MPE is usually associated with a severe increase of pleural fluid and many patients carry several liters of such liquid in their thoracic cavities. This amount of pleural fluid interferes with lung expansion and causes dyspnea and dull chest pain [7]. Of note, in case of unilateral MPE, a mediastinal shift may occur and cause compression of the contralateral lung. Therefore, breathing difficulties are not necessarily less severe in these patients.

Large amounts of pleural fluid dampen breathing sounds that are heard during auscultation and result in dullness to percussion.

Because MPE is generally diagnosed in patients suffering from metastasizing cancer, they often present with malaise, loss of appetite, weight loss or cachexia, anemia, leukocytosis and other symptoms considered part of the paraneoplastic syndrome.

Depending on the primary tumor and tumor staging, additional symptoms may be present. They may range from hoarseness, chronic cough and hemoptysis in case of bronchogenic carcinoma to fever, lymphadenopathy and recurrent infections in patients suffering from lymphoproliferative disorders.

• Pain

  NSAIDS can be used for pain control and do not adversely impact the chance of successful pleurodesis. [ncbi.nlm.nih.gov]

  Pain control with NSAIDs was not superior to opioid treatment, with comparable mean pain scores while the chest tube was in situ, as assessed by the visual analogue scale, of 22.1 and 23.8 mm, respectively. [oncologypro.esmo.org]

• Congestive Heart Failure

  The most common cause of pleural effusion is congestive heart failure. Lung diseases, like COPD, tuberculosis, and acute lung injury, cause pneumothorax. Injury to the chest is the most common cause of hemothorax. [icdlist.com]

  Pleural effusions are caused principally by congestive heart failure, malignancy, and infection. Patients present with the symptoms of cough, dyspnea, decreased exercise tolerance, and chest pain. [meds.com]

  The majority of these are caused by Congestive Heart Failure (CHF), pneumonia, malignancy, and pulmonary emboli [ 1 ]. Approximately 178,000 thoracenteses are performed each year in the U.S. in an effort to assist with diagnosis or therapy [ 2 ]. [omicsonline.org]

  In addition to asbestos-related causes, pleural effusion may arise from other conditions, including pneumonia, tuberculosis, pulmonary embolism, various cancers and congestive heart failure. [asbestos.com]

  Of note, severe pleural effusions may be caused by a variety of other pathologies that should be considered as possible differential diagnoses: Congestive heart failure is related to an increased preload and elevated hydrostatic pressure. [symptoma.com]

• Recurrent Pleural Effusion

  Unfortunately, he died for recurrent pleural effusion and pulmonary complication 6 months later. Identifying the origin of malignant pleural effusion is important to provide treatment guidance. [ncbi.nlm.nih.gov]

  Intervention: Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. [doi.org]

  An indwelling pleural catheter offers a novel means to manage recurrent malignant pleural effusion and may remove the need for repeated thoracocentesis. [hkmj.org]

  Recurrent malignant pleural effusion due to pleural carcinosis is one of the most common findings in oncology. It affects about 56 000 patients per year in Germany alone. [aerzteblatt.de]

• Pathologist

  Diagnosing a malignant pleural effusion To diagnose a malignant pleural effusion, a pathologist studies a pleural fluid sample to look for cancer cells. [swedish.org]

• Infertility

  Measuring the amount of AMH in the blood may help diagnose infertility and other conditions, such as polycystic ovarian syndrome, menopause, and certain types of ovarian tumors. [cancer.gov]

• Pleural Effusion

  BACKGROUND: Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. [ncbi.nlm.nih.gov]

  FDA-regulated Device Product: No Keywords provided by Lui Mei Sze, The University of Hong Kong: malignant pleural effusion lung cancer Additional relevant MeSH terms: Layout table for MeSH terms Lung Neoplasms Pleural Effusion Pleural Effusion, Malignant [clinicaltrials.gov]

• Malignant Pleural Effusion

  INTRODUCTION: Malignant pleural effusion can be recurrent despite active anti-cancer treatment. Significant malignant pleural effusion leads to debilitating dyspnoea and worsening quality of life in patients with advanced cancer. [ncbi.nlm.nih.gov]

  FDA-regulated Device Product: No Keywords provided by Lui Mei Sze, The University of Hong Kong: malignant pleural effusion lung cancer Additional relevant MeSH terms: Layout table for MeSH terms Lung Neoplasms Pleural Effusion Pleural Effusion, Malignant [clinicaltrials.gov]

• Dyspnea

  A 73-year-old man presented with dyspnea, right-sided pleural effusion, and bilateral pulmonary infiltrates. [ncbi.nlm.nih.gov]

