Pleuroperitoneal shunt for malignant pleural effusions

The malignant pleural effusion was introduced into the abdominal cavity by the manual compression of a pleuroperitoneal shunt tube, which was indwelt in the subcutaneous tissue of the lateral chest under local anesthesia. Seven patients having malignant pleural effusion, due to lung cancer in 4 and breast cancer in 3, were used as subjects. This technique caused no serious complications. Retention of pleural effusion was markedly reduced in all of the 7 patients. Three patients, whose performance status (P.S.) was preoperatively determined to be 3 or 2, could be discharged during early periods. This technique seemed to be highly feasible in these patients, but not in those having P.S. of 4. Since peritoneal dissemination of the tumor was seen in 1 of 3 patients examined by autopsy, there is a possibility that this technique might have contributed to spread and scattering of tumor cells in the peritoneal cavity. These results suggested that this technique is useful therapeutic means for the treatment of patients in whom hospitalization is necessary due to the presence of malignant pleural effusion, while this technique involves the risk of artificial induction of peritoneal dissemination of tumor cells. Therefore, the application of this technique should be decided based on the prognosis of each patient.     

Interferon instillation for malignant pleural effusions

BACKGROUND: Malignant pleural effusions can be managed in various ways includinginstillation of antineoplastic agents. Instillations of alfainterferon-2b (IFN-     

Optimal therapy of malignant pleural effusions

A randomized phase III trial of bleomycin, tetracycline and talc following chest tube drainage and a meta-analysis of relative benefit of bleomycin and tetracycline as sclerosing agents were performed to determine the optimal approach to malignant pleural effusion (MPE). Fifty patients were randomized to receive bleomycin (n=16), tetracycline (n=19) or talc (n=16) following chest tube drainage. Treatment groups were balanced for pretreatment characteristics. The study was ended prematurely because of the removal of parenteral tetracycline from the market. Overall, 52% of randomized patients had successful control of effusion 30 days after sclerosis. There were no differences between any of the three treatment groups in terms of 30 day control of effusion, overall survival (6 months), resclerosis rate, pain with sclerosis, fever, or duration of hospitalization (6 days). A meta-analysis was performed using the four previously reported trials of tetracycline vs. bleomycin and revealed a 20.6% advantage to the use of bleomycin (95% C.I. 7.9%-33.3%) (p=0.002). This phase III failed to demonstrate a significant difference between the three agents in terms of control of MPE at 30 days, side effects or survival. However, because of small sample size, this study lacks sufficient power to observe potentially clinically important differences between treatment groups. Inclusion of data from four previous trials in a meta-analysis showed that bleomycin may be superior. The median duration of hospitalization and the overall success rate of all three sclerosing agents in this study argue convincingly that new approaches to palliate MPE are needed.     

良恶性胸腔积液的鉴别诊断

胸腔积液是一个常见的临床表现,其良恶性的判断治疗和与预后密切相关.许多方法和指标都曾尝试用于恶性胸腔积液的诊断,各有利弊.随着分子生物学和实验技术的迅速发展,新的诊断指标和检测方法不断涌现.本文综述了近年来相关的临床研究结果,对各种诊断方法进行了客观评价.     

胸腔积液VEGF和Endostatin检测的鉴别诊断价值

目的:探讨血管内皮生长因子(VEGF)和Endostatin联合检测在肺癌患者胸腔积液中的诊断价值.方法:采用ELISA方法检测70例肺癌和46例结核性胸膜炎并胸腔积液患者胸腔积液中VEGF和Endostatin表达水平,同时采用电化学发光法测定CEA、CYFRA211和NSE表达水平.结果:肺癌胸腔积液中VEGF和Endostatin表达水平明显高于结核性胸膜炎组,差异有统计学意义,P<0.01.VEGF在诊断恶性胸腔积液中的灵敏度、特异性和准确率分别为74.28%、67.39%和71.55%;Endostatin的评价指标分别为70.00%、82.61%和75.00%;而VEGF和Endostatin联合检测时各项评价指标均有很大提高,分别为82.86%、95.65%和87.93%.结论:胸腔积液中VEGF和Endostatin水平的增高有助于恶性胸腔积液的诊断,两者联合检测能提高灵敏度、特异性和准确性.     

Small bore catheter drainage and sclerotherapy for malignant pleural effusions

The accumulation of large amounts of fluid in the pleural space is a common sequela of disseminated carcinomatosis. Traditional management has included therapeutic thoracentesis or the placement of a large bore chest tube for drainage with the subsequent installation of a sclerosing agent in an attempt to achieve pleural symphysis. An evaluation of all patients treated in this manner during a 4-year period was undertaken to assess the degree of success obtained with a large bore standard chest tube versus a small pigtail catheter. A study group consisting of 20 patients with a total of 24 pleural effusions was treated with drainage and sclerotherapy. In this group, eight of 13 effusions were adequately treated with pigtail catheter drainage and sclerotherapy, compared with four of 11 effusions adequately treated with standard chest tube drainage and sclerotherapy. Although the numbers are small, it appears that pigtail catheter drainage and sclerosis is at least as successful as the more traditional drainage with the standard chest tube.     

