粘质沙雷菌菌苗治疗恶性胸腔积液的临床观察

目的：评价粘质沙雷菌菌苗（Ｓ－３１１抗癌菌苗）治疗恶性胸腔积液的作用和毒性。方法：３５例恶性胸腔积液患应用Ｓ－３１１抗癌菌苗胸腔内给药治疗。结果：有效率８８．６％（３１／３５），完全缓解率４８．６％（１７／３７）。不良反应有发热、寒颤和胸痛。结论：Ｓ－３１１抗癌菌菌苗治疗恶性胸腔积液疗效肯定。     

Preliminary results of a new small-bore percutaneous pleural catheter used for treatment of malignant pleural effusions in ECOG PS 3-4 patients

Background

In cancer patients with malignant pleural effusions(MPEs),the commonest procedure to treat them with palliative intention is talc pleurodesis (TP) which can be obtained with talc slurry (TS) using small-bore catheters(SBC)or with thoracoscopic poudrage. SBC use is therefore rapidly increasing. The aim of this paper is to present our preliminary TP results using a new percutaneous chest drainage system(UNICO^®,Redax,Mirandola Modena, Italy).

Methods

In the period 1st March-20th of July 2011,seven consecutive ECOG PS 3-4 patients(4 females, mean age 73.2 ± 12.1 years),unfit for thoracoscopic talc poudrage, were enrolled in our study. All patients received many thoracentesis before the placement of a chest drainage(median thoracentesis number:4.42 ± 1.13).UNICO^® was bedside placed in all cases and TS was administered through the drainage when the overall fluid amount didn’t exceed 150-200 ml/24 h and the lung was correctly re-expanded at the chest X-ray control.

Results

There were no clinical complications following the placement of the drainage: its placement was easy, safe and well-tolerated by all patients. The median chest tube stay, before TS, was 7.2 ± 2.7 days while the median chest tube stay after TS was 1.5 ± 0.7 days. A satisfactory radiological lung expansion was achieved in all cases; PL effectiveness and dyspnea relief were complete in 6 and 4 cases, respectively. No patients required any further thoracentesis.

Conclusions

TS through UNICO^® is safe and efficient. The drainage was well-tolerated by all patients, even in case of its long-term stay. We may conclude that bedside TS through this new small-bore percutaneous drainage should be proposed as a viable clinical solution for MPEs in ECOG PS 3-4 patients, unfit for a thoracoscopic procedure. Moreover, with this device, we believe that TS might be an accessible procedure for pulmonologists and oncologists too.     

从恶性胸腔积液体外诱导成熟树突细胞

背景与目的:树突细胞(dendriticcells,DCs)具有激活初始T细胞、引发抗原特异性免疫反应的特性。本研究拟用体外培养的方法,从肺癌患者恶性胸腔积液中诱导出功能健全的DCs。方法:取16例肺癌患者胸腔积液500～1000ml,用密度梯度离心辅以免疫磁珠分选的方法,分离出DCs前体细胞,加入IL鄄4、GM鄄CSF、TNF鄄α诱导出DCs。用电镜和光镜观察培养的DCs,用流式细胞仪检测DCs的表面分子。将不同培养时间的DCs和肿瘤浸润性淋巴细胞(tumorinfiltrativelymphocytes,TILs)作混合淋巴细胞反应,了解DCs对TILs的激活作用。结果:在体外能诱导出恶性胸腔积液来源的功能健全的DCs,电镜和光镜分析表明,这类DCs具有成熟DCs的典型形态;当DCs体外培养到第48h时,表面分子的表达率与培养0h、24h、92h、192h的DCs比较相对较高;DCs可使TILs细胞扩增。结论:可从肺癌患者恶性胸腔积液中诱导具有成熟功能的DCs。     

