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Doi:10.1016/j.ccm.2005.12.002

Vanderbilt University, T-1218 Medical Center North, Nashville, TN 37232 – 2659, USA Frequently, the etiology of a pleural effusion is in only minimally meet the exudative criteria (eg, the question after the initial thoracentesis. In this article, protein ratio is 0.52 or the LDH ratio is 0.63).
I assume that the pleural effusion persists after the Moreover, the patients with transudates who are initial diagnostic workup, which includes measure- misclassified are usually receiving diuretics If ment of a pleural fluid marker for tuberculosis, such the pleural fluid LDH is more than the upper limit for as adenosine deaminase (ADA) or g-interferon.
the serum LDH or if the protein level is more than4.0 g/dL, the patient does not have a transudate.
These transudates that are misclassified as exudates Diseases that cause undiagnosed persistent pleural can be classified correctly if the difference or gradient between the protein levels in the serum and thepleural fluid is measured. If this gradient is greater When a patient with a persistent undiagnosed than 3.1 g/dL, the exudative classification by Light’s pleural effusion is encountered, the first step to be criteria can be ignored, because almost all such considered is the list of the diseases most likely to be patients have a transudative pleural effusion associated with a persistent undiagnosed pleural The protein gradient alone should not be used to effusion The first question to answer in a separate transudates from exudates because, by itself, patient with a persistent undiagnosed pleural effusion it misidentifies approximately 13% of exudates as is whether the effusion is a transudate or an exudate.
For the past several decades, this differentiation hasbeen made by measuring the levels of protein andlactate dehydrogenase (LDH) in the pleural fluid and in the serum (Light’s criteria). If one or more of thefollowing criteria are met, the patient has an exuda- Congestive heart failure is the most common 1. Pleural fluid protein or serum protein > 0.5 cause of pleural effusion At times in patients with 2. Pleural fluid LDH or serum LDH > 0.6 persistent pleural effusion, it is not obvious that the 3. Pleural fluid LDH > 0.67 the normal upper limit heart failure is the cause of the effusion. Certainly, symptoms of congestive heart failure, such asdyspnea on exertion, orthopnea, paroxysmal noctur- Light’s criteria are sensitive at identifying exu- nal dyspnea, and nocturia, should be sought when the dates, but they also identify up to 25% of transudative history is taken. In addition, signs of congestive heart pleural effusions as being exudative pleural effusions failure, such as basilar rales, S3 gallop, distended Usually, the transudates that are misclassified neck veins, and pedal edema, should be soughtduring the physical examination. If the patientclinically has congestive heart failure but the initial pleural fluid analysis reveals an exudate that just 0272-5231/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
have pleural fluid N terminal pro-BNP levels less produce a persistent undiagnosed pleuraleffusion If the patient has overt cirrhosis and massive ascites, the diagnosis of hepatic hydrothorax is easy.
If the patient does not have ascites, however, the diagnosis of hepatic hydrothorax may be difficult to establish. In 1998, Kakizaki and colleagues reviewed the literature and were able to find 28 cases of hepatic hydrothorax without ascites. Of these  Cerebrospinal fluid leaks to the pleura 28 cases, 27 were on the right side. The only left-sided effusion occurred in a patient who had a tear in the left diaphragm as a result of a splenectomy. Themean serum albumin in these 28 cases was 2.7 g/dL, with a range of 1.9 to 3.6 g/dL The explanation for the pleural effusion in the absence of overt ascites is that the patients have defects in their diaphragm.
