洛铂腔内灌注治疗恶性胸腹腔积液的临床观察

目的 观察胸腹腔内灌注洛铂治疗恶性胸腹腔积液的疗效及毒副反应。方法 2010年11月至2012年11月收治32例恶性胸腹腔积液患者,经B超检查定位胸腹腔置管,尽量抽净积液,洛铂30mg／m2胸腹腔灌注,每周1次,连续2周,最多灌注4次;治疗2周后评价疗效及毒副反应。结果 32例患者均完成2次以上胸腹腔灌注,完全缓解9例（28.1％）,部分缓解15 例（46.9％）,无变化8例（25.0％）。全组患者的总有效率为75.0％,胸腔积液有效率为80.0％,腹腔积液有效率为66.7％。毒副反应主要包括胸（腹）痛、发热、血小板减少和轻度消化道反应,经对症处理后好转。结论 洛铂胸腹腔灌注治疗恶性胸腹腔积液的疗效确切,毒副反应小,值得临床推广。     

腔内应用重组人血管内皮抑制素和／或顺铂治疗恶性胸腹腔积液的前瞻性、随机对照、全国多中心Ⅲ期临床研究

目的 观察和确证腔内应用重组人血管内皮抑制素注射液（恩度）和／或顺铂治疗恶性胸腹腔积液的有效性和安全性。方法 2011年1月至2014年1月, 在全国14家大型医院肿瘤中心开展前瞻性、随机、平行对照、多中心的Ⅲ期临床研究（ClinicalTrials.gov注册号：NCT01327235）。入选中等量以上恶性胸腹腔积液患者,随机分为A组（恩度单药组）、B组（顺铂单药组）和C组（恩度联合顺铂组）。3组均在充分穿刺抽液或引流后给药。A组腔内注射恩度,45 mg／次（胸腔）或60 mg／次（腹腔）;B组腔内注射顺铂,40 mg／次;C组为上述两种药物联合应用,剂量相同;3组给药时间均为d1、d4、d7,连用3次为1个疗程。参照WHO标准,严密观察客观缓解率（ORR）、疾病进展时间（TTP）、生活质量（QOL）以及Karnofsky功能状态评分（KPS）,并评价安全性。结果 全分析集（FAS） 共纳入317例,其中A组105例,B组104例,C组108例;符合方案集（PPS） 共纳入275例,其中A组98例,B组89例,C组88例。FAS和PPS分别有298例和273例可评价疗效。FAS中A、B、C 3组的ORR分别为48.51％、46.39％和63.00％ （P=0.0373）,两两比较,C组较A、B组高（P=0.0189）。其中,既往无腔内治疗、胸腔积液、女性、无全身化疗、积液初治、充分引流、血性积液以及非胃癌来源的患者,应用恩度具有更好的ORR（P＜0.05或P＜0.01）。对于血性积液, A、C组ORR分别为71.05％和80.00％,均显著优于B组的45.16％ （P=0.0090）;其中,对于血性胸腔积液,A、C组ORR分别为71.42％和88.88％,均显著优于B组的40.00％ （P=0.0013）。A、B、C组的中位TTP分别为68.869天、44.951天和69.030天 （P=0.0121）;两两比较,A、C组的中位TTP均长于B组 （P=0.0240, P=0.0046）。第3次和第6次用药后,A组QOL评分和KPS评分获得改善人群的比例均显著高于B、C组（P＜0.05或P＜0.01）。安全性方面,317例均进入安全分析集分析。A组不良事件发生率显著低于B组（P=0.0005）,B、C组之间差异无统计学意义（P=0.2866）。结论 采用恩度腔内给药治疗恶性胸腹腔积液具有较好疗效,尤其是对血性积液;恩度与顺铂联合应用具有协同作用,可以进一步提高疗效,延长TTP,改善患者QOL,且不增加化疗药物的不良反应,值得临床上积极推广应用。     

奈达铂腔内灌注治疗肺癌胸腔积液的临床观察

目的：观察奈达铂胸腔灌注治疗肺癌胸腔积液的临床疗效及安全性.方法：确诊为肺癌恶性胸腔积液的患者56例,分为2组.采用中心静脉导管胸腔闭式引流排尽胸水后,治疗组29例,给予胸腔灌注奈达铂治疗,对照组27例,给予胸腔灌注顺铂治疗.胸腔内注射间歇5-7天1次,共计不超过3次.结果：治疗组控制胸水的有效率68.9%,对照组59.2%（P＞0.05）.治疗组生活质量的有效率72.4%,对照组59.2%（P＜0.05）.毒副反应方面,治疗组在恶心、呕吐,胸痛,疲乏感方面的发生率低于对照组（P＜0.05）.结论：奈达铂腔内灌注治疗肺癌恶性胸腔积液,疗效可靠,不良反应较轻,安全性较高.     

