调节性T细胞及其在结核性及恶性胸腔积液中的研究进展

胸腔积液是常见的内科疾病,肺、胸膜和肺外疾病均可引起,其病因以渗出性胸膜炎最为常见,渗出性胸腔积液最常见的病因是结核性胸膜炎和恶性胸腔积液。结核性胸膜炎是由于胸膜下结核杆菌感染诱发严重的迟发型超敏反应而引起,恶性胸腔积液由恶性肿瘤胸膜转移或恶性胸膜间皮瘤引起,     

胸腔镜手术对老年不明原因胸腔积液的诊断和治疗

目前鉴别胸腔积液性质的方法包括诊断性胸腔穿刺、胸腔积液检查、胸部X线摄片、超声检查、胸膜活检等,但有部分患者经过上述检查仍难以作出正确诊断,即所谓"不明原因的胸腔积液".随着电视胸腔镜技术的发展和仪器的进步,胸腔镜手术成为诊断和治疗胸膜疾病的有效方式.本文拟探讨胸腔镜对不明原因恶性胸腔积液的诊断和治疗效果.     

胸腔积液和血清中脯氨酸肽酶检测对结核性和恶性胸腔积液的诊断价值

胸腔积液是一种临床常见的胸膜病变,其发生原因很多,常见的有胸膜炎、胸膜肿瘤,或继发于全身其他系统的疾病.良性疾病以感染性胸腔积液多见,其中又以结核性胸腔积液最为常见,恶性胸腔积液的病因以肺癌最为常见.因良、恶性胸腔积液的治疗和预后截然不同,及时准确地鉴别其性质有重要的临床指导意义.     

闭式经皮胸膜刷检——一种诊断恶性胸腔积液的新方法

胸腔积液是恶性肿瘤常见的并发症。胸水细胞学检查和闭式胸膜活检是诊断恶性胸腔积液最常用的两种方法,但它们的诊断结果并不总令人满意。经胸腔镜直视下活检和胸廓切开术对原因未明的胸腔积液虽有很高的诊断率,但费用高,创伤性较大,并非适宜所有的胸腔积液患者。为此,作者介绍一种新的诊断恶性胸腔积液的方法——闭式经皮胸膜刷检,并与胸水细胞学检查和闭式胸膜活检相比较。 对象与方法 选择43例临床怀疑为恶性胸腔积液的患者为研究对象。术前肌注阿托品0.6mg。操作在X线透视检查室内进行。患者取坐位,两臂交叉置于面前的桌面上,     

结核性与恶性胸腔积液内科胸腔镜下特征比较及诊断相关因素分析

目的对比结核性与恶性胸腔积液内科胸腔镜下的特征及常见危险因素、临床表现的差异,为不明原因胸腔积液鉴别诊断提供依据。方法收集山西医科大学第一医院呼吸科2016年1月至2018年1月“胸腔积液待查”的90例患者临床资料,均因病因不明行内科胸腔镜下胸膜活检,按病理结果分为结核组与恶性组,对比分析2组镜下特征和常见危险因素、临床表现等指标。结果90例患者经胸腔镜和病理检查明确诊断85例,确诊率为944%,其中结核性胸腔积液40例,恶性胸腔积液36例。结核组镜下表现以胸膜充血水肿、广泛粘连、胸膜均匀一致小结节为主(χ^2值分别为23.175、7.361、6.064,P值均<005);恶性组镜下表现以胸膜增生增厚、大小不等结节、白斑样改变、肿块为主(χ^2值分别为23.095、8.717、11.577、5.127,P值均<005)。单因素回归分析:发热、体质量减轻对结核性胸腔积液诊断有意义;年龄>40岁、气促、病程>1个月、吸烟指数>400年支及血性胸腔积液对恶性胸腔积液的诊断有提示意义。多因素回归分析:发热和体质量减轻是结核性胸腔积液的特征性表现;年龄>40岁、病程>1个月、吸烟指数>400年支和血性胸腔积液对恶性胸腔积液诊断有较大价值。结论内科胸腔镜是确诊不明原因胸腔积液的有效检查方法,恶性胸腔积液和结核性胸腔积液是最常见的病因。危险因素、临床表现等指标及内镜下特征性表现对结核性与恶性胸腔积液鉴别有较大提示意义。     

