in an attempt to achieve pleural symphysis. An evaluation of all patients treated in this manner during a 4-year period was undertaken to assess the degree of success obtained with a large bore standard chest tube versus a small pigtail catheter. A study group consisting of 20 patients with a total of 24 pleural effusions was treated with drainage and sclerotherapy. In this group, eight of 13 effusions were adequately treated with pigtail catheter drainage and sclerotherapy, compared with four of 11 effusions adequately treated with standard chest tube drainage and sclerotherapy. Although the numbers are small, it appears that pigtail catheter drainage and sclerosis is at least as successful as the more traditional drainage with the standard chest tube.     

端粒酶检测在良恶性胸腔积液鉴别诊断中的应用价值

端粒酶是一种能以自带RNA为模板，反转录合成端粒DNA加于染色体末端的核糖核酸蛋白酶，作用是维持染色体稳定，使细胞具有永生化特性。胸腔积液可由多种疾病引起，与肿瘤因素有关者占30％～60％。作为目前最具特异性和普遍性的恶性肿瘤标志物，检测胸腔积液中端粒酶的活性，对早期发现肿瘤，具有重要意义。     

恶性胸腔积液治疗进展

恶性胸腔积液是由肺癌等恶性肿瘤侵犯胸膜或胸膜原发性肿瘤所致,是晚期恶性肿瘤的并发症,如不及时治疗,平均生存期仅有数月.如何进行有效的治疗对提高患者生活质量、延长生存期有重要意义.     

Diagnosis and treatment of malignant pleural effusion

Summary Pleural effusion is a common and important complication of malignancy which may at times be difficult to diagnose or treat. Its well recognized association with numerous diseases plus the limitations of our usual diagnostic tests may occasionally cause difficulty. In the oncology patient there are a number of common medical problems associated with the development of pleural effusion which frequently coexist with the malignancy. Pleural effusion may be a presenting or late sign of cancer, and when recurrent can be a vexing symptomatic problem. Fortunately, an increasing number of effective diagnostic and therapeutic modalities are available which, when judiciously applied, facilitate our approach.     

胸膜固定术治疗恶性胸腔积液的研究进展

恶性胸腔积液（malignant pleural effusion,MPE）是癌症患者的一种常见并发症,预后普遍较差。随着全球癌症发病率的不断增高以及多数癌症患者预期寿命的延长,MPE的发病率和相关医疗费用呈现逐渐上升趋势。虽然针对MPE的姑息性治疗方案众多,但是其效果并不确切,MPE的临床管理仍存在较大挑战。胸膜固定术是MPE的主要治疗方式之一,可有效缓解积液相关症状,降低胸膜再次干预的风险。本文将从胸膜固定术治疗MPE的机制、硬化剂种类和硬化剂输注途径三个方面展开综述,为临床实践中开展更加有效、合理、个体化的MPE管理方案提供思路。      

Tumor necrosis factor-alpha promotes malignant pleural effusion

Tumor necrosis factor (TNF)-alpha is present in the microenvironment of human tumors, including malignant pleural effusion (MPE). Although the cytokine is produced in the pleural cavity by both tumor and host cells, its effects on MPE formation are unknown. In these studies, we sought to determine the role of TNF-alpha in the pathogenesis of MPE and to assess the therapeutic effects of its neutralization in a preclinical model. For this, MPEs were generated in immunocompetent mice using intrapleural injection of mouse lung adenocarcinoma cells. The roles of tumor- and host-derived TNF-alpha were assessed using combined experimentation with TNF-alpha gene-deficient mice and in vivo TNF-alpha neutralization. To expand the scope of preclinical data, TNF-alpha and vascular endothelial growth factor (VEGF) expression were determined in human cancer cell lines and human MPE. In the MPE model, TNF-alpha of host and tumor origin was present. TNF-alpha neutralization significantly limited tumor dissemination, effusion formation, vascular hyperpermeability, TNF-alpha and VEGF expression, and angiogenesis, thereby improving survival. In contrast, these variables were not different between TNF-alpha gene-sufficient and TNF-alpha gene-deficient mice. In mouse cancer cells, TNF-alpha functioned via nuclear factor-kappaB- and neutral sphingomyelinase-dependent pathways to induce TNF-alpha and VEGF, respectively. These results were recapitulated in human cancer cells, and a correlation was detected between TNF-alpha and VEGF content of human MPE. We conclude that tumor-derived TNF-alpha is important in the development of MPE in mice, and provide preclinical evidence supporting the efficacy of TNF-alpha blockade against malignant pleural disease.     

Aberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusion

Accumulating evidence implicates epigenetic changes such as hypermethylation in carcinogenesis. We investigated whether DNA methylation of 5 tumor suppressor genes in pleural fluid samples could aid in diagnosis of malignant effusion. In samples from 47 patients with malignant pleural effusions and 34 with nonmalignant effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta (RARbeta). Promoter hypermethylation was associated with malignant effusion for MGMT (Odds ratio (OR) = infinity), p16(INK4a) (OR = infinity), RASSF1A (OR = 13.8; CI, 1.71-112), and RARbeta (OR = 3.17; CI, 1.10-9.11), but not for DAPK. Instead, DAPK methylation was associated with the length of smoking (p < 0.05). Patients with hypermethylation of MGMT, p16(INK4a), RASSF1A or RARbeta were 5.68 times more likely to have malignant effusions than patients without methylation (p = 0.008). Methylations per patient were more numerous for lung cancer than nonmalignant pulmonary disease (0.915 vs. 0.206, p < 0.001). Sensitivity, specificity, and positive predictive value of methylation in one or more genes for diagnosis of malignant effusion were 59.6%, 79.4%, and 80.0% respectively. In conclusion, aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could be a valuable diagnostic marker for malignant pleural effusion.     

Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion

Background:

Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion.

Methods:

In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.

Results:

Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients.

Conclusion:

These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.     

化疗联合深部热疗治疗胸腔恶性积液的临床观察

目的：恶性胸腔积液是晚期肺癌的常见并发症，全身化疗联合胸腔内药物注射是治疗恶性胸腔积液最常用的方法之一，但存在疗效不稳定、药物毒副反应大等问题。本研究的目的是观察热疗联合化疗治疗恶性胸腔积液的疗效、毒副反应和患者的生活质量。方法：确诊为晚期肺癌所致恶性胸腔积液的初治患者60例，分为热化疗和单纯化疗两组。热化疗组：采用胸腔穿刺置入中心静脉导管术尽可能排尽胸水后，给予吉西他滨1000mg／m^2，d1、d8，胸腔注射顺铂40mg／次，隔日1次，共3次。胸腔局部化疗24h后采用TYHP700-Ⅰ体外高频热疗机进行患侧胸腔的深部热疗，根据患者实际耐受情况设定治疗功率300～1000W，治疗时间40～60min，每21天为1周期，共治疗4个周期。单纯化疗组：给予吉西他滨1000mg／m^2，d1、d8，胸腔注射顺铂40mg／次，隔日1次，共3次，每21天为1周期，共治疗4个周期。结果：热化疗组控制胸水的总有效率为90．0％，单纯化疗组为66．7％（P=0．024）。两组毒副反应仅见一过性发热、轻度气胸和胸膜反应等。两组生活质量好转率分别为72．0％和40．0％（P=0．013）。结论：采用热疗联合化疗治疗恶性胸腔积液疗效确切，毒副反应小，安全性高。