An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.     

Local application of anti-cancer drugs for the treatment of malignant pleural and pericardial effusion

Pleural effusion is a common complication in patients with malignant neoplasm. A randomized controlled study of intrapleural instillation of Adriamycin (control group, 30 patients) and Adriamycin Nocardia rubra cell wall skeleton (N-CWS group, 26 patients) with tube thoracostomy was performed in 55 patients with malignant pleural effusion due to primary lung cancer. The response rates for control of pleural effusion were 73.4% in the N-CWS group and 46.1% in the N-CWS group. These results suggest that intrapleural instillation using a combination of anti-cancer agent and immunopotentiator is an effective treatment for malignant pleurisy. Cardiac tamponade secondary to cancer is a life-threatening complication requiring immediate treatment. Twenty-four patients with malignant pericardial effusion were treated by intrapericardial instillation of anti-cancer drugs, such as Carbazilquinone, Mitomycin-C or ACNU, with pericardial drainage. The range of survival time from the instillation of anti-cancer drug was 3-365 days (average days). In only 4 patients, reaccumulation of pericardial effusion was recognized. There were no serious complications with this procedure. It was considered that local instillation of anti-cancer agents with pericardial drainage was a useful therapeutic modality for malignant pericarditis.     

检测肿瘤标志物ProGRP、NSE、CYFRA21-1、CEA对胸腔积液鉴别诊断价值的研究

背景与目的 恶性胸腔积液多由肺癌引起，肿瘤标志物检测对其鉴别诊断有一定临床价值。本研究的目的是探讨血清及胸腔积液胃泌素前体释放肽片断31—98（ProGRP）、神经元烯醇化酶（NSE）、细胞角蛋白19（cYFRA21—1）和癌胚抗原（CEA）单项或联合检测对肺癌所致恶性胸腔积液鉴别诊断与组织学分型的临床价值。方法 将肺癌所致的恶性胸腔积液患者按原发肿瘤类型分为小细胞肺癌（SCLC）组、肺腺癌组及肺鳞癌组，同时以良性胸腔积液组、健康对照组作为对照。评估胸腔积液ProGRP、NSE、CYFRA21—1和CEA单项及联合检测对各组恶性胸腔积液的诊断价值。结果 血清及胸腔积液ProGRP、NSE、CYFRA21—1、CEA在各恶性胸腔积液组的水平均明显高于对照组（P〈0．01）。SCLC组检测胸腔积液ProGRP的Youden指数和诊断准确性最高；肺腺癌和肺鳞癌组则以胸腔积液CEA＋CYFRA21—1联合检测（按平行试验）的Youden指数及诊断准确性最高。结论胸腔积液肿瘤标志物系列（ProGRP、NSE、CYFRA21—1、CEA）检查对恶性胸腔积液的鉴别诊断与组织学分型有很大的临床价值。胸腔积液ProGRP为SCLC所致恶性胸腔积液的最佳肿瘤标志物；胸腔积液cEA＋cYFRA21—1联合检测（按平行试验）为肺腺癌、肺鳞癌所致恶性胸腔积液较好的辅助诊断指标。     

恶性胸水与水通道蛋白AQP1之间相关性探讨

拟阐明水通道蛋白AQP1与恶性胸水产生机制的相关性,给予临床治疗提供科学依据。方法：利用免疫组织化学法和荧光定量PCR方法检测AQP1、CD34和TNF-α mRNA表达水平,并探讨其与胸水之间的相关性。结果：免疫组织化学方法检测结果提示AQP1在正常肺近胸膜下的毛细血管内皮细胞中强阳性表达,间皮细胞中弱表达。荧光定量PCR结果有胸水的肺癌组织中CD34和TNF-α mRNA的表达量比对照组、无胸水肺癌组织和炎性胸水相比增多,差异有统计学意义（P<0.05）。CD34的表达与VEGF有着密切的正相关,但AQP1的表达与CD34不相关,伴有胸水的肺癌组织中AQP1表达相对减少。结论：NSCLC伴有胸水时其癌组织中TNF-α和VEGF高表达导致新生毛细血管增多,即CD34表达增多;肿瘤来源TNF-α导致血管通透性增高,导致胸腔内渗出液不断增多;新生血管大量出现但相应的AQP1并未同步增多,导致机体水的严重失衡最后形成恶性胸水,推测癌性胸水与AQP1具有潜在联系。     

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.     