恶性胸腔积液的处理

恶性胸腔积液是恶性肿瘤胸膜转移或原发于胸膜的恶性肿瘤所致,为恶性肿瘤常见并发症之一。据统计24%~50%的渗出性胸腔积液源于恶性病变,50%的癌症转移患者最终发生恶性胸腔积液[1-4]。恶性胸腔积液中占前3位的分别为肺癌(36.3%)、乳腺癌(25%)和淋巴瘤(8%~26%)。恶性胸腔积液增长迅速,常伴有胸闷、气急、心悸、不能平卧等症状,如不及时治疗可造成患者呼吸循环功能障碍、低蛋白血症、贫血,严重者甚至危及生命。因而,迅速、有效地治疗恶性胸腔积液是整个肿瘤多学科治疗中的重要环节[5]。最常见的导致恶性胸腔积液的肺癌在1997年的肺癌分期中为…     

胸膜活检联合液基细胞学检查对恶性胸腔积液的诊断价值

目的 探讨胸膜活检联合液基细胞学检查对恶性胸腔积液的诊断价值.方法 分析我院2006年5月～2011年12月经病理组织学或细胞学检查诊断为恶性胸腔积液的46例病人,对胸膜活检联合液基细胞学检查对恶性胸腔积液的诊断率进行分析.结果 胸膜活检、液基细胞学检查、胸膜活检联合液基细胞学检查对恶性胸腔积液的诊断率分别为63.0%、82.6%、91.3%.结论 胸膜活检联合液基细胞学检查可明显提高恶性胸腔积液的诊断率.     

胸液溶菌酶和γ-干扰素的检测对结核性胸膜炎的诊断价值

胸腔积液可由感染、结缔组织病、变态反应性疾病及恶性肿瘤等多种原因引起,结核性胸膜炎和胸部肿瘤引起的胸腔积液最为常见。结核性胸膜炎最可靠的诊断依据是胸液结核分枝杆菌的检测和胸膜活检病理检查,阳性率分别为：胸液涂片5.8%,胸液培养30%左右,胸膜活检69.9%～82%^[1]。尽管采用了多种诊断方法,但仍有20%的胸腔积液存在病因诊断问题^[2]。近年随着分子生物学和细胞生物学的发展,许多文献报道溶菌酶和干扰素水平在结核性及恶性胸腔积液鉴别诊断中的意义。本文对结核性及恶性胸腔积液胸液溶菌酶和γ-干扰素水平进行检测,探讨其临床诊断价值。     

恶性胸腔积液的实验诊断进展

恶性胸腔积液是由恶性肿瘤胸膜转移或原发于胸膜的恶性肿瘤所致,早期诊断困难,临床迫切需要实验室提供检查手段,以诊断恶性胸腔积液.本文就恶性胸腔积液的实验诊断进行综述.     

电子支气管镜替代胸腔镜在恶性胸腔积液诊断中的应用

目的探讨电子支气管镜替代胸腔镜检查对恶性胸腔积液的诊断价值及恶性胸腔积液在支气管镜直视下的胸膜改变。方法对我院2008年10月～2010年10月间,应用电子支气管镜（Olympus BF-260）替代胸腔镜检查并确诊的33例恶性胸腔积液患者进行回顾性分析,所有患者经胸腔积液细胞学、痰细胞学、支气管镜检查等仍不能确诊胸腔积液性质,行电子支气管镜替代胸腔镜检查,直视下观察胸膜变化,并对可疑组织行活检进行病理检查。结果 33例患者最终诊断：胸膜转移癌25例,其中肺鳞癌2例,肺腺癌19例,小细胞癌1例,消化道肿瘤转移1例,其他部位转移癌2例;恶性胸膜间皮瘤5例;不能明确的恶性肿瘤3例。结论恶性胸腔积液胸膜上有不同程度的病损;电子支气管镜替代胸腔镜检查是一项安全、有效、易操作的检查方法。     

The efficacy and safety of intrapleural hyperthermic perfusion in patients with malignant pleural effusion undergoing video-assisted thoracic surgery: a single-arm clinical trial