VEGF及Angiopoietin-2对恶性胸腔积液的诊断价值

目的：探讨检测血管内皮生长因子（vascular endothelial growth factor,VEGF）及血管生成素-2（An—giopoietin-2,Ang-2）对恶性胸腔积液的诊断价值。方法：选择恶性胸腔积液患者31例,良性胸腔积液3例,（Roc）曲线计算上述指标的诊断敏感度、特异度及ROC曲线下面积。并对VEGF及Ang-2之间的相关性进行分析。结果：恶I生胸腔积液中的VEGF及Ang-2含量（1106±555vs527±229,19．26±6．39VS12．25±7．1）明显高于良性胸腔积液（P〈0．05）;VEGF诊断恶性胸腔积液的敏感度及特异度分别是：82％和90％,Ang-2诊断的敏感度及特异度分别是：65％和71％;恶性胸腔积液中Ang-2的含量与VEGF的含量呈正相关。结论：VEGF及Ang-2可作为恶性胸腔积液诊断的良好指标,可指导选择对患者进行进-步的侵入性检查。     

流式细胞仪DNA倍体分析用于良恶性胸腔积液的鉴别诊断

流式细胞术是近年来应用较广泛的一种现代细胞分析技术.研究显示,流式细胞术DNA倍体分析可以在92%的实体肿瘤上检测到DNA异倍体的存在.因此也被用到了恶性胸腔积液的诊断中.本文回顾了现有流式细胞术DNA倍体分析用于恶性胸腔积液诊断的研究,评估其临床可行性.     

Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.     

博莱霉素联合白细胞介素- 2治疗非小细胞肺癌胸腔积液的临床观察

 目的 观察博莱霉素（BLM）联合白细胞介素- 2（IL-2）治疗非小细胞肺癌（NSCLC）胸腔积液的疗效及毒副反应。方法 采用中心静脉导管建立闭式引流，在胸腔积液基本干净、肺复张基础上注入BLM 60 mg加生理盐水50 ml， IL-2 200万U。结果 36例患者中完全缓解（CR）20例占55.5 %，部分缓解（PR）12例占33.3 %，稳定（SD）4例占11.1 %， CR+PR 88.5 %，仅部分病例有发热，胸痛，皮疹，恶心。结论 BLM联合IL-2治疗NSCLC胸腔积液疗效好，毒副反应小，易为患者所接受。     

恶性胸腔/腹腔积液RRM1 mRNA表达水平和吉西他滨体外药敏的关系

目的：分析恶性胸腔/腹腔积液中肿瘤细胞核糖核苷酸还原酶M1亚基（ribonucleotide reductase M1,RRM1）基因的表达水平与吉西他滨体外药物敏感性的关系。方法：收集24例经病理确诊的Ⅳ期恶性肿瘤患者的恶性胸腔/腹腔积液,分离原代肿瘤细胞,采用CCK8（cell counting kit8）法体外药物敏感试验检测原代肿瘤细胞对吉西他滨药物敏感性;实时荧光定量PCR检测原代肿瘤细胞RRM1 mRNA的相对表达水平。结果：在恶性胸腔/腹腔积液中,肿瘤细胞的RRM1 mRNA的相对表达水平与恶性肿瘤患者的临床特征无明显相关性,但是与吉西他滨药物敏感性呈负相关（r=-0.497,P=0.013）;既往曾使用化疗药物的恶性肿瘤患者恶性胸腔/腹腔积液原代肿瘤细胞对吉西他滨敏感性低于未化疗患者（42.94%vs67.88%,P=0.006）。结论：恶性胸腔/腹腔积液中肿瘤细胞RRM1 mRNA的相对表达水平与吉西他滨体外药物敏感性相关。     

胸腔镜在恶性胸腔积液诊断和治疗上的应用

目的　探讨胸腔镜在恶性胸腔积液诊断和治疗上的价值。方法　对15例原因不明的胸腔积液患者作胸腔镜检查,并经胸腔镜喷入滑石粉及顺铂治疗。结果　所有病例经胸腔镜行活检均确诊为恶性病变,总诊断率为100%。经滑石粉喷入和顺铂局部治疗后14例获得完全的胸膜固定,持久的成功率为93.3%。结论　胸腔镜对胸腔积液病因诊断有较高临床实用价值,滑石粉胸膜固定加顺铂治疗是控制恶性胸腔积液、治疗晚期癌症的一种有效方法。     

