【作者】 李际强；

【导师】 刘伟胜；

【作者基本信息】 广州中医药大学 ， 中医内科学， 2007， 博士

【摘要】 恶性胸腔积液是大部分中晚期肿瘤患者的主要临床症状及体征，它的产生及发展直接影响着患者的生活质量和生存期，严重的胸腔积液甚至可危及生命，因此，恶性胸腔积液的治疗在整个肿瘤综合治疗中显得尤为重要。目前治疗恶性积液的方法较多，但因化疗药物的毒副作用较大，以及手术等方法晚期病人多难以耐受。中医中药在治疗恶性积液方面有一定的方法，但目前恶性胸腔积液的中医证候方面的研究尚少。资料表明药腔内注射中药制剂既可以提高疗效，与化疗药有协同作用，又可增强机体免疫力，改善生活质量，可起到减毒增效的效果。近年来热物理疗法(又称热灌注疗法，简称热疗)安全有效正逐渐应用于肿瘤的综合治疗中。一、肺癌并胸腔积液患者T淋巴细胞亚群与中医证候的相关性研究1．目的：探讨肺癌并胸腔积液的中医证型与T淋巴细胞亚群与NK细胞的相关性。2．方法：选择明确诊断为肺癌并胸腔积液的患者72例，并选择同期的肺癌无胸腔积液的147例患者作为对照组，根据肺癌的中医辨证，分型为气滞血瘀、痰瘀蕴结、痰热蕴肺、阴虚毒热、气阴两虚、肺脾气虚、肺肾两虚型，前三者为实证，后四者为虚证。同时选择16例正常人做为正常对照组。并对以上患者及正常人的T淋巴细胞亚群(CD3~+、CD4~+、CD8~+、CD4~+／CD8~+)及NK细胞标志物CD(16+56)~+进行检测。3．结果：肺癌并胸腔积液患者CD3~+、CD4~+／CD8~+、CD(16+56)~+均显著低于正常组(P＜0.01或P＜0.05)，与对照组比较，各项指标差异无显著性(P＞0.05)；实证患者的CD3~+、CD4~+均显著高于虚证组(P＜0.01)；与气滞血瘀证、痰瘀蕴结证比较，阴虚毒热、气阴两虚、肺肾两虚的外周血CD3~+均明显低于前者(P＜0.01或P＜0.05)，阴虚毒热与肺肾两虚型的CD4~+明显低于气滞血瘀组(P＜0.05)，阴虚毒热组的CD4~+低于痰瘀蕴结证(P＜0.05)；肺肾两虚的患者CD(16+56)~+明显高于气滞血瘀证与痰瘀蕴结证(P＜0.05)；KPS≧60肺癌并胸积液患者CD3~+明显高于KPS＜60患者(P＜0.05)；肺癌并胸腔积液患者ZPS的评分越高，其CD3~+越低(P＜0.05)。4．结论：肺癌并胸腔积液患者的中医证型与细胞免疫功能具有相关性，可能为肺癌临床辨证治疗提供较为客观的免疫学指标。二、102例恶性胸腔积液患者中医证候的临床分析1．目的：探讨恶性胸腔积液的中医证候分布规律及证候群指标，为其中医辨证规范化提供依据。2．方法：采用前瞻性方法，收集本院就诊的恶性胸腔积液患者的四诊资料，构建证候四诊合参指标数据库，运用描述性统计及聚类分析方法进行分析。3．结果：共收集102例恶性胸腔积液患者资料，中医证候多以肺脾两虚，痰瘀互结证(病例数54人；占52.94％)；脾肾两虚，痰饮犯肺证(病例数29人，占28.43％)；阴虚内热，瘀毒内生证(病例数10人，占9.80％)；气阴两虚，痰热犯肺证(病例数9例，占8.82％)。其中，肺脾两虚，痰瘀互结证最多，其次为脾肾两虚，痰饮犯肺证，阴虚内热，瘀毒内生证与气阴两虚，痰热犯肺证相对较少。4．结论：本资料中，恶性胸腔积液中医证候具有一定的规律性，常为虚实夹杂证，以单独实证或虚证难以概括整个证型，其中医证候分布与感染性胸腔积液不同。研究结果可为恶性胸腔积液中医证候诊断指标的标准化提供一定的依据。三、热物理疗法配合中药腔内灌注治疗恶性胸腔积液的临床研究1．目的：1．1研究热物理疗法配合中药腔内灌注治疗恶性胸腔积液的临床疗效与不良反应。1．2热物理疗法对中医证候的影响及与不同中医证候分型患者疗效的相关性。2．研究方法：将55例诊断为恶性胸腔积液的患者随机分为治疗组(体腔热物理治疗配合中药灌注组)21例，对照1组(中药灌注组)14例，对照2组(热灌注腔内化疗组)20例。治疗后，观察各组的临床疗效与不良反应。3．研究结果：3．1临床疗效：患者治疗四周后观察疗效，治疗组CR8例，PR12例，SD1例，总有效率为95.24％；对照1组CR3例，PR9例，SD2例，总有效率85.71％；对照2组CR10例，PR8例，SD1例，PD1例，总有效率为90％。三组总有效率比较统计学差异无显著性，而有效(CR+PR)的患者中，治疗组的CR与对照1组的CR病例数比较差异有显著性(P＜0.05)。3．2不良反应：三组患者治疗前后白细胞、红细胞及血小板以肝肾功能，经统计学分析，差异无显著性(P＞0.05)。热灌注化疗组有5例出现不良反应，3例消化道症状，如恶心、呕吐；1例出现骨髓抑制；1例合并血胸。5例不良反应对症处理后可缓解。治疗组有一例可疑腔内感染而出现发热，但予以抗感染治疗后可改善。3．3治疗前后中医证候的变化：中药灌注组治疗前后中医证型未发生明显的变化，而热化疗组在5例出现伤阴的表现如口干咽燥等。3．4治疗前后生存质量的评价：治疗组治疗前后KPS比较，差异有显著性(P＜0.05)，ZPS治疗前后比较差异无显著性(P＞0.05)。3．5热物理疗法的疗效与恶性胸腔积液中医证候的相关性分析：肺脾气虚型、肺肾两虚型的有效率(CR+PR)高于气阴两虚型与阴虚内热型(P＜0.05)。4．结论：热物理疗法配合中药康艾腔内灌注是治疗恶性胸腔积液的一种较好的方法，其疗效肯定，能改善患者的生存质量，不良反应少。初步研究表明，热物理疗法更适合中医辨证为肺脾气虚及肺肾两虚的患者，此结论有待更大样本量去证实。更多还原

【Abstract】 Malignant pleural effusion(MPE) is mainly clinical symptom of greatly part of the later period tumor sufferer, its creation and development influence the sufferer’s living quality and existence period directly, the serious MPE even can endanger life, therefore, the treatment of MPE is very important in compositive treatment of tumor. Presciently, there are many methods treating MPE, but because of the poisonous side effect of the chemotherapy medicine and not subjecting the surgical operation etc. for the patient in later period. There are many methods of curing MPE with The Chinese medicine, but the study for Traditional Chinese differentiation of MPE is still little. The data expressed the infusion with Chinese herbal medicine product into thorax can raise curative effect of the chemotherapy medicine, and it can increase the immunity of patient, improving life quality, reducing the poison of chemotherapy. The heat physical therapy (heat infuses therapy, Thermotherapy) has applied in the treatment of MPE recently, it is a safe and effective treatment.