When fluid is present in the peritoneal space, it flows immediately into the pleural space, because the pleu- ral pressure is negative compared with the peritoneal pressure. This diagnosis can be established by dem- onstrating radioactivity in the thorax after the intra- peritoneal injection of technetium-99m (99mTc)-sulfur  Ovarian hyperstimulation syndrome Rheumatoid pleuritis Another cause of a chronic transudative pleural effusion is the nephrotic syndrome. More than 20% of patients with the nephrotic syndrome have pleural effusions, which are usually bilateral Therefore, all patients with chronic transudative pleural effu- sions should be evaluated for proteinuria and hypoproteinemia. It should be remembered that the incidence of pulmonary emboli is high with the nephrotic syndrome and this possibility shouldbe considered in all patients with the nephroticsyndrome and a pleural effusion.
barely meets Light’s criteria, the difference betweenthe pleural fluid and serum protein should be measured as detailed previously. If this gradient isgreater than 3.1 g/dL, the effusion can be attributed to A transudative pleural effusion can result when the congestive heart failure. If the patient has a there is retroperitoneal urinary leakage secondary to transudative effusion but does not have obvious heart urinary tract obstruction or trauma with subsequent failure, further investigations of cardiac function, dissection of the urine into the pleural space such as echocardiography, are indicated. It has This diagnosis is easy if it is considered as the pleural recently been shown that measurement of the levels fluid looks and smells like urine. Confirmation of the of pro-brain natriuretic peptide (BNP) in pleural fluid diagnosis can be made by demonstrating that the is useful in establishing the diagnosis of congestive pleural fluid creatinine is greater than the serum heart failure. Patients with congestive heart failure creatinine The pleural fluid with urinothorax have pleural fluid N terminal pro-BNP levels greater may also have a low glucose level and a low pH than 1500 pg/mL, whereas almost all other patients level. The only other instances in which a transuda- tive pleural effusion has a low glucose or low pH suggestive of malignancy All 28 patients who level is when there is systemic hypoglycemia or had all four characteristics had a malignancy, whereas none of the 21 patients with one criterion at most hada malignancy When patients with pleural effusions attributable to the most common types of tumors are analyzed, On rare occasions, cerebrospinal fluid (CSF) can some interesting observations can be made. The collect in the pleural space and produce a pleural tumor that causes the highest number of pleural effusion. This most commonly occurs after ventricu- effusions is lung cancer When patients with lung lopleural shunting but can also occur after pene- cancer are first evaluated, approximately 15% have a trating injuries and fractures of the thoracic spine pleural effusion but 50% of patients with as well as after thoracic spinal surgery The disseminated lung cancer develop a pleural effusion diagnosis should be suggested by the appearance The tumor that causes the second highest number of the pleural fluid, which appears to be CSF. The of pleural effusions is breast cancer Patients with protein levels are usually very low. The diagnosis breast carcinoma rarely present with a pleural can be confirmed by radionuclide cisternography effusion. The mean interval between the diagnosis Another way to establish the diagnosis is by of the primary tumor and the appearance of a pleural demonstrating the presence of b2-transferrin in the effusion is 2 years Hematologic malignancies pleural fluid This substance is normally present (lymphomas and leukemias) cause the third highest number of malignant pleural effusions Approxi-mately 10% of patients with Hodgkin’s lymphomaand 25% of patients with non-Hodgkin’s lymphoma have pleural effusions at presentation. Those who doalmost invariably have intrathoracic lymph node involvement If the patient has AIDS andcutaneous Kaposi’s sarcoma, the likely diagnosis is There is no doubt that malignancy causes more a pleural effusion attributable to Kaposi’s sarcoma.
