A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions

BACKGROUND: The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). METHODS: In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. RESULTS: The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. CONCLUSIONS: A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis.     

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。     

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。     

Home-management of malignant pleural effusion with an indwelling pleural catheter: Ten years experience

Background

More than one half of patients with cancer have a malignant pleural effusion (MPE) at some time during their life span. Recurrent malignant pleural effusions impair respiratory functions and worsen the quality of life. Once a patient develops MPE, only fluid drainage relieves pulmonary compression and dyspnea. Optimal treatment is however, still controversial. In patients not suitable for pleurodesis, or with recurrent MPE after pleurodesis, or with trapped lung, the outpatient intermittent drainage through a subcutaneous tunneled indwelling pleural catheter (IPC) is a possible choice.

Methods

In ten years, we treated 90 patients by outpatient insertion of IPC. Eligibility for IPC required previous thoracentesis with histological confirmation of malignancy and chest roentgenogram evidence of effusion. All patients treated were made aware of their malignancy and positive cytology in the pleural effusion.

Results

Mean survival was 197 days (range 23–296 days). Median time of draining interval was 7.0 days with maximum amount of effusion drained off being 1000 ml. Pleurodesis occurred in 37 (41.1%) patients with a mean time of pleurodesis of 51 days (range 34–78 days). No major complication was recorded.

Conclusions

The IPC is a useful device in the management of recurrent MPE. Treatment can be entirely accomplished at home and the complication rate is low.     

微创中心静脉导管留置治疗恶性胸腔积液34例观察

目的 观察利用微创中心静脉导管留置胸腔在恶性胸腔积液的诊断和治疗中的作用.方法 2002年～2003年2月在外院内科治疗的大量或中等恶性胸腔积液的患者34例,利用微创技术应用美国ARROW公司中心静脉导管留置胸腔抽取胸液脱落细胞学检查,待结果阳性,给予胸腔注药,顺铂50mg～80mg,力尔凡100mg或胞必佳1 000u,地塞米松10mg,注药结束后,给予止吐药静点或静推,观察疗效及并发症.另选30例恶性胸腔积液患者常规穿刺、注药治疗为对照组,在疾病、病期、治疗药物方面与治疗组一致,没有分组差异,疗效分析采用χ2检验,平均确诊时间采用t检验.结果 在治疗效果中,治疗组CR 9例、PR 19例,有效率达82.35%,对照组CR 2例、PR 11例,有效率为40.33%,χ2＝10.539,P＜0.01.确诊时间治疗组1～8天,平均5.0天;对照组1～24天,平均14.5天,t＝8.7,P＜0.05.具有显著差异.无严重并发症.结论 利用微创技术采用中心静脉导管留置胸腔在诊断和治疗恶性胸腔积液方面具有优势,值得临床推广.     

Long-term indwelling pleural catheter (PleurX) for malignant pleural effusion unsuitable for talc pleurodesis

Aims

Talc pleurodesis using talc slurry via chest tube is a primary option in malignant pleural effusion, since life expectancy is short and surgical decortication is hazardous. Incomplete lung expansion after fluid evacuation, and/or excessive fluid secretion predicts failure of pleurodesis. A mini-invasive alternative was investigated.

Methods

Between March 2004 and September 2005, 51 consecutive patients with malignant pleural effusion, and clinically considered unsuitable for talc pleurodesis, received an indwelling pleural catheter (Denver PleurX). In 47, implantation was done bedside using local anaesthesia. There were 24 men and 27 women, median age 63 (range 36–85) years, receiving 39 right side, 10 left side, and 2 bilateral catheters. There were 19 non-small cell lung cancer cases, 7 mesothelioma, and 25 with other malignancy. Chemotherapy was being given to 18 patients and was not interrupted.

Results

Discharge to home was possible in 71% (36 of 71 patients) on the following day. At 2 years follow-up in September 2007, one patient was alive. Mean survival was 3 months (range 5 days to 37+ months) for all patients, with best median survivals of 5.5–6 months in breast and ovarian cancer. Catheter was removed or replaced in 15% (8 of 51 patients) due to infection, air leak, or blockage. One patient requested decortication for excessive fluid secretion. None required surgery or died due to catheter-related complications. Pleural fusion with subsequent catheter removal was achieved in 21% (11 of 51 patients).

Conclusions

An indwelling pleural catheter is a safe alternative for patients with malignant pleural effusion unsuitable for talc pleurodesis. In some, pleural fusion may be achieved.     