Ⅰ. Relative Research between the Traditional Chinese Differentiations of MPE Caused by Lung Cancer and T lymphocyte Subsets, NnaturaI Killer Cells1. Objective To investigate the relation-ship between the Traditional Chinese differentiation in patients of MPE caused by lung cancer and the cell immunity function.2. Method To proceed diagnosis and differentiation in TCM, there are Qi stagnation and blood stasis, Accumulation of phlegm and stagnation, Accumulation of phlegm and heat in lung, Yin asthenia and virulent heat, Asthenia of both qi and yin, Asthenia of both lung and spleen, Asthenia of both lung and kidney. 72 cases of MPE caused by lung cancer were studied, and 147 cases of lung cancer which have no MPE were as control group. To analyze the T lymphocyte subsets (CD3~+、CD4~+、CD8~+、CD4~+/CD8~+) and CD(16＋56)~+ of NK cell for them. 3. Results CD3~+、CD4~+/CD8~+ ratio、CD(16＋56)~+ decreased significantly in MPE caused by lung cancer group as compared with normal group(P＜0.01 or P＜0.05). Compared with the control group, vvarious index were no difference (P＞0.05). CD3~+、CD4~+ decreased significantly in Asthenia syndrome of lung cancer group as compared with asthenia syndrome(P＜0.01). CD3~+ decreased significantly in Yin asthenia and virulent heat, Asthenia of both qi and yin, Asthenia of both lung and spleen, Asthenia of both lung and kidney syndrome of MPE caused by lung cancer as compared with Qi stagnation and blood stasis, Accumulation of phlegm and stagnation syndrome(P＜0.01 or P＜0.05). CD4~+ decreased significantly in Yin asthenia and virulent heat, Asthenia of both lung and kidney syndrome as compared with Qi stagnation and blood stasis (P＜0.05). CD4~+ decreased significantly in Yin asthenia and virulent heat as compared with Accumulation of phlegm and stagnation syndrome(P＜0.05). CD(16＋56)~+ increased significantly in Asthenia of both lung and kidney syndrome as compared with Qi stagnation and blood stasis, Accumulation of phlegm and stagnation syndrome (P＜0.05). CD3~+ increased significantly in MPE caused by lung cancer of KPS≧60 as compared with KPS＜60 group (P＜0.05). ZPS of MPE caused by lung cancer is more high, CD3~+ is more low (P＜0.05).4. Conclusion The Traditional Chinese differentiation and cell immunity function of MPE by lung cancer sufferer have relativity, the possibility provides more objective immunology index sign for the lung cancer clinical treatment based on syndrome differentiation.Ⅱ. A Clinical Study on TCM Syndrome Patterns of 102 oases of MPE1. Objective To observe the distributing rule and diagnosis criterion of TCM syndrome of MPE, to providing basis of standardization of syndrome differentiation of MPE.2. Methods Adopt the prospect method, to collect the clinic data of MPE in our hospital, setting up databases, to analyze the TCM syndrome based on the description covariance and clustering analysis method.3. Results 102 cases of MPE were observed, there are four TCM syndromes, which are Asthenia