  Though some patients are initially asymptomatic, the majority will eventually develop dyspnea at rest. [doi.org]

• Cough

  Most common presenting symptoms were breathlessness (86%) and cough (86%). All (100%) of the malignant pleural effusions were exudative. Pleural fluid cytology was positive in 86% while pleural biopsy was positive only in 44%. [ncbi.nlm.nih.gov]

  Dyspnea and cough were significant symptoms in one study 4which is consistent with our finding. In our study, breathlessness, cough, chest pain, weight loss, loss of appetite, and sputum production are common symptoms of malignant pleural effusion. [internalmedicine.imedpub.com]

• Pleuritic Pain

  Pleuritic pain and hypertensive peaks were the most frequently observed serious adverse events (11 and 10 episodes, respectively). [ncbi.nlm.nih.gov]

  Patients may be asymptomatic or have pleuritic pain. If associated with a sizeable pleural effusion, then respiratory compromise may be evident. If a tumor is from the chest wall, then musculoskeletal pain or even a palpable mass may be present. [radiopaedia.org]

  Many cause dyspnea, pleuritic chest pain, or both. Pleuritic chest pain, a vague discomfort or sharp pain that worsens during inspiration, indicates inflammation of the parietal pleura. [merckmanuals.com]

  One patient experienced vasovagal reflex during the procedure with systemic hypotension and intense pleuritic pain. Hypotension was treated with intravenous fluids and the pain was controlled with narcotics. The patient recovered without incident. [ispub.com]

  Pulmonary embolism (tends to produce a comparatively small effusion but disproportionate dyspnoea and pleuritic pain; 80% are exudates, 20% are transudates). Rare causes: Superior vena cava obstruction (usually due to lung cancer). [patient.info]

• Heart Failure

  This situation most commonly is seen in patients with heart failure. The disappearance of the apparent mass when the heart failure is treated definitively establishes the diagnosis of pseudotumor (i.e., vanishing tumor). [aafp.org]

  The most common cause of pleural effusion is congestive heart failure. Lung diseases, like COPD, tuberculosis, and acute lung injury, cause pneumothorax. Injury to the chest is the most common cause of hemothorax. [icdlist.com]

  Additionally, venous return to the heart is largely restricted by the increased intrathoracic pressure and this condition may eventually cause heart failure. As per definition, MPE is associated with malignant neoplasms. [symptoma.com]

  Heart failure is the most common cause, followed by cirrhosis with ascites and by hypoalbuminemia, usually due to the nephrotic syndrome. [merckmanuals.com]

  Pleural effusions are caused principally by congestive heart failure, malignancy, and infection. Patients present with the symptoms of cough, dyspnea, decreased exercise tolerance, and chest pain. [meds.com]

• Withdrawn

  A minimum 50 to 60mL of pleural fluid should be withdrawn for analysis).  Consider sending larger volumes of fluid (100- 200mL) for cell block and molecular testing (e.g. epidermal growth factor receptor [EGFR]). 23.  Conclusive evidence of a malignant [slideshare.net]

  As fluid is withdrawn, pleural pressure will drop slowly and the lung will expand gradually. Once the entire effusion has been removed, the lung will make contact with the chest wall and the elastance obtained will be normal. [thoracicmedicine.org]

  Our results are in contrast to those of previous meta-analyses 5, including the recently withdrawn Cochrane analysis which suggested improved success rates of talc pleurodesis utilizing TTI. [f1000research.com]

  Observations on pleural pressures as fluid is withdrawn during thoracentesis. Am Rev Respir Dis. 1980;121:799–804. 70. Salamonsen MR, Lo AK, Ng AC, et al. [dovepress.com]

  Observations on pleural pressures as fluid is withdrawn during thoracentesis. Am Rev Respir Dis 1980 ; 121 : 799 –804. ↵ Lan RS, Lo SK, Chuang ML, Yang CT, Tsao TCY, Lee CH. [doi.org]

Anamnestic data, particularly in patients with a medical history of malignancies, should prompt the suspicion of MPE in patients presenting with dyspnea and diminished breathing sounds.