persistent undiagnosed exudative pleural effusions This diagnosis is usually established at bronchoscopy, than any other cause. It should be emphasized that which demonstrates erythematous or violaceous there is no huge hurry to establish this diagnosis, macules or papules in the respiratory tree however, because (1) the presence of the effusion There are several primary tumors of the pleura that indicates that the patient has metastases to the pleura should be considered if the patient has an undiag- and the malignancy cannot be cured surgically, (2) nosed pleural effusion. If the patient has a history of most malignant pleural effusions are attributable to asbestos exposure, mesothelioma should be consid- tumors that cannot be cured with chemotherapy, and ered. Thoracoscopy or thoracotomy is usually (3) there is no evidence that attempts to create a necessary to make this diagnosis If the patient pleurodesis early improve the quality of the pa- has AIDS and has a lymphocytic pleural effusion with a high LDH level, the diagnosis of a primary Most patients who have a pleural malignancy effusion lymphoma is likely This diagnosis usually have other characteristics suggesting malig- can usually be established with pleural fluid nancy. For example, in the series of 211 patients cytology and flow cytometry If the patient had received an artificial pneumothorax many years biopsy of the pleura was negative in 29 patients who previously, a likely diagnosis is pyothorax-associated were eventually proven to have malignant pleural effusions. All these patients were strongly suspectedof having a malignant effusion by clinical criteria, such as weight loss, constitutional symptoms, or ahistory of a previous cancer, however Ferrer and The diagnosis of parapneumonic effusion is easy coworkers recently evaluated the characteristics in the patient with an acute febrile illness, purulent of patients undergoing thoracoscopy who turned out sputum, and pulmonary infiltrates. On occasion, to have a malignancy. They found four clinical however, particularly with anaerobic infections, the characteristics that were suggestive of malignancy: patient may present with a chronic illness. In one symptoms for more than 1 month, absence of fever, study of 47 patients with anaerobic parapneumonic blood-tinged pleural fluid, and chest CT scan findings effusions, the median duration of symptoms before presentation was 10 days and 60% of the patients had onstrates concomitant parenchymal and pleural ab- substantial weight loss (mean of 29 lb) There- normalities and mediastinal lymphadenopathy.
fore, if the patient has a chronic illness withpredominantly neutrophils in the pleural fluid, it is imperative to obtain anaerobic cultures of the pleuralfluid. Because patients with actinomycosis and Fungal disease is responsible for a small percent- nocardiosis sometimes have a chronic pleural effu- age of pleural effusions At times, however, sion with predominantly neutrophils, cultures for blastomycosis and coccidioidomycosis may cause a these organisms should be obtained in patients with chronic lymphocytic pleural effusion Accord- chronic neutrophilic pleural effusions.
ingly, cultures for fungi should be obtained in thepatient with a chronic undiagnosed pleural effusion with predominantly lymphocytes in the pleural fluid.
It is unknown whether the lymphocytic effusions Throughout the world, tuberculosis remains one attributable to fungal diseases have a high ADA level.
of the principal causes of pleural effusion. It isimportant to make this diagnosis, because if the patient has pleural tuberculosis and is not treated, theeffusion resolves but the patient has a greater than This is one diagnosis that should always be 50% chance of developing active pulmonary or considered in a patient with a chronic undiagnosed extrapulmonary tuberculosis over the next 5 years pleural effusion. Some patients with a pancreatic Therefore, all patients with a chronic undiag- pseudocyst develop a direct sinus tract between the nosed pleural effusion should be evaluated for tuber- pancreas and the pleural space The sinus tract culosis. The easiest way to do this is to measure decompresses the pancreas; therefore, the patient the pleural fluid level of ADA or g-interferon. If the presents with symptoms usually referable only to level of ADA is less than 40 IU/L or the level of the chest. The patient with a chronic pancreatic g-interferon is less than 140 pg/mL, the diagnosis can pleural effusion is usually chronically ill and looks be virtually excluded In one study, Ferrer and like he or she has cancer. The diagnosis is virtually colleagues followed 40 patients with a chronic established if the level of amylase in the pleural fluid undiagnosed pleural effusion and a pleural fluid ADA is greater than 1000 U/L It is important to level less than 43 IU/L for a mean of 5 years, and consider this diagnosis, because the patient can be none developed tuberculosis. Patients with lympho- cytic pleural effusions because of other etiologiesalmost always have pleural fluid ADA levels less than 40 IU/L If the pleural fluid ADA level isgreater than 40 IU/L or the level of g-interferon Subphrenic, intrahepatic, intrasplenic, and intra- exceeds 140 pg/mL and empyema and rheumatoid pancreatic abscesses are all associated with a pleural pleuritis are excluded, the patient probably has effusion in a large percentage of patients Patients with an intra-abdominal abscess are usually chroni-cally ill with fever and weight loss. The pleural fluid is sterile and contains predominantly neutrophils. Thediagnosis can be made with a CT or ultrasound scan The diagnosis of a pulmonary embolism should be considered in every patient with an undiagnosedpleural effusion. Pleural effusions occur in at least Effusion after coronary artery bypass graft surgery 30% of patients