香菇多糖联合顺铂治疗恶性胸腔积液

目的：观察香菇多糖联合顺铂胸腔灌注与单用顺铂治疗恶性胸腔积液的有效性和安全性。方法：收治恶性胸腔积液患者７３例,香菇多糖联合顺铂组（Ａ组）３８例,单用顺铂组（Ｂ组）３５例。用一次性中心静脉导管行胸腔置管和闭式引流胸液,Ａ组胸腔给药：香菇多糖４ｍｇ＋生理盐水２０ｍｌ,顺铂４０ｍｇ／ｍ２＋生理盐水５０ｍｌ;Ｂ组胸腔给药：顺铂４０ｍｇ／ｍ２＋生理盐水５０ｍｌ。结果：Ａ组患者总有效率和生活质量改善率均优于Ｂ组（Ｐ＜０.０５）,两组毒副反应相近。结论：胸腔闭式引流后灌注香菇多糖联用顺铂治疗恶性胸腔积液的疗效优于单用顺铂,且毒副反应轻微。     

复方苦参注射液联合顺铂热灌注治疗恶性胸腹腔积液近期临床研究

目的探讨复方苦参注射液联合顺铂针经热灌注机治疗恶性胸腹腔积液的疗效。方法恶性胸腹腔积液患者112例,随机分为联合组（66例）和单药组（46例）。单药组胸或腹腔内均单注入顺铂60mg溶于0．9％NaCl溶液40ml中;联合组顺铂60mg溶于0．9％NaCl溶液（胸腔内量为1000ml,腹腔内量为1500m1）中,用体腔热灌注治疗机加温（灌注液温度分别为胸、腹腔内42～44％和45℃）后,注入胸、腹腔,再加复方苦参注射液20ml胸、腹腔注入。两组均1周1次,平均连用3次为1个疗程。观察2组的胸、腹腔积液消失情况及Karnofsky评分变化情况。结果联合组有效率为97％,明显高于单药组有效率的56％。2组总有效率及治疗前后Kamofsky评分比较差异均有统计学意义（均P〈0．05）。结论复方苦参注射液联合顺铂注射液胸腹腔内热灌注化疗法治疗恶性胸腹腔积液疗效肯定,明显优于传统的单纯化疗药灌注,值得临床推广。     

斑蝥酸钠维生素B6联合顺铂腔内灌注治疗恶性胸腹腔积液的疗效观察

恶性胸腹腔积液是一种常见并难以处治的进展期肿瘤并发症,分为漏出液和渗出液,多是疾患不可治愈的征象.恶性胸腔积液多见于肺癌、乳腺癌、白血病等患者,其治疗目的是缓解积液引起的症状.但淋巴瘤、精原细胞瘤患者即使出现恶性胸腔积液,也有较大的治愈可能.现将斑蝥酸钠维生素B6联合顺铂腔内灌注治疗恶性胸腹腔积液的疗效观察报告如下.     

胸膜固定术联合培美曲赛治疗老年非小细胞肺癌并发恶性胸腔积液的临床观察

目的 观察局部胸膜固定术联合培美曲塞全身化疗治疗老年非小细胞肺癌（NSCLC）并发恶性胸腔积液的有效性和安全性。方法 64例老年NSCLC并发恶性胸腔积液患者随机分为A、B两组,治疗前均采用中心静脉导管行胸腔置管闭式引流术。A组31例, 仅行局部胸膜固定术,具体为：香菇多糖4mg+顺铂40mg／m²,局部胸腔注入,每周1次,连续2～3周。B组33例,在A组治疗的基础上再给予单药培美曲塞全身化疗,具体方案为：培美曲塞500mg／m² d₁,3周为1周期,共2周期。结果 A组胸腔积液缓解有效率为64.6％,B组为87.9％,差异有统计学意义（P＜0.05）;A组KPS评分改善率为71.0％,B组为909％,差异有统计学意义（P＜0.05）。两组患者毒副反应均较轻,其中B组白细胞减少的发生率为36.4%,高于A组的12.9%（P＜0.05）。结论 局部胸膜固定术联合培美曲塞全身化疗治疗老年NSCLC并发恶性胸腔积液疗效优于单纯胸膜固定术,且毒副反应轻微,易耐受。     