BackgroundPatients with malignant pleural effusion (MPE) are usually treated with an indwelling pleural catheter (IPC) or pleurodesis. However, most do not achieve a satisfactory control rate of pleural effusion and have poor prognosis. Distilled water has cytocidal effects of hypotonic shock and can result in the lysis of cancer cells which was used in surgery to eradicate cancer cells. However, there is no study focusing on the efficacy of intrapleural hyperthemic perfusion for MPE under video-assisted thoracoscopic surgery (VATS). This study explored the efficacy and safety of intrapleural hyperthermic perfusion (IHP) with distilled water in patients with MPE.MethodsIn this retrospective, single-arm trial, patients admitted to department of cardiothoracic surgery of Taizhou hospital and diagnosed with MPE caused by non-small cell lung cancer from January 2014 and December 2018 were included. The clinical characteristics including age, gender smoking history, Karnofsky score, volume of pleural effusion, TNM cancer stage, pathology, genetic test of patients were collected. Patients were treated with hyperthermic perfusion. The pleural cavity was perfused with 43.0 ℃ distilled water for 60 minutes under video-assisted thoracic surgery (VATS). The efficacy of treatment was defined as follows: (I) complete remission (CR; no recurrence of pleural effusion after IHP for at least four weeks); (II) partial remission (PR; pleural effusion was decreased by 50% and the condition lasted for 4 weeks; or (III) no remission (NR; no decrease in pleural effusion). Kaplan-Meier method with a log-rank test was used for survival analysis. Cox proportional hazards regression models were applied to perform univariate and multivariate analysesResultsFrom January 2014 through December 2018, 30 patients with MPE caused by non-small cell lung cancer (NSCLC) were treated with hyperthermic perfusion. There were no serious reportable clinical complications associated with the procedure. The response rate was 96.7%, with 63.3% experiencing PR and 33.3% achieving CR. The overall survival (OS) ranged from 2 to 46 months. The median survival was 12 months.ConclusionsIHP proved to be a feasible and safe strategy for patients with MPE in our study but it still needs to be verified with a larger, prospective and randomized trial in the future.     

恩度和顺铂治疗原发性肺癌合并恶性胸腔积液的短期疗效对比分析

目的回顾性分析69例肺癌合并恶性胸腔积液(malignant pleural effusion, MPE)患者的临床资料,探讨恩度与顺铂胸腔内灌注治疗肺癌合并MPE的短期疗效和不良反应。 方法收集陆军军医大学新桥医院2016年至2018年6月收治的69例肺癌合并MPE患者的临床资料,根据治疗方法的不同,分为恩度组23例,顺铂组46例。两组治疗前均已排尽胸水,恩度组胸腔灌注恩度30 mg,每周2次,顺铂组胸腔灌注顺铂30 mg/m²,每周2次,比较两种药物的疗效及不良反应的差异。 结果恩度组的客观有效率(objective response rate, ORR)为56.5%,顺铂组ORR为26.1%。恩度组的治疗效果显著优于顺铂组,差异有统计学意义(P<0.05)。分层分析发现,在血性胸腔积液患者中,恩度组ORR 88.9%,顺铂组ORR 5%,差异有统计学意义(P<0.05)。在非血性胸腔积液患者中,恩度组ORR 35.7%,顺铂组ORR 42.3%。胸腔积液中癌胚抗原(carcinoembryonic antigen, CEA)数值较低(<100 μg/L)的患者中,恩度组ORR 53.8%,顺铂组ORR 8.3%,差异有统计学意义(P<0.05)。胸腔积液中CEA数值较高(≥100 μg/L)的患者中,恩度组ORR 50%,顺铂组ORR 45.4%。 结论恩度胸腔内灌注治疗原发性肺癌合并MPE是一种安全有效的治疗方法,疗效优于顺铂,尤其对于血性胸腔积液患者、胸腔积液中CEA数值较低(<100 μg/L)的患者,效果更为明显。且恩度组较顺铂组不良反应更小,安全性好,能明显改善患者生活质量。     

Multiple myeloma with myelomatous pleural effusion: a case report and review of the literature

Multiple myeloma (MM) is a malignant neoplasm of plasma cell origin. Pleural effusion may develop in the setting of MM due to various reasons, but myelomatous pleural effusion (MPE) is rare. We report a case of MPE in a patient with advanced MM. A 76-year-old woman with MM was admitted to hospital because of dyspnea. Chest X-ray showed right-sided pleural effusion. Protein electrophoresis of the pleural fluid showed monoclonal protein, and cytology demonstrated monoclonal plasma cells. Hospice care was implemented, and the patient died one month later. We present an analysis of the clinical characteristics of 57 MPE cases reported in the English literature. Our review revealed that MPE patients had poor overall survival irrespective of whether MPE develops in the course of their disease or presents as the initial manifestation of MM. Based on this analysis, MPE is a poor prognostic factor, and aggressive treatment should be considered, especially for patients with early-onset MPE.     