Quantities of pleural fluid that exceed 250 ml are generally well visible on plain radiographs obtained in lateral decubitus position. Even smaller amounts may be detected applying sonography [8]. The latter technique may also guide the aspiration of a fluid sample by thoracocentesis. This sample should then be examined chemically and cytologically. MPE is an exudative type of pleural effusion and thus, each µl contains more than 30 µg of protein and significantly more than 1,000 cells. Its specific weight is > 1018. Cytologic analysis may reveal important hints as to the underlying cancerous process. If a precise diagnosis cannot be made, a pleural biopsy may be required and should be obtained under sonographic guidance or via thoracoscopy [9]. Of note, severe pleural effusions may be caused by a variety of other pathologies that should be considered as possible differential diagnoses:

• Congestive heart failure is related to an increased preload and elevated hydrostatic pressure.
• Conditions like malnutrition, protein losing enteropathy, renal or hepatic insufficiency may lead to hypoalbuminemia and thereby evoke pleural effusion.
• Vasculopathies affecting capillary permeability may account for excess filtration of pleural fluid.
• Pulmonary disorders associated with atelectasis, possibly due to endobronchial obstruction, lead to more negative intrathoracic pressures and cause an increase of pleural fluid.
• Additionally, inflammatory processes taking place within the thoracic cavity, mainly those related to pneumonia, may impede adequate lymph drainage by obstruction of lymphatic vessels.
• Direct obstruction of the thoracic duct will also cause pleural effusion.

Some of these conditions may be caused by a malignant neoplasm and in these cases, the patient should be diagnosed with paramalignant pleural effusion instead of MPE [10]. Some patients may present both MPE and paramalignant pleural effusion.

Although radiography and/or sonography may be helpful in assessing the overall condition of the thoracic cavity, magnetic resonance imaging and computed tomography scans are usually applied to detect pulmonary, cardiac and pleural pathologies as well as neoplasms located in extrathoracic organs.

The result of diagnostic imaging should be used to prepare treatment, i.e., to evaluate the severity, extent and localization of pleural effusion.

• Atelectasis

  With regards to the lungs, atelectasis may diminish the intrathoracic space occupied by the lungs, may reduce intrathoracic pressure and increase the pull on capillaries. [symptoma.com]

  If the lung does not re-expand to touch the chest wall, one must consider pleural adhesions or lung entrapment by tumor preventing full expansion, or atelectasis due to endobronchial obstruction by tumor. [clevelandclinicmeded.com]

  However, it is indicated when endobronchial lesions are suspected because of haemoptysis, atelectasis, or large effusions without contralateral mediastinal shift. [intechopen.com]

  His chest X-ray was suggestive of bilateral pleural effusion with ill-defined ground glass opacity and basal atelectasis with multiple lytic lesions. [casereports.in]

  This is also preferred in those patients having atelectasis and pulmonary infiltrates on chest X-ray and/or CT scan. [lungindia.com]

• Mediastinal Shift

  A patient presented to the emergency department with a malignant pleural effusion associated with shortness of breath, and radiographic evidence of mediastinal shift and hypotension. [ncbi.nlm.nih.gov]

  There may not be a mediastinal shift if the mediastinum is fixed secondary to a large lung mass or lymphadenopathy. A decubitus film may show layering of the fluid. [clevelandclinicmeded.com]

  However, it is indicated when endobronchial lesions are suspected because of haemoptysis, atelectasis, or large effusions without contralateral mediastinal shift. [doi.org]

  Massive right pleural effusion resulting in mediastinal shift to the left. Right-sided pleural effusion after partial drainage showing improved left mediastinal shift. [emedicine.medscape.com]

  Of note, in case of unilateral MPE, a mediastinal shift may occur and cause compression of the contralateral lung. Therefore, breathing difficulties are not necessarily less severe in these patients. [symptoma.com]

• Pericardial Effusion

  For pericardial effusions due to inflammation of the sac, treating the inflammation also treats the effusion. [webmd.com]

  Article / Publication Details First-Page Preview Abstract Advanced malignant tumors are often associated with malignant pleural and/or pericardial effusions. [karger.com]

  In our series, of 7 patients with transudative pleural effusion, 6 may have been caused by pericardial effusion, mediastinal involvement of the malignancy, and obstruction of the bronchus and great vessels in other words, by the malignancy itself. [kjim.org]

  Abstract Malignant fluid, a commonly seen tumor associated complication, mainly includes peritoneal effusion, malignant pleural effusion and pericardial effusion. [ncbi.nlm.nih.gov]

  Controlling malignant pericardial effusion by intrapericardial carboplatin administration in patients with primary non-small-cell lung cancer. Br J Cancer. 2000; 83（7）: 858-62. [haigan.gr.jp]

• Pleural Mass

  […] differential of nodular pleural thickening differential of a pleural effusion differential of a single pleural mass Promoted articles (advertising) [radiopaedia.org]

  There was also involvement of bilateral neural foramina along the entire length of mass interval with increased pleural effusion and paraspinal mass in the lower chest. [casereports.in]