检测糖链抗原CA242对恶性胸液的诊断价值

目的 评价新型肿瘤标记物糖链抗原(CA242),以及联合检测CA242、组织多肽抗原（TPA）、神经元特异性烯醇化酶（NSE）和癌胚抗原（CEA）对诊断肺癌合并胸腔积液的临床价值。方法 应用ELISA法对57例肺癌合并胸腔积液及30例结核性胸膜炎患者血清及胸液进行检测。结果 肺癌患者血清及胸液四项肿瘤标志物平均浓度均高于结核性胸膜炎（P＜0．01）。血清及胸液CA242对诊断肺癌胸腔积液敏感性分别为53．6％（31／57）、61．4％（35／57），肺腺癌为65．7％（23／36）、66．7％（24／36）、特异性90．0％（27／30）。联合检测二项及二项以上阳性者。血清及胸液诊断肺癌特异性分别为96．7％（29／30）、100．0％（30／30），敏感性分别为75．4％（43／57）、77．2％（44／57）。结论 检测血清及胸液CA242有助于诊断肺癌合并胸腔积液，四项标志物联合检测可以显著提高肺癌合并胸腔积液诊断的敏感性和特异性。     

Response and pharmacokinetics of cisplatin instilled into the pleural cavity

The response and pharmacokinetics of cisplatin instilled into the pleural cavity were studied in 11 patients with malignant pleural effusion; 10 patients had primary lung cancer and one had breast cancer. All of them were adenocarcinoma histologically. In five of the 11 patients effusion disappeared and its cytology became negative for malignancy after four weeks. In the other six patients effusion was reduced and its cytology became negative for malignancy after four weeks. Toxicity was almost similar to that in systemic administration of cisplatin but a few patients had chest pain and fever possibly due to local irritation. The pharmacokinetics showed that a high concentration of cisplatin (free-form, 48.9 micrograms/ml) was maintained over a long period (free from (t 1/2) beta = 33.6 hours) in the pleural cavity. This was regarded as the reason for the high response to this therapy. The intrapleural instillation of cisplatin into the pleural cavity therefore seems to be an effective modality for malignant pleural effusion.     

康莱特注射液治疗恶性胸、腹水30例临床观察

目的:观察康莱特治疗晚期肿瘤伴恶性胸、腹水患者的近期疗效、不良反应。方法:所有病例均为经病理学检查或胸腹水细胞学检查确诊的肿瘤患者伴恶性胸、腹水,抽水后注入康莱特注射液100m l,一周后重复。结果:治疗后客观疗效有效率63%,KPS评分有不同程度提高,毒副反应轻微。结论:康莱特是治疗恶性胸、腹水安全有效的药物之一。     

胸水中Klotho蛋白表达水平在鉴别良恶性胸腔积液中的意义

目的:探讨胸水中Klotho蛋白表达水平是否可以作为鉴别良恶性胸腔积液的生物标记物。方法:收集2016年8月至2017年8月我科住院的胸腔积液原因待查患者的基本信息,收集胸水标本,分为良性胸腔积液组（33例）,恶性胸腔积液组（21例）,采用ELISA方法检测胸水标本中Klotho蛋白的表达水平。结果:恶性胸腔积液组Klotho蛋白表达水平明显高于良性胸腔积液组(P<0.001),且Klotho蛋白表达水平与年龄、尿素氮/肌酐、血清/胸水癌胚抗原（CEA）无明显相关性。结论:Klotho蛋白在恶性胸腔积液中的表达水平明显升高,且不受年龄及肾功能的影响,可以作为鉴别良恶性胸腔积液的生物标记物,仍需要更大样本量临床研究进一步证实。     

44例结直肠癌合并恶性胸腹腔积液患者的预后分析

目的探讨结直肠癌合并恶性胸腹腔积液的预后因素。方法回顾性分析2001年1月至2010年12月中国医学科学院肿瘤医院内科结直肠癌合并恶性胸腹腔积液患者的临床资料。结果 44例患者中,治疗后积液完全消失2例,减少16例,稳定6例,增多20例。中位总生存时间为8个月。单因素分析结果显示,KPS评分、肝转移、治疗模式、积液控制率、白蛋白以及胆红素水平与总生存时间有关。结论 KPS评分≥80分、无肝转移、全身化疗、积液控制好、白蛋白和胆红素水平正常的患者预后更好。     

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.     