with pulmonary emboli andthey are almost always exudative Most pleural Approximately 10% of patients who undergo effusions associated with pulmonary emboli are coronary artery bypass graft (CABG) surgery have small, and it is uncommon for the effusion to occupy a pleural effusion that occupies more than 25% of more than one third of the hemithorax Patients their hemithorax 28 days after surgery The with undiagnosed pleural effusions should have the primary symptom (if any) of a patient with a post- possibility of a pulmonary embolism investigated CABG pleural effusion is dyspnea; chest pain and with a spiral CT scan The spiral CT scan not fever are distinctly unusual The pleural fluid in only identifies vascular filling defects, which are these patients is an exudate characterized by a highly suggestive of pulmonary embolism, but dem- predominance of lymphocytes and an LDH level approximately equal to the upper limit of normal for and an exudative pleural effusion, the diagnosis of serum Although the pleural fluid is similar to constrictive pericarditis should be considered. It is the pleural fluid in patients with tuberculous pleuritis, important to realize that the findings of echocardi- these two entities may be differentiated by the pleural ography may be normal in the patient with constric- fluid level of ADA; the ADA level is less than 40 U/L tive pericarditis and that cardiac catheterization may in patients with a post-CABG effusion The importance of these effusions is to know that they canpersist for years on rare occasions and not to be too aggressive in pursuing a diagnosis if the pleuralfluid findings are as expected.
Meigs’ syndrome is the constellation of a benign pelvic neoplasm associated with ascites and pleural effusion in which surgical extirpation of the tumorresults in permanent disappearance of the ascites and Postcardiac injury syndrome (PCIS), also known pleural effusion The pleural fluid is an exudate as Dressler’s syndrome, is characterized by the with a relatively low cell count, which may some- development of fever, pleuropericarditis, and paren- chymal pulmonary infiltrates in the weeks after importance of Meigs’ syndrome is that not all patients trauma to the pericardium or myocardium The with a pelvic mass, ascites, and a pleural effusion PCIS has been reported after myocardial infarction, cardiac surgery, blunt chest trauma, percutaneous leftventricular puncture, pacemaker implantation, and angioplasty. The PCIS differs from the pleuraleffusion after CABG surgery, because fever and chest This syndrome is a serious complication of pain invariably occur with the PCIS and are rare after ovulation induction. The clinical picture is charac- CABG surgery. After cardiac injury, symptoms terized by massive ovarian enlargement with multiple usually develop between the first and third weeks cysts, hemoconcentration, and the third space accu- but can develop any time between 3 days and 1 year mulation of fluid. Patients with the syndrome present The pleural fluid is frankly bloody in approxi- within 2 to 3 weeks after receiving the human mately 30% of patients, and the differential cell count chorionic gonadotropin with abdominal pain and may reveal predominantly neutrophils or mononu- distention; a nonproductive cough; and dyspnea clear cells, depending on the acuteness of the pro- caused by the ascites, pleural effusion, or both. The pleural effusion is usually bilateral, and the pleuralfluid is an exudate with predominantly neutrophils pericardial effusion have a concomitant pleuraleffusion In patients with inflammatory pericar- Chronic pleural effusions may be a manifestation ditis, most of the associated pleural effusions are of rheumatoid pleuritis, and the diagnosis is usually unilateral and left-sided The characteristics of straightforward. Classically, the effusion occurs in the pleural fluid seen in conjunction with pericardial older men who have subcutaneous nodules. The pleu- disease are not well described The possibility ral fluid is an exudate with low glucose, low pH, and of pericardial effusion should be evaluated in any high LDH levels. The first manifestation of rheuma- patient with cardiomegaly and an isolated left pleu- toid disease is virtually never a pleural effusion Approximately 60% of patients with constrictive pericarditis have a concomitant pleural effusion The associated pleural effusion is bilateral and In contrast to rheumatoid pleuritis, patients with symmetric in most of these patients. In one report of systemic lupus erythematosus (SLE) may present four patients with constrictive pericarditis, the pleural with a pleural effusion. The possibility of drug- fluid was transudative in one and exudative in three induced lupus should always be considered in a We recently reported one patient with constric- patient with an undiagnosed pleural effusion. Drugs tive pericarditis who had a pleural fluid protein level that are most commonly incriminated in drug-induced of 4.0 g/dL When a patient is seen with edema lupus are hydralazine, procainamide, isoniazid, phe- nytoin, and chlorpromazine The diagnosis of manifest at widely varying times. The pleural SLE with pleural involvement is based on the usual effusions are bilateral in approximately 50% of criteria for the diagnosis of lupus. Measurement of patients and vary in size from small to massive the pleural fluid antinuclear antibody (ANA) levels Once a pleural effusion has occurred with this or performance of lupus erythematosus prepa- syndrome, it tends to persist and recur rapidly after rations on the pleural fluid do not assist in a thoracentesis. The pleural fluid is usually a clear yellow exudate with a normal glucose level andpredominantly lymphocytes in the pleural fluid differential. The pleural fluid LDH level tends to below relative to the pleural fluid protein level.
