Tools
Malignant Pleural Effusion
Introduction
Malignant pleural effusion (MPE) is characterized by malignant cells in the pleural fluid.[1] The presence of MPE denotes systemic dissemination of cancer and meets the criteria for M1a disease, as per the American Joint Committee on Cancer TNM (with T describing the size of the tumor and any spread of cancer into nearby tissue; N describing the spread of cancer to nearby lymph nodes; and M describing the metastasis staging system).[2] Malignant cells from pleural lavage performed in patients without a coexistent pleural effusion have been identified as an indicator of micrometastatic disease and are associated with a higher recurrence rate and poorer survival.[3] The tumor or blood-borne spread may directly affect the parietal and visceral pleurae.[4] While secondary spread from the visceral pleura may involve the parietal pleura, direct seeding of the latter has also been described.[5]
The pathophysiology is attributed to a disturbance of the Starling forces that govern and dictate fluid biomechanics within the pleural space.[6] Pleural fluid production is influenced by the difference between hydrostatic and oncotic pressures within the pulmonary circulation and pleural space. Meanwhile, absorption is predominantly controlled by lymphatic vessels in the parietal pleura, which actively transport excess fluid into the lymphatic system for drainage into the bloodstream.[7] Excess fluid may accumulate as a result of an inability to drain the fluid from the pleural space, which has been postulated to arise as a result of the clogging of the stomata within the parietal pleura or metastatic involvement of hilar and mediastinal lymph nodes.[8]
Lung, breast, and hematological malignancies are the major cancers associated with direct, contiguous, or hematogenous pleural involvement. About 50% to 55% of patients with pleural involvement develop effusion.[9] Wet pleural involvement is associated with a poorer prognosis than dry pleural disease.[10] Between 42% and 77% of effusions in cancer patients have been documented to be exudative. The incidence of eosinophilic pleural effusions, defined as exudative pleural effusions containing more than 10% eosinophils, has gradually increased in recent years, reflecting efforts to distinguish malignant eosinophilic pleural effusion as a distinct entity.[11][12] While malignant pleural involvement may be a cause of effusion in a patient with cancer, other etiologies also need to be considered among the differential.[13]
MPEs must be differentiated from paramalignant pleural effusions, which are not caused by direct pleural involvement by the tumor.[14] A trapped lung is an entity characterized by the failure of a chronically nonexpanded lung to reexpand following drainage of the pleural fluid, which may be caused by extensive involvement of the visceral pleura.[15] Septated pleural effusions, characterized by the development of septated fibrin pockets, may represent an underlying cause of failure to achieve successful drainage and complete resolution of dyspnea.[16]
The global incidence of MPE is 70 cases per 100,000 people. In the United States, MPE led to 361,270 hospital admissions in 2016, incurring costs of $10.1 billion. Consequently, MPE substantially impacts the healthcare system due to its high rate of hospital readmissions and significant resource utilization.[17] MPE significantly impacts patients' quality of life, causing symptoms such as breathlessness, pain, cachexia, fatigue, and reduced daily activity. The condition is also associated with a poor prognosis, with a median survival rate of 3 to 12 months.[18]
Dyspnea is the most common presenting complaint associated with pleural involvement by the tumor.[19] Management goals include palliation of symptoms, with minimal impact on the quality of life, while ensuring treatment cost-effectiveness.[20] Therapeutic approaches vary widely, given the broad range of treatment options. However, a concerted effort has been made recently to move toward patient-related outcomes compared to successful pleurodesis as markers of successful palliation.[21] The role of vascular endothelial growth factor and host-tumor cell interactions in the pleural microenvironment (consisting of inflammatory, mesothelial, and endothelial cells) has been the subject of growing scrutiny.[22][23][24] Novel immunotherapy approaches have been targeted toward understanding the role of the CD8+ T-cells and the associated immune responses to translocated microbial agents in the pathogenesis of this condition.
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The development of MPE is multifactorial. Identifying these influences can guide treatment decisions.
Anatomical Factors
Normal pleural space lies between the parietal and visceral pleurae. While the parietal pleura lines the inner thoracic wall, including the bilateral medial mediastinum, subcostal right and left diaphragmatic leaflets, inner ribs, and associated musculature, the visceral pleura lies in close approximation with the lung parenchyma. The visceral and parietal pleurae join at the hilum.[25] Close apposition and maintenance of negative pressure within the intrapleural space ensure adherence of visceral to parietal pleura. Pleural fluid under normal physiological conditions also promotes the sliding motion of the parietal over the visceral pleura.[26]
The average fluid volume in the pleural space measures 10 mL/0.13 (0.26 +/- 0.1) mL/kg body weight.[27] Intrinsic factors like direct tumor cell infiltration, hormonal disequilibrium, anatomical disruption, and extrinsic factors that include limited respiratory motion, pleural stomata blockage, and mechanical compression interfere with the ability of the pleural lymphatics to function effectively. Both intrinsic and extrinsic factors contribute to a decreased pleural fluid resorption, with the resultant accumulation of excess fluid in the pleural space.[25]
Physiological Factors
Increased pleural fluid production and decreased reabsorption have been associated with the development of MPE. Tumor cells' capacity to initiate this cycle likely hinges on a unique transcriptional repertoire, leading to significant vasoactive events within the pleural space.[28]
Molecular Factors
Molecules predisposing to the development of pleural vessels' hyperpermeability, which leads to the overproduction of pleural fluid, comprise 3 different chemical mediators.[29] The first class consists of inflammatory cytokines such as interleukin 2, tumor necrosis factor, and interferon.[30] The second group comprises proangiogenic molecules such as angiopoietin 1 and 2. The third includes molecules such as vascular endothelial growth factor, chemokine (C-C motif ligand), matrix metalloproteinases, and osteopontin, which have been implicated directly in the pathogenesis of increased vascular permeability.[31][32]
Genetic Factors
Mutations in KRAS, EGFR, MET, BRAF, PIK3CA, and RET are associated with the development of MPE. Coupled with advancements in MPE sequencing techniques, identifying these genes may pave the way for targeted therapies in the near future.[33][34]
Impact on Respiratory Physiology
The development of pleural effusion has been associated with a reduction in the partial pressure of oxygen in the blood. The occurrence of a mild intrapulmonary shunt also predisposes to the development of reduced arterial oxygenation. A dramatic relief in the sensation of breathlessness following a successful thoracentesis procedure has also led to an added emphasis on the impact of pleural fluid accumulation on respiratory dynamics.
The activation of mechanoreceptors in response to pleural fluid accumulation, stretch, cough, and altered lung volumes has been shown to underlie the pathophysiology of dyspnea in MPE. Hemidiaphragmatic movement alterations and the diaphragm's paradoxical movement have been identified. Shifts in inspiratory muscle pressure-volume curves, predisposing to an unfavorable pressure-volume interdependence between increased thoracic volume and pressure, have resulted in pleural fluid accumulation. Length-tension relationship alterations have also been shown to predispose to dyspnea.[35][36]
Epidemiology
MPE is characterized by fluid buildup between the lung and the chest wall due to cancer cells in the pleura. The condition is a frequent complication of cancer, with approximately 500,000 new cases reported annually in the United States and Europe combined. MPE affects up to 20% of patients with cancer and can be linked to any type of cancer, including primary pleural malignancies like mesothelioma and secondary metastases from cancers such as lung, breast, and ovarian neoplasms.
Effusions usually signify advanced malignancy, with an overall survival approaching 3 to 12 months after initial diagnosis.[37] The 5-year survival of lung cancer patients with wet pleural disease is estimated to be 3%.[38] While small cell carcinoma cells directly invade the pleura, non-small cell lung cancer causes indirect impairment of pleural lymphatic function.[39][40]
Ipsilateral pleural involvement is seen in 90% of lung cancer cases.[41] Contralateral pleural effusion is seen in 10% of cases.[42] Between 2% and 11% of patients with breast cancer present with MPE, which is usually caused by direct dissemination via pleural lymphatics. Most cases of breast cancer-related MPE are associated with triple-negative disease that has a poor prognosis.[43] An elevated Ki-67 in the pleural fluid is also associated with a poor outcome.[44][45]
Pleural effusion in ovarian cancer may represent a comparatively better prognosis when compared to other tumors. About 15% of patients may present with wet pleural disease as the first sign of cancer.[46] Positive pleural fluid cytology represents the International Federation of Gynecology and Obstetrics (FIGO) stage IV-a disease.[47] While over three-fourths of patients present with ipsilateral disease, one-fourth of cases may show bilateral involvement. MPE is seen in both Hodgkin and non-Hodgkin disease.[48][49][50]
While 20% of patients with Hodgkin lymphoma may present with MPE at the time of diagnosis, effusions may represent a disease progression in around 60% of patients. MPE is associated with a poor prognosis and may represent chemotherapy-resistant disease.[51] Diffuse large B-cell and follicular lymphoma represent the leading causes of non-Hodgkin lymphoma presenting with MPE.
Both pleural space infiltration and tumor-immune cell interactions in the pleural microenvironment represent underlying pathophysiological mechanisms.[50][52] MPE associated with unusually aggressive malignant mesothelioma is seen in nearly 50% to 94% of cases and represents a distinct biologically active disease process that protects the tumor from chemotherapy and promotes tumor growth.[53] Bilateral pleural effusions are seen in 15% of those who are noncritically ill and 55% of the critically ill population.[54][55]
Pathophysiology
The pleura can be invaded by lymphangitic spread or direct infiltration from neighboring structures such as the diaphragm, pericardium, and chest wall. However, autopsy studies indicate that tumor cells primarily reach the pleura via the bloodstream, initially affecting the visceral pleura. From there, malignant cells spread to the parietal pleura through either tumor seeding along adhesions or exfoliation and floating in the pleural fluid. Tumor cells adhere to the mesothelium, evade the pleural immune defenses, invade the pleural tissue, and access necessary nutrients and growth factors upon reaching the parietal pleura.
History and Physical
A brief clinical history helps identify the various MPE etiologies. Identifying various comorbidities helps determine the patient's physiological reserve and may have management implications.
Historical Features
Clinical presentation depends upon the extent of effusion, rapidity of development, and physiological reserves of the patient.[56] Common MPE symptoms include dyspnea, pain, cough, and clubbing.
Dyspnea
Dyspnea is the most common presenting complaint arising from pleural effusion, seen in more than 50% of all cases.[57] Mechanical factors such as a decrease in chest wall compliance, altered biomechanics resulting from a contralateral mediastinal shift, decrease in ipsilateral lung volume, activation of compensatory reflex phenomenon (from chest wall receptors), and caudal displacement of the diaphragm have been identified as contributory factors. A sense of breathlessness out of proportion to the amount of collected fluid may be seen due to coexistent lung collapse, pulmonary arterial hypertension, and ventilation-perfusion mismatch.[58]
Dyspnea in cancer may cause functional impairment and can be assessed using the unidimensional and multidimensional scale.[59] While a numerical rating and visual analog scales have been commonly used to measure dyspnea, the oxygen cost diagram, Borg scale, modified Borg scale, and St George respiratory symptom assessment questionnaire have also been used.[60][61][62][63]
Other assessment tools include the dyspnea interview schedule, pulmonary functional status scale, and baseline dyspnea index.[64] Nonpharmacological approaches in managing dyspnea in advanced disease focus on the subjective experience of breathlessness. Emphasizing the need to quantify the impact of dyspnea on functional activities of daily living necessitates using multidimensional scales to assess breathlessness. A minimal clinically significant difference (MCID) of approximately 10 on a visual analog scale of 100 signals a clinically important improvement in chronic breathlessness in clinical trials.[65]
Pain
Chest wall pain signifies the presence of underlying chest wall involvement or malignant pleural mesothelioma.[66] Visceral pain from pleural involvement may increase upon taking a deep breath, a manifestation known as pleuritic chest pain.[67] However, a dull, aching pain may be more common than the classically described pleuritic pain. Pain radiation to the right shoulder may signal diaphragmatic involvement. Chest pain may also signal localized chest wall involvement or rib fractures.
Cough
Coughing may be productive and associated with hemoptysis. This symptom denotes underlying pleural inflammation, which may accompany tumor involvement of the pleura or bronchi. Constitutional symptoms such as loss of appetite, loss of weight, easy fatiguability, and lethargy may indicate advanced disease.[68]
Clubbing
Lovibond and Schamroth signs, along with a distal phalangeal to interphalangeal depth ratio greater than 1, are physical indicators that aid in determining the presence of clubbing.[69][70] Depth at the nail bed is compared with depth at the interphalangeal fold. Values greater than 1 indicate a diagnosis of finger clubbing, irrespective of the patient's age. Measurements are made using a Harpenden skinfold caliper.[71] Tissue hypoxia, chronic inflammation, and abnormal vascularization have been shown to underlie the pathogenesis of clubbing.[72]
Symptomatology related to paraneoplastic manifestations
Paraneoplastic manifestations include muscle weakness, as happens in Lambert-Eaton myasthenic syndrome from small-cell lung cancer.[73] Drowsiness, obtundation, and seizures may occur from hyponatremia associated with the syndrome of inappropriate antidiuretic hormone.[74] Squamous cell lung cancer can cause hypercalcemia, resulting in confusion and increased frequency of micturition.[75] Cushing striae, obesity, buffalo hump, and proximal muscle weakness may all manifest from Cushing syndrome due to ectopic adrenocorticotropic hormone production from small cell lung cancer.[76]
Headache, engorged anterior chest wall veins, dyspnea, voice alteration, confusion, obtundation, and facial and brachial swelling can arise from superior vena cava obstruction by small cell lung cancer.[77] Miosis, ptosis, anhidrosis, and apparent enophthalmos comprise Horner syndrome from a superior sulcus or Pancoast tumor due to adenocarcinoma.[78] Hypertrophic pulmonary osteoarthropathy is most commonly associated with non-small cell lung cancer.[79][80]
Other parts of history
A history of occupational asbestos exposure should be sought due to asbestos’ frequent association with lung cancer and mesothelioma.[81] A family history of malignancy may offer a clue to an underlying malignancy. A review of medications should also be performed, as drugs such as amiodarone, nitrofurantoin, and methotrexate are associated with developing exudative effusion.[82]
Physical Examination
The physical examination complements the patient's history by providing objective findings that may account for the symptoms of pleural effusion. A thorough and accurate physical examination can guide subsequent diagnostic and management approaches. All parts of the examination are important, but special attention must be given to the general physical examination and chest inspection, percussion, and auscultation.
General physical examination
Poor performance status may signal an urgent need for imminent palliation. Prognostication may be performed using a palliative prognostic scale, a component of the palliative prognostic index (PPI). A score greater than 4.5 on the PPI may signal a survival of less than 6 weeks.[83] Pallor, clubbing (hypertrophic pulmonary osteoarthropathy), and left supraclavicular lymphadenopathy (Trosier sign) may signal advanced illness.
Inspection
Chest inspection visually identifies signs of pleural effusion. This step may reveal asymmetrical chest wall expansion, tracheal shift, intercostal fullness, Trail sign, scars of previously performed thoracocentesis or biopsies, and a predominance of abdominal breathing.[84]
Percussion and cardinal rules
Dullness is usually observed on percussion. The percussion note has been traditionally described as woody and dull. Joseph Leopold Auenbrugger is regarded as the inventor of direct percussion, which has been replaced mainly by the digit-to-digital percussion method. Percussion is preferentially performed with the patient sitting up. Topographic comparative percussion is performed in the apical regions, fourth and fifth intercostal spaces (right middle and lingular lobes), and basal lung areas.
During percussion, the middle finger of the left hand (pleximeter) should be firmly placed on the chest wall, with the other fingers off. The middle finger of the right hand (plessor) strikes the middle phalanx of the pleximeter finger perpendicularly in the intercostal spaces or directly over the clavicle, moving from more resonant to less resonant areas or vice versa, ensuring differences between areas are felt. The plessor finger's sudden movement originates from the relaxed wrist, keeping the pleximeter finger parallel to the percussed organ's border. Notes are compared bilaterally.
The force of the stroke of the plessor finger depends upon patient factors (eg, age, sex, and build), tissue type, differential diagnoses being considered, the area being examined, and thickness of the chest wall. Damping of the percussion stroke can be avoided by withdrawing the plessor finger immediately after striking the middle phalanx. Both the sound and the feeling of the percussion note are considered crucial to formulating a differential diagnosis. Heavy percussion enhances resonance in large lung areas, potentially masking subtle abnormalities in sound quality, necessitating a gentler technique to avoid missing small note impairments.[85][86]
Auscultation
Diminished or absent breath sounds are present on auscultation. A pleural rub is usually heard in dry pleurisy.