Clinical evaluation of various tumor markers in pleural effusion and in the serum

Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.     

Comparison of intrapleural OK-432 and cisplatin for malignant pleural effusion in lung cancer patients

Malignant pleural effusion is typical of complications in advanced lung cancer patients, most of whom complain of dyspnea. The standard treatment for symptomatic pleural effusion is intrapleural administration of a chemical agent. In Japan, OK-432, a streptococcal preparation, and cisplatin (CDDP) have been among the most frequently used chemical agents. There have been very few reports on the efficacy of chemical agents for malignant pleural effusion. We compared therapeutic efficacy and toxicity of intrapleural OK-432 with CDDP in a case-control study. The subjects consisted of 32 lung cancer patients with malignant pleural effusion who were admitted to our hospital between January 2000 and June 2004. The therapeutic efficacy was assessed from duration of chest drainage after intrapleural administration, response rate, time to progression of malignant pleural effusion, and survival time. No statistically significant difference was observed for therapeutic efficacy. Although the OK-432-treated group had only grade 1 fever, chest pain, nausea, the CDDP-treated group had a grade 2 increase in creatinine and grade 3 nausea. Intrapleural OK-432 seemed to be better tolerated in the treatment of malignant pleural effusion than intrapleural CDDP.     

K-ras and rho A mutations in malignant pleural effusion

Mutations of the Kristen ras (K-ras) gene have been implicated in the pathogenesis of human lung cancer, especially adenocarcinoma, and have been proposed to be a prognostic factor. The K-ras mutation in codon 12 is detectable even in cell-free fluids by using the enriched polymerase chain reaction (PCR) technique. On the other hand, based on experimental results, the rho A mutation in codon 14 is also proposed to be oncogenic as observed in the K-ras mutation. Malignant pleural effusion is a common complication of lung cancer. We studied the point mutation of K-ras codon 12 and rho A codon 14 using enriched PCR in specimens of pleural effusion. Forty patients with pleural effusion were enrolled in this study. The causes of pleural effusion were non-small cell lung cancer (18 cases), small cell lung cancer (6 cases), malignant mesothelioma (2 cases), metastatic lung tumor (5 cases), thymoma (1 case), malignant lymphoma (1 case), and pleuritis tuberculosa (7 cases). The K-ras mutation was detected in 4 of 14 cases with adenocarcinoma, 1 of 3 cases with squamous cell carcinoma, 1 of 1 case with large cell carcinoma, and 1 of 5 cases with metastatic lung tumor, respectively. The rho A mutation was not detected in any pleural effusion examined in this study. Our study demonstrates the usefullness of pleural effusion as a clinical specimen for a search of point mutation of oncogenes. The K-ras codon 12 mutation is readily detected in pleural effusion, and the demonstration of this mutation has potentially important implications for the diagnosis of malignant pleural effusion.     

肺癌胸膜全肺切除术的围术期处理

目的：总结对于肺癌伴胸膜转移和恶性胸水行胸膜全肺切除手术的围术期处理经验。方法：1988年1月～2003年1月对21例肺癌伴胸膜转移和恶性胸水患者行胸膜全肺切除术。肺部原发病灶位于左肺8例,右肺13例。病理分类：鳞状细胞癌1例,腺癌12例,腺鳞癌2例,肺泡细胞癌6例。结果：术后呼吸机机械通气支持12例,平均支持时间4．5小时。无围手术期死亡,无支气管胸膜瘘、脓胸、大出血等严重并发症。随访已死亡16例,生存期为5～34个月,其余5例患者随访24～29个月仍生存,全组中位生存时间18个月。结论：加强围术期处理,对常见并发症重点防范、早期治疗,是降低手术风险、促进此类患者康复的关键。     