When a patient is evaluated with a chronic undiagnosed pleural effusion, the list of drugs that the patient is taking should be carefully reviewed,because the ingestion of certain drugs can lead to the The prevalence of pleural effusions with uremia is development of a pleural effusion. The primary drugs approximately 3% As many as 50% of patients associated with the development of a pleural effusion on long-term hemodialysis have a pleural effusion are nitrofurantoin (a urinary antiseptic), dantrolene There is not a close relation between the degree (a muscle relaxant), and the ergot alkaloids, such as of uremia and the occurrence of a pleural effusion bromocriptine or pergolide, that are used to treat More than 50% of the patients are symptomatic, Parkinson’s disease Other drugs that have been with fever (50%), chest pain (30%), cough (35%), reported to induce pleural effusions include methy- and dyspnea (20%) being the most common symp- sergide, amiodarone, procarbazine, methotrexate, toms The pleural fluid is an exudate, and the clozapine, dapsone, metronidazole, mitomycin, iso- differential usually reveals predominantly lym- tretinoin, propylthiouracil, simvastatin, warfarin, and phocytes Tests of renal function should be obtained in every patient with an undiagnosed exu- induced pleural effusions have peripheral eosino- philia. When the drug is discontinued, the effusionusually resolves rapidly When there is intense inflammation in the pleural space, a fibrous peel may form over the visceral Exposure to asbestos can lead to the development pleura. This peel can prevent the underlying lung of an exudative pleural effusion. In one series of from expanding; therefore, the lung is said to be 1135 asymptomatic asbestos workers, the prevalence trapped The initial event producing the pleural of pleural effusion was 3% In this series, all the inflammation is usually a pleural infection or a patients developed effusions within 20 years of the hemothorax, but it can be a spontaneous pneumo- initial exposure and many had done so within 5 years thorax, thoracic operations (particularly CABG sur- of the initial exposure The prevalence of pleural gery) uremia, or collagen vascular disease. The effusion was directly related to the total asbestos pleural fluid is usually clear yellow and is a border- exposure. Patients with asbestos pleural effusions are line exudate with predominantly mononuclear cells.
usually asymptomatic The effusion tends to The diagnosis can be made by measuring the pleu- last several months and then clears, leaving no ral pressure while fluid is withdrawn during a residual disease. The pleural fluid is an exudate and thoracentesis. If the initial pleural pressure is less can contain predominantly neutrophils or mononu- than À10 cm H2O or if the pleural pressure falls more clear cells If a patient with a pleural effusion has than 20 cm H2O per 1000 mL of fluid removed, the a history of asbestos exposure and is asymptomatic, diagnosis is confirmed provided that the patient the patient can probably be observed to determine if the effusion disappears spontaneously.