  […] fluid, or [ 4 ] CT findings suggestive of malignancy (pulmonary or pleural masses, pulmonary atelectasis, or lymphadenopathy) [ 43 ]. [intechopen.com]

• Pleural Effusion

  BACKGROUND: Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. [ncbi.nlm.nih.gov]

  FDA-regulated Device Product: No Keywords provided by Lui Mei Sze, The University of Hong Kong: malignant pleural effusion lung cancer Additional relevant MeSH terms: Layout table for MeSH terms Lung Neoplasms Pleural Effusion Pleural Effusion, Malignant [clinicaltrials.gov]

In general, treatment for MPE is palliative. Removal of fluid may be realized by means of thoracocentesis, thoracostomy or implantation of an indwelling pleural catheter. The latter options allow for continuous drainage of accumulating pleural fluid, while thoracocentesis is an acute measure that may have to be repeated if reaccumulation of fluid is not prevented effectively.

Reduction of the pleural space by means of pleurodesis may be required to avoid renewed pleural effusion. In order for pleural adhesion to occur, excess pleural fluid needs to be drained previously by any of the aforementioned methods. Otherwise, the accumulated fluid in the pleural space may impede contact of visceral and parietal pleura. Distinct methods are available: Instillation of talc or other mediators of sterile inflammation causes adhesion of visceral and parietal pleura in what is known as chemical pleurodesis. On the other hand, surgical or mechanical pleurodesis requires roughening of the pleura, i.e., mechanical irritation to induce an inflammatory reaction.

The average life expectancy of people diagnosed with MPE is six months and the majority of patients does not survive for more than a year [7]. Because MPE is associated with malignancies, often with metastasizing tumors, morbidity and mortality do not only result from respiratory insufficiency due to pleural effusion but also from the underlying disease.

MPE results from the presence of neoplastic cells within the pleural space. Tumor cells may reach the pleura via the lymphatic system - which is indeed the most common way of metastatic spread into the pleura -, via blood vessels or by direct infiltration from adjacent tissues.

Carcinoma of the respiratory tract, namely lung adenocarcinoma and bronchogenic carcinoma, is most frequently diagnosed in MPE patients [3]. Breast carcinoma and distinct types of lymphoproliferative disease, both Hodgkin's disease and non-Hodgkin's lymphoma, tend to metastasize into the pleura, too. According to current estimates, mesothelioma accounts for less than 10% of all MPE cases. In some patients diagnosed with MPE, no primary tumor can be identified.

MPE is a common complication of advanced malignancy and it has been estimated that 10-20% of all patients who die from cancer present some degree of MPE. Thus, the annual incidence might approximate 5 per 10,000 inhabitants.

The risk for malignancies and consequently the risk for MPE increase with age. However, the disease may also be diagnosed in young patients [4].

The entirety of the mesothelial lining of the thoracic cavity is designated pleura and is composed of a visceral layer that mainly covers the lungs and a parietal layer that covers the thoracic wall. There is virtually no room between both layers and a healthy adult disposes of about 15 ml of pleural fluid that greatly facilitate lung movement.

Both visceral and parietal pleura produce up to 10 liters of pleural fluid daily, whereby this fluid is essentially an ultrafiltrate of capillary blood [5]. Lymph capillaries, principally those of the parietal pleura, reabsorb that liquid. Under physiological conditions, filtration and reabsorption are in equilibrium, a state that avoids accumulation of excess pleural fluid that would interfere with lung expansion. This equilibrium may be altered by a variety of factors not necessarily related with malignant neoplasms. An increased hydrostatic pressure, possibly caused by cardiac disorders, a reduced oncotic pressure, maybe related to hypoalbuminemia, and an elevated capillary permeability due to vascular pathologies may augment pleural fluid formation. Depending on the severity of these conditions, lymphatic capillaries may not be able to completely reabsorb excess fluid. With regards to the lungs, atelectasis may diminish the intrathoracic space occupied by the lungs, may reduce intrathoracic pressure and increase the pull on capillaries. Additionally, pleural effusion may result from limitations in lymphatic reabsorption itself. In this scenario, even normal filtration may lead to an accumulation of fluid within the pleural space. The lymphatic system may be disturbed at the level of pleural capillaries, larger vessels or even the thoracic duct.

Malignancies may alter the above described equilibrium of forces by means of altering the function of any component of the system. For instance, pleural tumors may directly interfere with capillary permeability and lymph capillary function, thus increasing pleural fluid formation and reducing reabsorption [6]. They may also interrupt lymph flow at more distal points, likely by local mass effects. Of note, chemotherapeutic or radiation cancer therapy may induce tissue fibrosis and excess connective tissue may affect reabsorption of pleural fluid and subsequent lymph drainage in a very similar manner.