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.     

Management of recurrent malignant pleural effusions with a chronic indwelling pleural catheter

Many patients with various forms of cancer develop sooner or later malignant pleural effusions, resulting in feelings of discomfort and reduced quality of life. Several palliative options exist, including repeated thoracocentesis and pleurodesis with a sclerosing agent. However, these "therapeutic" possibilities are not always successful and sometimes even contraindicated. Also, patients need to visit the hospital regularly or have to stay hospitalised for several days. A chronic indwelling pleural catheter could provide a simple, completely outpatient way to provide respiratory relief and improvement in quality of life in patients with malignant pleural effusions. We evaluated retrospectively the course of 17 patients with malignant pleural effusions who were treated with a chronic indwelling pleural catheter (PleurX). Eligible patients were selected in the years 2001-2003 from a single institution. In 70-80% of patients, catheter use was uncomplicated and provided significant symptom relief. Mean duration of catheter use was 2.3 (range 1-6) months. Mean fluid removal was 360 (range 150-1000 cc) per 24 h in the first weeks of treatment. Infection was seen in two (12%) patients, dislocation of the catheter in three (18%). In the final analysis, catheter use was unsatisfactory in two patients (12%). We conclude that a chronic indwelling catheter is a very useful tool in the management of recurrent malignant pleural effusions. Treatment can be accomplished completely at home, whereas complications are rare.     

三种临床治疗恶性胸腔积液方案的成本-效果分析

目的:探索不同药物治疗恶性胸腔积液的成本一效果比。方法:96例中量以上的恶性胸腔积液患者(男性62例,女性34例,平均年龄为56·8岁)分为3组,胸液引流后分别予博莱霉素、天地欣、沙培林腔内注射治疗,并运用临床经济学的成本一效果分析进行评价。结果:在3种药物治疗方案中,博莱霉素组有效率为56·25%,1个疗程该药物费用为924·80元,有效率每增加1个百分点,成本为16·44元;天地欣组有效率为66·67%,1个疗程该药物费用为1108·00元,有效率每增加1个百分点,成本为16·62元:沙培林组有效率为76·47%,1个疗程该药物费用为2354·12元,有效率每增加1个百分点,成本为30·78元。结论:不同药物适合不同经济状况的患者。     

Pharmacokinetics of intrapleural cisplatin for the treatment of malignant pleural effusions

We determined the toxicity and pharmacokinetics of high-dose intrapleural cisplatin (CDDP) as a treatment of malignant pleural effusions (MPE). Fourteen patients with MPE were enrolled in this study. After complete drainage of the fluid, a catheter was inserted into the pleural cavity during a thoracoscopy. CDDP (300 mg) was administered via the catheter in a 6-h infusion. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 6, and 24 h as well as 4, 14, and 21 days after intrapleural administration. The dosage of CDDP ranged from 153 to 203 mg/m2. The time interval between infusion was prolonged until a maximum of 109 days. Only 7/40 infusions were associated with adverse effects in 4 patients (18%). Residual concentrations in pleural fluid (0.66+/-0.07 microgram /ml) were three-fold higher than in plasma (0.13+/-0.07 microgram/ml). In pleural fluid, maximal concentration (Cmax) varied from 19 to 900 microgram/ml and in plasma from 0.34 to 3.65 microgram/ml. AUC in plasma during the three courses was 112+/-49 microgram/ml/d. The T1/2 was 31+/-33 days higher than that previously reported after intravenous administration (8-15 days). Although intrapleural CDDP has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion with a good tolerance, it cannot be recommended for the standard control of malignant pleural effusion. Indeed we observed a great variability of intrapleural CDDP concentration depending on the extent of pleural invasion and plasma diffusion. Further studies are needed to determine the value of high-dose intrapleural CDDP for the treatment of MPE.     

Immunosuppressive mechanisms in the microenvironment of malignant pleural effusions

Malignant effusions in serous cavities constitute a unique milieu for direct contact of tumor cells with host lymphoid cells in a fluid phase. The aim of this study was to depict agents responsible for suppression of lymphoid cells with putative anti-tumor potential. Pleural effusions drawn from 44 (18 non-malignant and 26 malignant) patients were tested for selected cytokines--interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1) and soluble Fas ligand (sFasL) and nuclear membrane proteins (NMPs) content by ELISA. TCR-zeta expression of T cells and TUNEL reaction for apoptosis were evaluated by three color flow cytometry. Both cytokine concentrations were found to be significantly elevated in malignant pleural effusions (MPE) as compared to non-malignant ones. It was also true for sFasL content. Moreover, NMPs corresponding to decoy cell fragments, were also heightened in MPE. Concentrations of NMPs correlated with the percent of apoptotic (TUNEL+) T CD3+ lymphocytes and inversely correlated with the percent of T cells. The low expression of TCR-zeta chain on T cells corresponded to high concentration of sFasL in MPE. In conclusion, the above data suggest that out of three suppression agents tested, only sFasL appears to show correlation with the downregulation of T cells in MPE.     