When pleural fluid is found to be milky or ex- The yellow nail syndrome consists of the triad of tremely turbid, the possibility of a chylothorax or a deformed yellow nails, lymphedema, and pleural pseudochylothorax should be considered. When tur- effusions The three separate entities may become bid fluid is found, the first step is to centrifuge the fluid. If the supernatant remains turbid, the The patient should be questioned carefully regarding turbidity is attributable to a high lipid content in the medications he or she is taking to determine the pleural fluid and the patient has a chylothorax whether he or she is taking a medication that causes a pleural effusion or is associated with drug-induced A chylothorax is usually easy to differentiate from lupus erythematosus. The patient should be ques- a pseudochylothorax on clinical grounds. Patients tioned carefully about previous pleural problems, with a chylothorax have an acute illness, and their which raise the likelihood of a pseudochylothorax or pleural surfaces are normal on CT. In contrast, patients with a pseudochylothorax usually have hada pleural effusion for more than 5 years, and their pleural surfaces are markedly thickened on CT.
Measurement of the lipid levels in the pleural fluid In the patient with a chronic undiagnosed pleural is also useful in distinguishing these two conditions.
effusion, it is worthwhile to repeat a careful physical Pleural fluid from a chylothorax has a triglyceride examination. If the patient has a transudative pleural level greater than 110 mg/dL, and the ratio of the effusion, signs of congestive heart failure, such as pleural fluid to serum cholesterol is less than 1.0. In basilar rales, an S3 gallop, or distended neck veins, contrast, fluid from a pseudochylothorax has choles- should be sought. In addition, evidence of ascites terol crystals or a cholesterol level greater than should be carefully sought. The presence of pedal 200 mg/dL and higher than the simultaneous serum edema suggests congestive heart failure, cirrhosis with hepatic hydrothorax, nephrotic syndrome, peri-cardial disease, or the yellow nail syndrome.
If the patient has an exudative effusion, a careful Tests to consider for patients with persistent search for lymphadenopathy or other masses that would suggest malignancy is indicated. In women,a careful breast examination and a careful pelvic examination should be done to evaluate these loca-tions for masses. Abdominal tenderness suggests an There are certain points in the patient’s history that intra-abdominal abscess. Distant heart sounds, a peri- should receive special attention if the patient has a cardial friction rub, or Kussmaul’s sign (increased persistent undiagnosed pleural effusion. If a patient jugular venous pressure that increases during inspi- has a transudative pleural effusion, particular attention ration) suggests pericardial disease. Ascites and a should be paid to symptoms of congestive heart pelvic mass raise the possibility of Meigs’ syndrome.
failure, such as dyspnea on exertion, orthopnea, Deformed joints and subcutaneous nodules make paroxysmal nocturnal dyspnea, and nocturia. In rheumatoid pleuritis likely. The presence of yel- addition, historical evidence of cirrhosis, alcoholism, low nails establishes the diagnosis of the yellow or chronic hepatitis should be sought with the possibility of a hepatic hydrothorax in mind. A historyof trauma or surgery to the thoracic spine should be sought with the diagnosis of a CSF leak in mind.
If the patient has an exudative pleural effusion, a Several blood tests should be routinely obtained in history of malignancy should be sought. Malignant patients with a persistent undiagnosed pleural effu- pleural effusions have been known to develop as long sion. The level of albumin and globulin should be as 20 years after the primary tumor was diagnosed measured to determine whether the patient has A history of exposure to asbestos should be cirrhosis or the nephrotic syndrome, and liver sought, because this would suggest mesothelioma or function tests should be obtained to ascertain if there an asbestos pleural effusion. A history of fever is chronic hepatitis. Additionally, I obtain a complete suggests a chronic anaerobic, tuberculous, or fungal blood cell count with a differential. A serum ANA infection or an intra-abdominal abscess. A history of test should be obtained with the diagnosis of SLE in alcoholism or previous pancreatic disease raises the mind. Blood urea nitrogen (BUN) and creatinine possibility of a chronic pancreatic pleural effusion. A levels should be obtained to evaluate the possibility history of CABG surgery or myocardial trauma of uremia, and a urinalysis should be obtained to suggests a post-CABG surgery pleural effusion or the PCIS, respectively. A history of rheumatoid Several special tests on the pleural fluid are also disease raises the possibility of rheumatoid pleuritis.