Egophony
Egophony refers to a change in the vocal timber from E to A (but not pitch or volume). Egophony is usually heard as a high-pitched nasal sound and described by Laennec as the bleating of a goat. This sound is characterized by its intensity and suddenness—usually confined over a small area on one side of the chest. An absence of a similar change in sound over the contralateral side should be used before making a definitive diagnosis. The mechanism underlying egophony is fluid accumulation enhancing the transmission of high-frequency sounds while filtering out low-frequency sounds.
Whispering pectoriloquy
Pectoriloquy is the increased voice resonance while passing through the lung structures. A whispered sound is heard clearly after placing a stethoscope over the patient's chest. Both whispered pectoriloquy and egophony may be appreciated at the upper border of the pleural effusion.
Summary of physical findings
Findings of dullness to percussion and decreased vocal fremitus have been used clinically to diagnose pleural effusion. Percussive dullness makes the diagnosis likely, though a chest radiograph is best obtained for confirmation. If clinical suspicion is low, the absence of reduced vocal fremitus reduces the likelihood of diagnosis, typically suggesting against a chest radiograph unless reduced vocal fremitus is detected on physical examination.
According to Auenbrugger and Forbes, dullness is a prerequisite for diagnosing pleural effusion. However, this particular physical finding may be challenging to discern in bilateral pleural effusion. Percussive sounds have been shown to penetrate up to a maximum depth of 6 cm (2 cm of chest wall and 4 cm of fluid). At least 500 mL of fluid should be present in the pleural cavity to yield positive findings on physical examination. Significant tachypnea, markedly decreased chest expansion, absent tactile fremitus and breath sounds, contralateral tracheal or mediastinal shift (Trail sign and tracheal deviation), bulging intercostal spaces, and egophony have been shown to correlate with accumulation of more than 1500 mL of fluid in the pleural space.[87]
Evaluation
Evaluation of suspected MPE cases is often accomplished using various modalities. Specific techniques involve imaging and histopathological diagnosis, as discussed below.
Imaging
Imaging is crucial in diagnosing MPE as it helps detect and evaluate pleural fluid accumulation, assess the extent of pleural involvement, identify underlying malignancies, guide thoracentesis, and monitor treatment response. Detailed visualization of pleural fluid and underlying structures facilitates precise placement of thoracentesis or chest tubes, helps in planning and monitoring pleurodesis, and enables the assessment of tumor response to chemotherapy or radiotherapy.
Chest radiograph
A posteroanterior chest radiograph is usually the first-line investigation used for evaluating the signs and symptoms of pleural effusion in the cancer setting.[88] A minimum quantity of 200 mL of fluid must be present in the pleural space for the diagnosis to be made on a posteroanterior chest radiograph. In comparison, 50 mL of fluid may be visible on a lateral chest radiograph.[89] Costophrenic angle blunting on the posteroanterior view requires the presence of 175 mL of fluid.[90] The fluid volume of fewer than 500 mL (detected in roughly 10%-15% effusion) does not usually produce symptoms.
Costophrenic angle blunting, mediastinal shift, rib crowding, and hemidiaphragm elevation are radiographic findings that may point toward a diagnosis. A massive effusion occupies an entire hemithorax and is more commonly associated with a mediastinal shift and diaphragmatic inversion. The presence of a massive effusion, loculation, and loss of volume of the lung ipsilateral to the involved site should increase suspicion of an underlying malignant etiology.[91] A mass lesion may also be visualized in the case of a lung primary. Hilar prominence may suggest a central lesion or lymphadenopathy. The absence of a mediastinal shift may represent underlying fibrosis (fixity of the mediastinum) or extensive pleural involvement (malignant pleural mesothelioma).[92]
Thoracic ultrasound
Thoracic ultrasonography is more sensitive than chest radiography.[93] Ultrasonography may help diagnose smaller amounts of fluids and guide diagnostic and therapeutic procedures.[94] Transducer probes of 3.5 to 5 MHz frequency can provide a good penetration depth and optimum spatial resolution. Septations (loculated collections), hemothorax, and organized collections may be identified.[95] An ultrasound may also distinguish between an effusion, consolidation, and thickened pleura. Pleural metastases may be characterized as relatively small lenticular hypoechoic masses in close apposition to the chest wall or masses with complex echogenicity.[96]
The shred sign can diagnose pulmonary nontranslobar consolidation with a sensitivity of 90% and a specificity of 98%.[97] Lung movement may be visualized as pleural sliding, which may be lost with the development of postprocedure pneumothorax.[98] Pleural thickening (>1 cm), pleural nodularity, visceral pleural thickening, and diaphragmatic thickening (>7 mm) may also indicate malignancy.
Evidence supports the use of preprocedural ultrasonography in identifying the optimal thoracentesis site. A grading system proposed by Smargiassi et al uses anatomical extent, visible radiological landmarks, and several intercostal spaces to stratify the severity of pleural effusion. A large pleural effusion is classified as one where the upper lung lobe is partially displaced, includes atelectasis of the lower lobe or partial atelectasis of the upper lobe, and involves 3 to 4 intercostal spaces. A massive pleural effusion is characterized by the total collapse of the lung, atelectasis of the whole lung with the hilum visible, and involvement of 4 or more intercostal spaces.[99] Thoracic ultrasound has also been associated with reducing the incidence of hemothorax and pneumothorax following thoracentesis.[100] Ultrasound imaging also has a role in the rapid identification of postprocedural pneumothorax.
Contrast-enhanced chest computed tomography
Mediastinal lymph node involvement and associated parenchymal disease may be better visualized on computed tomography (CT), considered the gold standard screening examination in those with underlying pleural malignancy.[101] Circumferential pleural thickening, pleural nodularity, parietal pleural thickening of more than 1 cm, and mediastinal pleural involvement are all considered pointers of a diagnosis of malignancy. CT scanning has a high specificity and poor sensitivity. Other potential limitations include the inability to distinguish between malignant pleural mesothelioma and pleural metastasis. Nodular pleural thickening, mediastinal pleural thickening, circumferential thickening encasing the lung, and thickening of parietal pleura over 1 cm may also be useful markers in identifying malignant pleural involvement.[102]
A CT scan scoring system proposed by Pocel et al for differentiating between malignant and benign conditions includes the following parameters: the presence of pleural lesions measuring more than 1 cm, hepatic metastasis, pulmonary mass or nodule measuring more than 1 cm, pericardial effusion, absence of loculations, and absence of cardiac silhouette enlargement. A score of more than 7 out of 10 may be used to detect malignancy with a sensitivity and specificity of 88% and 94%, respectively.[103]
Dual-energy spectral CT imaging, which can generate material decomposition images and monochromatic image sets with fast kilovoltage switching, has been shown to have added utility in distinguishing benign from malignant pleural lesions. A combination of patient age, clinical history, and information on CT value measurement (at both high and low energy levels) and the adequate atomic number obtained in a single spectral scan help identify malignant pleural disease.[104]
Positron emission tomography/dynamic imaging
While early or indolent disease may give rise to false negatives, inflammatory pleural involvement, rheumatoid disease, and pleurodesis procedures performed may be associated with false-positive results.[105] Dynamic imaging may help characterize mixed lesions (pleural asbestosis, malignant pleural mesothelioma) and target specific areas within the pleura.[106] Bury et al first suggested the utility of a scoring system for characterizing pleural disease. This score, which includes unilateral masses or nodules with increased pleural thickening, multiple nodules, effusions with increased F18-fluorodeoxyglucose uptake, and extrapulmonary malignancy, distinguishes benign from malignant disease with 83% sensitivity and 92% specificity.[107]
Magnetic resonance imaging
Magnetic resonance imaging (MRI) offers better soft tissue resolution than CT scanning. MRI is more sensitive in detecting chest wall and diaphragmatic involvement.[108][109] The exclusion of MRI-based imaging from diagnostic algorithms can be attributed to higher costs, limited availability, and difficulty in imaging the lung parenchyma. Diffusion-weighted imaging is useful in differentiating between benign and malignant pleural diseases.[110]
Histopathological Diagnosis
Histopathological analysis is crucial for MPE, providing detailed information about cell types and tissue architecture that can differentiate malignant cells from reactive mesothelial cells. Techniques such as pleural fluid cytology, cell block preparation, and pleural biopsy, including image-guided and thoracoscopic biopsies, enhance diagnostic accuracy. Despite challenges like low yield and difficulty distinguishing cell types, advancements in histopathological methods and immunohistochemistry significantly improve the detection and characterization of MPE, guiding effective treatment strategies.
Diagnostic thoracentesis
The standard panel of tests that must be performed on a pleural fluid sample includes pleural fluid protein, glucose, pH, lactate dehydrogenase, cytology, and microbiology.[111] About 40 to 60 cc of pleural fluid is considered optimum for diagnosing MPE.[112] While the yield of pleural fluid analysis approaches 6% to 32% for diagnosing mesothelioma, the test has been shown to have a comparatively higher sensitivity in diagnosing adenocarcinoma (80%).[113][114] While primarily exudative, transudative MPE may be seen in 5% to 10% of cases.[115] Repeat procedures may increase the yield by a third; however, more than 2 repeat procedures are less productive.[116]
Pleural fluid analysis
Normal physicochemical characteristics include pH between 7.60 and 7.64, protein levels of less than 2% (2 gm/dL), less than 100 white blood cells per cubic mm, glucose content similar to that of plasma, lactate dehydrogenase (LDH) level less than half of that present within the plasma. The following parameters may be used in making a diagnosis of malignant etiology underlying the accumulation of pleural fluid: pH less than 7.30, LDH levels greater than 1000 U/l, reduced pleural fluid glucose concentration (30 to 50 mg/dL), and lymphocyte values greater than 50% to 70%.[117]
Pleural fluid tumor marker levels have been used to diagnose MPE. Carcinoembryonic antigen, mucin, and Leu-1 are elevated in effusions with an underlying malignant etiology. In addition to the standard Light criteria, which are based on pleural fluid protein and LDH levels, exudative effusions can be identified by cloudy appearance, specific gravity above 1.020, total proteins of 2.9 g/dL, cholesterol levels, CT scan attenuation, and serum-pleural fluid albumin gradient.[118]
An issue that remains a deterrent in diagnosing malignant effusion using conventional cytology is differentiating malignant cells from reactive mesothelial cells.[119] The inability to study the tissue architecture due to a lack of tissue specimens must also be addressed. Overcrowding of cells and processing artifacts may also contribute to the low yield.[120] The cytocentrifuge or millipore filter can evaluate malignant cells in the pleural fluid.[121]
Pleural fluid cell block
The cell-block technique for processing fluids was first introduced in 1896.[122] Retaining tissue fragments, vital to diagnosing, is a potential advantage over conventional cytology.[123] Various cell-block preparation methods include the formalin, agar, and thrombin clot methods.[124] The underlying principle involves the formation of a gel from cross-linking of proteins that do not get dissolved upon the processing of tissue samples.[125] Another advantage of this technique is preserving the antigenicity and cytomorphological characteristics. The increase in sensitivity of the procedure may be attributed to higher cellularity, preservation of cellular architecture, and morphological patterns of malignant cells. Immunohistochemistry analysis and special staining may also be performed on the cell block specimen.[126]
Pleural biopsy
Given the limited diagnostic yield of conventional cytology and the absence of standardized protocols for cell block techniques, pleural biopsy is recommended for patients with negative cytology results.[127] Closed pleural biopsy methods like Abrams, Cope, Vim Silverman, or cutting-needle biopsy are commonly used.[128] However, these methods may have reduced yield when used on early-stage tumors or neoplasms with uneven distribution. The procedure's ease and cost-effectiveness make it preferred over more complex techniques such as medical thoracoscopy. An increased yield is noted when this procedure is combined with cytological techniques. A diagnostic yield approaching 60% has been reported using blind closed pleural biopsy. Adding imaging techniques (eg, ultrasonography and CT) may help improve diagnostic yields.[129]
Image-guided biopsies
Ultrasound- and CT-guided biopsies have been used to obtain representative pleural samples for diagnostic purposes. Both have shown sensitivity in the range of 70% to 90%. Imaging-guided biopsy can increase the sensitivity of diagnosing MPE to 80%.
Thoracoscopy
Medical thoracoscopy is recommended when effusion thickness is less than 10 mm on a CT scan. This method improves diagnostic accuracy as it allows for direct visualization of the area of interest and tumor tissue sampling. Significant pathological changes in the diseased pleura include nodules, adhesions, plaques, ulcers, and hyperemia. Thoracoscopy has been shown to have a complication rate of less than 8% when performed by trained professionals. Transient chest pain due to the indwelling catheter, cough, and chest discomfort associated with lung reexpansion after drainage of a large amount of fluid has been reported following medical thoracoscopy.
Pleural manometry
German physician Heinrich Quincke was the first to pioneer pleural manometry to measure the pressure within the pleural space in 1878. Techniques used to measure pleural pressures include a hemodynamic electronic transducer, electronic manometer, and U-tube water manometer. Hemodynamic electronic transducers provide the most reliable and accurate measures of intrapleural pressures. The thickness of the normal pleural space is 20 μm, and 50 mL of fluid in the pleural space is required to ensure that the effect of local deformation forces on the measurement of pleural pressures can be nullified.
Elastic forces of the chest wall, lung, and effusion volume influence pressure within the pleural space. Gravity, ventilatory pressures, and forces produced due to cardiac contraction associated with lymphatic drainage generate pleural pressures. Lan et al were the first to describe the utility of manometry in optimizing pleurodesis in those with malignant pleural effusion. Real-time manometry has been proposed to identify an unexpandable lung following thoracentesis. However, consensus is lacking regarding the specific pressure cutoffs that distinguish between normal and unexpanded lungs.
Treatment / Management
A definitive procedure is defined as one aimed at providing long-term relief from symptoms associated with pleural effusion.[130] For this reason, serial thoracentesis is not considered a definitive procedure in the joint guidelines published by the European Respiratory Society and the European Association of Cardiothoracic Surgery.