Malignant pleural effusion from lung adenocarcinoma treated by gefitinib

Small molecule inhibitors targeting epidermal growth factor receptor (EGFR) are known to be active against non-small cell lung cancer (NSCLC) although the pharmacodynamics of these agents on malignant pleural effusion (MPE) remains unclear. Here we describe a case of lung adenocarcinoma with massive MPE treated successfully by gefitinib and chest drainage. Using sequential MPE samples before and during gefitinib therapy, the morphological changes and apoptosis of cancer cells were analyzed. Apoptosis of cancer cells was detected as early as 4 hours on, but not before, gefitinib therapy, suggesting that the pharmacodynamic assessment of such molecular targeting agents might be feasible for MPE.     

分泌性磷蛋白1在肺癌所致恶性胸腔积液中的表达及其诊断价值

目的 探讨分泌性磷蛋白1(SPP1,别名osteopontin)在晚期肺癌所致恶性胸腔积液(MPE)中的表达及其作为辅助诊断的可能性.方法 选取96例肺癌患者MPE标本为病例组,遴选24例肺部良性疾病患者胸腔积液标本为对照组,使用ELISA法检测标本SPP1表达量.采用SPSS16.0软件统计,并用t检验分析病例组与对照组SPP1的表达水平,建立ROC曲线甄选cutoff界值.结果 在120例胸腔积液标本中,病例组SPP1含量(-x±s=1568.9±1297.15 ng/ml)较对照组(-x±s =644.12±480.50 n/ml)显著增高(t =4.766,P＜0.01),cutoff界值=1247.90 ng/ml(敏感度=38.54％,特异度=95.83％,曲线下面积0.662,95％,CI0.554～0.770).结论 SPP1在MPE中显著升高,胸腔积液中SPP1表达水平可用于MPE辅助诊断,但不适宜临床常规诊断.     

Diagnosis and management of malignant pleural effusions

Abstract:   Malignant pleural effusions (MPEs) complicate the clinical course of patients with a broad array of malignancies, which are most often due to lymphomas or carcinomas of the breast, lung, gastrointestinal tract or ovaries. Patients may present with a MPE as the initial manifestation of a cancer or develop an effusion during the advanced phases of a known malignancy. In either circumstance, the median survival after presentation with a MPE is 4 months. Effusions may result from direct pleural invasion (MPE) or indirect effects (paraneoplastic effusions), such as impairment of fluid efflux from the pleural space by lymphatic obstruction or pleural effects of cancer radiation or drug therapy. Because only 50% of patients with cancer who develop a pleural effusion during their clinical course have a MPE, careful evaluation of the effusion to establish its aetiology is required to direct therapy. Management is palliative with interventions directed towards decreasing the volume of intrapleural fluid and the severity of associated symptoms.     

Mammalian target of rapamycin (mTOR) inhibition does not prevent lung adenocarcinoma‐induced malignant pleural effusion

The impact of temsirolimus was investigated in a murine model of malignant pleural effusion (MPE) created with intrapleural injection of Lewis Lung Cancer (LLC) cells. Temsirolimus (1 or 20 mg/kg) did not affect the pleural fluid volume or the number of pleural tumour foci. In addition, temsirolimus did not affect vascular endothelial growth factor expression by LLC cells in vitro. In conclusion, temsirolimus did not curtail experimental lung‐adenocarcinoma‐induced MPE.     