细管胸腔闭式引流与常规胸腔穿刺控制恶性胸腔积液随机对照研究

背景与目的恶性胸腔积液是晚期恶性肿瘤常见的一个问题。治疗多为姑息性，常采用胸腔穿刺或粗管闭式引流。粗管闭式引流损伤大，易感染，患者活动受限。本研究的目的是观察细孔径导管胸腔闭式引流后注药治疗恶性胸腔积液的临床疗效。方法将恶性胸腔积液患者随机分成两组，分别进行中心静脉导管闭式引流和常规胸腔穿刺，并均于胸腔内注入顺铂（cisplatin，DDP）和白介素-2（interleukin-2，IL-2）。结果细孔径导管闭式引流组胸腔积液的控制率为80．00％，明显优于常规穿刺组的36．67％（P〈0．01）。细孔径导管闭式引流组的不良反应少于常规穿刺组。结论应用细孔径导管装置引流恶性胸腔积液操作安全、简便，能最大限度地排净胸腔积液，对控制癌性胸腔积液有较好的疗效，能显著改善患者生活质量。     

联合检测染色体及腺苷脱氨酶对鉴别良恶性胸腔积液的价值

为了探讨联合检测染色体和腺苷脱氨酶(ADA)对良恶性胸腔积液的鉴别诊断价值,采用直接制片法进行胸腔积液染色体检查,以中期分裂相细胞超二倍体和多倍体数目≥10%为恶性标准,同时采用改良的Martineck氏法测定ADA活性,其值<25U/L为恶性标准。结果分析显示,染色体与ADA检查对恶性胸腔积液诊断的敏感性分别为71·4%和83·9%,特异性分别为100·0%和90·0%。同时符合二项者的敏感性为67·9%,特异性为100·0%,符合其中之一者的敏感性为92·9%,特异性为90·0%。初步研究结果提示,联合检测有助于提高良恶性胸腔积液的鉴别诊断。     

Incidence and risk factors of pleural effusions in patients with POEMS syndrome

Information regarding the characteristics of pleural effusions in patients with POEMS syndrome is limited. The aim of this study was to describe the incidence and risk factors of pleural effusions in patients with POEMS syndrome and characterize the pleural fluid biochemistry in those patients. A retrospective review of 96 patients with POEMS syndrome was conducted. The patients were divided into groups with and without pleural effusions. The clinical data were obtained from medical charts. Risk factors were studied with univariate and multivariate analysis. The median age at the time of diagnosis of POEMS syndrome was 45.1 years, and the median disease duration was 30.4 months. Pleural effusions were detected in 41 (42.7%) of the 96 patients. Increased serum vascular endothelial growth factor (VEGF), complement component 3 (C3), Lambda light chain, tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 levels and low albumin as well as cardiac disease were found to be significantly correlated with pleural effusions. By multivariate logistic regression, independent risk factors for pleural effusions in POEMS syndrome were VEGF [odds ratio (OR): 2.46, 95% confidence interval (CI): 1.720–3.414, p = 0.01], TNF‐α (OR: 3.64, 95% CI: 1.073–4.338, p = 0.04) and C3 (OR: 3.77, 95% CI: 1.225–3.591, p = 0.02) levels. Pleural effusions are the most common thoracic involvement findings in patients with POEMS syndrome, and all the pleural fluids are exudates. Serum VEGF, TNF‐α and C3 levels are identified as important risk factors for presence of pleural effusions in POEMS syndrome. Copyright © 2014 John Wiley & Sons, Ltd.     

力尔凡治疗恶性胸腔积液的临床研究

目的：观察力尔凡治疗恶性胸腔积液的疗效及副作用。方法：对60例恶性胸腔积液患者引流尽胸腔积液后，腔内注入力尔凡30mg，B超检查，观察效果。结果：控制胸腔积液cR18例，PR27例，有效率达75％。不良反应主要是胸痛和发热。结论：力尔凡能有效控制胸腔积液，提高患者的生活质量，是治疗恶性胸腔积液的有效药物之一。     

Up-regulation of pro-angiogenic factors and establishment of tolerance in malignant pleural effusions

Introduction

Malignant pleural effusions (MPEs) are a significant source of cancer morbidity and mortality. Currently there is no cure for MPEs and treatments only palliate the symptoms. The purpose of this study was to determine if there are differences in markers of angiogenesis and immune phenotypes between adenocarcinoma-induced MPEs and benign pleural effusions (BPEs).