Thoracentesis
The incidence of recurrence after a single thoracentesis procedure was found to be 4.2 days, with a rate of recurrence approaching 98% within 30 days of completing the procedure. Thoracentesis does not aim to prevent fluid reaccumulation or allow continued drainage. The procedure confirms the presence of fluid and lung reexpansion following pleural fluid drainage. No absolute contraindications to thoracentesis have been mentioned. However, small fluid accumulations and ongoing positive pressure ventilation may predispose to the development of pneumothorax. Additionally, both thrombocytopenia and uncorrected coagulopathy predispose to hemorrhage after the procedure.[131](A1)
Tension pneumothorax, often associated with hemodynamic compromise, may also be seen in the performance of thoracentesis in those receiving positive pressure ventilation.[132] Requisite sedation and analgesia have been recommended in the pediatric population to ensure minimal movements during the procedure.[133] Excessive movements during thoracentesis have been shown to predispose to increased damage to vascular structures and underlying lung parenchyma.[134] The presence of skin infection at the needle insertion site may promote microbial entry into the pleural space.[135](A1)
Anatomical localization
The normal site for pleural fluid aspiration is the 7th intercostal space in the posterior axillary line (near the scapular tip).[136] Posterior intercostal artery laceration poses a significant bleeding risk during the procedure.[137] The posterior intercostal artery runs within the subcostal groove along the posteroinferior border of the superior rib, which has the neurovascular bundle.[138] A site above the inferior rib should be chosen to avoid the bundle. A decrease in the practical, safe space has been documented in older individuals, along with a considerable variation in the course (mean distance from the spine). Variability has also been demonstrated in the course of the posterior intercostal artery, increasing in more posterior positions.[139](B2)
Conduct of the procedure
While adults may undergo the procedure in the upright, seated, or lateral position, pediatric patients may be held in the burping position by an assistant.[140] The needle insertion site is prepared with chlorhexidine. Draping ensures access to the anatomical area of interest. The skin entry site is localized using the available anatomical landmarks and confirmed with ultrasound. Under all aseptic precautions perpendicular to the skin, the needle is advanced to infiltrate the underlying subcutaneous tissue and reach the periosteum, which may be infiltrated with the local anesthetic agent. The needle must be advanced over the superior border of the inferior rib to avoid injury to the neurovascular bundle, which lies along the lower border of the superior rib within the intercostal space. Gentle aspiration may be carried out until pleural fluid has been obtained.[141]
The insertion depth where access to the fluid is obtained should be noted, and an over-the-need catheter should be inserted for atraumatic fluid removal. Attracting a 3-way stopcock along with tubing may facilitate the drainage of large fluid volumes.[142] A heparinized syringe, which needs to be kept closed until the measurement has been completed, may be indicated if a pH measurement has been planned.[143] The procedure may be terminated for pleuritic chest pain, chest tightness, and significant cough, which may signal underlying damage to the lung parenchyma.[144][145] Large-volume thoracentesis has been defined as removing more than 1 liter of pleural fluid.[146] Thoracentesis tolerance may improve using slower or gravity drainage instead of rapid suction evacuation.(A1)
Repeat thoracentesis is recommended for patients with slow fluid accumulation, potential systemic therapy response, advanced disease, poor performance status, or limited life expectancy. Repeating the procedure is also suitable for patients receiving systemic treatment for underlying malignancies, such as small cell lung cancer, lymphoma, or epidermal growth factor receptor-mutated adenocarcinoma that may prevent fluid reaccumulation.[147] Delayed pleurodesis, linked to extensive disease and increased pleural tumor burden, can have reduced effectiveness and may cause trapped lung, contraindicating the procedure. In patients with mediastinal shift, monitoring pleural pressure or removing smaller fluid amounts (300-500 mL) at a time may be necessary to prevent complications from a rapid pleural pressure drop.[148][149] (A1)
Volumes over 1.5 L are associated with reexpansion pulmonary edema. However, some expert groups recommend safely removing 1200 to 1800 mL of pleural fluid in a single session.[150][151] During simultaneous pleural pressure monitoring, negative pressure must not exceed -20 mm Hg. Real-time ultrasonographic guidance is used increasingly to minimize complications like pneumothorax.[152] Bilateral thoracentesis under ultrasonographic guidance has been performed safely in patients with bilateral pleural effusions without causing pneumothorax.(B3)
Complications
While pneumothorax remains a genuine concern, pain, shortness of breath, and vasovagal syncope have also been noted. Cough is known to occur commonly during the procedure. However, only a cough severe enough to cause significant discomfort is an indication for terminating the procedure. Other authors propose procedure termination at the onset of coughing, as this has been shown to denote pulmonary injury. Rare complications include bleeding, reexpansion, pulmonary edema, and organ puncture.[153] Repeat thoracentesis has also been shown to be associated with complications of hypoproteinemia, empyema, pneumothorax, and loculated pleural effusion. History of receiving radiotherapy or superior vena cava obstruction also predisposes patients to develop dilated venous channels, risking vascular injury.[154](B3)
Reexpansion pulmonary edema
Pinault was the first to describe edema occurrence following thoracentesis in 1853. Drainage of more than 1.5 L of fluid has been associated with the development of reexpansion pulmonary edema. This condition has been shown to develop frequently in the first hour following thoracentesis and tends to occur within 24 hours in most patients. Although unilateral edema is a common occurrence, bilateral cases have been described. Pulmonary edema is caused by increased capillary permeability from hypoxia-mediated endothelial injury, free radical damage, surfactant depletion, pulmonary arterial pressure changes, and sudden blood flow and capillary expansion. High perfusion due to pulmonary vasoconstriction, abrupt pressure variations, decreased lymphatic flow, and venous constriction also contribute to its etiopathogenesis.
Preventing this phenomenon involves avoiding negative intrapleural pressures and prolonged lung collapse.[155] The chronicity of the effusion, bronchial obstruction, and reexpansion technique also impact development.[156] The condition may present asymptomatically (with only radiological signs), with breathlessness, or as acute respiratory distress syndrome.[157] Cough, pink frothy expectoration, and cyanosis may denote severe lung involvement. Infection is considered a close differential. Though the patient may demonstrate initial worsening during the first 1 or 2 days, the pathological process is considered self-resolving and usually resolves within 3 to 5 days of occurrence.[158](B3)
Untreated pulmonary edema may be associated with a poorer outcome and has been estimated to be potentially lethal in 20% of cases.[159] Lung injury predisposes to the development of edema and atelectasis.[160][161] The degree of intrapulmonary shunting, ventilation-perfusion mismatch, decreased compliance, and intraalveolar fluid determine the severity grade.[162] Hypotension may accompany sufficient fluid accumulation within the pulmonary interstitium.[163] (B2)
Patchy ground-glass opacities, consolidation, interlobar septal thickening, and intralobular interstitial thickening have been described on high-resolution chest CT.[164] Bronchovascular bundle thickening and ill-defined ground-glass opacities have been described less commonly. Supportive management is advised to ensure adequate oxygenation and perfusion till the resolution of lung injury.[165][166] This approach may include serial chest radiographs (showing nonspecific initial findings of unilateral opacification of air spaces), arterial blood gas analysis, supplemental oxygen treatment in the event of hypoxia, and intubation and mechanical ventilation (positive end-expiratory pressure ventilation) in the presence of severe pulmonary involvement.[167](B2)
Hypotension management may require intravenous volume expansion with parenteral fluids, inotropes, and plasma expanders. The use of diuretics is contraindicated due to their tendency to worsen a fluid-depleted state. Adequate positioning with lateral decubitus on the affected side may reduce shunting and improve oxygenation.
Chemical Pleurodesis
Lucius Splengler was the first to perform chemical pleurodesis in 1901. The procedure involves pleural space obliteration and artificial symphysis creation between the visceral and parietal pleura. An inflammatory reaction within the pleural space activates the coagulation cascade, forming fibrogenic cytokines that promote the development of pleurodesis by collagen production.[168] The beneficial effects of pleurodesis were observed within weeks or months of the procedure. The procedure aims to prevent fluid reaccumulation within the pleural space.[169] Pleurodesis is usually offered to patients with advanced cancer not deemed suitable for systemic cancer-directed treatment as a palliative intervention.[170] (A1)
Active pleurodesis involves mechanically or physically injuring the pleura, such as through mechanical abrasion during video-assisted thoracoscopic surgery or inducing intrapleural adhesions using chemical agents like talc, bleomycin, povidone-iodine, and Corynebacterium parvum. Antibiotics (eg, tetracycline, doxycycline, erythromycin, and minocycline), antiseptics (eg, silver nitrate and iodopovidone), chemotherapeutic agents (eg, mitomycin, bleomycin, cytarabine, doxorubicin, and mitoxantrone), microorganisms (Corynebacterium parvum and Streptococcus pyogenes or OK432), and autologous blood are also used. Both pleural catheters and medical thoracoscopy have been used to introduce sclerosing agents into the pleural cavity. Life expectancy and patient factors are crucial in determining the procedure's acceptability.[171] Two major contraindications to pleurodesis include the presence of a non-re-expanded or trapped lung and loculated pleural effusion. The type of cancer, extent of pleural involvement, and sclerosant type used for pleurodesis determine the degree of effectiveness of pleurodesis.
Procedure Details
Pleurodesis may be performed through a 28- to 32-French gauge chest tube or a pigtail catheter in a premedicated patient provided adequate analgesia.[172] In practice, some clinicians recommend that nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, and corticosteroids be avoided 48 hours before and 5 days following the procedure to avoid interference with the fibrotic pleural response to the sclerosant.[173] Greater than 150 mL/day aspirate, radiograph demonstrating residual fluid, suspicion of pleural infection, and a lack of informed consent are contraindications to the procedure. Lung inflation should be confirmed by auscultation and chest radiograph.(B3)
Specific risks of bleeding, pain, and procedure failure rates (approaching 20%) should be explained to the patient. The risk of acute respiratory distress syndrome using talc as a sclerosing agent is less than 1%.[174] A combination of lidocaine and a sclerosing agent is instilled through the chest tube or indwelling pleural catheter into the pleural space. The dose of lidocaine in a single patient should not exceed 3 mg/kg, and altered pharmacokinetics should keep in mind the sarcopenic status of the patient with advanced cancer. When using talc, the solution must be thoroughly agitated for proper dissolution. Further movement of the container or syringe must be avoided once the slurry is prepared to prevent talc particle precipitation.[175](B2)
The catheter should be flushed with normal saline after the slurry has been installed.[176] Recommendations on patient rotation for up to 1 hour to ensure uniform distribution of the sclerosant vary among authorities, with caution advised by some. Variability exists in the recommended withholding time of the sclerosant mixture in the pleural space after drain clamping, with durations ranging from 1 to 6 hours.[177][178] The drain should be unclamped and removed 24 to 48 hours after ensuring lung reexpansion and pleural cavity drainage.(B2)
Respiratory rate, temperature, pain intensity, pulse rate, oxygen saturation, blood pressure, and characteristics of the fluid drained should be monitored. A postprocedure chest radiograph should be performed to rule out pneumothorax and confirm pleural fluid eradication. Drain or catheter may be removed after 24 to 48 hours of sclerosant administration and following confirmation of a normal chest radiograph, decrease in pleural fluid drainage to less than 100 mL, and absence of air leak.[179](B3)
Patients in the recently concluded TAPPS trial were discharged following a pleurodesis procedure (talc slurry or thoracoscopic talc insufflation) when the total pleural fluid drain output was less than 250 mL daily.[180] Although prophylactic radiotherapy has no role in preventing procedure tract metastases, local palliative radiotherapy may be indicated in the presence of painful nodules in patients with malignant pleural mesothelioma.[181](A1)
Pleurodesis efficacy is classified into complete response (no pleural fluid reaccumulation), partial response (residual fluid without symptomatic reaccumulation needing further drainage for up to 6 months), and failure (requiring additional procedures, depending on patient survival and follow-up).[182] Chest pain has been reported as the most common complication after pleurodesis, followed by fever. Acute respiratory distress syndrome with talc and visual loss due to large quantities of povidone-iodine have also been reported.[183] Using povidone-iodine as a sclerosant is indicated when talc is unavailable or contraindicated. Thoracoscopic talc poudrage was introduced by Bethune in 1934 as a method of producing adhesiolysis before lobectomy. Chambers reported using thoracoscopic talc slurry in humans for the first time.[184][185](A1)
Contraindications to talc pleurodesis for recurrent pleural effusion may include pregnancy, prior intrapleural procedures or thoracic irradiation, recent changes in systemic therapy within the past 2 months, and chylous or bilateral pleural effusions. Talc may be administered in the pleural cavity prepared as a slurry, admixed with normal saline, or insufflated in a powdered form via a medical thoracoscopic procedure (single port of entry).[186] Medical-grade talc has been shown to activate pleural mesothelial cells to produce significantly higher essential fibroblast growth factor (also basic fibroblast growth factor or bFGF) levels. BFGF has been hypothesized to be the chemical mediator responsible for pleurodesis [187]. Thoracoscopic talc insufflation (TTI) enables direct pleural visualization, adhesiolysis, and treatment of loculated pleural effusions.[188] The procedure is effective for managing cases with previous ipsilateral surgery, attempted adhesiolysis, and trapped lung. However, TTI has been associated with a higher incidence of respiratory complications such as atelectasis, pneumonia, and respiratory failure.(A1)
Risk factors for a failed pleurodesis include a history of prior irradiation and a chest tube in place for more than 10 days.[189] Underlying causes for a failure of the procedure include uneven distribution of the agent within the lung, failure of the lung to reexpand following the procedure, and high tumor burden with low fluid pH. High tumor burden may be defined as having multiple pleural nodules on all aspects of the visceral and parietal pleura and adherence of the lobes with themselves and the parietal pleura. Prior thoracic irradiation might also increase the risk of developing a pleurocutaneous fistula.[190] (B2)
The recently completed TAPPS trial found no differences between TTI and bedside chest drain talc slurry procedures in terms of pleurodesis failure at 90 days post-randomization. The trial suggests definitive evidence of their equivalence, as no significant differences were observed in secondary outcomes, including pleurodesis failure up to the 180-day visit, mortality, hospital stay duration, radiological effusion clearance, and patient-reported outcomes.[191] Talc poudrage is less cost-effective than talc slurry. Another potential drawback of TTI would be the inability to perform the procedure safely under local anesthetic guidance in patients with advanced cancer considered to be frail.[192] (A1)
Indwelling Pleural Catheter Placement
Inserting an indwelling pleural catheter (IPC) is safe and effective for draining smaller or loculated recurrent pleural effusions.[193] The increased use of bedside imaging has bolstered its viability for alleviating respiratory symptoms.[194] This procedure is well-tolerated by patients with advanced cancer. While the presence of a catheter induces inflammation and promotes autopleurodesis (between the visceral and parietal pleura), rapid lung reexpansion is facilitated by the negative suction pressure from vacuum bottles.[195] (B2)
Bertolaccini et al pointed out the lower complication rates and advocated early implantation of IPCs over repeated needle thoracentesis.[196] The AMPLE and ASAP 2 trials have demonstrated higher rates and shorter times to autopleurodesis in those treated with an IPC and aggressive drainage than those treated with an IPC and alternate-day drainage.[197] Malignant pleural effusion is unsuitable for pleurodesis. Recurrent pleural effusions after pleurodesis and trapped lung have been considered conventional indications for inserting an IPC. Multiloculated effusions, infection at the insertion site, malignant skin infiltration at the insertion site, and coagulopathy are potential contraindications to IPC insertion. Pleural empyema, accidental dislodgement, drain malfunction, and spontaneous fracture have been reported as possible complications.(A1)
Comparison of Various Treatment Modalities
The meta-analysis by Sivakumar et al found that TTI, talc slurry, and IPCs similarly improve health-related quality-of-life parameters over 12 weeks, but long-term data is lacking due to high attrition rates. The authors concluded that the lack of randomized control trials in this setting mars the evidence of the comparative efficacy of these 3 procedures.[198] Successful outpatient rapid pleurodesis has been demonstrated using thoracoscopy and talc slurry with the insertion of a tunneled pleural catheter in the same setting. A prospective randomized control trial conducted by Reddy et al revealed that patients undergoing rapid pleurodesis with a combination of procedures may be discharged on the day of those procedures. A trial by Olfert et al also demonstrated IPC as a cost-effective treatment method.[199] Bhatnagar et al reported a median time to achieve pleurodesis of 4 days using drug-eluting IPCs.(B2)
The results of the ongoing SWIFT trial are expected to provide further insight into the efficacy and safety profile of drug-eluting pleural catheters. The sclerosant used in these trials consists of a slow-release coating of silver nitrate.[200] Dipper et al's Cochrane network meta-analysis indicated that 20 out of 100 patients required a repeat procedure post-talc pleurodesis, 19 out of 100 post-talc slurry, and 52 out of 100 after bleomycin treatment. The group’s findings suggest that talc poudrage and talc slurry are superior to other methods for pleurodesis. The group also identified catheter site infection (cellulitis) and pleural infection as potential complications of IPC insertion. This network meta-analysis supports bedside-graded talc as the sclerosant of choice, given the years of experience with this modality. The authors opine that searching for a single ideal procedure for managing a complex problem may prove futile.[201] considering patient preferences and practical issues in the real-life setting (eg, patient and family experience) may represent a sensible way forward. (A1)
Special Scenarios
Special circumstances influence treatment choices. Careful consideration of these situations is crucial to improve patient outcomes.
Trapped lung
"Trapped lung" describes a form of advanced lung pathology, often in patients with a history of molecular pathological epidemiology (MPE0, characterized by the lung's inability to expand fully, resulting in the failure of the visceral pleura to adhere to the parietal pleura and leaving a residual cavity. The term "lung entrapment" refers to the lung's failure to reexpand due to an active pleural process and visceral pleural peel formation. In contrast, "trapped lung" denotes a similar condition that occurred in the past. Growth factor production increases fibroblast proliferation and collagen production, leading to fibrotic reorganization of the visceral pleura.[202] A ventilation-perfusion mismatch due to the altered respiratory ventilatory dynamics leads to dyspnea, potentially adversely impacting the quality of life.[203]
A trapped lung may result from pleural thickening that limits the visceral pleura's movement, potentially leading to a fibrinous exudate around the lung. Potential causes include direct malignant cell infiltration, fibrosis within the visceral pleura, pleural carcinomatosis, radiation-induced fibrosis, and proximal endobronchial obstruction causing distal lung collapse or chronic atelectasis with a concurrent malignant or paramalignant pleural effusion. The radiological finding of pneumothorax ex vacuo, which has been characterized by the failure of the lung to expand after pleural fluid drainage, may represent a trapped lung. Thoracic ultrasonography may help differentiate between pleural thickening, pleural fluid, and consolidation.[204] Non expandable lung/unexpanded lung (NEL/UL) is a clinical entity defined by the apposition of the lung to less than 25% to 50% of the chest wall. This entity represents a potentially reversible condition that may revert to its original state with the institution of antitumor therapy. NEL may also represent a scenario where the lung, unable to reexpand due to a prolonged collection period, can fully reexpand after the effusion is drained.[205]
All NEL cases do not meet the criteria for a trapped lung. Patients with a NEL have been shown to develop autopleurodesis using an IPC.[206] Diagnosis is made upon clinical examination. Occurrence of severe dull or sharp pleuritic chest pain and cough during thoracentesis and thoracic ultrasonography has been used to diagnose trapped lung. Though video-assisted thoracoscopy has been used as a definitive diagnostic modality, the measurement of pleural fluid elastance using pleural manometry also represents a promising approach.