体腔热灌注化疗治疗恶性胸腹腔积液临床研究

目的：研究体腔热灌注化疗治疗恶性胸腹腔积液的疗效与不良反应。方法：67例恶性胸腹腔积液患者分为治疗组（35例）和对照组（32例）。胸腹腔穿刺行闭式引流干净胸腹腔积液后,治疗组给予5-氟尿嘧啶1000mg加上43℃-45℃的生理盐水,胸腔积液患者需2000ml-2500ml生理盐水;腹腔积液患者需2500ml-3000 ml生理盐水,以HGGZ-102体腔热灌注治疗系统注入胸腹腔,使进入胸腹腔的液体温度维持在41℃-43℃,循环2h;对照组给予生理盐水100ml＋5-氟尿嘧啶1000mg胸腹腔注入。两组均每周灌注1次,连续灌注3周,评定疗效。结果：治疗组有效率88.6%,Karnofsky评分增加率85.7%;对照组有效率62.5%,Karnofsky评分增加率59.4%。治疗组胸腹腔积液控制率、Karnofsky评分增加率均优于对照组（P〈0.05）。两组不良反应无明显差异。两组生存期无统计学差异（P〉0.05）。结论：体腔热灌注化疗治疗恶性胸腹水近期疗效好且安全。     

华蟾素联合卡介菌多糖核酸或顺铂腔内注射治疗恶性胸腹腔积液

目的：探讨华蟾素联合卡介菌多糖核酸（polysaccharide nucleic acid fraction of Bacillus Calmette Gu6rin for injection，BCG-PSN）或顺铂行腔内注射治疗恶性胸腹腔积液的疗效。方法：将70例恶性胸腹腔积液患者随机分为2组，试验组35例抽取胸腹腔积液后腔内灌注华蟾素20mL和卡介菌多糖核酸18mL；对照组35例采用华蟾素20mL和顺铂60mg腔内灌注。每周1次，连续2～4周后，进行疗效对比研究。结果：试验组24例恶性胸腔积液有效率为83．3％，11例恶性腹腔积液有效率为63.6％，试验组治疗恶性胸腹腔积液总有效率为77．1％；KPS评分提高26例，稳定7例，降低2例。对照组22例恶性胸腔积液有效率为86．4％，13例恶性腹腔积液有效率为69．2％，对照组治疗恶性胸腹腔积液总有效率80．0％；KPS评分提高16例，稳定11例，降低8例。2组疗效比较差异无统计学意义（P〉0．05），但试验组不良反应更小，生活质量改善更显著（P〈0．05）。结论：华蟾素联合卡介菌多糖核酸或顺铂腔内注射治疗恶性胸腹腔积液均有效，而华蟾素联合卡介菌多糖核酸不良反应更小，尤其适合治疗晚期不能耐受腔内化疗的患者。     

榄香烯乳联合顺铂胸腔灌注治疗恶性胸腔积液疗效及安全性的Meta分析

目的:系统评价榄香烯乳联合顺铂胸腔灌注治疗恶性胸腔积液的临床疗效和安全性。方法:以“榄香烯乳、顺铂、恶性胸腔积液”等为关键词,计算机检索如下数据库:Pubmed、CNKI、万方医学网、FMRS等,纳入榄香烯乳联合顺铂胸腔灌注治疗恶性胸腔积液的随机对照试验（RCT）,并用RevMan 5.3软件进行Meta分析。结果:本文纳入6个研究,包括463例恶性胸腔积液患者,所有研究均采用随机对照方法。Meta分析结果显示,榄香烯乳联合顺铂胸腔灌注治疗恶性胸腔积液有效率优于单纯用顺铂胸腔灌注,差异具有统计学意义（P＜0.000 1）,且并不增加药物不良反应。结论:榄香烯乳联合顺铂胸腔灌注治疗恶性胸腔积液疗效优于单用顺铂,且不良反应发生率低。     