indicated. The least expensive test is to smell the pleural fluid. If the pleural fluid smells like urine, the most series, however, cytology is much more patient probably has an urinothorax, whereas if the sensitive in establishing the diagnosis. Moreover, pleural fluid smells feculent, the patient probably has if the cytology of the fluid is negative, the pleural an anaerobic pleural infection. As mentioned pre- biopsy is usually nondiagnostic. In one series of viously, the ADA or g-interferon should be measured 118 patients from the Mayo Clinic who had a ma- in the pleural fluid to assess whether the patient has lignancy involving the pleura but negative pleu- pleural tuberculosis. Flow cytometry on the pleural ral fluid cytology, the needle biopsy of the pleura fluid is indicated if lymphoma is suspected If was positive in only 20 (17%) patients Because the pleural fluid is milky or cloudy, it should be thoracoscopy is diagnostic in more than 90% of pa- centrifuged, and if the supernatant remains milky or tients with a pleural malignancy and negative cy- cloudy, the pleural fluid should be sent for measure- tology, it is the preferred diagnostic procedure in ment of cholesterol and triglycerides. Every time a patients with a cytology-negative pleural effusion thoracentesis is performed in a patient with a who are suspected of having a pleural malignancy.
persistent undiagnosed pleural effusion, a pleural A needle biopsy of the pleura is indicated if the pa- fluid LDH level should be determined. If this LDH tient has an undiagnosed pleural effusion that is level tends to decrease with time, the pleural process not improving and thoracoscopy is not available. A is resolving and one can be conservative in the needle biopsy of the pleura is also indicated if pleural approach to the patient. Alternatively, if the LDH tuberculosis is suspected and a pleural fluid marker level is increasing with time, the process is getting for tuberculosis is unavailable or equivocal If the worse and one should be aggressive in pursuing a patient has pleura thickening on contrast-enhanced CT, consideration should be given to performing animage-guided cutting needle biopsy of the pleura. In one report the diagnosis of mesothelioma wasestablished in 18 (86%) of 21 patients.
Most patients with an undiagnosed persistent pleural effusion should have a spiral CT scan of the chest. With the spiral CT scan, the diagnosisof pulmonary emboli can be established In When one is dealing with patients with pleural addition, parenchymal infiltrates and masses, pleural effusions, thoracoscopic procedures should be used masses or thickening, and mediastinal lymphadenopa- only when less invasive diagnostic methods, such as thy can be identified. Finally, pericardial thickening thoracentesis with cytology and markers for tuber- and pericardial effusions can be identified on the culosis, have not yielded a diagnosis. In the series of CT scan. While the patient is receiving the CT scan, it 620 patients reported by Kendall and coworkers is reasonable to obtain abdominal cuts also. These can only 48 (8%) required thoracoscopy for a diagnosis.
demonstrate abdominal masses, lymphadenopathy, The final diagnoses in these 48 patients were a and ascites. An echocardiogram is indicated if malignancy in 24, a parapneumonic effusion in 7, a congestive heart failure is suspected but is not rheumatoid pleural effusion in 4, congestive heart definitely established and if a pericardial effusion is failure in 3, and pulmonary interstitial fibrosis in 2. In suspected. It is important to remember that the 8 patients, no diagnosis was established with the echocardiogram may not reveal any abnormality if combination of the clinical presentation and thora- the patient has constrictive pericarditis If coscopy; 6 of these patients were subsequently constrictive pericarditis is suspected, the patient diagnosed has having a malignancy (mesothelioma should undergo right heart catheterization.
in 3 patients and adenocarcinoma in 3 patients) In general, if the patient has a malignancy, thoracoscopy establishes the diagnosis in approxi-mately 90% of cases The diagnosis of For the past 50 years, most cases of tuberculous tuberculous pleuritis can almost always be estab- pleuritis have been diagnosed with a needle biopsy of lished with thoracoscopy It should be empha- the pleura. In the past 10 years, however, it has been sized, however, that thoracoscopy rarely establishes demonstrated that markers for tuberculosis obtained the diagnosis of benign disease other than tuber- from the pleural fluid, such as the ADA or culosis One advantage of thoracoscopy in the g-interferon, are efficient at establishing this diagno- diagnosis of pleural disease is that pleurodesis can be sis. The other diagnosis that can be established with performed at the time of the procedure. In general, a needle biopsy of the pleura is pleural malignancy. In thoracoscopy is indicated in the patient with an undiagnosed pleural effusion who is not improving had no recurrence of their pleural effusion; however, spontaneously, provided that the patient has a sig- 13 of these 51 patients were eventually found to have nificant likelihood of malignancy or tuberculosis.