Vincristine (Vinca-alkaloid) as a sclerosing agent for malignant pleural effusions

Vincristine, extracted from Vinca rosea Linn., is an effective antineoplastic chemotherapeutic drug used in oncology practice. This drug has never been used as a sclerosing agent for the treatment of malignant pleural effusion for reasons unknown. A study was conducted to examine the use of Vinca-Alkaloid as a sclerosing agent (pleurodesis) for the palliative treatment of malignant pleural effusions. The study included 15 patients, all diagnosed to have cytology-proven malignant pleural effusions. Intercostal tube drainage followed by chemical sclerotherapy with 2 mg vincristine was performed on all patients and a high success rate was noted. Twelve procedures out of 15 (12/15) achieved complete resolution of pleural fluid with a success rate of 80%. In two procedures the pleural effusion was reduced and then recurred but did not require re-aspiration. One procedure failed and repeated pleural aspiration was required. In this study, with adequate pleural drainage and the proper technique, vincristine was found to be an effective sclerosing agent for malignant pleural effusion. Further randomized trials are necessary in order to establish the role of this drug.     

Tetracycline pleurodesis for malignant pleural effusions. A 10-year retrospective study

We retrospectively examined the use of tetracycline pleurodesis for the palliative treatment of malignant pleural effusions. Twenty-five patients (32 procedures) were identified for study. In contrast to higher success rates in prior reports, 13 procedures (40.6%) failed as repeated pleural drainage was required. Only five procedures (15.6%) achieved complete resolution of pleural fluid. In 14 procedures (43.8%) pleural effusions recurred but were not treated. In some of these cases the effusion may have been reduced sufficiently to relieve symptoms, while in others the high short-term mortality rate (29% in 30 days) and the development of loculated effusions (34%) may have led to the decision not to treat. Instillation of a larger dose of tetracycline (greater than or equal to 1 g) was associated with a better outcome. Although adequate pleural drainage and proper technique were used, other factors such as the presence of pleural masses, atelectasis, loculations, and patient performance status were not uniformly controlled. Greater attention to these factors and use of a larger dose of tetracycline (greater than or equal to 1 g) may increase the likelihood of a successful pleural symphysis.     

Evaluation of inflammatory cytokines in malignant and benign pleural effusions

We measured the levels of inflammatory cytokines interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and serum in 65 consecutive patients: 32 with malignant pleural effusion (MPE) (group A), and 33 with inflammatory benign pleural effusion (BPE) (group B). Serum levels of 15 healthy individuals served as control. Concentrations of IL-1alpha were higher in serum compared to pleural fluid in both groups (47.1+/-33.9 vs. 25.9+/-1.7 fmol/ml, p<0.001, in group A; and 39.9+/-30.9 vs. 25.4+/-16.3 fmol/ml, p<0.02, in group B). Similarly, concentrations of IL-1beta and IL-2 were significantly higher in serum compared to pleural fluid in both groups. In contrast, IL-6, IL-8 and TNF-alpha were found at high concentration in MPE in comparison to serum IL-6: 171.8+/-60.4 vs. 7. 2+/-7 fmol/ml (p<0.001), IL-8: 1175.15+/-2385.6 vs. 285.2+/-187.2 pg/ml (p<0.05), TNF-alpha: 204.9+/-82.9 vs. 79.4+/-31.9 fmol/ml (p<0. 001). Similarly, pleural concentrations of IL-6, IL-8 and TNF-alpha were higher in BPE patients in comparison to serum IL-6: 124.3+/-56. 2 vs. 8.6+/-6.4 fmol/ml (p<0.001) IL-8: 2109.2+/-4121.5 vs. 291. 6+/-197.9 pg/ml (p<0.02), TNF-alpha: 183.8+/-28.2 vs. 86.2+/-23.9 fmol/ml (p<0.001). These data suggest that IL-6, IL-8 and TNF-alpha might be secreted locally at the site of active disease both in benign and malignant pleural effusions.     

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.     

BCG treatment of malignant pleural effusions in the rat.

Intrapleurally injected cells of an ascitic rat tumour produced intrapleural effusions and solid pleural deposits. BCG, or its methanol extraction residue (MER) injected into the pleural space, suppressed tumour development and prolonged survival. Treatment was effective if given a few days before or after tumour injection. In contrast, active specific immunotherapy by repeated s.c. injection of viable or radiation-attenuated tumour cells in admixture with BCG was unsuccessful, and did not improve the response to intrapleural BCG treatment.