胸腔镜下热灌注化疗治疗恶性胸腔积液的疗效观察

目的探讨胸腔镜下热灌注化疗对恶性胸腔积液患者的治疗效果。方法 44例恶性胸腔积液患者于全麻下用胸腔镜探察胸腔,并行胸膜活检,用人工心肺机将预充液（NS3000ml＋顺铂300mg）加热至42.0～44.0℃后,通过两根导管连接至胸腔内,循环灌注胸腔约60min。结果胸水控制有效率为97.7%,KPS评分升高率为70.4%,未见明显的毒副作用。结论胸腔镜下胸腔内热灌注化疗具有快速诊断、创伤小、控制胸水效果好、副作用小的优点。     

人表皮生长因子受体-2、癌胚抗原、腺苷脱氨酶对鉴别肺癌相关性恶性胸腔积液和结核性胸腔积液的诊断价值

目的探讨胸腔积液中人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)、癌胚抗原(carcinoembryonic antigen,CEA)和腺苷脱氨酶(adenosine deaminase,ADA)三者及三者联合检测对鉴别和结核性胸腔积液的诊断价值。方法选择20例肺癌相关性恶性胸腔积液(malignant pleural effusion,MPE)患者,20例结核性胸膜炎(tuberculous pleurisy,TBP)患者,均诊断明确,分别采用酶联免疫吸附法、化学发光法和酶比色分析法检测两组病例胸液和血清HER-2、CEA和ADA水平。用免疫组织化学方法(SP法)检测胸液沉渣细胞HER-2蛋白。结果①MPE组胸液HER-2水平为(6.18±2.35)ng/mL,显著高于TBP组(3.06±1.18)ng/mL(P0.01),MPE组血清HER-2水平(3.89±1.98)ng/mL也显著高于TBP组(2.31±0.65)ng/mL(P0.05);②TBP组胸液ADA水平(40.70±20.60)U/L显著高于MPE组(13.40±3.18)U/L(P0.01);③MPE组胸液CEA水平为(66.50±43.60)ng/mL,显著高于TBP组(7.91±4.20)ng/mL(P0.01);④检测胸液中HER-2、ADA、CEA水平诊断恶性胸液的灵敏度、特异度、准确度分别为80.0%、95.0%、87.5%;70.0%、90.0%、80.0%;70.0%、100.0%、85.0%。联合检测HER-2、ADA、CEA三者水平诊断恶性胸液的灵敏度、特异度、准确度分别为90.0%、95.0%、92.5%;⑤MPE胸液沉渣细胞免疫组织化学方法(SP法)检测HER-2阳性率达85.0%。结论①单项检测胸液HER-2、CEA、ADA水平对鉴别肺癌相关性MPE和TBP有临床诊断价值;②胸腔积液沉渣细胞免疫组化法HER-2阳性表达率高,且具有较高特异性,有助于肺癌相关性的诊断;③联合检测胸液中HER-2、ADA、CEA水平对鉴别肺癌相关性MPE和TBP具有更理想的临床诊断价值。     

白细胞介素22在结核性胸膜炎与恶性胸腔积液中生物学特性的研究进展

白细胞介素22（IL-22）是IL-10细胞因子家族成员之一,通过与IL-22R1、IL-10R2二聚体结合发挥作用。主要由T辅助细胞(T-helper cell)22（Th22）、Th17和Th1细胞表达,部分自然杀伤细胞（NK细胞）、γδT（T细胞受体的一种）细胞和淋巴组织可诱导（LTi）细胞也可表达。结核性胸腔积液和恶性胸腔积液中都存在显著升高的IL-22,主要来源于受趋化因子作用募集于胸膜腔的外周血CD4⁺ T淋巴细胞和胸膜腔局部在IL-6、IL-23、IL-1β和肿瘤坏死因子-α（TNF-α）等细胞因子作用下分化而来的CD4⁺ T细胞。在胸膜腔中,IL-22通过促进基质金属蛋白酶（matrix metalloproteinases,MMPs）的表达发挥免疫病理作用,并通过介导NK细胞产生溶解因子减少寄生于单核细胞来源的巨噬细胞内的结核分枝杆菌生长。在恶性胸腔积液中,IL-22可通过促进肿瘤细胞增殖、迁移,并且通过增加黏附分子的表达促进与胸膜间皮细胞（pleural mesothelial cells,PMCs）的黏附发挥作用。研究IL-22在上述两种疾病中的作用机制,将会为免疫诊断与治疗开辟新的途径。