Any one of these pathogenetic mechanisms or a combination thereof may lead to an accumulation of several liters of pleural fluid within the pleural space. This great amount of liquid strongly reduces the space at the lungs' disposal and thus causes dyspnea and possibly fatal respiratory failure. Additionally, venous return to the heart is largely restricted by the increased intrathoracic pressure and this condition may eventually cause heart failure.

As per definition, MPE is associated with malignant neoplasms. Thus, any measure that decreases the individual risk of cancer may also be considered as a preventive measure for MPE. In this context, avoidance of exposure to carcinogens like cigarette smoke and asbestos, reduction of exposure to radiation and preventive medical examinations may be mentioned as examples.

Malignant pleural effusion (MPE) refers to a cancer-related accumulation of excess fluid in the pleural space [1]. It is a rather common complication of advanced cancer and may cause the amount of pleural fluid to multiply from physiological 15 ml to various liters. Therefore, MPE strongly interferes with respiration and causes severe dyspnea. Most MPE patients also claim chest pain. Because of the severity of the underlying disease and MPE, prognosis is generally poor and the average life expectancy of patients diagnosed with this disease is about half a year.

Few cases of MPE result from primary pleural tumors, i.e., from mesothelioma. Commonly, malignant neoplasms of the respiratory tract, of breast, gastrointestinal or urogenital tract metastasize into the pleura. Lymphoproliferative disorders are also frequently associated with pleural metastases. Some thoracic tumors, mainly those originating from the respiratory tract and the breast, may also directly infiltrate the mesothelial lining of the thoracic cavity. However, virtually every neoplasm may affect the pleura and cause MPE [2].

Treatment is palliative and primarily consists in tube thoracostomy or implantation of tunneled pleural catheters and pleurodesis. These procedures aim at reducing renewed accumulation of pleural fluid, dyspnea and discomfort, and may thus augment life quality.

Of note, MPE needs to be distinguished from paramalignant pleural effusion, which is generally caused by other pathologies. The latter should, however, be considered as differential diagnoses. Please refer to chapter Workup for details.

Pleura is the name of the inner lining of the thoracic cavity, i.e., the pleura coats lungs and inner chest wall. Between the lung-coating visceral pleura and the chest wall-lining parietal pleura, there is a very tiny room that is filled with a few milliliters of pleural fluid and it's called the pleural space. This fluid serves as a lubricant and allows for lung movement. Under physiological conditions, formation and reabsorption of pleural fluid are in a tightly regulated equilibrium. If that balance is disturbed and more pleural fluid is produced or less liquid is absorbed, the pleural space fills with fluid, possibly with several liters of it. This may happen if there are tumor cells in pleura and pleural space. This condition is called malignant pleural effusion (MPE).

Causes

Virtually every malignant tumor may metastasize into the pleura. Neoplasms growing within the thoracic cavity - lung cancer, for instance - may also infiltrate the pleural space directly. In some cases, a malignant tumor may directly originate from the pleura. This type of cancer is known as mesothelioma.

Lung adenocarcinoma, bronchogenic carcinoma, breast carcinoma and lymphoproliferative disorders like Hodgkin's disease and non-Hodgkin's lymphoma are most commonly related with MPE.

Symptoms

Fluid accumulation within the pleural space interferes with lung expansion and complicates breathing. Thus, MPE generally manifests in form of breathing difficulties. Chest pain may also be claimed.

Additional symptoms are mainly caused by the underlying malignancy.

Diagnosis

If a patient presents with symptoms characteristic for pleural effusion, this condition is diagnosed by sonography or plain radiography. A fluid sample will need to be obtained in order to identify the source of pleural effusion. If tumor cells are found within that sample, the patient may be diagnosed with MPE.

Further workup will aim at assessing the overall condition of the patient and consists in identification of the primary tumor and localization of possible metastasis.

Treatment

Therapy of MPE is generally palliative. Removal of the accumulated fluid may improve life quality by relieving breathing difficulties. Thoracocentesis, thoracostomy and implantation of a pleural catheter are possible therapeutic approaches. Some methods allow for continuous drainage of pleural fluid and thus avoid reaccumulation of great amounts of liquid. Pleurodesis, i.e., adhesion of visceral and parietal pleura, is an alternative treatment option. Pleurodesis reduces the pleural space and thus leaves no room for pleural fluid to reaccumulate.

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