Pleural fluid elastance is measured by the decrease in pleural fluid pressures in cm H2O after 500 mL of fluid is removed by thoracentesis. In a trapped lung with MPE, the pleural pressure is low and tends to drop significantly as fluid is removed. Pleural fluid elastance of more than 14.5 cm H2O per liter has been shown to represent a pleural space mechanical abnormality.[207] The following strategies are considered potentially beneficial in managing trapped lungs: IPC, surgical pleurectomy or decortication, pleuroperitoneal shunting, and intrapleural fibrinolysis.
Persistent air leaks
The possibility of developing pneumothorax after ultrasound-guided thoracentesis is slight (3%-4%) but significant. A small fraction of individuals who develop pneumothorax will require chest tube insertion.[208] An air leak manifests as a collection of air bubbles in the drainage bag connected to the chest drain.[209] A persistent air leak is defined as one that exists for more than 5 to 7 days following chest tube insertion.[210] Communication between the sterile pleural space and the tracheobronchial tree in the form of alveolar pleural fistulous communication or bronchopleural fistula may be the underlying cause.
The American College of Chest Physicians has advised a period of conservative management for 4 days, during which the fistulous communication is expected to close on its own.[211] A thoracic surgery opinion with consideration of pleurodesis may be indicated if watchful management fails. Minimally invasive approaches may be considered for nonsurgical candidates and individuals who refuse surgical management. Autologous blood patch pleurodesis, Heimlich valves, endobronchial valves, tissue adhesives, and occlusive devices can also be used to obliterate communication.[212] A definitive surgical approach or open thoracotomy with chemical or mechanical pleurodesis or pleurectomy has been proposed as the definitive surgical approach.(B3)
Septated pleural effusion
Fibrin-rich effusion fluids can lead to the development of pockets within the effusion. Significant adhesions have been demonstrated in almost 40% of patients on thoracoscopy by Bielsa et al.[213] Significant adhesions are defined as those that obstruct more than one-third of the field of view in thoracoscopy.[214] In patients undergoing chest drain insertion, an increasing number of septations have been associated with the failure to achieve adequate relief of dyspnea.[215](A1)
Septations must be distinguished from vascularized adhesions, which may develop when fibrinous septations are infiltrated with fibroblasts and organized with collagen fibrils. Despite their interchangeable use in literature, these terms need clear definitions to emphasize their impact on prognosis. An ultrasound-based grading system characterizes the severity of septations or organized adhesions based on their nature and number.
Significant adhesions may cause failure of an effusion to drain effectively. Fibrous septations and adhesions may be differentiated based on thoracoscopy. While fibrinous adhesions can be divided easily, dense organized adhesions usually show the presence of blood vessels on thoracoscopy.[216] A CT scan does not help visualize septations directly. However, indirect evidence of septations, such as air pockets, may be seen. Adhesiolysis with the intrapleural instillation of fibrinolytic has been used to facilitate drainage of septated pleural effusion.[217](A1)
The TIME 3 trial demonstrated no clinically significant improvement in dyspnea or time to pleurodesis failure rates over 1 year with intrapleural streptokinase instillation in nondraining malignant septated pleural effusions. No significant differences were reported between the urokinase and placebo groups in quality of life parameters at any time during the study. The study has been critiqued for the possible impact of fibrinolytic agents on the efficacy of repeat procedures, but these concerns remain unproven. Given the short half-life of these agents, any substantial impact on the efficacy of repeat drainage and pleurodesis procedures is not expected.
Another concern with fibrinolytic use remains the possibility of bleeding into the pleural fluid, which has been attributed to the presence of friable vessels within the hemorrhagic fluid due to neoangiogenesis. However, the risk of bleeding has remained minimal with the concomitant use of an IPC and does not seem to represent a substantial concern. The authors conclude that intrapleural thrombolytic agents improve lung reexpansion but do not increase successful pleurodesis rates. The persistent dyspnea in these patients has led to reconsidering the use of drainage catheters in this context. Alternative methods for palliation of breathlessness in advanced cancer have been advocated.[218](A1)
Malignant eosinophilic pleural effusion
Malignant eosinophilic pleural effusion (MEPE) is defined as having more than 10% of eosinophils in the differential white blood cell count in the first thoracentesis exudative effusion and histological confirmation of malignancy. Repeated thoracentesis, blood or air in the pleural space, and drug interactions may be confounding factors that must be ruled out before a diagnosis of MEPE can be made conclusively. Lung cancer (ie, non-small cell adenocarcinoma and squamous cell carcinoma), metastasis to the lung, non-Hodgkin lymphoma, and dysgerminoma are the common etiologies underlying MEPE.[219] (B2)
MEPE’s pathogenesis involves 2 steps: accumulation and migration. Accumulation of eosinophils occurs due to increased production within the bone marrow. Migration is promoted by the firm cytoadherence of these eosinophils to endothelial cells. Increased production of cytokines such as interleukins 33, 4, and 5, which have been shown to have chemoattractant properties that aid in eosinophilic migration, has been reported in patients with non-small cell lung cancer.[220] Tumor-homing eosinophils are also shown to secrete chemokines, stimulating T-cell expansion within the tumor microenvironment. Eosinophils have been shown to enhance the maturation of dendritic cells in the tumor microenvironment, which overcomes tumor tolerance and has been associated with a better prognosis.[221] Though cancer-directed therapies can control pleural fluid formation in small-cell lung cancer, strategies that improve survival are still needed. Measures to palliate symptoms are similar to the ones employed for non-eosinophilic malignant pleural effusion. The percentage of eosinophils may represent an important marker of prognosis, and further research on this topic has been advocated. (B3)
Hemorrhagic malignant pleural effusion
Hemorrhagic malignant pleural effusion (HMPE) occurs with a frequency of 47% to 50%. HMPE is usually characterized by a pronounced degree of dyspnea, higher chest pain incidence, general physical deterioration, cooccurrence with large effusion, and thickening with parietal pleural effusion. Cytological analysis usually reveals an increased percentage of malignant cells in the pleural fluid. Thickened parietal pleura with hemorrhagic nodules may be visualized on thoracoscopy. Talc pleurodesis and thoracoscopic talc poudrage are less effective. HMPE is usually associated with poor survival and higher rates of pleurodesis.[222]
Palliative symptom-directed management of dyspnea in advanced cancer
Dyspnea has been defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations of variable intensity.[223] Ambrosino et al have suggested that differences in language, culture, race, and gender can influence the subjective experience of breathlessness.[224] Refractory breathlessness has been defined as breathlessness that persists despite optimal treatment of the underlying condition and has been associated with a shortened life expectancy.[225] Refractory breathlessness is especially frightening for patients and families and results in the use of acute hospital services.[226] The term "chronic breathlessness syndrome" has been suggested to delineate a syndrome that consists of breathlessness that persists despite optimal management of the underlying pathophysiology.[227](A1)
The feeling of breathlessness in advanced cancer has been explained by a mismatch between afferent sensory information sent by the afferent receptors and the respiratory motor command from the cortex and brainstem.[228] The biopsychosocial model and the breathing, thinking, and functioning models have been used to explain the physiopathology of dyspnea in advanced cancer.[229] Notably, breathlessness arises from interactions among physiological, psychological, social, and environmental factors. The sensation of dyspnea can induce secondary physiological and behavioral responses.[230] The degree of physiological impairment, as indicated by hypoxemia or a low forced expiratory volume in 1 second, weakly correlates with a person's subjective sensation of breathlessness, complicating treatment efforts.[231] (A1)
Patient-reported outcomes are considered the gold standard in the assessment of breathlessness.[232] While unidimensional tools such as numerical rating and visual analog scales may be used, assessing the subjective experience of the patient and its impact on functional outcomes is of utmost importance.[233] The London Chest Activities of Daily Living Scale has been shown to effectively measure the impact of breathlessness on functional and social activity in patients with refractory breathlessness in advanced disease.[234] Episodic breathlessness should be identified, characterized as a separate entity, and managed according to prescribed guidelines.[235](A1)
The management of chronic breathlessness syndrome usually requires specialist palliative medicine input. Palliative interventions, including pharmacological and nonpharmacological management, are provided through visits across many settings. Nonpharmacological interventions may be recommended for patients experiencing breathlessness due to advanced cancer or MPE resistant to other treatments.
Nonpharmacological interventions include using a handheld fan for facial cooling, practicing breathing retraining, trying mobility aids, promoting self-management with activity pacing and relaxation techniques, participating in exercise-based rehabilitation, and exploring complementary and alternative treatments. Among pharmacological options, only opioids and oxygen are helpful. Correct opioid dosing is essential, and doses between 10 and 30 mg of extended-release morphine sulfate have been used. A rescue dose or immediate-release morphine of about 1/6 of the patient's total daily morphine dose may be considered for exacerbation of breathlessness if required.
Supplemental oxygen (palliative oxygen therapy) is indicated in patients with chronic severe hypoxemia (partial pressure of oxygen or PaO2 <7.3 kPa, corresponding to an oxygen saturation level >88%).[236] Evidence from clinical trials does not support using benzodiazepines for the relief of breathlessness. These medications are not advised as first-line interventions.[237] Benzodiazepines may be used to alleviate anxiety associated with air hunger as second or third-line treatments when opioids are not effective. Steroids have been advised to manage breathlessness refractory to other treatment options.[238] (A1)
Noninvasive ventilation may improve oxygenation and hypoventilation and support chest wall muscles.[226] A trial of noninvasive ventilation should be considered in chronic severe breathlessness, especially in patients with acute hypercapnic respiratory failure. Refractory breathlessness is also recognized as an indication to provide palliative sedation at the end of life.[239] The use of palliative sedation for refractory symptoms at the end of life can be justified by the ethical doctrine of double effect, developed by the Roman Catholic church, originating back to the Salamanticensis theologians of the 16th and 17th centuries.[240](A1)
Caregiver distress
A substantial body of data demonstrates that carers of individuals with chronic breathlessness experience profound anxiety, isolation, exhaustion, and poor sleep. This distress is heightened when they witness their loved ones having an episode of breathlessness. A feeling of powerless (inability to help) and exhaustion from the extra physical work adds to the genesis and propagation of caregiver distress. Psychoeducation and the provision of psychological support may be necessary. Recognition and acknowledgment of symptoms are practical first steps in managing caregiver distress.[241] The phenomenon of compassion fatigue (burnout and secondary traumatic stress) in healthcare professionals involved in caring for patients with terminal life-limiting illnesses also needs to be recognized.[242] Preparatory grief and existential suffering in patients with advanced cancer near the end of life often require intervention from a specialist palliative care team.[243](A1)
Differential Diagnosis
Clinical differential diagnoses
These conditions include raised hemidiaphragm (ie, due to phrenic nerve palsy or liver enlargement), pleural thickening (secondary to previous tuberculosis, empyema), plaques, consolidation, and lobar collapse.
Radiological differential diagnoses
These conditions include pleural thickening, benign and malignant plaques, pseudo-plaques, and inferior pulmonary ligament. Pseudo-plaques are defined as plaque-like lung opacities formed by small nodules contiguous with the visceral pleura. These plaques are formed by small coalescent nodules, commonly seen in sarcoidosis, coal workers' pneumoconiosis, and silicosis.
Histopathological differential diagnoses
Nonspecific pleuritis arises from cytology-negative exudative pleural effusion without a definable etiology after histopathological analysis. Possible etiologies may include radiation- and chemotherapy-induced pleuritis. From 3% to 12% of patients with nonspecific pleuritis are diagnosed with a pleural malignancy upon regular surveillance.
Other types of effusion
Paramalignant pleural effusion and MPE must be differentiated due to their distinct prognostic implications. Paramalignant effusions may result from various pathophysiological processes, including tumor-related obstruction, thoracic duct obstruction, pulmonary embolism, and hypoalbuminemia causing low colloidal osmotic pressure. Superior vena cava obstruction may occur as a late complication of mediastinal radiotherapy or due to increased venous pressures from local tumor effects. Treatment-related effusions can arise from radiotherapy, conventional chemotherapy (eg, bleomycin, procarbazine, cyclophosphamide, and methotrexate), targeted therapy (eg, dasatinib), and immunotherapy. Other causes of pleural fluid accumulation include congestive heart failure, hepatic decompensation, and renal failure.
Prognosis
The LENT, modified LENT, and PROMISE scores have been developed to predict MPE-related outcomes [244]. A lack of inclusion of newer targeted therapies within its purview has been pointed out as a potential drawback of using older prognostication systems.[245]
The LENT score consists of the following parameters: pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, neutrophil-to-lymphocyte ratio, and tumor type. The PROMISE score uses a more diverse range of biomarkers to predict the 3-month mortality and success rate of pleurodesis in this cohort of patients.[246] Protein expression levels of tissue inhibitors of metalloproteases-1, cadherin-1, platelet-derived growth factor, vascular endothelial growth factor, and interleukin-4 are predicted biomarkers in the PROMISE model.[247]
The SELECT score uses the following markers to predict 90-day survival in these patients: sex, Eastern Cooperative Oncology Group, leucocyte count, epidermal growth factor receptor status, chemotherapy, and primary tumor type. The SELECT score has been shown to perform better than the LENT and PROMISE scores in prognosticating survival. The modified LENT score is comparable to the SELECT score in prognosticating survival.
Prognostication individualization in this domain is also suggested, highlighting the need for systems incorporating patient preferences, newer targeted therapy, immunotherapy approaches, and symptom burden within their purview. Prognostication in advanced disease may involve using various tools such as the PPI, which consists of the palliative performance scale, edema, dyspnea, reduced oral intake, and delirium. A score of more than 4.5 is usually associated with a survival of fewer than 6 weeks. Chest tube drainage, chemical pleurodesis, and thoracoscopy-guided talc drainage have been recommended over repeated procedures due to the risk of developing adhesions with the performance of repeat thoracentesis.[248] Having an actionable mutation in non-small cell lung cancer with MPE poses a similar recurrence risk to having no actionable mutation. In a study by Scwalk et al, larger pleural effusion size, pleural fluid lactate dehydrogenase, and positive cytological examination results have been associated with a higher recurrence rate of pleural effusions.[249]
Complications
Trapped lung, persistent air leaks after chest tube insertion (for iatrogenic pneumothorax), and septated effusion are all potential MPE complications. Treatment complications have been mentioned in other parts of this activity, such as complications associated with procedures used for draining pleural fluid (ie, thoracoscopic talc poudrage, talc slurry, tunneled catheter insertion, and pleurodesis). MPE does not have a cure, and symptom palliation is the primary treatment goal. The financial challenges of repeated procedures for families already burdened by the costs of cancer treatment must be recognized.[250]
Deterrence and Patient Education
The American Thoracic Society has developed an important monograph to educate patients about the indications, risks, care, and removal of indwelling catheters to treat MPE. Regular follow-up with healthcare professionals is recommended.[251]
Pearls and Other Issues
Tumor clonal evolution owing to pharmacological pressure to anticancer treatment has been shown to underlie the differences in mutations in the primary tumor and pleural metastases. Personalized MPE therapy based on the actionable mutation discovered in the malignant pleural cells may represent the future of definitive treatment. Crizotinib effectively reduces the amount of pleural effluent in a patient with lung adenocarcinoma with ALK mutation by Sun et al.[252] The utility of intrapleural immune stimulants is also being explored as a potential antitumor and sclerosant treatment. Ren et al have demonstrated increased survival in patients undergoing pleurodesis with a Staphylococcus aureus bioproduct mixture due to its immune-stimulating effect on T-cells, which might predispose to tumor cell apoptosis in malignant mesothelioma.[253]
Enhancing Healthcare Team Outcomes
The interprofessional approach is essential to MPE management. The treatment of medical issues in advanced cancer may play a critical role in improving the patient's survival and significantly impacting quality of life. Dyspnea is one of the key symptoms that has been shown to substantially affect the quality of life of patients with advanced cancer.