of both lung and spleen, Accumulation of phlegm and stagnation (n=54, 52.94%); Asthenia of both kidney and spleen, attack on the lung by retained fluid(n=29, 9.80%); Yin asthenia and heat, stagnation of virulent heat (n=10, 9.80%), Asthenia of both qi and yin, Accumulation of phlegm and heat in lung (n=9, 8.82%).4. Conclusion In this data, TCM syndrome of MPE have certain regulation, often mixing up Asthenia and asthenia syndrome, which is different from pleural effusion caused by infection. The research result can provide a certain basis of standardization of TCM syndrome differentiation of MPE.Ⅲ. Clinical study of thermotherapy combining with infusing Kang-ai injection into thorax for malignant pleural effusion1. Objective1. 1 To study the results of thermotherapy and side effects of thermotherapy combining with infusing Kang-ai injection into thorax for MPE.1.2 To Inquiry into the affection of thermotherapy to TCM syndrome differentiation of MPE; to study the relation-ship between the Traditional Chinese differentiation and the Curative effect.2. Methods To divide 55 patients with MPE into three groups at random. The three groups were respective given thermotherapy combining with infusing Kang-ai injection into thorax (therapeutic group, 21cases), the infusion of Kang-ai injection into thorax (control group 1, 14 cases), thermotherapy combining with intracavitary injection of Cisplati (control group 2, 20 cases). To study the results of thermotherapy and side effects of three groups.3. Results3.1 the results of thermotherapy: After four weeks treatment, The response rate of pleural effusion was 95.24% in therapeutic group(CR was 8 cases, PR was 12 cases, SD was 1 cases), 85.71% in control group 1 (CR was 3 cases, PR was 9cases, SD was 2 cases), 90% in control group 2 (CR was 10 cases, PR was 8 cases, SD was 1 case, PD was 1 case).3.2 side effects: WBC, WBC, PLT, the liver and kidney function have no variety in the before and in the after treatment(P＞0.05). there were 5 cases of patients having side effects in control group 2, 3 cases had digest symptom, such as disgusted, vomit; Marrow of 1 case were restrained, 1 case combined hemothorax. They had alleviated by treatment. 1 case had a fever in therapeutic group, which was a suspicious infection.3.3 the variety of TCM syndrome: There was no variety after treatment compared with before treatment in therapeutic group. 5 cases in control group 2 impaired yin, such as swallows dry.3.4 The quality of life: KPS oftherapeutic group increasing after treatment(P＜0.05).3.5 The relation-ship between the Traditional Chinese differentiation and the Curative effect. Efficient of Astheniaofboth lung and spleen, Asthenia of both kidney and spleen was better than Yin asthenia and heat, Asthenia of both qi and yin (P＜0.05).4. Conclusion The thermotherapy for MPE was a new, safe and effective treatment. It has affirmative curative effect, can improve the sufferer’s existence quality, have little side effects. The initial research expresses that thermotherapy suits asthenia of both lung and spleen, asthenia of both kidney and spleen, this conclusion needs the larger sample quantity to confirm.更多还原