malignant disease (lymphoma in 6 patients, meso-thelioma in 4 patients, and other malignancy in3 patients). In another study of 21 patients subjected to open pleural biopsy for undiagnosed pleural effu-sion, no diagnosis was obtained in 7 (33%) Bronchoscopy can be diagnostically useful in patients with a pleural effusion if the patient hasone of the following four characteristics When faced with a patient with an undiagnosed 1. A pulmonary infiltrate is present on the chest pleural effusion, the first question to be answered is radiograph or chest CT. If an infiltrate is present, whether the patient has a transudate or an exudate.
particular attention should be paid to the area This is most commonly done with Light’s criteria. If with the infiltrate at the time of bronchoscopy.
it seems clinically that the patient has a transudative 2. Hemoptysis is present. The presence of hemop- effusion but Light’s exudative criteria are met, the tysis in the patient with a pleural effusion in- demonstration of a serum pleural fluid protein creases the likelihood of malignancy with an gradient of greater than 3.1 g/dL indicates that the endobronchial lesion or pulmonary embolus. The effusion is transudative. The diagnosis of congestive former can be diagnosed with bronchoscopy.
heart failure is strongly suggested if the pleural fluid 3. The pleural effusion is massive. The most com- BNP level is greater than 1500 pg/mL. Patients with mon cause of a massive pleural effusion is undiagnosed exudative effusions should have a spiral malignancy, particularly lung cancer, and this CT scan to evaluate the possibility of a pulmonary diagnosis can be established at bronchoscopy.
embolism and to demonstrate parenchymal, pleural, The other two leading causes of massive pleu- or mediastinal disease. Patients with a malignant ral effusion are hepatic hydrothorax and tuber- pleural effusion usually have the following character- culous pleuritis; these diagnoses cannot be istics: symptoms for more than 1 month, absence of fever, blood-tinged pleural fluid, and chest CT scan 4. The mediastinum is shifted toward the side of the effusion. With this finding, an obstruct-ing endobronchial lesion is probably respon-sible, and this can be identified and biopsied [1] Light RW, MacGregor MI, Luchsinger PC, et al.
Pleural effusions: the diagnostic separation of transu-dates and exudates. Ann Intern Med 1972;77:507 – 14.
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video-assisted thoracoscopy. If both procedures are [3] Burgess LJ, Maritz FJ, Taljaard JJ. Comparative available, thoracoscopy is usually preferred because it analysis of the biochemical parameters used to dis- is associated with less morbidity. The primary tinguish between pleural transudates and exudates.
indication for an open pleural biopsy is progressive undiagnosed pleural disease in an institution where [4] Romero-Candeira S, Hernandez L, Romero-Brufao S, thoracoscopy is not available or when there is a et al. Is it meaningful to use biochemical parameters to contraindication for thoracoscopy, such as marked discriminate between transudative and exudative pleu- adhesions between the visceral and parietal pleura.
ral effusions? Chest 2002;122:1524 – 9.
One should realize that even with an open biopsy [5] Romero-Candeira S, Fernandez C, Martin C, et al.
Influence of diuretics on the concentration of proteins of the pleura, a diagnosis is not always obtained. In and other components of pleural transudates in patients one study, the experience at the Mayo Clinic between with heart failure. Am J Med 2001;110:681 – 6.
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Effects of childhood body size on breast cancer tumour characteristics Jingmei Li1,2, Keith Humphreys1, Louise Eriksson1, Kamila Czene1, Jianjun Liu2 and Per 1Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Box 281, 171 2Human Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672, Corresponding author: Jingmei Li, Jingmei.Li@ki.se A

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