Kaifi JT, Toth JW, Gusani NJ, Kimchi ET, Staveley-O'Carroll KF, Belani CP, Reed MF.
Multidisciplinary management of malignant pleural effusion.
J Surg Oncol. 2012 Jun 1;105(7):731-8. doi: 10.1002/jso.22100. Epub 2011 Sep 29.
Abstract/Text
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.
Copyright © 2011 Wiley Periodicals, Inc.
American Thoracic Society.
Management of malignant pleural effusions.
Am J Respir Crit Care Med. 2000 Nov;162(5):1987-2001. doi: 10.1164/ajrccm.162.5.ats8-00.
Abstract/Text
Garcia LW, Ducatman BS, Wang HH.
The value of multiple fluid specimens in the cytological diagnosis of malignancy.
Mod Pathol. 1994 Aug;7(6):665-8.
Abstract/Text
Multiple fluid specimens of a patient are often received in the cytology laboratory. Both clinicians and pathologists question the optimal number of specimens required to detect a malignancy. We reviewed the computerized cytology files at Boston's Beth Israel Hospital from 1988 to 1991 to identify patients with two or more specimens from the same anatomic site. Two hundred and fifteen patients with a total of 570 specimens were identified. Before December 19, 1990, two direct smears were examined per fluid sample. After December 19, 1990, two direct smears and two cytospin preparations were examined. Medical records of patients without a positive diagnosis of cytology were reviewed. Overall, a cytological diagnosis of malignancy was made on at least one specimen for 55 patients (26%). The first positive diagnosis was made on the initial specimen in 36 patients (65%), on the second in 15 patients (27%), the third in three patients (5%), and the fifth in one patient (2%). For those specimens prepared with the two techniques described above (two direct and two concentrated smears), the first positive diagnosis was made on the initial specimen in 89% of the cases. Medical record review uncovered 55 additional patients who had clinical evidence of malignancy. Of these, 22 (40%) had at least one suspicious diagnosis of their fluid specimens. The first suspicious diagnosis was made with three or fewer specimens in all 22 patients. The majority of malignant effusions are detected with two specimens. Examination of more than three specimens is of little value. Multiple preparatory, especially concentration, techniques may increase the probability of detecting malignancy in one specimen.
Welker L, Müller M, Holz O, Vollmer E, Magnussen H, Jörres RA.
Cytological diagnosis of malignant mesothelioma--improvement by additional analysis of hyaluronic acid in pleural effusions.
Virchows Arch. 2007 Apr;450(4):455-61. doi: 10.1007/s00428-007-0375-x. Epub 2007 Feb 15.
Abstract/Text
Cytology allows the diagnosis of malignant mesothelioma (MM) from effusions with high specificity but low sensitivity. Conversely, elevated levels of hyaluronic acid (HA) in effusions are sensitive indicators of MM, although specificity is insufficient. We studied whether the cytological diagnosis of MM could be improved by HA analysis. HA was analysed in patients with histologically confirmed MM (n=162), adenocarcinoma or other malignant tumours (n=100) and in 90 patients with benign pleural diseases. In 77 out of 162 effusions, all, and in 33 some, cytological criteria of MM were satisfied. The cut-off value of HA showing maximum diagnostic reliability (86%) regarding MM was 30 mg/l (sensitivity 87%, specificity 86%). A HA value of 100 mg/l yielded 39 and 98%, respectively. Seventy three out of 77 patients with cytological findings indicative of MM showed HA levels greater than 30 mg/l as well as 27 of 33 patients with suspicious lesions. These 100 patients were correctly recognised as having MM. The addition of HA analysis to cytology, requiring all or some criteria of MM as positive, increased sensitivity for MM from 48 to 71-91%, whereas specificity only slightly decreased to 94-96%. We conclude that the combined cytological and HA analysis of pleural effusions had the potential to improve the diagnosis of MM.
Pettersson T, Fröseth B, Riska H, Klockars M.
Concentration of hyaluronic acid in pleural fluid as a diagnostic aid for malignant mesothelioma.