The correctable causes of breathlessness must be treated before proceeding to pharmacological measures that decrease the patient's perception of discomfort due to breathlessness. Treatment aggressiveness is a contentious but essential region that requires family participation. Medical oncologists, respiratory medicine physicians, surgical oncologists, and palliative medicine experts may deliver therapeutic interventions for managing MPE.
Managing pleural effusion in patients with advanced cancer at the end of life is a challenge that demands another look at the conventional role of a palliative medicine consult. Patients with advanced cancer, with a unique set of physical (medical and surgical), psychological, social, and spiritual issues, present unique inpatient admission challenges in the palliative medicine ward. The European Society of Medical Oncology has proposed using patient-centered care to encompass palliative and supportive care provision. The Society’s definition of the patient-centered approach includes assessment, monitoring, interventions, and management of cancer-related symptoms and anticancer treatment-related complications. These guidelines remain the only official guidelines that acknowledge the role of the supportive and palliative medicine expert in directly managing this medical condition.
References
Egan AM, McPhillips D, Sarkar S, Breen DP. Malignant pleural effusion. QJM : monthly journal of the Association of Physicians. 2014 Mar:107(3):179-84. doi: 10.1093/qjmed/hct245. Epub 2013 Dec 24 [PubMed PMID: 24368856]
Wrona A, Jassem J. [The new TNM classification in lung cancer]. Pneumonologia i alergologia polska. 2010:78(6):407-17 [PubMed PMID: 21077033]
Jiao X, Krasna MJ. Clinical significance of micrometastasis in lung and esophageal cancer: a new paradigm in thoracic oncology. The Annals of thoracic surgery. 2002 Jul:74(1):278-84 [PubMed PMID: 12118789]
Uzbeck MH, Almeida FA, Sarkiss MG, Morice RC, Jimenez CA, Eapen GA, Kennedy MP. Management of malignant pleural effusions. Advances in therapy. 2010 Jun:27(6):334-47. doi: 10.1007/S12325-010-0031-8. Epub 2010 Jun 10 [PubMed PMID: 20544327]
Level 3 (low-level) evidenceKoegelenberg CFN, Shaw JA, Irusen EM, Lee YCG. Contemporary best practice in the management of malignant pleural effusion. Therapeutic advances in respiratory disease. 2018 Jan-Dec:12():1753466618785098. doi: 10.1177/1753466618785098. Epub [PubMed PMID: 29952251]
Level 3 (low-level) evidenceSahn SA. The pathophysiology of pleural effusions. Annual review of medicine. 1990:41():7-13 [PubMed PMID: 2184750]
Level 3 (low-level) evidenceMordant P, Arame A, Legras A, Le Pimpec Barthes F, Riquet M. [Pleural lymphatics and effusions]. Revue de pneumologie clinique. 2013 Jun:69(3):175-80. doi: 10.1016/j.pneumo.2013.01.006. Epub 2013 Mar 19 [PubMed PMID: 23523230]
Agalioti T, Giannou AD, Stathopoulos GT. Pleural involvement in lung cancer. Journal of thoracic disease. 2015 Jun:7(6):1021-30. doi: 10.3978/j.issn.2072-1439.2015.04.23. Epub [PubMed PMID: 26150915]
Barrelet L. [Management of malignant pleural effusions secondary to breast cancer]. Revue medicale de la Suisse romande. 1980 Sep:100(9):787-9 [PubMed PMID: 7455479]
Level 3 (low-level) evidenceJiménez D, Díaz G, Gil D, Cicero A, Pérez-Rodríguez E, Sueiro A, Light RW. Etiology and prognostic significance of massive pleural effusions. Respiratory medicine. 2005 Sep:99(9):1183-7 [PubMed PMID: 16085221]
Kalomenidis I, Light RW. Eosinophilic pleural effusions. Current opinion in pulmonary medicine. 2003 Jul:9(4):254-60 [PubMed PMID: 12806236]
Level 3 (low-level) evidenceKalomenidis I, Light RW. Pathogenesis of the eosinophilic pleural effusions. Current opinion in pulmonary medicine. 2004 Jul:10(4):289-93 [PubMed PMID: 15220754]
Level 3 (low-level) evidenceAlexandrakis MG, Passam FH, Kyriakou DS, Bouros D. Pleural effusions in hematologic malignancies. Chest. 2004 Apr:125(4):1546-55 [PubMed PMID: 15078773]
Herrera Lara S, Fernández-Fabrellas E, Juan Samper G, Marco Buades J, Andreu Lapiedra R, Pinilla Moreno A, Morales Suárez-Varela M. Predicting Malignant and Paramalignant Pleural Effusions by Combining Clinical, Radiological and Pleural Fluid Analytical Parameters. Lung. 2017 Oct:195(5):653-660. doi: 10.1007/s00408-017-0032-3. Epub 2017 Jun 27 [PubMed PMID: 28656381]
Liew K, Stride P. Trapped lung. Internal medicine journal. 2012 Feb:42(2):217. doi: 10.1111/j.1445-5994.2011.02659.x. Epub [PubMed PMID: 22356497]
Level 3 (low-level) evidenceBanka R, Terrington D, Mishra EK. Management of Septated Malignant Pleural Effusions. Current pulmonology reports. 2018:7(1):1-5. doi: 10.1007/s13665-018-0194-3. Epub 2018 Jan 20 [PubMed PMID: 29568725]
Roberts ME, Rahman NM, Maskell NA, Bibby AC, Blyth KG, Corcoran JP, Edey A, Evison M, de Fonseka D, Hallifax R, Harden S, Lawrie I, Lim E, McCracken DJ, Mercer R, Mishra EK, Nicholson AG, Noorzad F, Opstad K, Parsonage M, Stanton AE, Walker S, BTS Pleural Guideline Development Group. British Thoracic Society Guideline for pleural disease. Thorax. 2023 Jul:78(Suppl 3):s1-s42. doi: 10.1136/thorax-2022-219784. Epub [PubMed PMID: 37433578]
Gonnelli F, Hassan W, Bonifazi M, Pinelli V, Bedawi EO, Porcel JM, Rahman NM, Mei F. Malignant pleural effusion: current understanding and therapeutic approach. Respiratory research. 2024 Jan 19:25(1):47. doi: 10.1186/s12931-024-02684-7. Epub 2024 Jan 19 [PubMed PMID: 38243259]
Level 3 (low-level) evidenceBibby AC, Dorn P, Psallidas I, Porcel JM, Janssen J, Froudarakis M, Subotic D, Astoul P, Licht P, Schmid R, Scherpereel A, Rahman NM, Cardillo G, Maskell NA. ERS/EACTS statement on the management of malignant pleural effusions. The European respiratory journal. 2018 Jul:52(1):. pii: 1800349. doi: 10.1183/13993003.00349-2018. Epub 2018 Jul 27 [PubMed PMID: 30054348]
Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, Iyer NP, Lee YCG, Lewis SZ, Maskell NA, Rahman NM, Sterman DH, Wahidi MM, Balekian AA. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. American journal of respiratory and critical care medicine. 2018 Oct 1:198(7):839-849. doi: 10.1164/rccm.201807-1415ST. Epub [PubMed PMID: 30272503]
Level 1 (high-level) evidenceZahid I, Routledge T, Billè A, Scarci M. What is the best treatment for malignant pleural effusions? Interactive cardiovascular and thoracic surgery. 2011 May:12(5):818-23. doi: 10.1510/icvts.2010.254789. Epub 2011 Feb 16 [PubMed PMID: 21325469]
Murthy V, Katzman D, Sterman DH. Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy. The clinical respiratory journal. 2019 May:13(5):272-279. doi: 10.1111/crj.13010. Epub 2019 Mar 24 [PubMed PMID: 30810270]
Wu DW, Chang WA, Liu KT, Yen MC, Kuo PL. Vascular endothelial growth factor and protein level in pleural effusion for differentiating malignant from benign pleural effusion. Oncology letters. 2017 Sep:14(3):3657-3662. doi: 10.3892/ol.2017.6631. Epub 2017 Jul 20 [PubMed PMID: 28927127]
Level 3 (low-level) evidenceBradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion. Current oncology reports. 2013 Jun:15(3):207-16. doi: 10.1007/s11912-013-0315-7. Epub [PubMed PMID: 23568600]
Yalcin NG, Choong CK, Eizenberg N. Anatomy and pathophysiology of the pleura and pleural space. Thoracic surgery clinics. 2013 Feb:23(1):1-10, v. doi: 10.1016/j.thorsurg.2012.10.008. Epub [PubMed PMID: 23206712]
Lai-Fook SJ. Pleural mechanics and fluid exchange. Physiological reviews. 2004 Apr:84(2):385-410 [PubMed PMID: 15044678]
Level 3 (low-level) evidenceNoppen M, De Waele M, Li R, Gucht KV, D'Haese J, Gerlo E, Vincken W. Volume and cellular content of normal pleural fluid in humans examined by pleural lavage. American journal of respiratory and critical care medicine. 2000 Sep:162(3 Pt 1):1023-6 [PubMed PMID: 10988124]
Stathopoulos GT, Kalomenidis I. Malignant pleural effusion: tumor-host interactions unleashed. American journal of respiratory and critical care medicine. 2012 Sep 15:186(6):487-92. doi: 10.1164/rccm.201203-0465PP. Epub 2012 May 31 [PubMed PMID: 22652027]
Level 3 (low-level) evidenceRodriguez-Canales J, Parra-Cuentas E, Wistuba II. Diagnosis and Molecular Classification of Lung Cancer. Cancer treatment and research. 2016:170():25-46. doi: 10.1007/978-3-319-40389-2_2. Epub [PubMed PMID: 27535388]
Jantz MA, Antony VB. Pathophysiology of the pleura. Respiration; international review of thoracic diseases. 2008:75(2):121-33. doi: 10.1159/000113629. Epub 2008 Mar 6 [PubMed PMID: 18332619]
Kamińska K, Szczylik C, Bielecka ZF, Bartnik E, Porta C, Lian F, Czarnecka AM. The role of the cell-cell interactions in cancer progression. Journal of cellular and molecular medicine. 2015 Feb:19(2):283-96. doi: 10.1111/jcmm.12408. Epub 2015 Jan 19 [PubMed PMID: 25598217]
Level 3 (low-level) evidenceHsu LH, Soong TC, Chu NM, Huang CY, Kao SH, Lin YF. The Inflammatory Cytokine Profile of Patients with Malignant Pleural Effusion Treated with Pleurodesis. Journal of clinical medicine. 2020 Dec 11:9(12):. doi: 10.3390/jcm9124010. Epub 2020 Dec 11 [PubMed PMID: 33322487]
Agalioti T, Giannou AD, Krontira AC, Kanellakis NI, Kati D, Vreka M, Pepe M, Spella M, Lilis I, Zazara DE, Nikolouli E, Spiropoulou N, Papadakis A, Papadia K, Voulgaridis A, Harokopos V, Stamou P, Meiners S, Eickelberg O, Snyder LA, Antimisiaris SG, Kardamakis D, Psallidas I, Marazioti A, Stathopoulos GT. Mutant KRAS promotes malignant pleural effusion formation. Nature communications. 2017 May 16:8():15205. doi: 10.1038/ncomms15205. Epub 2017 May 16 [PubMed PMID: 28508873]
Skok K, Hladnik G, Grm A, Crnjac A. Malignant Pleural Effusion and Its Current Management: A Review. Medicina (Kaunas, Lithuania). 2019 Aug 15:55(8):. doi: 10.3390/medicina55080490. Epub 2019 Aug 15 [PubMed PMID: 31443309]
Thomas R, Jenkins S, Eastwood PR, Lee YC, Singh B. Physiology of breathlessness associated with pleural effusions. Current opinion in pulmonary medicine. 2015 Jul:21(4):338-45. doi: 10.1097/MCP.0000000000000174. Epub [PubMed PMID: 25978627]
Level 3 (low-level) evidenceAguilera Garcia Y, Palkar A, Koenig SJ, Narasimhan M, Mayo PH. Assessment of Diaphragm Function and Pleural Pressures During Thoracentesis. Chest. 2020 Jan:157(1):205-211. doi: 10.1016/j.chest.2019.07.019. Epub 2019 Aug 6 [PubMed PMID: 31398347]
Kaul V, McCracken DJ, Rahman NM, Epelbaum O. Contemporary Approach to the Diagnosis of Malignant Pleural Effusion. Annals of the American Thoracic Society. 2019 Sep:16(9):1099-1106. doi: 10.1513/AnnalsATS.201902-189CME. Epub [PubMed PMID: 31216176]
Okamoto T, Iwata T, Mizobuchi T, Hoshino H, Moriya Y, Yoshida S, Yoshino I. Pulmonary resection for lung cancer with malignant pleural disease first detected at thoracotomy. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2012 Jan:41(1):25-30. doi: 10.1016/j.ejcts.2011.04.010. Epub [PubMed PMID: 21616674]
Level 2 (mid-level) evidenceRyu JS, Ryu HJ, Lee SN, Memon A, Lee SK, Nam HS, Kim HJ, Lee KH, Cho JH, Hwang SS. Prognostic impact of minimal pleural effusion in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 Mar 20:32(9):960-7. doi: 10.1200/JCO.2013.50.5453. Epub 2014 Feb 18 [PubMed PMID: 24550423]
Level 2 (mid-level) evidenceManac'h D, Riquet M, Medioni J, Le Pimpec-Barthes F, Dujon A, Danel C. Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor. The Annals of thoracic surgery. 2001 Apr:71(4):1088-93 [PubMed PMID: 11308141]
Level 2 (mid-level) evidencePorcel JM. Malignant pleural effusions because of lung cancer. Current opinion in pulmonary medicine. 2016 Jul:22(4):356-61. doi: 10.1097/MCP.0000000000000264. Epub [PubMed PMID: 27055072]
Level 3 (low-level) evidenceRoberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ, BTS Pleural Disease Guideline Group. Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug:65 Suppl 2():ii32-40. doi: 10.1136/thx.2010.136994. Epub [PubMed PMID: 20696691]
van Galen KP, Visser HP, van der Ploeg T, Smorenburg CH. Prognostic factors in patients with breast cancer and malignant pleural effusion. The breast journal. 2010 Nov-Dec:16(6):675-7. doi: 10.1111/j.1524-4741.2010.00986.x. Epub [PubMed PMID: 21070453]
Level 3 (low-level) evidenceMoghaddam NA, Rahmani A, Taheri D, Desfuli MM. Proliferative index using Ki-67 index in reactive mesothelial versus metastatic adenocarcinoma cells in serous fluid. Advanced biomedical research. 2012:1():29. doi: 10.4103/2277-9175.98155. Epub 2012 Jul 6 [PubMed PMID: 23210088]
Sikora J, Dworacki G, Trybus M, Batura-Gabryel H, Zeromski J. Correlation between DNA content, expression of Ki-67 antigen of tumor cells and immunophenotype of lymphocytes from malignant pleural effusions. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 1998:19(3):196-204 [PubMed PMID: 9591046]
Porcel JM, Diaz JP, Chi DS. Clinical implications of pleural effusions in ovarian cancer. Respirology (Carlton, Vic.). 2012 Oct:17(7):1060-7. doi: 10.1111/j.1440-1843.2012.02177.x. Epub [PubMed PMID: 22458298]
Ataseven B, Chiva LM, Harter P, Gonzalez-Martin A, du Bois A. FIGO stage IV epithelial ovarian, fallopian tube and peritoneal cancer revisited. Gynecologic oncology. 2016 Sep:142(3):597-607. doi: 10.1016/j.ygyno.2016.06.013. Epub 2016 Jun 19 [PubMed PMID: 27335253]
Das DK, Gupta SK, Ayyagari S, Bambery PK, Datta BN, Datta U. Pleural effusions in non-Hodgkin's lymphoma. A cytomorphologic, cytochemical and immunologic study. Acta cytologica. 1987 Mar-Apr:31(2):119-24 [PubMed PMID: 3548191]