Multidisciplinary management of malignant pleural effusion

Approximately 50% of patients with metastatic disease develop a malignant pleural effusion (MPE). Prompt clinical evaluation and treatment to achieve successful palliation are the main goals of management of MPE. Optimal treatment is still controversial and there is no universal standard approach. Management options include observation, thoracentesis, indwelling pleural catheter (IPC) or chest tube placement, pleurodesis, and surgical pleurectomy. The treatment for each patient should be based on symptoms, general condition, and life expectancy.     

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions.

CYFRA 21-1 assay, measuring cytokeratin 19 fragments, was compared with carcinoembryonic antigen (CEA) assay, as an addition to cytological analysis for the diagnosis of malignant effusions. Both markers were determined with commercial enzyme immunoassays in pleural fluid from 196 patients. Cytological analysis and/or pleural biopsy confirmed the malignant origin of the effusion in 99 patients (76 carcinomas, nine pleural mesotheliomas and 14 non-epithelial malignancies). Effusions were confirmed as benign in 97 patients (33 cardiac failures, 39 infectious diseases--including 12 tuberculosis-- and 25 miscellaneous effusions). Both markers were significantly higher in malignant than in benign effusions. All the patients with non-epithelial malignancies presented CYFRA and CEA values lower than the 95% diagnostic specificity thresholds (100 and 6 ng ml(-1) respectively). The diagnostic sensitivity in the group of carcinomas and mesotheliomas was similar for CYFRA (58.8%) and CEA (64.7%). However, CEA had a significantly higher sensitivity in carcinomas (72.4% vs 55.3%), while CYFRA had a clearly higher sensitivity in mesotheliomas (89.9% vs 0%). Interestingly, 12 out of the 16 malignant effusions with a negative cytology were CEA and/or CYFRA positive. Regarding their high diagnostic sensitivity and their complementarity, CEA and CYFRA appear to be very useful for the diagnosis of malignant pleural effusions when cytology is negative.     

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.     

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。     

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 evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.     

Ratios of pleural fluid to serum immunoglobulins in malignant pleural effusions

Pleural fluid and serum protein electrophoresis and quantitative immunoglobulin measurements were carried out in patients with pleural effusions. The mean pleural fluid/serum ratios of IgA, IgG, and IgM were elevated in patients with malignant pleural effusions compared with patients with nonmalignant pleural effusions (P less than 0.04). The sensitivity of a pleural/serum IgA, IgG ratio P greater than 0.6 was 46%, 69%, respectively, and for IgM ratio greater than 0.5 was 28%. The specificity for these same ratios was 89%, 74%, and 100% respectively.     

Antibody-guided irradiation of malignant pleural and pericardial effusions

Tumour-associated monoclonal antibodies (HMFG1, HMFG2 and AUA1) radiolabelled with iodine-131 were given intracavitary (intrapleurally and intrapericardially) to patients with malignant effusions. Ten out of 13 effusions (3 pericardial and 7 pleural) responded completely with no fluid reaccumulation between 3 and 18 months. No clinical or other toxicity was observed. This new method of treatment for recurrent malignant effusions is non-toxic and effective resulting in improved quality of life, and, in some cases, prolongation of survival.     

Diagnostic value of ferritin in malignant pleural and peritoneal effusions

The diagnostic usefulness of ferritin measurements in pleural and peritoneal effusions has been evaluated in 57 patients. Mean (+/- standard error [SE]) ferritin levels were 291 +/- 50 ng/ml in 24 patients with noninflammatory transudates (Group I), 942 +/- 253 in 15 patients with nonmalignant exudates (Group II), and 1805 +/- 257 in 18 patients with malignant exudates (Group III). The mean (+/- SE) ratio of effusion/serum ferritin in Groups I, II, and III was 0.7 +/- 0.1, 2.7 +/- 0.7, and 5.7 +/- 1.2, respectively. The specificity and predictive value of a ferritin ratio in excess of 1.5 in distinguishing transudates from all exudates and in distinguishing transudates from malignant exudates were both very high (94%) to 96%). In the lower range of values considerable overlap existed between ferritin ratios obtained in patients with benign versus malignant inflammatory exudates. However, very high ferritin levels (greater than 3000 ng/ml) and ferritin ratios (greater than 20:1) were only encountered in malignant exudates. These results indicate that the measurement of ferritin levels and ferritin ratios may be a useful aid in the diagnosis of malignant pleural and peritoneal effusions.     