Chest. 1988 Nov;94(5):1037-9. doi: 10.1378/chest.94.5.1037.
Abstract/Text
Hyaluronic acid (HA) was determined with a radiometric assay in the serum and pleural fluid of 85 patients with pleural effusions, including 15 with malignant mesothelioma, 32 with other cancer, 31 with nonmalignant inflammatory diseases, and seven with congestive heart failure. With a cutoff level at 100 mg/L, the pleural fluid concentration of HA was raised in 73 percent of patients (11 of 15) with malignant mesothelioma and in 23 percent with nonmalignant inflammatory diseases, but in none with other cancer and in none with congestive heart failure. The median concentration of pleural fluid HA was significantly higher in patients with mesothelioma than in those with other cancer (p less than 0.005). Determination of carcinoembryonic antigen (CEA) in pleural fluid further helped to differentiate between mesothelioma and other types of cancer; concentrations of CEA above 10 micrograms/L were found in four of 15 (27 percent) patients with mesothelioma, but in 38 percent of the patients with other cancer. We concluded that in the differential diagnosis of pleural effusions associated with malignant tumors a high concentration of HA in pleural fluid combined with a low concentration of CEA suggests malignant mesothelioma as opposed to other types of cancer.
Lee JH, Chang JH.
Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer.
Chest. 2005 Oct;128(4):2298-303. doi: 10.1378/chest.128.4.2298.
Abstract/Text
STUDY OBJECTIVES: To assess the diagnostic values of carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments (CYFRA 21-1) as markers of pleurisy in primary lung cancer.
DESIGN: Prospective case-control study.
SETTING: A tertiary university hospital.
PATIENTS: Thirty-four patients with lung cancer and 16 patients with tuberculous pleurisy.
MEASUREMENTS AND RESULTS: Levels of CEA, NSE, and CYFRA 21-1 were measured by immunoassay in the serum and pleural fluid of patients with lung cancer and of patients with tuberculous pleurisy. Patients with lung cancer were found to have significantly higher serum and pleural fluid levels of CEA and CYFRA 21-1 than patients with tuberculous pleurisy. Using cutoff values of 5 ng/mL, 20 ng/mL, and 3.3 ng/mL for serum CEA, NSE, and CYFRA 21-1, respectively, the sensitivities and specificities of these tumor markers were as follows for differentiating malignant effusion from benign: CEA, 68% and 93%; NSE, 34% and 93%; and CYFRA 21-1, 45% and 100%. Using cutoff values of 5 ng/mL, 20 ng/mL, and 45 ng/mL for pleural fluid, the sensitivities and specificities were as follows: CEA, 82% and 94%; NSE, 36% and 94%; and CYFRA 21-1, 61% and 81%. A combination of pleural fluid CEA and NSE increased sensitivity and specificity.
CONCLUSIONS: In the diagnosis of malignant effusion associated with lung cancer, the determinations of CEA and NSE in pleural fluid could enhance diagnostic yield better than those of all three tumor markers.
Shitrit D, Zingerman B, Shitrit AB, Shlomi D, Kramer MR.
Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature.
Oncologist. 2005 Aug;10(7):501-7. doi: 10.1634/theoncologist.10-7-501.
Abstract/Text
Levels of tumor markers in pleural effusions may help to establish the diagnosis of pleural malignancy, but the precise diagnostic value of each marker remains unclear. The aim of this study was to assess the diagnostic value of five common pleural fluid tumor markers, carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, cancer antigen (CA) 15-3, CA 19-9, and CA 125, and to review the literature from the past 15 years. Pleural fluid samples were collected prospectively from 116 patients and assayed for CEA, CYFRA 21-1, CA 15-3, CA 19-9, and CA 125 levels. A MEDLINE search of the English-language literature from the past 15 years was also done. Effusions were classified as benign or malignant on the basis of their definitive pathologic or cytologic diagnoses. The levels of all pleural tumor markers were statistically significantly higher in the malignant group than in the benign group. The marker with the highest accuracy was CEA (85.3%); CA 15-3, CYFRA 21-1, and CA 19-9 had similar accuracies (75.2%, 72.4%, and 71.5%, respectively), and CA 125 had the lowest accuracy (40.5%). On univariate analysis, tumor-marker combinations did not result in a greater accuracy than that of CEA alone. On multivariate logistic regression, CA 15-3 and CYFRA 21-1 were significant predictors of malignancy. Among the nine reports in the literature comparing 11 different tumor markers, CEA, CA 15-3, and CYFRA 21-1 yielded the best results. We conclude that pleural fluid analysis should include CEA for the diagnosis of malignancy. CA 15-3 and CYFRA 21-1 may serve as alternative options.