Level 2 (mid-level) evidenceAntony VB, Loddenkemper R, Astoul P, Boutin C, Goldstraw P, Hott J, Rodriguez Panadero F, Sahn SA. Management of malignant pleural effusions. The European respiratory journal. 2001 Aug:18(2):402-19 [PubMed PMID: 11529302]
Das DK. Serous effusions in malignant lymphomas: a review. Diagnostic cytopathology. 2006 May:34(5):335-47 [PubMed PMID: 16604559]
Hunter BD, Dhakal S, Voci S, Goldstein NP, Constine LS. Pleural effusions in patients with Hodgkin lymphoma: clinical predictors and associations with outcome. Leukemia & lymphoma. 2014 Aug:55(8):1822-6. doi: 10.3109/10428194.2013.836599. Epub 2014 Feb 4 [PubMed PMID: 24237578]
Bianchi C, Bianchi T. Non-Hodgkin Lymphoma and Pleural Mesothelioma in a Person Exposed to Asbestos. Turk patoloji dergisi. 2018:34(2):190-193. doi: 10.5146/tjpath.2015.01332. Epub [PubMed PMID: 28272659]
Rodríguez Panadero F. Diagnosis and treatment of malignant pleural mesothelioma. Archivos de bronconeumologia. 2015 Apr:51(4):177-84. doi: 10.1016/j.arbres.2014.06.005. Epub 2014 Jul 22 [PubMed PMID: 25059587]
Puchalski JT, Argento AC, Murphy TE, Araujo KL, Oliva IB, Rubinowitz AN, Pisani MA. Etiologies of bilateral pleural effusions. Respiratory medicine. 2013 Feb:107(2):284-91. doi: 10.1016/j.rmed.2012.10.004. Epub 2012 Dec 7 [PubMed PMID: 23219348]
McCarten KM, Nadel HR, Shulkin BL, Cho SY. Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma. Pediatric radiology. 2019 Oct:49(11):1545-1564. doi: 10.1007/s00247-019-04529-8. Epub 2019 Oct 16 [PubMed PMID: 31620854]
Asciak R, Rahman NM. Malignant Pleural Effusion: From Diagnostics to Therapeutics. Clinics in chest medicine. 2018 Mar:39(1):181-193. doi: 10.1016/j.ccm.2017.11.004. Epub 2017 Dec 13 [PubMed PMID: 29433714]
Roh J, Ahn HY, Kim I, Son JH, Seol HY, Kim MH, Lee MK, Eom JS. Clinical course of asymptomatic malignant pleural effusion in non-small cell lung cancer patients: A multicenter retrospective study. Medicine. 2021 May 14:100(19):e25748. doi: 10.1097/MD.0000000000025748. Epub [PubMed PMID: 34106603]
Level 2 (mid-level) evidenceDiaz-Guzman E, Budev MM. Accuracy of the physical examination in evaluating pleural effusion. Cleveland Clinic journal of medicine. 2008 Apr:75(4):297-303 [PubMed PMID: 18491436]
Elliott-Button HL, Johnson MJ, Nwulu U, Clark J. Identification and Assessment of Breathlessness in Clinical Practice: A Systematic Review and Narrative Synthesis. Journal of pain and symptom management. 2020 Mar:59(3):724-733.e19. doi: 10.1016/j.jpainsymman.2019.10.014. Epub 2019 Oct 23 [PubMed PMID: 31655187]
Level 1 (high-level) evidenceJanssens JP, Breitenstein E, Rochat T, Fitting JW. Does the 'oxygen cost diagram' reflect changes in six minute walking distance in follow up studies? Respiratory medicine. 1999 Nov:93(11):810-5 [PubMed PMID: 10603630]
Johnson MJ, Close L, Gillon SC, Molassiotis A, Lee PH, Farquhar MC, Breathlessness Research Interest Group (BRIG). Use of the modified Borg scale and numerical rating scale to measure chronic breathlessness: a pooled data analysis. The European respiratory journal. 2016 Jun:47(6):1861-4. doi: 10.1183/13993003.02089-2015. Epub 2016 Mar 17 [PubMed PMID: 26989107]
Vanhoutte EK, Faber CG, van Nes SI, Jacobs BC, van Doorn PA, van Koningsveld R, Cornblath DR, van der Kooi AJ, Cats EA, van den Berg LH, Notermans NC, van der Pol WL, Hermans MC, van der Beek NA, Gorson KC, Eurelings M, Engelsman J, Boot H, Meijer RJ, Lauria G, Tennant A, Merkies IS, PeriNomS Study Group. Modifying the Medical Research Council grading system through Rasch analyses. Brain : a journal of neurology. 2012 May:135(Pt 5):1639-49. doi: 10.1093/brain/awr318. Epub 2011 Dec 20 [PubMed PMID: 22189568]
Rutkowska A, Rutkowski S, Wrzeciono A, Czech O, Szczegielniak J, Jastrzębski D. Short-Term Changes in Quality of Life in Patients with Advanced Lung Cancer during In-Hospital Exercise Training and Chemotherapy Treatment: A Randomized Controlled Trial. Journal of clinical medicine. 2021 Apr 18:10(8):. doi: 10.3390/jcm10081761. Epub 2021 Apr 18 [PubMed PMID: 33919571]
Level 2 (mid-level) evidenceMcKenzie E, Hwang MK, Chan S, Zhang L, Zaki P, Tsao M, Barnes E, Razvi Y, Drost L, Yee C, Chow E. Predictors of dyspnea in patients with advanced cancer. Annals of palliative medicine. 2018 Oct:7(4):427-436. doi: 10.21037/apm.2018.06.09. Epub 2018 Jul 13 [PubMed PMID: 30180735]
Ekström M, Johnson MJ, Huang C, Currow DC. Minimal clinically important differences in average, best, worst and current intensity and unpleasantness of chronic breathlessness. The European respiratory journal. 2020 Aug:56(2):. pii: 1902202. doi: 10.1183/13993003.02202-2019. Epub 2020 Aug 13 [PubMed PMID: 32341113]
Moore AJ, Parker RJ, Wiggins J. Malignant mesothelioma. Orphanet journal of rare diseases. 2008 Dec 19:3():34. doi: 10.1186/1750-1172-3-34. Epub 2008 Dec 19 [PubMed PMID: 19099560]
Reamy BV, Williams PM, Odom MR. Pleuritic Chest Pain: Sorting Through the Differential Diagnosis. American family physician. 2017 Sep 1:96(5):306-312 [PubMed PMID: 28925655]
Spiro SG, Gould MK, Colice GL, American College of Chest Physicians. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007 Sep:132(3 Suppl):149S-160S [PubMed PMID: 17873166]
Level 1 (high-level) evidenceCallemeyn J, Van Haecke P, Peetermans WE, Blockmans D. Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance. Acta clinica Belgica. 2016 Jun:71(3):123-30. doi: 10.1080/17843286.2016.1152672. Epub 2016 Apr 22 [PubMed PMID: 27104368]
Matsuura N. Schamroth sign. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2019 Nov 11:191(45):E1251. doi: 10.1503/cmaj.190515. Epub [PubMed PMID: 31712360]
Vandemergel X, Renneboog B. Prevalence, aetiologies and significance of clubbing in a department of general internal medicine. European journal of internal medicine. 2008 Jul:19(5):325-9. doi: 10.1016/j.ejim.2007.05.015. Epub 2008 Feb 11 [PubMed PMID: 18549933]
Spicknall KE, Zirwas MJ, English JC 3rd. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. Journal of the American Academy of Dermatology. 2005 Jun:52(6):1020-8 [PubMed PMID: 15928621]
Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ. Lambert-Eaton Myasthenic Syndrome. Neurologic clinics. 2018 May:36(2):379-394. doi: 10.1016/j.ncl.2018.01.008. Epub [PubMed PMID: 29655456]
Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clinic proceedings. 2010 Sep:85(9):838-54. doi: 10.4065/mcp.2010.0099. Epub [PubMed PMID: 20810794]
Burzyantseva O, Dharmasena S, Jayawardena S, Rupanagudi VA, Krishnan P. Hypercalcemia-leukocytosis syndrome in a patient with cavitating squamous cell carcinoma of the lung. Cases journal. 2009 Jan 31:2(1):108. doi: 10.1186/1757-1626-2-108. Epub 2009 Jan 31 [PubMed PMID: 19183491]
Level 3 (low-level) evidenceZhang HY, Zhao J. Ectopic Cushing syndrome in small cell lung cancer: A case report and literature review. Thoracic cancer. 2017 Mar:8(2):114-117. doi: 10.1111/1759-7714.12403. Epub 2016 Nov 8 [PubMed PMID: 28102935]
Level 3 (low-level) evidenceZimmerman S, Davis M. Rapid Fire: Superior Vena Cava Syndrome. Emergency medicine clinics of North America. 2018 Aug:36(3):577-584. doi: 10.1016/j.emc.2018.04.011. Epub 2018 Jun 12 [PubMed PMID: 30037444]
Foroulis CN, Zarogoulidis P, Darwiche K, Katsikogiannis N, Machairiotis N, Karapantzos I, Tsakiridis K, Huang H, Zarogoulidis K. Superior sulcus (Pancoast) tumors: current evidence on diagnosis and radical treatment. Journal of thoracic disease. 2013 Sep:5 Suppl 4(Suppl 4):S342-58. doi: 10.3978/j.issn.2072-1439.2013.04.08. Epub [PubMed PMID: 24102007]
Martínez-Lavín M. Hypertrophic osteoarthropathy. Best practice & research. Clinical rheumatology. 2020 Jun:34(3):101507. doi: 10.1016/j.berh.2020.101507. Epub 2020 Apr 11 [PubMed PMID: 32291203]
Yap FY, Skalski MR, Patel DB, Schein AJ, White EA, Tomasian A, Masih S, Matcuk GR Jr. Hypertrophic Osteoarthropathy: Clinical and Imaging Features. Radiographics : a review publication of the Radiological Society of North America, Inc. 2017 Jan-Feb:37(1):157-195. doi: 10.1148/rg.2017160052. Epub 2016 Dec 9 [PubMed PMID: 27935768]
Klebe S, Leigh J, Henderson DW, Nurminen M. Asbestos, Smoking and Lung Cancer: An Update. International journal of environmental research and public health. 2019 Dec 30:17(1):. doi: 10.3390/ijerph17010258. Epub 2019 Dec 30 [PubMed PMID: 31905913]
Roden AC, Camus P. Iatrogenic pulmonary lesions. Seminars in diagnostic pathology. 2018 Jul:35(4):260-271. doi: 10.1053/j.semdp.2018.03.002. Epub 2018 Mar 23 [PubMed PMID: 29631763]
Morita T, Tsunoda J, Inoue S, Chihara S. The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 1999 May:7(3):128-33 [PubMed PMID: 10335930]
Level 2 (mid-level) evidenceLight RW. Clinical practice. Pleural effusion. The New England journal of medicine. 2002 Jun 20:346(25):1971-7 [PubMed PMID: 12075059]
Level 3 (low-level) evidenceYernault JC, Bohadana AB. Chest percussion. The European respiratory journal. 1995 Oct:8(10):1756-60 [PubMed PMID: 8586135]
Keller EM. [Plessimeter Percussion]. Pneumologie (Stuttgart, Germany). 2019 Jan:73(1):34-39. doi: 10.1055/s-0043-125015. Epub 2018 Dec 7 [PubMed PMID: 30536248]
Wong CL, Holroyd-Leduc J, Straus SE. Does this patient have a pleural effusion? JAMA. 2009 Jan 21:301(3):309-17. doi: 10.1001/jama.2008.937. Epub [PubMed PMID: 19155458]
Karkhanis VS, Joshi JM. Pleural effusion: diagnosis, treatment, and management. Open access emergency medicine : OAEM. 2012:4():31-52. doi: 10.2147/OAEM.S29942. Epub 2012 Jun 22 [PubMed PMID: 27147861]
Blackmore CC, Black WC, Dallas RV, Crow HC. Pleural fluid volume estimation: a chest radiograph prediction rule. Academic radiology. 1996 Feb:3(2):103-9 [PubMed PMID: 8796649]
Level 2 (mid-level) evidenceWoodring JH. Recognition of pleural effusion on supine radiographs: how much fluid is required? AJR. American journal of roentgenology. 1984 Jan:142(1):59-64 [PubMed PMID: 6606966]
Reuter S, Lindgaard D, Laursen C, Fischer BM, Clementsen PF, Bodtger U. Computed tomography of the chest in unilateral pleural effusions: outcome of the British Thoracic Society guideline. Journal of thoracic disease. 2019 Apr:11(4):1336-1346. doi: 10.21037/jtd.2019.03.75. Epub [PubMed PMID: 31179075]
Khajotia R. Respiratory Clinics: MEDIASTINAL SHIFT: A SIGN OF SIGNIFICANT CLINICAL AND RADIOLOGICAL IMPORTANCE IN DIAGNOSIS OF MALIGNANT PLEURAL EFFUSION. Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia. 2012:7(1):34-6 [PubMed PMID: 25606244]
Level 3 (low-level) evidenceHansell L, Milross M, Delaney A, Tian DH, Ntoumenopoulos G. Lung ultrasound has greater accuracy than conventional respiratory assessment tools for the diagnosis of pleural effusion, lung consolidation and collapse: a systematic review. Journal of physiotherapy. 2021 Jan:67(1):41-48. doi: 10.1016/j.jphys.2020.12.002. Epub [PubMed PMID: 33353830]
Level 1 (high-level) evidenceHavelock T, Teoh R, Laws D, Gleeson F, BTS Pleural Disease Guideline Group. Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug:65 Suppl 2():ii61-76. doi: 10.1136/thx.2010.137026. Epub [PubMed PMID: 20696688]
Yu H. Management of pleural effusion, empyema, and lung abscess. Seminars in interventional radiology. 2011 Mar:28(1):75-86. doi: 10.1055/s-0031-1273942. Epub [PubMed PMID: 22379278]
Sureka B, Thukral BB, Mittal MK, Mittal A, Sinha M. Radiological review of pleural tumors. The Indian journal of radiology & imaging. 2013 Oct:23(4):313-20. doi: 10.4103/0971-3026.125577. Epub [PubMed PMID: 24604935]
Lichtenstein DA. Lung ultrasound in the critically ill. Annals of intensive care. 2014 Jan 9:4(1):1. doi: 10.1186/2110-5820-4-1. Epub 2014 Jan 9 [PubMed PMID: 24401163]
Husain LF, Hagopian L, Wayman D, Baker WE, Carmody KA. Sonographic diagnosis of pneumothorax. Journal of emergencies, trauma, and shock. 2012 Jan:5(1):76-81. doi: 10.4103/0974-2700.93116. Epub [PubMed PMID: 22416161]
Smargiassi A, Inchingolo R, Zanforlin A, Valente S, Soldati G, Corbo GM. Description of free-flowing pleural effusions in medical reports after echographic assessment. Respiration; international review of thoracic diseases. 2013:85(5):439-41. doi: 10.1159/000346991. Epub 2013 Mar 19 [PubMed PMID: 23548724]
Level 3 (low-level) evidenceCantey EP, Walter JM, Corbridge T, Barsuk JH. Complications of thoracentesis: incidence, risk factors, and strategies for prevention. Current opinion in pulmonary medicine. 2016 Jul:22(4):378-85. doi: 10.1097/MCP.0000000000000285. Epub [PubMed PMID: 27093476]
Level 3 (low-level) evidencePurandare NC, Rangarajan V. Imaging of lung cancer: Implications on staging and management. The Indian journal of radiology & imaging. 2015 Apr-Jun:25(2):109-20. doi: 10.4103/0971-3026.155831. Epub [PubMed PMID: 25969634]
Leung AN, Müller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR. American journal of roentgenology. 1990 Mar:154(3):487-92 [PubMed PMID: 2106209]
Porcel JM, Pardina M, Bielsa S, González A, Light RW. Derivation and validation of a CT scan scoring system for discriminating malignant from benign pleural effusions. Chest. 2015 Feb:147(2):513-519. doi: 10.1378/chest.14-0013. Epub [PubMed PMID: 25255186]
Level 1 (high-level) evidenceZhang X, Duan H, Yu Y, Ma C, Ren Z, Lei Y, He T, Zhang M. Differential diagnosis between benign and malignant pleural effusion with dual-energy spectral CT. PloS one. 2018:13(4):e0193714. doi: 10.1371/journal.pone.0193714. Epub 2018 Apr 11 [PubMed PMID: 29641601]
Amarante MP, Younes RN, Rigo L, de Sousa Cruz MR. Interpretation of PET/CT findings in patients with advanced lung cancer who have undergone pleurodesis. Ecancermedicalscience. 2014:8():452. doi: 10.3332/ecancer.2014.452. Epub 2014 Aug 12 [PubMed PMID: 25183997]
Level 3 (low-level) evidenceElboga U, Yılmaz M, Uyar M, Zeki Çelen Y, Bakır K, Dikensoy O. The role of FDG PET-CT in differential diagnosis of pleural pathologies. Revista espanola de medicina nuclear e imagen molecular. 2012 Jul-Aug:31(4):187-91. doi: 10.1016/j.remn.2011.06.002. Epub 2011 Sep 22 [PubMed PMID: 23067687]
Level 2 (mid-level) evidenceYang MF, Tong ZH, Wang Z, Zhang YY, Xu LL, Wang XJ, Li W, Wu XZ, Wang W, Zhang YH, Jiang T, Shi HZ. Development and validation of the PET-CT score for diagnosis of malignant pleural effusion. European journal of nuclear medicine and molecular imaging. 2019 Jul:46(7):1457-1467. doi: 10.1007/s00259-019-04287-7. Epub 2019 Mar 22 [PubMed PMID: 30903197]
Level 1 (high-level) evidenceCardinale L, Ardissone F, Gned D, Sverzellati N, Piacibello E, Veltri A. Diagnostic Imaging and workup of Malignant Pleural Mesothelioma. Acta bio-medica : Atenei Parmensis. 2017 Aug 23:88(2):134-142. doi: 10.23750/abm.v88i2.5558. Epub 2017 Aug 23 [PubMed PMID: 28845826]
Schaefer-Prokop C, Prokop M. New imaging techniques in the treatment guidelines for lung cancer. The European respiratory journal. Supplement. 2002 Feb:35():71s-83s [PubMed PMID: 12064683]
Usuda K, Iwai S, Funasaki A, Sekimura A, Motono N, Matoba M, Doai M, Yamada S, Ueda Y, Uramoto H. Diffusion-Weighted Imaging Can Differentiate between Malignant and Benign Pleural Diseases. Cancers. 2019 Jun 12:11(6):. doi: 10.3390/cancers11060811. Epub 2019 Jun 12 [PubMed PMID: 31212757]
Mercer RM, Corcoran JP, Porcel JM, Rahman NM, Psallidas I. Interpreting pleural fluid results . Clinical medicine (London, England). 2019 May:19(3):213-217. doi: 10.7861/clinmedicine.19-3-213. Epub [PubMed PMID: 31092513]
Wu H, Khosla R, Rohatgi PK, Chauhan SS, Paal E, Chen W. The minimum volume of pleural fluid required to diagnose malignant pleural effusion: A retrospective study. Lung India : official organ of Indian Chest Society. 2017 Jan-Feb:34(1):34-37. doi: 10.4103/0970-2113.197120. Epub [PubMed PMID: 28144058]
Level 2 (mid-level) evidenceRenshaw AA, Dean BR, Antman KH, Sugarbaker DJ, Cibas ES. The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Chest. 1997 Jan:111(1):106-9 [PubMed PMID: 8996002]
Level 2 (mid-level) evidenceKaur G, Nijhawan R, Gupta N, Singh N, Rajwanshi A. Pleural fluid cytology samples in cases of suspected lung cancer: An experience from a tertiary care centre. Diagnostic cytopathology. 2017 Mar:45(3):195-201. doi: 10.1002/dc.23659. Epub 2017 Jan 23 [PubMed PMID: 28112486]
Level 3 (low-level) evidenceRyu JS, Ryu ST, Kim YS, Cho JH, Lee HL. What is the clinical significance of transudative malignant pleural effusion? The Korean journal of internal medicine. 2003 Dec:18(4):230-3 [PubMed PMID: 14717231]
Level 2 (mid-level) evidenceArnold DT, De Fonseka D, Perry S, Morley A, Harvey JE, Medford A, Brett M, Maskell NA. Investigating unilateral pleural effusions: the role of cytology. The European respiratory journal. 2018 Nov:52(5):. pii: 1801254. doi: 10.1183/13993003.01254-2018. Epub 2018 Nov 8 [PubMed PMID: 30262573]
Kim CH, Oh HG, Lee SY, Lim JK, Lee YH, Seo H, Yoo SS, Lee SY, Cha SI, Park JY, Lee J. Differential diagnosis between lymphoma-associated malignant pleural effusion and tuberculous pleural effusion. Annals of translational medicine. 2019 Aug:7(16):373. doi: 10.21037/atm.2019.07.17. Epub [PubMed PMID: 31555687]
Roth BJ, O'Meara TF, Cragun WH. The serum-effusion albumin gradient in the evaluation of pleural effusions. Chest. 1990 Sep:98(3):546-9 [PubMed PMID: 2152757]
Hasteh F, Lin GY, Weidner N, Michael CW. The use of immunohistochemistry to distinguish reactive mesothelial cells from malignant mesothelioma in cytologic effusions. Cancer cytopathology. 2010 Apr 25:118(2):90-6. doi: 10.1002/cncy.20071. Epub [PubMed PMID: 20209622]
Dixit R, Agarwal KC, Gokhroo A, Patil CB, Meena M, Shah NS, Arora P. Diagnosis and management options in malignant pleural effusions. Lung India : official organ of Indian Chest Society. 2017 Mar-Apr:34(2):160-166. doi: 10.4103/0970-2113.201305. Epub [PubMed PMID: 28360465]
Qamar I, Rehman S, Mehdi G, Maheshwari V, Ansari HA, Chauhan S. Utility of Cytospin and Cell block Technology in Evaluation of Body Fluids and Urine Samples: A Comparative Study. Journal of cytology. 2018 Apr-Jun:35(2):79-82. doi: 10.4103/JOC.JOC_240_16. Epub [PubMed PMID: 29643653]
Level 2 (mid-level) evidenceGarcía Carretero R, Manotas-Hidalgo M, Romero Brugera M, El Bouayadi Mohamed L. Pleural effusion of malignant aetiology: cell block technique to establish the diagnosis. BMJ case reports. 2016 Mar 18:2016():. doi: 10.1136/bcr-2016-215140. Epub 2016 Mar 18 [PubMed PMID: 26994057]
Level 3 (low-level) evidenceAssawasaksakul T, Boonsarngsuk V, Incharoen P. A comparative study of conventional cytology and cell block method in the diagnosis of pleural effusion. Journal of thoracic disease. 2017 Sep:9(9):3161-3167. doi: 10.21037/jtd.2017.08.52. Epub [PubMed PMID: 29221292]
Level 2 (mid-level) evidenceShidham VB. CellBlockistry: Chemistry and art of cell-block making - A detailed review of various historical options with recent advances. CytoJournal. 2019:16():12. doi: 10.4103/cytojournal.cytojournal_20_19. Epub 2019 Jun 28 [PubMed PMID: 31367220]
Level 3 (low-level) evidenceShivakumarswamy U, Arakeri SU, Karigowdar MH, Yelikar B. Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology. Journal of cytology. 2012 Jan:29(1):11-5. doi: 10.4103/0970-9371.93210. Epub [PubMed PMID: 22438610]
Shidham VB, Layfield LJ. Cell-blocks and immunohistochemistry. CytoJournal. 2021:18():2. doi: 10.25259/Cytojournal_83_2020. Epub 2021 Jan 30 [PubMed PMID: 33598043]
Bhattacharya S, Bairagya TD, Das A, Mandal A, Das SK. Closed pleural biopsy is still useful in the evaluation of malignant pleural effusion. Journal of laboratory physicians. 2012 Jan:4(1):35-8. doi: 10.4103/0974-2727.98669. Epub [PubMed PMID: 22923920]
Pereyra MF, San-José E, Ferreiro L, Golpe A, Antúnez J, González-Barcala FJ, Abdulkader I, Álvarez-Dobaño JM, Rodríguez-Núñez N, Valdés L. Role of blind closed pleural biopsy in the managment of pleural exudates. Canadian respiratory journal. 2013 Sep-Oct:20(5):362-6 [PubMed PMID: 23951560]
Level 2 (mid-level) evidenceKoegelenberg CF, Diacon AH. Pleural controversy: close needle pleural biopsy or thoracoscopy-which first? Respirology (Carlton, Vic.). 2011 Jul:16(5):738-46. doi: 10.1111/j.1440-1843.2011.01973.x. Epub [PubMed PMID: 21435098]
Level 3 (low-level) evidenceLan RS, Lo SK, Chuang ML, Yang CT, Tsao TC, Lee CH. Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion. Annals of internal medicine. 1997 May 15:126(10):768-74 [PubMed PMID: 9148649]
Fong C, Tan CWC, Tan DKY, See KC. Safety of Thoracentesis and Tube Thoracostomy in Patients With Uncorrected Coagulopathy: A Systematic Review and Meta-analysis. Chest. 2021 Nov:160(5):1875-1889. doi: 10.1016/j.chest.2021.04.036. Epub 2021 Apr 24 [PubMed PMID: 33905681]
Level 1 (high-level) evidenceGoligher EC, Leis JA, Fowler RA, Pinto R, Adhikari NK, Ferguson ND. Utility and safety of draining pleural effusions in mechanically ventilated patients: a systematic review and meta-analysis. Critical care (London, England). 2011:15(1):R46. doi: 10.1186/cc10009. Epub 2011 Feb 2 [PubMed PMID: 21288334]
Level 1 (high-level) evidenceSheta SA. Procedural sedation analgesia. Saudi journal of anaesthesia. 2010 Jan:4(1):11-6. doi: 10.4103/1658-354X.62608. Epub [PubMed PMID: 20668560]
Ault MJ, Rosen BT, Scher J, Feinglass J, Barsuk JH. Thoracentesis outcomes: a 12-year experience. Thorax. 2015 Feb:70(2):127-32. doi: 10.1136/thoraxjnl-2014-206114. Epub 2014 Nov 5 [PubMed PMID: 25378543]
Level 2 (mid-level) evidenceManian FA. The role of postoperative factors in surgical site infections: time to take notice. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014 Nov 1:59(9):1272-6. doi: 10.1093/cid/ciu552. Epub 2014 Jul 14 [PubMed PMID: 25028464]
Kwiatt M, Tarbox A, Seamon MJ, Swaroop M, Cipolla J, Allen C, Hallenbeck S, Davido HT, Lindsey DE, Doraiswamy VA, Galwankar S, Tulman D, Latchana N, Papadimos TJ, Cook CH, Stawicki SP. Thoracostomy tubes: A comprehensive review of complications and related topics. International journal of critical illness and injury science. 2014 Apr:4(2):143-55. doi: 10.4103/2229-5151.134182. Epub [PubMed PMID: 25024942]
Mansour W, Samaha G, El Bitar S, Esper Z, Maroun R. Intercostal Artery Laceration: Rare Complication of Thoracentesis and Role of Ultrasound in Early Detection. Case reports in pulmonology. 2017:2017():6491083. doi: 10.1155/2017/6491083. Epub 2017 Aug 2 [PubMed PMID: 28831322]
Level 3 (low-level) evidenceYacovone ML, Kartan R, Bautista M. Intercostal artery laceration following thoracentesis. Respiratory care. 2010 Nov:55(11):1495-8 [PubMed PMID: 20979678]
Level 3 (low-level) evidenceSalamonsen M, Ellis S, Paul E, Steinke K, Fielding D. Thoracic ultrasound demonstrates variable location of the intercostal artery. Respiration; international review of thoracic diseases. 2012:83(4):323-9. doi: 10.1159/000330920. Epub 2012 Feb 2 [PubMed PMID: 22301442]
Level 2 (mid-level) evidenceKalifatidis A, Lazaridis G, Baka S, Mpoukovinas I, Karavasilis V, Kioumis I, Pitsiou G, Papaiwannou A, Karavergou A, Tsakiridis K, Katsikogiannis N, Sarika E, Kapanidis K, Sakkas L, Korantzis I, Lampaki S, Zarogoulidis K, Zarogoulidis P. Thoracocentesis: from bench to bed. Journal of thoracic disease. 2015 Feb:7(Suppl 1):S1-4. doi: 10.3978/j.issn.2072-1439.2014.12.45. Epub [PubMed PMID: 25774301]
Sachdeva A, Shepherd RW, Lee HJ. Thoracentesis and thoracic ultrasound: state of the art in 2013. Clinics in chest medicine. 2013 Mar:34(1):1-9. doi: 10.1016/j.ccm.2012.11.005. Epub 2013 Jan 17 [PubMed PMID: 23411051]
Krausz M, Manny J. A safe method of thoracentesis. The Journal of thoracic and cardiovascular surgery. 1976 Aug:72(2):323-5 [PubMed PMID: 957750]
Jany B, Welte T. Pleural Effusion in Adults-Etiology, Diagnosis, and Treatment. Deutsches Arzteblatt international. 2019 May 24:116(21):377-386. doi: 10.3238/arztebl.2019.0377. Epub [PubMed PMID: 31315808]
MacDuff A, Arnold A, Harvey J, BTS Pleural Disease Guideline Group. Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010 Aug:65 Suppl 2():ii18-31. doi: 10.1136/thx.2010.136986. Epub [PubMed PMID: 20696690]
Lentz RJ, Shojaee S, Grosu HB, Rickman OB, Roller L, Pannu JK, DePew ZS, Debiane LG, Cicenia JC, Akulian J, Walston C, Sanchez TM, Davidson KR, Jagan N, Ahmad S, Gilbert C, Huggins JT, Chen H, Light RW, Yarmus L, Feller-Kopman D, Lee H, Rahman NM, Maldonado F, Interventional Pulmonary Outcomes Group. The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications: The GRAVITAS Multicenter Randomized Controlled Trial. Chest. 2020 Mar:157(3):702-711. doi: 10.1016/j.chest.2019.10.025. Epub 2019 Nov 9 [PubMed PMID: 31711990]
Level 1 (high-level) evidenceFeller-Kopman D, Berkowitz D, Boiselle P, Ernst A. Large-volume thoracentesis and the risk of reexpansion pulmonary edema. The Annals of thoracic surgery. 2007 Nov:84(5):1656-61 [PubMed PMID: 17954079]
Spella M, Giannou AD, Stathopoulos GT. Switching off malignant pleural effusion formation-fantasy or future? Journal of thoracic disease. 2015 Jun:7(6):1009-20. doi: 10.3978/j.issn.2072-1439.2015.05.20. Epub [PubMed PMID: 26150914]
Lentz RJ, Lerner AD, Pannu JK, Merrick CM, Roller L, Walston C, Valenti S, Goddard T, Chen H, Huggins JT, Rickman OB, Yarmus L, Psallidas I, Rahman NM, Light RW, Maldonado F. Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications: a multicentre, single-blind randomised controlled trial. The Lancet. Respiratory medicine. 2019 May:7(5):447-455. doi: 10.1016/S2213-2600(18)30421-1. Epub 2019 Feb 13 [PubMed PMID: 30772283]
Level 1 (high-level) evidenceMytinger A, Taylor T, Gershman E, Shojaee S. Pleural Disease Management: Manometry-guided Thoracentesis, Optimal Drainage Regimen of Indwelling Pleural Catheters, and Talc Poudrage versus Slurry for Malignant Pleural Effusion. American journal of respiratory and critical care medicine. 2020 Aug 1:202(3):448-450. doi: 10.1164/rccm.202003-0599RR. Epub [PubMed PMID: 32421351]
Sunderland N, Maweni R, Akunuri S, Karnovitch E. Re-expansion pulmonary oedema: a novel emergency therapeutic option. BMJ case reports. 2016 Apr 27:2016():. doi: 10.1136/bcr-2016-215076. Epub 2016 Apr 27 [PubMed PMID: 27122103]
Level 3 (low-level) evidenceVerhagen M, van Buijtenen JM, Geeraedts LM Jr. Reexpansion pulmonary edema after chest drainage for pneumothorax: A case report and literature overview. Respiratory medicine case reports. 2015:14():10-2. doi: 10.1016/j.rmcr.2014.10.002. Epub 2014 Nov 26 [PubMed PMID: 26029567]
Level 3 (low-level) evidenceCorcoran JP, Psallidas I, Wrightson JM, Hallifax RJ, Rahman NM. Pleural procedural complications: prevention and management. Journal of thoracic disease. 2015 Jun:7(6):1058-67. doi: 10.3978/j.issn.2072-1439.2015.04.42. Epub [PubMed PMID: 26150919]
Kasmani R, Irani F, Okoli K, Mahajan V. Re-expansion pulmonary edema following thoracentesis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2010 Dec 14:182(18):2000-2. doi: 10.1503/cmaj.090672. Epub 2010 Jul 19 [PubMed PMID: 20643838]
Level 3 (low-level) evidenceAustin A, Al-Faris F, Modi A, Chopra A. A transudative chylothorax associated with superior vena cava syndrome. Respiratory medicine case reports. 2019:28():100898. doi: 10.1016/j.rmcr.2019.100898. Epub 2019 Jul 8 [PubMed PMID: 31338288]