γ干扰素治疗恶性胸腹腔积液的临床观察

目的 观察γ干扰素治疗恶性胸腹腔积液的疗效。方法 经病理或细胞学证实的恶性胸腹水患者56例,尽量抽（放）净患者胸腹水后,胸膜腔内注入γ干扰素200－300万U＋0．9％盐水20ml,视胸腹水多少,5－10天后再重复治疗。结果 恶性胸水患者46例,CR：17（37．0％）,PR：17（37．0％）,NC：12（26．0％）,总有效率：CR＋PR：34（74．0％）。恶性腹水患者10例,CR：2例,PR：例,NC：4例。结论 γ干扰素治疗恶性胸腹腔积液发挥了生物反应调节剂局部治疗的优势,是治疗恶性胸腹水的又一有效药物。     

国产香菇多糖治疗恶性胸腹水──附16例报告

本文报告了应用国产香菇多糖（ＷＴ）治疗恶性胸腹腔积液１６例，获得显效５例（３１％），有效６例（３８％），总有效率为６９％；其中肺癌合并胸腔积液者疗效显著，有效率为８３．３％（５／６例）。治疗期间，未见ＬＮＴ有明显的毒副反应。因此，可以认为ＬＮＴ是治疗恶性胸腹腔积液的良好药物。关键词：     

Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

BACKGROUND: The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid. METHODS: The authors used methylation-specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death-associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor beta (RARbeta), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients). RESULTS: Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001). CONCLUSIONS: Cell-free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests.     

腔内热灌注联合贝伐珠单抗治疗恶性胸腹腔积液的疗效观察

目的 探讨腔内热灌注化疗联合贝伐珠单抗治疗恶性胸腹腔积液的临床疗效。方法 将本院2011年6月至2013年3月收治并确诊的80例恶性胸腹腔积液患者随机分为对照组（n=40）和观察组（n=40）,对照组仅接受单纯腔内热灌注化疗（每次给予顺铂30mg、地塞米松10mg、氟尿嘧啶750mg,每2周1次,连用2次）,观察组在热灌注化疗基础上联合贝伐珠单抗（每次200mg溶于100ml生理盐水中注入胸腔或腹腔,每周1次,连用4次）。根据世界卫生组织（WHO）相关标准、生活质量评分（KPS）及抗肿瘤药物不良反应的分级标准评估两组的近期疗效、生活质量和毒副反应情况。结果 所有患者均顺利完成治疗。观察组的有效率高于对照组（85.0％ vs. 57.5％, P＜0.05）,但两组疾病控制率的差异无统计学意义（P＞0.05）。对照组的生活质量评价改善16例（40.0％）,稳定14例（35.0％）,降低10例（25.0％）;观察组中改善34例（85.0％）,稳定4例（10.0％）,降低2例（5.0％）;观察组的生活质量优于对照组,差异有统计学意义（P＜0.05）。两组不良反应发生率的差异无统计学意义（P＞0.05）,均以1～2级为主,无严重不良反应发生。结论 腔内热灌注联合贝伐珠单抗治疗恶性胸腹腔积液的疗效较好,相关毒副反应轻,生活质量明显改善。     

胸水微量元素测定的临床意义探讨

我院近来对52例良、恶性胸水中铜、锌浓度进行了测定。其中良性胸水29例、恶性胸水23例。进行统计学分析发现,恶性胸水内铜明显高于良性胸水,而锌值较低,铜锌比值有显著差异(P<0.01),而且病程越长,差异性越大。本组资料证明,如胸水Cu/Zn>1.5,则有70％可能为恶性胸水,若>2.0,就应高度怀疑恶性胸水,同血清铜、锌浓度相比,波动较小,敏感性高、特异性强、操作简便,病人易于接受,是一种新的胸水鉴别诊断方法。     

Evaluation of pleural fluid human epididymis 4 (HE4) as a marker of malignant pleural effusion