Dekker A, Bupp PA.
Cytology of serous effusions. An investigation into the usefulness of cell blocks versus smears.
Am J Clin Pathol. 1978 Dec;70(6):855-60. doi: 10.1093/ajcp/70.6.855.
Abstract/Text
Approximately half of 351 body-cavity effusions from 263 patients were examined prospectively in paraffin-embedded cell blocks and in smears, while the other half were examined in smears alone. The number of suspect and positive fluids obtained with the combined cell block-and-smear technic was double that of specimens examined in smears only. No false-positive case was found. Tumors were subsequently demonstrated in 38% of the patients who had negative or atypical cytologic reports. Smears stained with the Papanicolaou technic generally have good definition of malignant cellular changes, wheras cell blocks are particularly useful when the cytologic abnormalities are misleading, such as in reactive mesothelial cells, or obscure, as in occasional well-differentiated adenocarcinomas. It is recommended that both cell blocks and smears be used in evaluating all fluids submitted to the cytology laboratory.
Shivakumarswamy U, Arakeri SU, Karigowdar MH, Yelikar B.
Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology.
J Cytol. 2012 Jan;29(1):11-5. doi: 10.4103/0970-9371.93210.
Abstract/Text
BACKGROUND: The cytological examinations of serous effusions have been well-accepted, and a positive diagnosis is often considered as a definitive diagnosis. It helps in staging, prognosis and management of the patients in malignancies and also gives information about various inflammatory and non-inflammatory lesions. Diagnostic problems arise in everyday practice to differentiate reactive atypical mesothelial cells and malignant cells by the routine conventional smear (CS) method.
AIMS: To compare the morphological features of the CS method with those of the cell block (CB) method and also to assess the utility and sensitivity of the CB method in the cytodiagnosis of pleural effusions.
MATERIALS AND METHODS: The study was conducted in the cytology section of the Department of Pathology. Sixty pleural fluid samples were subjected to diagnostic evaluation for over a period of 20 months. Along with the conventional smears, cell blocks were prepared by using 10% alcohol-formalin as a fixative agent. Statistical analysis with the 'z test' was performed to identify the cellularity, using the CS and CB methods. Mc. Naemer's χ(2)test was used to identify the additional yield for malignancy by the CB method.
RESULTS: Cellularity and additional yield for malignancy was 15% more by the CB method.
CONCLUSIONS: The CB method provides high cellularity, better architectural patterns, morphological features and an additional yield of malignant cells, and thereby, increases the sensitivity of the cytodiagnosis when compared with the CS method.
Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr.
Pleural effusions: the diagnostic separation of transudates and exudates.
Ann Intern Med. 1972 Oct;77(4):507-13. doi: 10.7326/0003-4819-77-4-507.
Abstract/Text
Valdés L, Alvarez D, San José E, Penela P, Valle JM, García-Pazos JM, Suárez J, Pose A.
Tuberculous pleurisy: a study of 254 patients.
Arch Intern Med. 1998 Oct 12;158(18):2017-21. doi: 10.1001/archinte.158.18.2017.
Abstract/Text
OBJECTIVES: To determine the age at which tuberculous pleural effusions occur, the radiological and biochemical characteristics of the effusions, the sensitivities of the various diagnostic tests, and the utility of combining clinical, radiological, and analytic data in diagnosis.
METHODS: We studied the case histories of 254 patients in whom tuberculous pleural effusions were diagnosed with certainty between January 1, 1989, and June 30, 1997, in a Spanish university hospital in a region with a high incidence of tuberculosis.
RESULTS: The mean (+/-SD) age of the patients was 34.1+/-18.1 years, and 62.2% were younger than 35 years. The effusion was on the right side in 55.9% of patients, on the left side in 42.5% of patients, and on both sides in 1.6% of patients. In 81.5% of patients, less than two thirds of the hemithorax was affected. Associated pulmonary lesions were detected in 18.9% of patients, of whom 14.6% exhibited cavitation. In 93.3% of the effusions, more than 50% of leukocytes were lymphocytes, and almost all had the biologic characteristics of exudates (98.8% had high total protein contents, 94.9% had high cholesterol levels, and 82.3% had high lactate dehydrogenase levels). All but 1 effusion (99.6%) had an adenosine deaminase (ADA) concentration higher than 47 U/L, 96.8% (123/127) of the effusions had high ADA2 levels, and 89% (73/82) of the effusions had high interferon gamma levels. Adenosine deaminase 2 contributed 72.2%+/-12.5% (mean +/- SD) of total ADA activity. Total ADA activity was significantly correlated with ADA2 (r = 0.83) and with interferon gamma (r = 0.30) levels. Definitive diagnosis was based on the observation of caseous granulomas in pleural biopsy tissue samples in 79.8% of patients, on the results of biopsy cultures in 11.7% of patients, and on pleural effusion cultures in the remaining 8.5% of patients. Results of the tuberculin skin test were positive in only 66.5% of patients.
CONCLUSIONS: In these patients, lymphocyte-rich exudative pleural effusions occurred, on average, at a young age, with no preference for either the right or the left side; normally affected no more than two thirds of the hemithorax; and were generally unaccompanied by pulmonary infiltrates. High ADA concentration was a highly sensitive diagnostic sign and was caused by a rise in ADA2 concentration. The most sensitive criterion based on pleural biopsy was the observation of caseous granulomas, and culture of biopsy material further increased overall sensitivity. Negative skin test results were no guarantee of the effusion being nontuberculous. This, together with the low mean age of the patients and the low frequency of associated pulmonary lesions, suggests that tuberculous pleural effusion is a primary form of tuberculosis in this region.
Riantawan P, Chaowalit P, Wongsangiem M, Rojanaraweewong P.
Diagnostic value of pleural fluid adenosine deaminase in tuberculous pleuritis with reference to HIV coinfection and a Bayesian analysis.
Chest. 1999 Jul;116(1):97-103. doi: 10.1378/chest.116.1.97.
Abstract/Text
OBJECTIVES: To evaluate the diagnostic use of pleural fluid adenosine deaminase (ADAPF) levels in tuberculous pleuritis (TBpl), with a special reference to HIV coinfection and a Bayesian analysis.
METHODS: We investigated a total of 216 patients with pleural effusion, including 100 with TBpl, 68 with malignant effusion, 6 with transudates, 19 with empyema, 15 with miscellaneous diseases, and 8 with diseases of unknown etiology.
RESULTS: The mean values (SE) of ADAPF were 110 (4.5) U/L in patients with TBpl vs 28 (5.3) U/L in patients with a malignancy, 18 (5.7) U/L in patients with transudates, 13 (2.1) U/L in patients with diseases of unknown etiology, 22 (5.1) U/L in patients with miscellaneous diseases, and 191 (26.3) U/L in patients with empyema (Kruskal-Wallis test, p < 0.001). The ADAPF level was 110 (4.5) U/L in 37 HIV-positive patients with TBpl vs 114 (4.1) U/L in 52 HIV-negative patients with TBpl (Mann-Whitney U test, p > 0.05). A receiver operating characteristic curve identified the best cutoff at 60 U/L, yielding measures for sensitivity (0.95), specificity (0.96), positive predictive values (PPVs; 0.96), and negative predictive values (0.95). A Bayesian analysis showed a posttest probability of PPV ranging from 0.5 to 0.99, resulting from a pretest probability of 0.05 to 0.9.
CONCLUSIONS: ADAPF is diagnostically useful across the various prevalences of TBpl, and its best diagnostic utility is in areas of intermediate prevalence of the disease. Moreover, the diagnostic value of ADAPF is independent of HIV serologic status.
Valdés L, San José E, Alvarez D, Sarandeses A, Pose A, Chomón B, Alvarez-Dobaño JM, Salgueiro M, Rodríguez Suárez JR.
Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma.
Chest. 1993 Feb;103(2):458-65. doi: 10.1378/chest.103.2.458.
Abstract/Text
We compared the parameters pleural adenosine deaminase (PADA, determined in 405 patients), the PADA/serum ADA ratio (P/SADA; 276 cases), pleural lysozyme (PLYS, 276 cases), the PLYS/serum LYS ratio (P/SLYS; 276 cases), and pleural interferon gamma (IFN, 145 cases) regarding their ability to differentiate tuberculous pleural effusions from others. The 405 pleural effusions were classified by previously established criteria as tuberculous (91), neoplastic (110), parapneumonic (58), empyemas (10), transudates (88), or miscellaneous (48). The intermean differences between the tuberculous group and each of the others were statistically significant for all five parameters (p < 0.01 for PLYS and P/SLYS with respect to the empyema group; p < 0.001 otherwise), except for PADA and P/SADA with respect to the empyema group. All the tuberculous pleurisy cases had PADA values of 47 U/L or more, as compared to only 5 percent of the other cases (sensitivity, 100 percent; specificity, 95 percent). P/SADA was above 1.5 in 85.7 percent of tuberculous effusions and 11 percent of the others (sensitivity, 85.7 percent; specificity, 89 percent). PLYS, with a diagnostic threshold of 15 g/ml, had a sensitivity of 85.7 percent and a specificity of 61.6 percent; P/SLYS, with a threshold of 1.1, had a sensitivity of 67.3 percent and a specificity of 90.3 percent; and IFN, with a threshold of 140 pg/ml, had a sensitivity of 94.2 percent and a specificity of 91.8 percent. The lowest misclassification rate was achieved by PADA, with statistically significant differences (p < 0.001) with respect to P/SADA, PLYS, and P/SLYS, but not with respect to IFN. The only significant pairwise correlations among these parameters were between P/SLYS and PADA and between P/SLYS and P/SADA. We conclude that PADA and IFN are useful parameters for early diagnosis of tuberculous pleurisy, and that the other parameters considered have no advantages over PADA and IFN for this purpose (though the high specificity of P/SLYS may be noted).
Zarić B, Kuruc V, Milovančev A, Markovic M, Šarčev T, Čanak V, Pavlović S.
Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase?
Lung. 2008 Jul-Aug;186(4):233-240. doi: 10.1007/s00408-008-9085-7. Epub 2008 Mar 21.
Abstract/Text
The objective of this study was to evaluate the utility of invasive and noninvasive diagnostic procedures in tuberculous pleurisy (TPE) in an area with intermediate incidence of tuberculosis. The aim was to determine the cutoff value for adenosine deaminase (ADA) and the sensitivity and specificity of ADA and evaluate pleural fluid cytology and pleural biopsy in the differential diagnosis of malignant and tuberculous pleurisy. The study included 121 patients. TPE was confirmed in 54 patients and malignant effusion in 67 patients. Criteria used for TPE diagnosis were positive cultures of effusion or biopsy specimen, tuberculous granulomas, or positive sputum cultures without other explanation for pleural effusion. Malignancy was diagnosed by either cytology or biopsy. The cutoff value of ADA in TPE was 49 U/L, sensitivity was 89.2%, specificity was 70.4%, positive predictive value (PPV) was 84.4%, and negative predictive value (NPV) was 78.4%. ADA activity below 16 U/L suggests that TPE is highly unlikely with sensitivity=38.5%, specificity=100%, PPV=100%, and NPV=57.4%. ADA effusion/serum ratio reached a cutoff in TPE of 1.7 (sensitivity=84.6%, specificity=72.2%, PPV=81.4%, NPV=71.4%). Sensitivity, specificity, PPV, and NPV of cytology evaluation for TPE are 72.2%, 70.1%, 66.1%, and 75.8%, respectively. Pleuroscopy-guided pleural biopsy had sensitivity=66.7%, specificity=100%, PPV=100%, and NPV=78.8%. In 27.8% of TPE cases, pleural fluid cultures were positive. There is no doubt that pleuroscopy-guided biopsy is of great value for TPE diagnosis; however, sensitivity and specificity of noninvasive tests, especially ADA, can help to distinguish between TB and malignancy.
Light RW.
Pleural effusions.
Med Clin North Am. 2011 Nov;95(6):1055-70. doi: 10.1016/j.mcna.2011.08.005. Epub 2011 Sep 25.
Abstract/Text
There are many diseases that cause pleural effusions. When a patient with a pleural effusion is first evaluated, one should determine if the patient has a transudate or an exudate. A diagnostic approach to the patient with an undiagnosed pleural effusion is outlined. The most common pleural effusions including those caused by congestive heart failure, cirrhosis, pneumonia, malignancy, tuberculosis, lupus erythematosus, rheumatoid disease, and chylothorax are discussed.
Copyright © 2011 Elsevier Inc. All rights reserved.
DeCamp MM Jr, Mentzer SJ, Swanson SJ, Sugarbaker DJ.
Malignant effusive disease of the pleura and pericardium.
Chest. 1997 Oct;112(4 Suppl):291S-295S. doi: 10.1378/chest.112.4_supplement.291s.
Abstract/Text
Malignant pleural and pericardial effusions are a common problem in the treatment of patients with lung cancer, breast cancer, or lymphoma and may occur with any malignancy. These effusions are frequently symptomatic and, in the case of the pleural space, may be the presenting sign of cancer. In other patients, they represent markers of recurrent, disseminated, or advanced disease. Given the poor prognosis of most patients presenting with these effusions, reducing symptoms and improving quality of life are the primary goals of treatment. Permanent drainage and/or obliteration of the pleural or pericardial space are crucial to the effective management of the effusion and will provide long-term palliation. Immediate relief can be accomplished via external drainage, but definitive therapy may often also require interventional radiology, cardiology, and thoracic surgery, as well as medical and radiation oncology. The pathophysiology, diagnosis, and treatment of malignant pleural and pericardial effusions are discussed in this article.
Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ; BTS Pleural Disease Guideline Group.
Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010.
Thorax. 2010 Aug;65 Suppl 2:ii32-40. doi: 10.1136/thx.2010.136994.
Abstract/Text
Shaw P, Agarwal R.
Pleurodesis for malignant pleural effusions.
Cochrane Database Syst Rev. 2004;(1):CD002916. doi: 10.1002/14651858.CD002916.pub2.
Abstract/Text
BACKGROUND: Approximately half of all patients with metastatic cancer develop a malignant pleural effusion which is likely to lead to a significant reduction in quality of life secondary to symptoms such as dyspnoea and cough. The aim of pleurodesis in these patients is to prevent re-accumulation of the effusion and thereby of symptoms, and avoid the need for repeated hospitalization for thoracocentesis. Numerous clinical studies have been performed to try to determine the optimal pleurodesis strategy, and synthesis of the available evidence should facilitate this.
OBJECTIVES: The aims of this review were to ascertain the optimal technique of pleurodesis in cases of malignant pleural effusion; to confirm the need for a sclerosant; and to clarify which, if any, of the sclerosants is the most effective.
SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials was searched for studies on 'pleurodesis'. Studies for inclusion were also identified from MEDLINE (1980 to June 2002) and EMBASE (1980 to May 2002). No language restriction was applied.
SELECTION CRITERIA: RCTs of adults subjects undergoing pleurodesis for pleural effusion in the context of metastatic malignancy (or a malignant process leading to pleural effusion) were included.
DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies for inclusion in the review, and extracted data using a standard data collection form. Primary outcome measures sought were effectiveness of pleurodesis as defined by freedom from recurrence of effusions, and mortality after pleurodesis. Secondary outcomes were adverse events due to pleurodesis. Dichotomous data were meta-analysed using a fixed effect model and expressed as relative risk. The number-needed-to-treat (NNT) was calculated for pleurodesis efficacy. In addition, for adverse events, the overall percentage of patients across studies exhibiting a particular adverse effect such as fever, pain, or gastrointestinal symptoms was calculated.
MAIN RESULTS: A total of 36 RCTs with 1499 subjects were eligible for meta-analysis. The use of sclerosants (mitozantrone, talc and tetracycline combined)compared with control (instillation of isotonic saline or equivalent pH isotonic saline or tube drainage alone) was associated with an increased efficacy of pleurodesis. The relative risk (RR) of non-recurrence of an effusion is 1.20 (95% CI 1.04 to 1.38) in favour of the use of sclerosants based on five studies with a total 228 subjects. Comparing different sclerosants, talc was found to be the most efficacious. The RR of effusion non-recurrence was 1.34 (95% CI 1.16 to 1.55) in favour of talc compared with bleomycin, tetracycline, mustine or tube drainage alone based on 10 studies comprising 308 subjects. This was not associated with increased mortality post pleurodesis. The RR of death was 1.19 (95% CI 0.08 to 1.77) for talc compared to bleomycin, tetracycline, mustine and tube drainage alone based on six studies of 186 subjects. Death was not reported in all studies and, when reported, was attributed to underlying disease, only one death being reported as procedure-related. In the comparison of thoracoscopic versus medical pleurodesis, thoracoscopic pleurodesis was found to be more effective. The RR of non-recurrence of effusion is 1.19 (95% CI 1.04 to 1.36) in favour of thoracoscopic pleurodesis compared with tube thoracostamy pleurodesis utilizing talc as sclerosant based on two studies with 112 subjects. Comparing thoracoscopic versus bedside instillation (with different sized chest tubes) of various sclerosants (tetracycline, bleomycin, talc or mustine) the RR of non-recurrence of effusion is 1.68 (95% CI 1.35 to 2.10) based on five studies with a total of 145 participants.Adverse events were not reported adequately to enable meta-analysis.
REVIEWER'S CONCLUSIONS: The available evidence supports the need for chemical sclerosants for successful pleurodesis, the use of talc as the sclerosant of choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy. There was no evidence for an increase in mortality following talc pleurodesis.
Dresler CM, Olak J, Herndon JE 2nd, Richards WG, Scalzetti E, Fleishman SB, Kernstine KH, Demmy T, Jablons DM, Kohman L, Daniel TM, Haasler GB, Sugarbaker DJ; Cooperative Groups Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cooperative Oncology Group; Radiation Therapy Oncology Group.
Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.
Chest. 2005 Mar;127(3):909-15. doi: 10.1378/chest.127.3.909.
Abstract/Text
STUDY OBJECTIVE: To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs).
DESIGN: A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE.
MEASUREMENTS: The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed.
RESULTS: Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures.
CONCLUSIONS: Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.
Stefani A, Natali P, Casali C, Morandi U.
Talc poudrage versus talc slurry in the treatment of malignant pleural effusion. A prospective comparative study.
Eur J Cardiothorac Surg. 2006 Dec;30(6):827-32. doi: 10.1016/j.ejcts.2006.10.002.
Abstract/Text
OBJECTIVE: The aim of this study was to investigate the effectiveness, safety and appropriate mode of administration of intrapleural talc for pleurodesis, in the treatment of malignant pleural effusion (MPE).
METHODS: Prospective not randomized trial was conducted to compare thoracoscopic talc poudrage (TP) with tube thoracostomy and talc slurry (TS) for the local control of malignant pleural effusion. Both procedures were previously standardized; 6g of talc was administered for each procedure. Only the patients with lung re-expansion after drainage entered the study. Patients at high risk for general anaesthesia, poor general conditions and short life-expectancy received talc slurry through a chest tube, at the bedside. All the other patients underwent videothoracoscopic talc poudrage, with a pneumatic atomizer, under general anaesthesia. Morbidity, 30-day freedom from recurrence and long-term results were assessed and the two groups were compared.
RESULTS: One hundred and nine patients entered the study (72 TP, 37 TS). Sixty-three patients in the TP group (87.5%) and 27 in the TS group (73%) had an immediate successful pleurodesis (p = 0.049); 53 patients (88.3%) and 16 patients (69.6%) had a successful pleurodesis 90 days after the procedure; 59 patients (81.9%) and 23 patients (62.2%), respectively, had a life-long pleural symphysis (p = 0.023). Adverse effects were generally mild: chest pain (36.1% in TP patients, 48.6% in TS patients) and fever (38.8% and 35.1%, respectively) were the more common but the difference was not significant between the two groups. We observed neither acute respiratory failure nor mortality due to the procedure.
CONCLUSIONS: Our study confirms that intrapleural talc carries good results in the treatment of malignant pleural effusion. TP was significantly more effective than TS; both methods were safe but TS had a higher incidence of thoracic pain during the procedure. Talc pleurodesis should be offered to every patient with MPE, apart from terminally ill ones, provided that a satisfying lung re-expansion has been achieved. TP should be performed whenever possible; otherwise, a slurry bedside procedure will be worthwhile, even in patients with low performance status (PS), though poorer results have to be expected. A careful selection is essential to define the proper technique.
Yoshida K, Sugiura T, Takifuji N, Kawahara M, Matsui K, Kudoh S, Takada M, Fukuoka M, Ariyoshi Y, Fukuda H, Saijo N.
Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515.
Lung Cancer. 2007 Dec;58(3):362-8. doi: 10.1016/j.lungcan.2007.07.009. Epub 2007 Aug 22.
Abstract/Text
To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes) or cisplatin plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1mg/kg (maximum 60mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10KE/body), or the PE arm: cisplatin (80mg/m(2)) and etoposide (80mg/m(2)). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3-4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.
Sohara Y.
Reexpansion pulmonary edema.
Ann Thorac Cardiovasc Surg. 2008 Aug;14(4):205-9.
Abstract/Text
When a rapidly reexpanding lung has been in a state of collapse for more than several days, pulmonary edema sometimes occurs in it. This is called reexpansion pulmonary edema (RPE). In this article, I present my views on the history, clinical features, morphophysiological features, pathogenesis, and treatment of RPE. Histological abnormalities of the pulmonary microvessels in a chronically collapsed lung will cause RPE, as well as mechanical stress exerted during reexpansion. Although the most effective treatment method is to treat the histological abnormalities of the pulmonary microvessels formed in a chronically collapsed lung, the cause of these abnormalities is not clear, making it difficult to put forward a precise treatment method. However, reasonably good effects can be expected from a symptomatic therapy that reduces the level of mechanical stress during reexpansion. In the future, it is expected that the cause of histological changes of the pulmonary microvessels in a chronically collapsed lung will be revealed, and appropriate therapies will therefore be developed according to this cause.
Lee YC, Light RW.
Management of malignant pleural effusions.
Respirology. 2004 Jun;9(2):148-56. doi: 10.1111/j.1440-1843.2004.00566.x.
Abstract/Text
Malignant pleural effusion is a common clinical problem. Evacuation of the pleural fluid and prevention of its reaccumulation are the main aims of management. Pleurodesis should be attempted early, although considerable practice variations exist in the way it is performed. There is a lack of consensus among respiratory physicians worldwide on the optimal method and agent for pleurodesis. Talc remains the most commonly used pleurodesing compound in most countries. While talc produces a higher success rate than other compounds, it generates more side-effects. The association between talc and ARDS continues to be debated. Ambulatory small-bore pleural catheter drainage followed by intrapleural instillation of a pleurodesing agent is increasingly accepted as an alternative to conventional in-patient pleurodesis. Development of novel methods to control pleural fluid formation should be made a high priority in future pleural research.