自体不成熟树突状细胞胸腔内注射治疗化疗耐药的肿瘤患者恶性胸腔积液

目的:观察体外扩增的不成熟树突状细胞(dendritic cells,DC)胸腔内注射对恶性胸腔积液的疗效和安全性。方法:从6例对化疗耐药的恶性胸腔积液患者采集外周血单个核细胞,体外细胞因子诱导培养获得不成熟DC,每4周患者胸腔内注射DC(5~10)×107个,连续3次为一疗程,观察治疗后患者胸腔积液的变化及治疗的不良反应,流式细胞仪检测胸水中T细胞、NK细胞亚群。结果:总体疗效为:CR 2例,PR 1例,SD 1例,PD 2例,有效率为50%(3/6),获益率(CR+PR+SD)为66.7%。2例CR均为肾癌患者,缓解时间达26周和147周;3例肺癌患者中1例PR、1例SD及1例PD;1例恶性胸膜间皮瘤PD;治疗中无严重不良反应发生。DC治疗后6例患者胸水中的T细胞百分率均较治疗前上升,但差异无统计学意义;NK细胞百分率较治疗前明显上升(P<0.05)。结论:采用无抗原加载的自体不成熟DC胸腔内注射治疗恶性胸腔积液的疗效肯定,可能主要是通过NK细胞介导,是一种安全、有效的治疗方法。     

Accumulation of 99mTc methylene diphosphonate in malignant pleural and ascitic effusion

Increased accumulation of radioactivity was observed in malignant pleural and ascitic effusion as to a patient with stomach cancer and in malignant pleural effusions as to 2 patients (1 with breast cancer and another with lung cancer) during the performance of routine whole-body bone scans with 99mTc methylene diphosphonate. This finding should strongly suggest malignancy.     

肺癌单克隆抗体检测良,恶性胸腔积液的评价

为了评价肺癌单克隆抗体检测良恶性胸腔积液的诊断与鉴别诊断价值，同步采集临床上明确诊断的６３例良恶性胸腔积液患者的胸水和血清，以及１０例正常人的血清，进行肺癌单抗金标免疫斑点渗透法的检测，并与癌胚抗原的检测比较。结果显示：恶性胸腔积液组肺癌单抗金标免疫斑点渗透法和癌胚抗原的阳性率明显高于良性胸腔积液组及正常组（Ｐ＜０．０１），而且肺癌单抗金标免疫斑点渗透法检测的阳性率高于癌胚抗原。在恶性胸腔积液中，肺癌单抗金标免疫斑点渗透法的灵敏度和特异度分别为６５．１％和１００．０％，癌胚抗原的灵敏度和特异度分别为５３．５％和９５．０％，两项指标联合检测的灵敏度和特异度分别为７６．７％和９５．０％。说明肺癌单抗金标免疫斑点渗透法对良恶性胸腔积液有鉴别诊断价值，而且优于癌胚抗原；两项指标联合检测可以提高对恶性胸腔积液的诊断符合率。     

Detection and comparison of epidermal growth factor receptor mutations in cells and fluid of malignant pleural effusion in non-small cell lung cancer

Cells or cell-free fluid of malignant pleural effusion could be important clinical specimen for epidermal growth factor receptor (EGFR) mutation screening in advanced non-small cell lung cancer (NSCLC) patients. However, their usefulness in mutation detection has not been well compared. In this study we recruited 26 East Asian NSCLC patients with malignant pleural effusion, determined the mutation status of EGFR in both cells and matched cell-free fluid with the use of sequencing and mutant-enriched PCR. After comparing the mutation spectrums, we found both the cells and cell-free pleural fluid may be feasible clinical specimen for EGFR mutation detection in unresectable NSCLC given sensitive genotyping assays employed. Direct sequencing could miss a significant portion of mutations in these heterogeneous specimens. More sensitive methods, such as mutant-enriched PCR and gene scan, could provide more reliable mutational information.     

肺癌胸水的综合治疗17例临床观察

 晚期肺癌胸水的治疗难度很大，目前虽已有一些治疗晚期肿瘤并胸水的方法，但用胸腔化疗加全身化疗治疗肺癌胸水的报道尚少。本文用顺铂胸腔内注入结合多药联用全身化疗治疗肺癌胸水，使胸水明显消失，肺部肿瘤缩小。