Pleural effusion is a commonly encountered problem in clinical practice, and pleural fluid analysis is usually the first step towards identifying the underlying etiology. Numerous studies have been published analyzing the potential utility of measuring biomarkers in pleural fluid as possible indicators of a malignant effusion; however, there are no studies that have examined the presence of human epididymis 4 (HE4) in pleural effusions. The aims of this study were to assess pleural effusion and serum concentrations of HE4 in patients with different types of pleural effusions and to evaluate the diagnostic performance of HE4 in detecting malignant pleural effusion. A prospective cohort study was carried out of 88 consecutive patients presenting with pleural effusions. The patients were divided into three groups: 22 patients with transudative effusions, 32 patients with non-malignant exudative effusions, and 34 patients with malignant pleural effusions. Blood and pleural fluid HE4 levels were measured using immunoassay. Both serum HE4 levels and pleural effusion HE4 levels were significantly higher in patients with malignant effusions than in patients with transudative or non-malignant exudative effusions. A pleural fluid HE4 cutoff value of 1,675?pmol/L was found to predict malignant pleural effusions with a diagnostic sensitivity of 85.3?% and specificity of 90.7?%. The current study reports a novel finding of increased serum and pleural fluid HE4 levels in patients with malignant effusions compared to non-malignant effusions. This finding has the potential to strengthen the diagnostic performance of tumor markers in detecting malignant pleural effusions.     

Clinical utility of pleural fluid YKL-40 as a marker of malignant pleural effusion

Pleural effusion is a common presenting feature of malignancy. Malignant pleural effusion is primarily diagnosed by pleural fluid cytology, pleural biopsy, and tumor markers. The glycoprotein YKL-40 is a new tumor marker that has shown to have a good diagnostic accuracy to detect malignant pleural effusion. However, there are only a few studies that have evaluated pleural fluid YKL-40 for detecting malignant pleural effusions. Hence, we conducted this study to evaluate the utility of pleural fluid YKL-40 to detect malignant pleural effusion. This is a cross-sectional study conducted between February 2016 and December 2017 in a tertiary care referral hospital. One hundred and forty-seven consecutive patients with pleural effusion were included in the study. These patients were divided into 3 groups, viz malignant, tuberculous, and parapneumonic pleural effusion, based on clinical features, radiological examination, and pleural fluid analysis. Pleural fluid YKL-40 levels were measured using enzyme-linked immunosorbent assay. Out of the 147 consecutive patients included in the study, 47 patients (31.97%) had malignant pleural effusion, 51 patients (34.69%) had tuberculous pleural effusion, and 49 patients (33.33%) had parapneumonic pleural effusion. The median pleural fluid YKL-40 level was higher in malignant pleural effusion (114.80 ng/mL) compared to tuberculous (93.17 ng/mL) and parapneumonic pleural effusion (89.87 ng/mL; P < 0.05). A diagnostic cut-off for pleural fluid YKL-40 value of 99.76 ng/mL detected malignant pleural effusion with 83% sensitivity, 87% specificity, positive predictive value (PPV) of 75%, negative predictive value (NPV) of 91.58%, and diagnostic accuracy of 85.71%. The level of pleural fluid YKL-40 is significantly elevated in malignant pleural effusion. In lymphocytic pleural effusions presenting with low adenosine deaminase levels and high YKL-40 levels, a thorough diagnostic search for malignancy is warranted.     

电视胸腔镜胸膜固定术治疗恶性胸腔积液的临床疗效及影响因素

目的:探讨电视胸腔镜胸膜固定术治疗恶性胸腔积液的临床效果,总结影响恶性胸腔积液的相关因素。方法:回顾性分析2011年1月至2013年1月87例恶性胸腔积液患者的临床资料。全部采用电视胸腔镜胸膜固定术治疗,观察其术后的临床效果,并分析影响中位生存时间的因素。结果:电视胸腔镜胸膜固定术治疗恶性胸腔积液的总有效率为63.2%。不良反应总发生率为9.1%。Karnfsky生活质量稳定以上的占97.7%。胸膜肥厚和包裹积液的总发生率为19.5%。肿瘤类型、CEA、LDH、蛋白质含量、沙培林灌注、胸水Glu水平均是电视胸腔镜胸膜固定术治疗恶性胸腔积液的主要影响因素（P<0.05）。结论:电视胸腔镜胸膜固定术治疗恶性胸腔积液临床效果确切,而肿瘤类型、CEA、LDH、蛋白质含量、沙培林灌注、胸水Glu水平是影响预后的相关因素。     

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.     

腔内灌注贝伐单抗治疗恶性胸腹腔积液的研究进展

恶性胸腹腔积液是晚期恶性肿瘤最严重并发症之一。对于胸腹腔积液全身化疗效果多不理想,常采用局部治疗。血管内皮生长因子可以促进恶性胸腹腔积液的生成,贝伐单抗是一种抗血管内皮生长因子的单克隆抗体,腔内灌注贝伐单抗在治疗恶性胸腹腔积液方面具有一定的疗效。