Methods

Pleural effusions were collected from patients with MPEs and BPEs. Cells were isolated from effusions and characterized using fluorescent cell sorting (FACS). Pleural effusions were evaluated by ELISA for VEGF-A. An angiogenesis protein array was completed to compare protein expression in malignant and non-malignant effusions.

Results

FACS analysis demonstrated lower accumulation of cytotoxic T-cells and significantly higher accumulation of monocytes, dendritic cells, mesothelial and tumor cells in MPEs compared to benign pleural effusions. MPEs were found to have 77-fold higher VEGF-A levels compared to BPEs. The angiogenesis protein array demonstrated elevated levels of pro-angiogenic factors VEGF-A, CXCL4 and MMP-8, and low levels of pro-inflammatory cytokines IL-8, MCP-1, and TGF-β1 in MPEs.

Conclusions

MPE is biased toward a Th2 dominant state. There is an increase in expression of VEGF-A and other pro-angiogenic factors in MPE. These data suggest there is a role for anti-angiogenesis therapy in patients with MPEs.     

Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells

Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial‐mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10³–7 × 10⁶ copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24^high tumor cells formed tumors in mice at a faster rate than CD24^low tumor cells, and shRNA‐mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells.     

DDP和沙培林胸腔用药联合NP方案对肺癌合并恶性胸腔积液近远期疗效的观察

目的　观察DDP和沙培林胸腔用药联合NP方案全身化疗治疗肺癌合并恶性胸腔积液的近远期疗效。方法　 32例肺癌合并恶性胸腔积液患者随机分成两组 ,A组 :1 6例 ,胸膜腔内单用药组 ,使用DDP和沙培林 ,B组 :1 6例 ,胸膜腔内用药并联合使用NP(NVB +DDP)方案全身化疗。结果　①A、B两组胸水控制短期有效率分别为 75 %和 87.5 % ,总有效率为 81 .3% ,两组比较无显著性差异 (P >0 .0 5 )。②A组1年、2年生存率分别为 4 3.75 %和 6 .2 5 % ,B组分别为 6 2 .5 %和 31 .2 5 % ,两组比较有显著性差异 (P <0 .0 5 )。结论　DDP和沙培林胸腔用药能有效控制胸水 ;     

力尔凡联合顺铂胸腔灌注治疗恶性胸水的临床观察

目的研究力尔凡联合顺铂治疗恶性胸腔积液的临床效果.方法将48例恶性胸水患者随机分为治疗组和对照组,治疗组25例应用力尔凡加顺铂胸腔灌注,对照组23例单纯应用顺铂治疗,观察治疗前后胸水的变化和副作用.结果治疗组控制胸水的有效率(CR PR)为96.0%,对照组为56.5%,两组相比差异有显著性(P＜0.01).治疗组副作用为轻度发热、胸痛,对照组为骨髓抑制、胃肠道反应及胸痛.结论力尔凡联合顺铂胸腔灌注能有效地控制恶性胸腔积液,毒副作用小,疗效肯定.     

胸腔持续闭式引流联用高聚生治疗恶性胸腔积液的疗效观察

目的：观察胸腔持续闭塞引流联用高聚生治疗恶性胸腔积液的疗效。方法：随机选择57例患者分为治疗组31例，对照组26例。治疗组采用胸腔持续闭塞引流联用高聚生的方法，对照组采用常规抽液并注入顺铂的方法，观察二组疗效。结果：治疗组有效率达100％，对照组80．77％。结论：应用胸腔持续闭式引流联用高聚生的方法治疗恶性胸腔积液方便可行，疗效理想，值得临床推广及进一步研究。     

Interleukin 22-producing CD4(+) T cells in malignant pleural effusion

Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment.