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Background

A pleural effusion is a collection of fluid within the pleural cavity, a thin space that exists between the chest wall and the lungs. Various disease states can lead to accumulation of fluid within this cavity.

OUTLINE

Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Special Stains/Immunohistochemistry/Electron Microscopy  
Differential Diagnosis  
Prognosis and Treatment  
Commonly Used Terms  

DISEASE ASSOCIATIONS CHARACTERIZATION
AORTIC DISSECTION  


Clinical significance of pleural effusion in acute aortic dissection.

Hata N, Tanaka K, Imaizumi T, Ohara T, Ohba T, Shinada T, Takano T.

Intensive Care Unit, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan.

Chest 2002 Mar;121(3):825-30 Abstract quote

STUDY OBJECTIVE: To clarify the clinical significance of pleural effusion in the clinical course of acute aortic dissection (AAD).

DESIGN: Retrospective clinical series.

SETTING: A university hospital.

PATIENTS: Fifty-five patients strongly suspected of having AAD because of severe chest or back pain. Patients with obvious ischemic heart disease, lung disease, and pleural disease were excluded.

INTERVENTIONS: An additional diagnosis of pleural effusion was made when evident by CT.

MEASUREMENTS AND RESULTS: Pleural effusion was detected in 42 of 48 patients (88%) with AAD (mean plus minus SD age, 65 plus minus 12 years; 35 men and 13 women), but in only 1 of 7 patients (14%) who proved not to have AAD (mean age, 74 +/- 10 years; 6 men and 1 woman). Effusion appeared at a mean of 4.5 days after onset of dissection. Thoracentesis performed in six patients showed a bloody effusion in three patients and an exudative effusion in three patients. In the six AAD patients without pleural effusion, four patients underwent surgery within 3 days after onset of dissection. In patients with AAD, effusion was demonstrated on the first CT after hospital admission in 18 patients, and was bilateral in 32 patients. WBC count in blood, serum C-reactive protein concentration, and body temperature were higher in patients with effusion (13,400 +/- 3,600/microL, 18.4 +/- 11.5 mg/dL, and 38.2 +/- 0.7 degrees C) than in those without effusion (10,300 +/- 2,900/microL, 4.5 +/- 4.2 mg/dL, and 37.0 +/- 1.0 degrees C, respectively).

CONCLUSIONS: Pleural effusion occurs frequently in patients with AAD, often in association with inflammatory reactions.

LYMPANGIOLEIOMYOMATOSIS  


Lymphangioleiomyomatosis: an unusual cause of dyspnea in young women.

Dahi H, Ie SR, David O, Rubio ER.

Section of Pulmonary Diseases, Critical Care, and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.\

J La State Med Soc 2002 Mar-Apr;154(2):78-81 Abstract quote

Lymphangioleiomyomatosis is a rare and complicated disorder that affects the young, almost exclusively women. It may be associated with the tuberous sclerosis complex, which includes renal angiolipoma, chylothorax and lymph node myomatosis. Its clinical pulmonary manifestations vary from simple cough to the development of recurrent pneumothoraces, hemoptysis, and even complicated pleural effusions.

Progressive dyspnea develops as the disease evolves. Eventually most patients require lung transplantation. This wide array of symptoms and signs makes the differential diagnosis extensive, and the clinician must be familiar with this disorder to arrive promptly to the correct diagnosis.

We report a case of a 36-year-old woman with a long history of recurrent pleuritic chest pain with associated dyspnea before being diagnosed with lymphangioleiomyomatosis. A review of the literature pertinent to this case is provided.

LUNG CANCER  

The significance of intraoperative pleural effusion during surgery for bronchogenic carcinoma.

Ruffini E, Rena O, Bongiovanni M, Cristofori R, Mancuso M, Filosso PL, Molinatti M, Maggi G.

Department of Thoracic Surgery, University of Torino, 3, Via Genova 10126, Torino, Italy.

Eur J Cardiothorac Surg 2002 Mar;21(3):508-13 Abstract quote

OBJECTIVES: To analyze patients submitted to thoracotomy for lung carcinoma presenting with an intraoperative pleural effusion (PE).

METHODS: From 1993 to 1999, 1279 patients received thoracotomy with curative intent for primary lung carcinoma. Intraoperatively, 52 patients (4%) presented a PE >100ml which was not diagnosed preoperatively. Of these, seven patients had received preoperative transthoracic fine-needle biopsy FNB and were excluded from the analysis. In the remaining 45 patients pleural fluid cytology was undertaken. In patients with cytology-negative PE, clinico-pathologic characteristics including intratumoral vascular invasion, intratumoral perineural invasion, peritumoral lymphocytic infiltrate, visceral, parietal and mediastinal pleural involvement, pTNM and survival were analyzed and compared with our total population of lung cancer patients operated on during the same period.

RESULTS: The mean amount of collected fluid was 210ml (100-450ml). Of the 45 patients with intraoperative PE, 16 (35%) received exploratory thoracotomy because of pleural carcinosis or major involvement of mediastinal structures; eight (18%) received resection of the tumor, although the cytologic examination of the pleural fluid eventually resulted positive for neoplastic cells. Median survival for the two groups was 6 and 9 months, respectively. Twenty-one patients (47%) received resection of the tumor with a cytology-negative pleural fluid. In this group, analysis of clinico-pathologic characteristics revealed that squamous cell type and mediastinal pleural involvement were significantly associated with the presence of intraoperative PE (P=0.01 and P=0.05, respectively); 3- and 5-year survivals of this group were similar to those observed in our total population of resected lung cancer patients (68 and 56% vs. 54 and 42%, P=0.27).

CONCLUSIONS: The presence of a PE at thoracotomy during surgery for lung carcinoma is an infrequent occurrence. In more than 50% of the cases cytology is positive and prognosis is poor. In the remaining cases, however, cytology is negative and the PE should be considered as reactive; in these patients a curative resection can be accomplished with an anticipated chance of long-term survival.

 

PATHOGENESIS CHARACTERIZATION
VASCULAR ENDOTHELIAL GROWTH FACTOR  


Vascular endothelial growth factor: the key mediator in pleural effusion formation.

Grove CS, Lee YC.

Asthma and Allergy Research Institute, University of Western Australia, Perth, Australia; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Curr Opin Pulm Med 2002 Jul;8(4):294-301 Abstract quote

Pleural effusion is common in clinical practice. Increased vascular permeability and leakage play a principal role in the development of exudative pleural effusions. In vitro and in vivo evidence have solidly established vascular endothelial growth factor (VEGF), a potent inducer of vascular permeability, as a crucial mediator in pleural fluid formation. VEGF is present in high quantities in human effusions.

In the pleural space, mesothelial cells, infiltrating inflammatory cells, and (in malignant pleuritis) cancer cells contribute to the VEGF accumulation in the pleural fluids. Pleural fluid VEGF is biologically active and may promote tumor growth and chemotaxis. Strategies to antagonize the VEGF activity at various target points of its signaling pathway have shown success in vitro and in animal models of malignant pleural or peritoneal effusions. Novel agents targeting VEGF activities are undergoing clinical trials.

Regulation of VEGF activity and vascular permeability represent a rapidly expanding field of research, which is likely to provide further insight in the pathophysiology of pleural fluid formation.

LABORATORY/RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  
LABORATORY MARKERS  
GENERAL  


New criteria for the differentiation between transudates and exudates.

Paramothayan NS, Barron J.

Department of Respiratory Medicine, St. Helier Hospital, Carshalton, Surrey SM5 1AA, UK.

 

J Clin Pathol 2002 Jan;55(1):69-71 Abstract quote

AIMS: To investigate whether cholesterol and lactate dehydrogenase (LDH) measurements in fluids are more sensitive and specific markers for differentiating between exudates and transudates, as confirmed clinically, than the measurement of fluid total protein concentrations alone.

PATIENTS/METHODS: Serum, pleural fluid, and ascitic fluid from 61 unselected patients were analysed retrospectively for LDH, cholesterol, and total protein. Clinical classification of transudate or exudate was reached independently by reviewing clinical details and laboratory data.

RESULTS: Of 54 samples (40 pleural fluid and 14 ascitic fluid), 30 were classified clinically as exudates and 24 as transudates. Fluid LDH and fluid to serum protein ratio measurements were equally good at differentiating between exudates and transudates, with a sensitivity of 90%, a specificity of 79%, a positive predictive value (PPV) of 84%, and a negative predictive value (NPV) of 86%. A combination of these parameters improved sensitivity to 100% and NPV to 100%, but lowered the specificity to 71% and PPV to 81%. This combination achieved a higher efficiency than Light's criteria.

CONCLUSION: Routine measurement of fluid LDH values and the calculation of fluid to serum total protein ratios will aid in differentiating exudates from transudates.


Diagnostic value of interleukin-1alpha, interleukin-6, and tumor necrosis factor in pleural effusions.

Xirouchaki N, Tzanakis N, Bouros D, Kyriakou D, Karkavitsas N, Alexandrakis M, Siafakas NM.

Department of Thoracic Medicine, Medical School, University of Crete, University General Hospital of Heraklion, Crete, Greece

Chest 2002 Mar;121(3):815-20 Abstract quote

STUDY OBJECTIVES: Interleukin (IL)-1alpha, IL-6, and tumor necrosis factor (TNF)-alpha were measured in pleural fluid from 57 patients with pleural effusion in order to evaluate the diagnostic utility of these cytokines. We studied 20 patients with malignant pleural effusion, 11 patients with parapneumonic pleural effusion, 9 patients with tuberculous pleural effusion, and 17 patients with transudative pleural effusion. Cytokines were measured by radioimmunoassay.

SETTING: University tertiary hospital.

RESULTS: The mean values of the three cytokines measured in pleural fluid or in serum were significantly higher in patients with exudates than with transudates (p < 0.05). The ratio of IL-6 in pleural fluid to serum was significantly higher in exudates than in transudates (p < 0.05). The level of IL-6 in pleural fluid was significantly higher in tuberculous than malignant (p < 0.007) or parapneumonic pleural effusions (p < 0.04). No significant difference between the three types of exudates was found in pleural fluid levels of IL-1alpha or TNF-alpha.

CONCLUSIONS: Serum levels of IL-1alpha, TNF-alpha, and in particular IL-6 can distinguish exudates from transudates, while pleural fluid IL-6 levels could be useful as an additional marker in the differential diagnosis of tuberculous, malignant, and parapneumonic exudates. Finally, our results suggest that there is local cytokine production in exudative pleural effusions.


Multilevel likelihood ratios for identifying exudative pleural effusions

Heffner JE, Sahn SA, Brown LK.

Medical University of South Carolina (Drs. Heffner and Sahn), Charleston, SC.

Chest 2002 Jun;121(6):1916-20 Abstract quote

Study objectives: To determine multilevel likelihood ratios for pleural fluid tests that are commonly used to discriminate between exudative and transudative pleural effusions.

DESIGN: Meta-analysis of patient-level data. Patient data: Selected studies included patients with diagnoses of exudative or transudative pleural effusions who underwent thoracentesis and laboratory analysis of their pleural fluid. Measurements and methods: Studies were identified by searching MEDLINE and related bibliographies. Data were obtained for 1,448 patients from seven primary investigators or extracted from dot plots in published reports. Likelihood ratios were calculated from extracted data stratified across ranges of test result values. R

ESULTS: Sufficient data were available to calculate multilevel likelihood ratios for the elements of Light's criteria (pleural fluid lactate dehydrogenase [LDH], ratio of pleural fluid to serum LDH, and ratio of pleural fluid to serum protein), pleural fluid protein, ratio of pleural fluid to serum cholesterol, pleural fluid cholesterol, and gradient of pleural fluid to serum albumin. Each of these tests provided levels of likelihood ratios through the most clinically relevant range (0 to 10).

CONCLUSION: Multilevel likelihood ratios combined with a clinician's estimation of the pretest probability of an exudative effusion improve the diagnostic accuracy of discriminating between exudative and transudative pleural effusions. Likelihood ratios avoid the use of confusing terms, such as "pseudoexudates," that derive from the use of single cutoff points for pleural fluid tests.

AMYLASE  


Amylase levels in pleural effusions: a consecutive unselected series of 841 patients.

Villena V, Perez V, Pozo F, Lopez-Encuentra A, Echave-Sustaeta J, Arenas J, Escribano PM.

Respiratory Medicine Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

Chest 2002 Feb;121(2):470-4 Abstract quote

STUDY OBJECTIVES: To describe the causes and relative frequency of amylase-rich pleural effusion (ARPE), and to study the origin and histologic type of the tumors with ARPE, the strength of the association between ARPE and the result of pleural cytology, and whether pleural amylase (PA) is a prognostic factor in the survival of patients with a malignant pleural effusion.

SETTING: Tertiary-care, university-affiliated hospital.

PATIENTS: Eight hundred forty-one consecutive patients with pleural effusion prospectively assessed from 1991 to 1999.

RESULTS: There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis, pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six percent of patients in our series and 61% of patients with ARPE had a neoplastic disease (odds ratio [OR], 3; p < 0.001); this association got much stronger for cases with PA levels > or = 600 IU/L (95th percentile); [OR, 10; p < 0.001]. The most frequent tumor origin was lung cancer (13 cases). Adenocarcinoma was the most frequent histologic type (18 cases). Two mesothelioma effusions were ARPEs. There was a positive association between ARPE and the finding of tumor cells in pleural fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels > or = 600 IU/L identified a group of patients with quite a short median survival (p = 0.016).

CONCLUSIONS: The most common cause of ARPE was neoplasm. There was a positive association between ARPE and malignancy, stronger with the highest levels (95th percentile). Lung cancer and adenocarcinoma were the most common tumor and histologic type associated with ARPE. Mesothelioma may also produce ARPE. There was an association between ARPE and the finding of tumor cells in the pleural fluid. The highest PA levels identified a group of patients with a median shorter survival.

COMPARITIVE GENOMIC HYBRIDIZATION  


The Potential Value of Comparative Genomic Hybridization Analysis in Effusion-and Fine Needle Aspiration Cytology.

Nagel H, Schulten HJ, Gunawan B, Brinck U, Fuzesi L.

Departments of Cytopathology (HN) and of Gastroenteropathology (HJS, BG, UB, LF), Georg-August-University, Gottingen, Germany.

Mod Pathol 2002 Aug;15(8):818-25 Abstract quote

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that provides an overview on chromosomal imbalances within the whole tumor cell genome. This method has yet not been applied in effusion cytology.

We performed CGH analysis in malignant effusions, fine needle aspirates, and imprint smears from eight ovarian adenocarcinomas, three breast carcinomas, one colon adenocarcinoma, and three malignant mesotheliomas. In part, CGH analysis from fresh frozen tissue and classic karyotyping served as controls. In this series, 14/15 cytologic specimens were suitable for extraction of high molecular weight DNA sufficient for reliable CGH analysis. CGH profiles from cytologic material were equal or even more significant in comparison with corresponding fresh frozen tumor samples. We conclude that CGH analysis from cytologic specimens may support the primary cytologic diagnosis of malignancy, especially in the differential diagnosis of benign proliferating mesothelium, malignant mesothelioma, and metastatic adenocarcinoma. CGH analysis of metastatic lesions may provide information on the site of the primary tumors and detects cytogenetic imbalances affecting oncogenes and tumor suppressor genes involved in tumor progression and metastatic spread.

C-REACTIVE PROTEIN  


Diagnostic value of C-reactive protein in exudative pleural effusions.

Garcia-Pachon E, Llorca I.

Department of Internal Medicine, Hospital Vega Baja, E-03314 Orihuela-, Alicante, Spain

Eur J Intern Med 2002 Jun;13(4):246-249 Abstract quote

BACKGROUND: Tests able to help in the diagnostic work-up of pleural exudates are needed. C-reactive protein (CRP) may be useful for distinguishing between benign and malignant exudates.

METHODS: A total of 123 consecutive patients diagnosed as having exudative pleural effusion (60 associated with malignancy and 63 benign effusions) were included in the study. Sensitivity, specificity, positive and negative predictive values (PV+, PV-), and positive and negative likelihood ratios (LR+, LR-) were established at different cut-off points.

RESULTS: Pleural fluid CRP level was 23+/-12 mg/l (mean+/-S.D.) in pleural exudates associated with malignancy and 50+/-33 mg/l in benign effusions (P<0.001). With a cut-off point below 20 mg/l for malignancy, sensitivity of CRP was 0.50, specificity 0.89, PV+ 0.81, PV- 0.65, LR+ 4.50, and LR- 0.65. With a cut-off point above 45 mg/l for benign diseases, sensitivity was 0.44, specificity 0.95, PV+ 0.90, PV- 0.62, LR+ 8.89, and LR- 0.58.

CONCLUSIONS: The pleural CRP level provides useful information for the study of pleural exudates. A level below 20 mg/l suggests a malignant origin and a level above 45 mg/l virtually rules out this possibility. Additional advantages of measuring CRP level are that it is an inexpensive test and is easy to perform.

FLOW CYTOMETRY  
Detection of Malignant Epithelial Cells in Effusions Using Flow Cytometric Immunophenotyping
An Analysis of 92 Cases


Ben Davidson, MD, PhD, etal

Am J Clin Pathol 2002;118:85-92 Abstract quote

We compared the efficiency of immunophenotyping using flow cytometry (FCM) and a combination of morphologic and immunocytochemical studies for detecting malignant cells in 92 effusions.

Cytologic results were as follows: carcinoma cells, 43 specimens; benign, 42 specimens; suggestive of nonepithelial malignancy, 7 specimens. After immunocytochemical analysis, 5 benign specimens were reclassified as malignant and 4 malignant epithelial specimens as benign. With FCM, cells positive for Ber-EP4, B72.3, AH6, and HB-TN were detected in 28 to 36 (64%-82%) of 44 carcinomas but only 2 to 12 (5%-29%) of 41 benign specimens. Significant association was seen for coexpression. Ber-EP4 and AH6 were the most sensitive; Ber-EP4 was the most specific. The presence of cells positive for 3 of 4 markers strongly suggested malignancy (34/44 carcinoma specimens [77%]; 3/41 reactive specimens [7%]). The presence of cells positive for all 4 markers was diagnostic of malignancy (17/44 malignant specimens [39%]; 0/41 reactive effusions [0%]). FCM and immunocytochemical results for Ber-EP4 expression showed excellent association.

FCM is a powerful tool for diagnosing difficult effusions and can quantify coexpression of various markers in fresh specimens. By using established cellular markers coupled with biological markers, FCM also has great promise for experimental purposes.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
CHYLOTHORAX  
PYOTHORAX ASSOCIATED LYMPHOMA  


Pyothorax-associated lymphoma: a review of 106 cases.

Nakatsuka S, Yao M, Hoshida Y, Yamamoto S, Iuchi K, Aozasa K.

Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan.

J Clin Oncol 2002 Oct 15;20(20):4255-60 Abstract quote

PURPOSE: Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of pyothorax. Full details of PAL are provided here.

PATIENTS AND METHODS: Clinical and pathologic findings were reviewed in 106 patients with PAL collected through a nationwide survey in Japan.

RESULTS: Age of the patients with PAL was 46 to 82 years (median, 64 years), with a male/female ratio of 12.3:1. All patients had a 20- to 64-year (median, 37-year) history of pyothorax resulting from artificial pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous pleuritis (17%). The most common symptoms on admission were chest and/or back pain (57%) and fever (43%). Laboratory data showed that the serum neuron-specific enolase level was occasionally elevated (3.55 to 168.7 ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell lung cancer. Histologically, PAL usually showed a diffuse proliferation of large cells of B-cell type (88%). In situ hybridization study showed that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive. PAL was responsive to chemotherapy, but the overall prognosis was poor, with a 5-year survival of 21.6%.

CONCLUSION: This study established the distinct nature of PAL as a disease entity. PAL is a non-Hodgkin's lymphoma of exclusively B-cell phenotype in the pleural cavity of patients with long-standing history of pyothorax, and is strongly associated with EBV infection. Development of PAL is closely related to antecedent chronic inflammatory condition; therefore, PAL should be defined as malignant lymphoma developing in chronic inflammation.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
SPECIAL STAINS  
IMMUNOPEROXIDASE  
WT1, Estrogen Receptor, and Progesterone Receptor as Markers for Breast or Ovarian Primary Sites in Metastatic Adenocarcinoma to Body Fluids


Benjamin H. Lee, MD, PhD, Jonathan L. Hecht, MD, PhD, Jack L. Pinkus, PhD, and Geraldine S. Pinkus, MD

Am J Clin Pathol 2002;117:745-750 Abstract quote

In tissue sections, detection of the Wilms tumor susceptibility gene 1 (WT1) protein, the hormonal receptors for estrogen (ER) and progesterone (PR), and gross cystic disease fluid protein (GCDFP) are useful for diagnosing ovarian and breast adenocarcinomas.

We evaluated these markers for cytology cell-block preparations from 96 effusion specimens (metastases from 29 breast, 22 ovarian, and 45 adenocarcinomas from other sites). WT1 protein was reactive in 19 cases metastatic from ovary (86%), 2 from breast (7%), and none from other sites (specificity, 97%). Of the metastatic breast carcinomas, 21 (72%) were reactive for ER, 15 (52%) for PR, and 13 (45%) for both (combined specificity, 84%). GCDFP was reactive in only 4 breast cancer cases (14%). Ovarian tumors also were frequently positive for ER (19 [86%]), PR (11 [50%]), or both (10 [45%]). WT1 protein is an effective marker for ovarian adenocarcinoma, especially in ascites.

The detection of ER and PR in metastatic adenocarcinoma from pleural or pericardial effusions can distinguish breast from lung primary sites. Reactivity for ER and PR did not distinguish between breast and ovarian metastases; however, studies for WT1 protein and GCDFP may aid in making this distinction.

TTF-1  


Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens.

Ng WK, Chow JC, Ng PK.

Department of Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.

Cancer 2002 Feb 25;96(1):43-8 Abstract quote

BACKGROUND: Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor selectively expressed in thyroid, lung and diencephalon. It has been shown to label pulmonary adenocarcinoma, thyroid tumors, and small cell carcinoma (pulmonary and extrapulmonary) with relatively high sensitivity and specificity. The usefulness of this immunostain in cytology specimens has not been thoroughly discussed in the literature.

METHODS: The authors evaluated 36 effusion cytology cases (17 pleural effusion, 18 ascitic fluid, and 1 pericardial effusion) diagnosed as metastatic adenocarcinoma and with cell blocks prepared from the file of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a three-year period from 1998 to early 2001. The clinical, radiologic, cytologic, and histologic (if any) findings were reviewed. A provisional diagnosis of the primary site was deduced for each of the 36 cases by clinical, radiologic, and/or histologic correlation. Immunohistochemical study was performed on the cell block sections of the effusion cytology specimens using mouse monoclonal antibody against TTF-1, after microwave heat-antigen retrieval. The results were correlated with the primary origin of the metastatic adenocarcinoma.

RESULTS: Among the 17 cases of metastatic pulmonary adenocarcinoma, 15 cases showed nuclear staining for TTF-1 in most of the tumor cells (sensitivity, 88.2%). None of the 19 cases of metastatic extrapulmonary adenocarcinoma expressed TTF-1 (specificity, 100%).

CONCLUSIONS: The current study validates TTF-1 as a highly sensitive and specific immunomarker for distinguishing between metastatic pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens, which are known to be associated with intrinsic artifact due to less than ideal cellular preservation.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
CHYLOUS EFFUSION  


The lipoprotein profile of chylous and nonchylous pleural effusions.

Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K.

Mayo Clin Proc 1980 Nov;55(11):700-4 Abstract quote

The lipoprotein electrophoregrams and the cholesterol and triglyceride levels of the pleural fluid were evaluated for patients with chylous pleural effusions, as defined by the presence of a distinctive band of chylomicrons on the lipoprotein electrophoregram, and in patients with nonchylous effusions of various causes.

One hundred forty-one patients were studied during a 3-year period. The chylous effusions had strikingly higher triglyceride levels (median 249, range 49 to 2,270 mg/dl) than the nonchylous group (median 33, range 13 to 107 mg/dl); there were no significant differences in cholesterol or protein between the two groups. The gross description of the fluid was a poor indicator of its origin, being described as consistent with chyle in less than 50% of cases of chylous effusions. The triglyceride values distinguished chylous effusion from nonchylous effusion; values greater than 110 mg/dl are highly suggestive of a chylous effusion. Equivocal cases--triglyceride values between 50 and 110 mg/dl--required lipoprotein analysis.

Pleural effusions of undetermined cause, regardless of gross appearance of the fluid, require that a screening triglyceride value be obtained to rule out a chylous effusion.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  
TREATMENT  
GENERAL  



Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline.

Colice GL, Curtis A, Deslauriers J, Heffner J, Light R, Littenberg B, Sahn S, Weinstein RA, Yusen RD.

Pulmonary and Respiratory Services, Washington Hospital Center, Washington, DC, USA.

 

Chest 2000 Oct;118(4):1158-71 Abstract quote

OBJECTIVE: A panel was convened by the Health and Science Policy Committee of the American College of Chest Physicians to develop a clinical practice guideline on the medical and surgical treatment of parapneumonic effusions (PPE) using evidence-based methods.

OPTIONS AND OUTCOMES CONSIDERED: Based on consensus of clinical opinion, the expert panel developed an annotated table for evaluating the risk for poor outcome in patients with PPE. Estimates of the risk for poor outcome were based on the clinical judgment that, without adequate drainage of the pleural space, the patient with PPE would be likely to have any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. Three variables, pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, were used in this annotated table to categorize patients into four separate risk levels for poor outcome: categories 1 (very low risk), 2 (low risk), 3 (moderate risk), and 4 (high risk). The panel's consensus opinion supported drainage for patients with moderate (category 3) or high (category 4) risk for a poor outcome, but not for patients with very low (category 1) or low (category 2) risk for a poor outcome. The medical literature was reviewed to evaluate the effectiveness of medical and surgical management approaches for patients with PPE at moderate or high risk for poor outcome. The panel grouped PPE management approaches into six categories: no drainage performed, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery (VATS), and surgery (including thoracotoiny with or without decortication and rib resection). The fibrinolytic approach required tube thoracostomy for administration of drug, and VATS included post-procedure tube thoracostomy. Surgery may have included concomitant lung resection and always included postoperative tube thoracostomy. All management approaches included appropriate treatment of the underlying pneumonia, including systemic antibiotics. Criteria for including articles in the panel review were adequate data provided for >/=20 adult patients with PPE to allow evaluation of at least one relevant outcome (death or need for a second intervention to manage the PPE); reasonable assurance provided that drainage was clinically appropriate (patients receiving drainage were either category 3 or category 4) and drainage procedure was adequately described; and original data were presented. The strength of panel recommendations on management of PPE was based on the following approach: level A, randomized, controlled trials with consistent results or individual randomized, controlled trial with narrow confidence interval (CI); level B, controlled cohort and case control series; level C, historically controlled series and case series; and level D, expert opinion without explicit critical appraisal or based on physiology, bench research, or "first principles."

EVIDENCE: The literature review revealed 24 articles eligible for full review by the panel, 19 of which dealt with the primary management approach to PPE and 5 with a rescue approach after a previous approach had failed. Of the 19 involving the primary management approach to PPE, there were 3 randomized, controlled trials, 2 historically controlled series, and 14 case series. The number of patients included in the randomized controlled trials was small; methodologic weaknesses were found in the 19 articles describing the results of primary management approaches to PPE. The proportion and 95% CI of patients suffering each of the two relevant outcomes (death and need for a second intervention to manage the PPE) were calculated for the pooled data for each management approach from the 19 articles on the primary management approach.


Malignant pleural effusions.

Reeder LB.

Cardiac and Thoracic Surgery, Henry Ford Hospital, 2799 West Grand Blvd., K-14, Detroit, MI 48202, USA.

Curr Treat Options Oncol 2001 Feb;2(1):93-6 Abstract quote

Malignant pleural effusions contribute to considerable morbidity in cancer patients and generally portend an overall poor prognosis. Treatment of malignant pleural effusions is palliative; therefore, quality of life issues, as well as the risks and benefits of the therapeutic options, become more critical.

In my opinion, factors such as in patient versus outpatient management and associated procedural discomfort are important in the decision-making process, and the patient should participate in these subjective considerations. It is difficult to compare results and determine the true efficacy of different techniques and agents because endpoints and response criteria as well as the extent and method of follow-up vary. In addition, the etiology of the primary complaint, dyspnea, is frequently multifactorial. However, malignant effusions recur, and therefore repeated thoracentesis, especially if the fluid rapidly reaccumulates, is usually not a good long-term solution unless the patient's overall prognosis and current condition prohibits a more invasive option. The standard option for recurrent effusions is insertion of a chest tube. If the lung re-expands, chemical pleurodesis is attempted to achieve adherence of the visceral to the parietal pleura.

Sterilized talc is the best sclerosant; it has good efficacy and cost effectiveness and can be administered easily as a slurry at the bedside via a chest tube with minimal patient discomfort and without more aggressive and invasive procedures.

CATHETER  


Malignant pleural effusions: treatment with tunneled long-term drainage catheters.

Pollak JS.

Section of Vascular and Interventional Radiology, Department of Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.

Curr Opin Pulm Med 2002 Jul;8(4):302-7 Abstract quote

Malignant pleural effusion is a significant cause of morbidity and a poor prognostic indicator. Traditional treatments have variable success and significant drawbacks, including a length of stay in the hospital.

Alternatively, a tunneled pleural catheter permits long-term drainage as an outpatient, cost-effectively controlling the effusion and related symptoms in over 80 to 90% of patients. Other advantages are the ability to treat trapped lungs and large locules. Spontaneous pleurodesis may occur in over 40% of patients, and the catheter can be used to administer sclerosant or antineoplastic agents. Complications tend to be minor and easily managed.

A tunneled pleural catheter should be considered for all patients with MPE having a reasonable expectancy of being an outpatient.

CHEMOTHERAPY  


Phase II study of repeated intrapleural chemotherapy using implantable access system for management of malignant pleural effusion.

Shoji T, Tanaka F, Yanagihara K, Inui K, Wada H.

Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.

Chest 2002 Mar;121(3):821-4 Abstract quote

STUDY OBJECTIVE: To examine the effectiveness of repeated intrapleural chemotherapy using an implantable access system (INFUSE-A-PORT; Horizon Medical Products; Manchester, GA) for the management of a malignant pleural effusion (MPE).

METHODS: Twenty-two patients with histologically proven MPEs (11 men and 11 women; mean age, 63.8 years; age range, 51 to 81 years; performance status, less-than-or-equal 3) were enrolled in this study. There were 17 patients with MPEs resulting from primary lung cancer; of whom 7 had metastatic disease (stage IV), 3 had stage IIIB disease, and 7 had postoperative recurrences. Three patients had MPEs that were caused by mesothelioma, and two had MPEs caused by breast cancer. Intrapleural catheters were placed by a video-assisted thoracoscopic procedure. The intrapleural administration of 5-fluorouracil (5-FU; 250 mg per body) and cisplatin (10 mg per body) using the implantable access system was performed biweekly at the outpatient clinic. Drainage of the MPEs through the port was performed only when the patients had some manifestations that occurred due to increasing effusion.

RESULTS: The mean total administered doses of 5-FU and cisplatin were 3,290 and 124 mg, respectively. The mean follow-up period was 431 days (range, 209 to 792 days). The median survival period was 403 days, and the longest survival period was 792 days. No treatment-related mortality, renal dysfunction, bone marrow suppression, or infection occurred. One patient experienced a hemothorax after eight instances of intrapleural administration. The port and the catheter were involved with the tumor in one patient.

CONCLUSIONS: Repeated intrapleural chemotherapy using the implantable access system is useful and safe for patients with MPEs. In the future, prospective randomized studies will be necessary to compare the efficacy of therapy for MPE using the implantable access system with that of pleurodesis

FIBRINOLYTIC AGENTS  


Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study.

Bouros D, Schiza S, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N.

Departments of Thoracic Medicine, Thoracic Surgery, and Clinical Pharmacology, Medical School, University of Crete, and University General Hospital, Heraklion, Crete, Greece.

Am J Respir Crit Care Med 1999 Jan;159(1):37-42 Abstract quote

Intrapleural administration of fibrinolytic agents has been shown to be effective and safe in the treatment of loculated parapneumonic pleural effusions. However, controlled studies of the possible role of the activity of urokinase (UK) through the volume effect are lacking. We therefore investigated the hypothesis that UK is effective through the lysis of pleural adhesions and not through the volume effect.

Thirty-one consecutive patients with multiloculated pleural effusions were randomly assigned to receive either intrapleural UK (15 patients) or normal saline (NS) (16 patients) for 3 d, in a double-blind manner. All patients had inadequate drainage through a chest tube (< 70 ml/24 h). UK was given daily through the chest tube in a dose of 100.000 IU diluted in 100 ml of NS. Controls were given the same volume of NS intrapleurally. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasonography (US) and/or computed tomography (CT). Clinical and radiographic improvement was noted in all but two patients in the UK group but in only four in the control group. The net mean volume drained during the 3-d treatment period was significantly greater in the UK group (970 +/- 75 ml versus 280 +/- 55 ml, p < 0.001). Pleural fluid drainage was complete in 13 (86.5%) patients in the UK group (two patients were treated through video-assisted thoracoscopy) but in only four (25%) in the control group. Twelve patients in the control group were subsequently treated with UK and six of them had complete drainage; the remaining six patients had complete drainage after video-assisted thoracoscopy.

Our results suggest that UK is effective in the treatment of loculated pleural effusions through the lysis of pleural adhesions and not through the volume effect.

TALC  


Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions.

Diacon AH, Wyser C, Bolliger CT, Tamm M, Pless M, Perruchoud AP, Soler M.

Department of Internal Medicine, University Hospital, Basel, Switzerland.

 

Am J Respir Crit Care Med 2000 Oct;162(4 Pt 1):1445-9 Abstract quote

Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions, but the best method for achieving this is still unknown.

In this prospective, randomized comparison of two well-established pleurodesis procedures, 36 patients with malignant pleural effusions, expanded lungs after drainage, and expected survival of > 1 mo received either bleomycin instillation (60E) via a small-bore thoracostomy tube or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy, safety, and cost could be evaluated for 32 treatments (17 bleomycin, 15 talc) in 31 patients. Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively, those after 90 d were 59% and 13%, respectively (p = 0.01), and those after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure showed any major adverse effect, and both were equally well tolerated. Cost estimation favored thoracoscopic talc poudrage, both for the initial hospitalization and with regard to recurrences.

In conclusion, thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion.


Distribution of talc suspension during treatment of malignant pleural effusion with talc pleurodesis.

Mager HJ, Maesen B, Verzijlbergen F, Schramel F.

Department of Pulmonary Diseases, Heart Lung Center Utrecht, Sint Antonius Ziekenhuis, PO Box 2500, NL-3430 EM, Nieuwegein, The Netherlands

Lung Cancer 2002 Apr;36(1):77-81 Abstract quote

Talc pleurodesis is an effective technique for the management of symptomatic malignant pleural effusions. It is assumed that a good dispersion of talc suspension contributes to the final success of this treatment.

For this purpose, guidelines often advise to rotate the patient after intra-pleural instillation of the sclerosant. This prospective, randomized study analyses the dispersion of talc suspension and the overall success rate in patients with malignant effusions. After instillation of 99mTc-sestamibi-labeled talc suspension ten subjects were rotated for 1 h, while the ten other patients remained in a stable supine body position. Scintigraphic imaging was done in two directions immediately after instillation and after 1 h with a clamped drain. The overall success of the treatment was assessed 1 month after the pleurodesis. The dispersion of talc was limited and unequal in 75% of the subjects. In two patients with apparently good distribution on anterior views, the lateral views of the scintigraphy showed only limited distribution. Rotation of the patients did not influence the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful in 85% of the patients after 1-month follow-up.

Standard rotation protocols for patients with malignant pleural effusion do not affect the overall dispersion of talc suspension and should be abolished because of the discomfort caused to the patients.

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Last Updated 11/12/2002

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