Tissue polypeptide antigen (TPA) in pleural effusions

The usefulness of tumor marker assay in pleural effusions for differential diagnosis is still debated. From the observation of common antigens on tissue polypeptide antigen (TPA) and keratins 8, 18 and 19 and vimentin, all substances contained in normal and neoplastic mesothelium, we felt it opportune to evaluate the use of TPA assay in 105 pleural effusions (46 benign and 59 malignant). The values were much higher than those found in blood. In hydrothorax the median value was 454 U/l (range, 59-1923), in exudative effusions 846 U/l (range, 258-4485), in metastatic pleural effusions 1277 U/l (range, 58-32352) and in mesotheliomas 7705 (range, 759-16000). The maximum value found in nonmalignant effusions was 4485 U/l; this value was taken as a cutoff level, so only 29.9% of the tumors were positive to the test. Our results showed this assay to be not very important for a differential diagnosis of malignant and nonmalignant pleural effusions. Nevertheless, the different TPA patterns in mesotheliomas (66.6% positive) and metastatic pleural effusions (15.9%) suggest that further studies are warranted.     

Malignant pleural effusions: meaning of pleural-fluid pH determination

In 36 patients with malignant pleural effusions, we determined the pH and the glucose concentration of the pleural fluid. Twenty-one of 36 patients (58.3%) had a low pH (less than 7.30) and 15 had a normal pH (greater than or equal to 7.30; 7.13 +/- 0.12 vs. 7.37 +/- 0.05; p less than 0.0005). The patients with low pH had significantly lower glucose concentrations than those with normal pH (2.7 +/- 1.4 vs. 6.3 +/- 2.9 mmol/l; p less than 0.0005). Twenty-one of 34 patients (61.7%) had a glucose concentration lower than a cut-off value of 4.4 mmol/l; of these, 17 (81%) had a low pH. The mean survival in the low-pH group was 4.8 +/- 4.4 months, whereas the mean survival in the normal-pH group was 5 +/- 8 months (p greater than 0.4). Twelve of 36 patients (33.3%) were treated with intrapleural Corynebacterium parvum (CBP) injections. Fourteen of 21 low-pH patients (66.6%) survived more than 2 months, and 4 of them are still alive. Six of 15 normal-pH patients (40%) survived more than 2 months, and 1 of them is still alive. Three of the 5 living patients were treated with CBP (2 in the low-pH group and 1 in the normal-pH groups). Our results confirm that pH and glucose concentrations in the pleural fluid of patients with malignant effusions are frequently low. However, the survival and the response to CBP pleurodesis in patients with low-pH malignant effusions are the same as those in patients with normal-pH malignant effusions.     

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.     

冀东满族肺腺癌患者胸液与相应肿瘤组织EGFR基因突变检测对比分析

目的:分析冀东满族肺腺癌患者胸液与相应肿瘤组织EGFR基因突变检测结果。方法:选取2010年9月至2014年9月间在我院胸外科治疗的74例有胸液的冀东满族肺腺癌患者为研究对象,采用变性高效液相色谱法(DHPLC)检测肺腺癌患者胸液及相应肿瘤组织样本中是否发生EGFR基因突变。结果:肿瘤组织EFGR基因突变检出率为50.00%,胸液样本EGFR基因突变检出率为52.70%,两者间无统计学差异(P＞0.05)。胸液上清、胸液沉淀、胸液上清与沉淀以及肿瘤组织EGFR基因检测结果一致性均良好。结论:肺腺癌患者胸液与相应肿瘤组织EGFR基因突变检测结果一致性良好,临床可通过胸液检测代替肿瘤组织检测,以期能够持续监测患者EGFR基因突变状态,以指导患者添加或者实施EGFR-TKIs治疗。     

治疗用粘质沙雷氏菌菌苗（S511）治疗癌性胸腔积液的Ⅱ期临床研究

目的 评价S311治疗癌性腔积液的疗效及毒副作用。方法 经胸穿或闭式引流抽净胸水后,胸腔注入S311 0.32mg,每周1次,连续3周,停药手观察1个月评价疗效。结果 241例患者完成胸腔注入S311治疗,总有效率92．1％,主要的不良反应为发热和胸痛,发生率分别为81．0％和52．2％,少数患者出现寒战,呼吸困难,恶心,呕吐,个别患者出现肝功能异常。结论 粘质沙雷氏菌菌苗（S311）是一种治疗癌性胸腔积液的有效药物。