Level 3 (low-level) evidenceMahajan VK, Simon M, Huber GL. Reexpansion pulmonary edema. Chest. 1979 Feb:75(2):192-4 [PubMed PMID: 421556]
Level 3 (low-level) evidenceMokotedi CM, Balik M. Is the mechanism of re-expansion pulmonary oedema in a heart-lung interaction? BMJ case reports. 2017 Jul 18:2017():. pii: bcr-2017-219340. doi: 10.1136/bcr-2017-219340. Epub 2017 Jul 18 [PubMed PMID: 28720600]
Level 3 (low-level) evidenceRodrigues AL, Lopes CE, Romaneli MT, Fraga Ade M, Pereira RM, Tresoldi AT. Reexpansion pulmonary edema in children. Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2013 Sep:31(3):411-5. doi: 10.1590/S0103-05822013000300021. Epub [PubMed PMID: 24142327]
Level 3 (low-level) evidenceVolpicelli G, Fogliati C, Radeschi G, Frascisco M. A case of unilateral re-expansion pulmonary oedema successfully treated with non-invasive continuous positive airway pressure. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2004 Oct:11(5):291-4 [PubMed PMID: 15359205]
Level 3 (low-level) evidenceJanocik SE, Roy TM, Killeen TR. Re-expansion pulmonary edema: a preventable complication. The Journal of the Kentucky Medical Association. 1993 Apr:91(4):143-8 [PubMed PMID: 8320499]
Level 3 (low-level) evidenceTarver RD, Broderick LS, Conces DJ Jr. Reexpansion pulmonary edema. Journal of thoracic imaging. 1996 Summer:11(3):198-209 [PubMed PMID: 8784733]
Level 3 (low-level) evidenceMalota M, Kowarik MC, Bechtold B, Kopp R. Reexpansion pulmonary edema following a posttraumatic pneumothorax: a case report and review of the literature. World journal of emergency surgery : WJES. 2011 Sep 2:6():32. doi: 10.1186/1749-7922-6-32. Epub 2011 Sep 2 [PubMed PMID: 21888638]
Level 3 (low-level) evidenceMorioka H, Takada K, Matsumoto S, Kojima E, Iwata S, Okachi S. Re-expansion pulmonary edema: evaluation of risk factors in 173 episodes of spontaneous pneumothorax. Respiratory investigation. 2013 Mar:51(1):35-9. doi: 10.1016/j.resinv.2012.09.003. Epub 2012 Nov 26 [PubMed PMID: 23561257]
Level 2 (mid-level) evidenceLam KN, Chew LS. Life threatening re-expansion hypotension and pulmonary oedema following treatment of a pneumothorax. Singapore medical journal. 1989 Oct:30(5):502-5 [PubMed PMID: 2617307]
Level 3 (low-level) evidenceGleeson T, Thiessen R, Müller N. Reexpansion pulmonary edema: computed tomography findings in 22 patients. Journal of thoracic imaging. 2011 Feb:26(1):36-41. doi: 10.1097/RTI.0b013e3181ced052. Epub [PubMed PMID: 20489660]
Level 2 (mid-level) evidenceKepka S, Lemaitre L, Marx T, Bilbault P, Desmettre T. A common gesture with a rare but potentially severe complication: Re-expansion pulmonary edema following chest tube drainage. Respiratory medicine case reports. 2019:27():100838. doi: 10.1016/j.rmcr.2019.100838. Epub 2019 Apr 12 [PubMed PMID: 31016133]
Level 3 (low-level) evidenceKomatsu T, Shibata S, Seo R, Tomii K, Ishihara K, Hayashi T, Takahashi Y. Unilateral re-expansion pulmonary edema following treatment of pneumothorax with exceptionally massive sputum production, followed by circulatory collapse. Canadian respiratory journal. 2010 Mar-Apr:17(2):53-5 [PubMed PMID: 20422058]
Level 3 (low-level) evidenceKim JJ, Kim YH, Choi SY, Jeong SC, Moon SW. Contralateral reexpansion pulmonary edema with ipsilateral collapsed lung after pleural effusion drainage: a case report. Journal of cardiothoracic surgery. 2015 May 8:10():68. doi: 10.1186/s13019-015-0272-3. Epub 2015 May 8 [PubMed PMID: 25952365]
Level 3 (low-level) evidenceMierzejewski M, Korczynski P, Krenke R, Janssen JP. Chemical pleurodesis - a review of mechanisms involved in pleural space obliteration. Respiratory research. 2019 Nov 7:20(1):247. doi: 10.1186/s12931-019-1204-x. Epub 2019 Nov 7 [PubMed PMID: 31699094]
Ibrahim IM, Dokhan AL, El-Sessy AA, Eltaweel MF. Povidone-iodine pleurodesis versus talc pleurodesis in preventing recurrence of malignant pleural effusion. Journal of cardiothoracic surgery. 2015 May 1:10():64. doi: 10.1186/s13019-015-0270-5. Epub 2015 May 1 [PubMed PMID: 25947235]
Özkul S, Turna A, Demirkaya A, Aksoy B, Kaynak K. Rapid pleurodesis is an outpatient alternative in patients with malignant pleural effusions: a prospective randomized controlled trial. Journal of thoracic disease. 2014 Dec:6(12):1731-5. doi: 10.3978/j.issn.2072-1439.2014.11.31. Epub [PubMed PMID: 25589966]
Level 1 (high-level) evidenceZamboni MM, da Silva CT Jr, Baretta R, Cunha ET, Cardoso GP. Important prognostic factors for survival in patients with malignant pleural effusion. BMC pulmonary medicine. 2015 Mar 28:15():29. doi: 10.1186/s12890-015-0025-z. Epub 2015 Mar 28 [PubMed PMID: 25887349]
Hallifax RJ, Psallidas I, Rahman NM. Chest Drain Size: the Debate Continues. Current pulmonology reports. 2017:6(1):26-29. doi: 10.1007/s13665-017-0162-3. Epub 2017 Jan 26 [PubMed PMID: 28344925]
Lardinois D, Vogt P, Yang L, Hegyi I, Baslam M, Weder W. Non-steroidal anti-inflammatory drugs decrease the quality of pleurodesis after mechanical pleural abrasion. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2004 May:25(5):865-71 [PubMed PMID: 15082296]
Level 3 (low-level) evidenceChen J, Li Z, Xu N, Zhang X, Wang Y, Lin D. Efficacy of medical thoracoscopic talc pleurodesis in malignant pleural effusion caused by different types of tumors and different pathological classifications of lung cancer. International journal of clinical and experimental medicine. 2015:8(10):18945-53 [PubMed PMID: 26770519]
Debeljak A, Kecelj P, Triller N, Letonja S, Kern I, Debevec L, Rozman A. Talc pleurodesis: comparison of talc slurry instillation with thoracoscopic talc insufflation for malignant pleural effusions. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2006 Oct-Dec:11(4):463-7 [PubMed PMID: 17309178]
Level 2 (mid-level) evidenceTerra RM, Teixeira LR, Bibas BJ, Pego-Fernandes PM, Vargas FS, Jatene FB. Effectiveness and safety of outpatient pleurodesis in patients with recurrent malignant pleural effusion and low performance status. Clinics (Sao Paulo, Brazil). 2011:66(2):211-6 [PubMed PMID: 21484035]
Olivares-Torres CA, Laniado-Laborín R, Chávez-García C, León-Gastelum C, Reyes-Escamilla A, Light RW. Iodopovidone pleurodesis for recurrent pleural effusions. Chest. 2002 Aug:122(2):581-3 [PubMed PMID: 12171835]
Neto JD, de Oliveira SF, Vianna SP, Terra RM. Efficacy and safety of iodopovidone pleurodesis in malignant pleural effusions. Respirology (Carlton, Vic.). 2010 Jan:15(1):115-8. doi: 10.1111/j.1440-1843.2009.01663.x. Epub 2009 Nov 23 [PubMed PMID: 19947987]
Level 2 (mid-level) evidenceMacEachern P, Tremblay A. Pleural controversy: pleurodesis versus indwelling pleural catheters for malignant effusions. Respirology (Carlton, Vic.). 2011 Jul:16(5):747-54. doi: 10.1111/j.1440-1843.2011.01986.x. Epub [PubMed PMID: 21545373]
Level 3 (low-level) evidenceBhatnagar R, Laskawiec-Szkonter M, Piotrowska HE, Kahan BC, Hooper CE, Davies HE, Harvey JE, Miller RF, Rahman NM, Maskell NA. Evaluating the efficacy of thoracoscopy and talc poudrage versus pleurodesis using talc slurry (TAPPS trial): protocol of an open-label randomised controlled trial. BMJ open. 2014 Nov 26:4(11):e007045. doi: 10.1136/bmjopen-2014-007045. Epub 2014 Nov 26 [PubMed PMID: 25428632]
Level 1 (high-level) evidenceHalford P, Clive AO. Is there a role for prophylactic radiotherapy to intervention tract sites in patients with malignant pleural mesothelioma? Translational lung cancer research. 2018 Oct:7(5):584-592. doi: 10.21037/tlcr.2018.07.06. Epub [PubMed PMID: 30450297]
American Thoracic Society. Management of malignant pleural effusions. American journal of respiratory and critical care medicine. 2000 Nov:162(5):1987-2001 [PubMed PMID: 11069845]
Level 1 (high-level) evidenceBrant A, Eaton T. Serious complications with talc slurry pleurodesis. Respirology (Carlton, Vic.). 2001 Sep:6(3):181-5 [PubMed PMID: 11555375]
Level 2 (mid-level) evidenceWeissberg D. Talc pleurodesis: a matter of priority. AJR. American journal of roentgenology. 1997 Sep:169(3):911 [PubMed PMID: 9275925]
Level 3 (low-level) evidenceDresler CM, Olak J, Herndon JE 2nd, Richards WG, Scalzetti E, Fleishman SB, Kernstine KH, Demmy T, Jablons DM, Kohman L, Daniel TM, Haasler GB, Sugarbaker DJ, Cooperative Groups Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, North Central Cooperative Oncology Group, Radiation Therapy Oncology Group. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005 Mar:127(3):909-15 [PubMed PMID: 15764775]
Level 1 (high-level) evidenceYim AP, Chan AT, Lee TW, Wan IY, Ho JK. Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion. The Annals of thoracic surgery. 1996 Dec:62(6):1655-8 [PubMed PMID: 8957368]
Level 1 (high-level) evidenceAntony VB, Nasreen N, Mohammed KA, Sriram PS, Frank W, Schoenfeld N, Loddenkemper R. Talc pleurodesis: basic fibroblast growth factor mediates pleural fibrosis. Chest. 2004 Nov:126(5):1522-8 [PubMed PMID: 15539722]
Shojaee S, Lee HJ. Thoracoscopy: medical versus surgical-in the management of pleural diseases. Journal of thoracic disease. 2015 Dec:7(Suppl 4):S339-51. doi: 10.3978/j.issn.2072-1439.2015.11.66. Epub [PubMed PMID: 26807282]
Steger V, Mika U, Toomes H, Walker T, Engel C, Kyriss T, Ziemer G, Friedel G. Who gains most? A 10-year experience with 611 thoracoscopic talc pleurodeses. The Annals of thoracic surgery. 2007 Jun:83(6):1940-5 [PubMed PMID: 17532375]
Level 2 (mid-level) evidencevan de Pas JM, van Roozendaal LM, Wanders SL, Custers FL, Vissers YLJ, de Loos ER. Bronchopleural Fistula After Concurrent Chemoradiotherapy. Advances in radiation oncology. 2020 May-Jun:5(3):511-515. doi: 10.1016/j.adro.2019.12.006. Epub 2020 Jan 12 [PubMed PMID: 32529148]
Level 3 (low-level) evidenceBhatnagar R, Piotrowska HEG, Laskawiec-Szkonter M, Kahan BC, Luengo-Fernandez R, Pepperell JCT, Evison MD, Holme J, Al-Aloul M, Psallidas I, Lim WS, Blyth KG, Roberts ME, Cox G, Downer NJ, Herre J, Sivasothy P, Menzies D, Munavvar M, Kyi MM, Ahmed L, West AG, Harrison RN, Prudon B, Hettiarachchi G, Chakrabarti B, Kavidasan A, Sutton BP, Zahan-Evans NJ, Quaddy JL, Edey AJ, Clive AO, Walker SP, Little MHR, Mei XW, Harvey JE, Hooper CE, Davies HE, Slade M, Sivier M, Miller RF, Rahman NM, Maskell NA. Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial. JAMA. 2020 Jan 7:323(1):60-69. doi: 10.1001/jama.2019.19997. Epub [PubMed PMID: 31804680]
Level 1 (high-level) evidenceBhatnagar R, Luengo-Fernandez R, Kahan BC, Rahman NM, Miller RF, Maskell NA. Thoracoscopy and talc poudrage compared with intercostal drainage and talc slurry infusion to manage malignant pleural effusion: the TAPPS RCT. Health technology assessment (Winchester, England). 2020 Jun:24(26):1-90. doi: 10.3310/hta24260. Epub [PubMed PMID: 32525474]
Chalhoub M, Saqib A, Castellano M. Indwelling pleural catheters: complications and management strategies. Journal of thoracic disease. 2018 Jul:10(7):4659-4666. doi: 10.21037/jtd.2018.04.160. Epub [PubMed PMID: 30174919]
Level 2 (mid-level) evidenceLui MM, Thomas R, Lee YC. Complications of indwelling pleural catheter use and their management. BMJ open respiratory research. 2016:3(1):e000123. doi: 10.1136/bmjresp-2015-000123. Epub 2016 Feb 5 [PubMed PMID: 26870384]
Lücke E, Steffen U, Riedel S, Schreiber J. [Efficacy and Safety of Indwelling Pleural Catheters]. Zentralblatt fur Chirurgie. 2018 Jun:143(3):290-295. doi: 10.1055/s-0043-123656. Epub 2018 Jan 11 [PubMed PMID: 29325199]
Bertolaccini L, Viti A, Terzi A. Management of malignant pleural effusions in patients with trapped lung with indwelling pleural catheter: how to do it. Journal of visualized surgery. 2016:2():44. doi: 10.21037/jovs.2016.02.06. Epub 2016 Mar 11 [PubMed PMID: 29078472]
Thomas R, Fysh ETH, Smith NA, Lee P, Kwan BCH, Yap E, Horwood FC, Piccolo F, Lam DCL, Garske LA, Shrestha R, Kosky C, Read CA, Murray K, Lee YCG. Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial. JAMA. 2017 Nov 21:318(19):1903-1912. doi: 10.1001/jama.2017.17426. Epub [PubMed PMID: 29164255]
Level 1 (high-level) evidenceSivakumar P, Saigal A, Ahmed L. Quality of life after interventions for malignant pleural effusions: a systematic review. BMJ supportive & palliative care. 2020 Mar:10(1):45-54. doi: 10.1136/bmjspcare-2018-001610. Epub 2019 Jun 26 [PubMed PMID: 31243020]
Level 2 (mid-level) evidenceOlfert JA, Penz ED, Manns BJ, Mishra EK, Davies HE, Miller RF, Luengo-Fernandez R, Gao S, Rahman NM. Cost-effectiveness of indwelling pleural catheter compared with talc in malignant pleural effusion. Respirology (Carlton, Vic.). 2017 May:22(4):764-770. doi: 10.1111/resp.12962. Epub 2016 Dec 16 [PubMed PMID: 27983774]
Bhatnagar R, Zahan-Evans N, Kearney C, Edey AJ, Stadon LJ, Tremblay A, Maskell NA. A Novel Drug-Eluting Indwelling Pleural Catheter for the Management of Malignant Effusions. American journal of respiratory and critical care medicine. 2018 Jan 1:197(1):136-138. doi: 10.1164/rccm.201701-0097LE. Epub [PubMed PMID: 28574275]
Dipper A, Jones HE, Bhatnagar R, Preston NJ, Maskell N, Clive AO. Interventions for the management of malignant pleural effusions: a network meta-analysis. The Cochrane database of systematic reviews. 2020 Apr 21:4(4):CD010529. doi: 10.1002/14651858.CD010529.pub3. Epub 2020 Apr 21 [PubMed PMID: 32315458]
Level 1 (high-level) evidenceBatra H, Antony VB. Pleural mesothelial cells in pleural and lung diseases. Journal of thoracic disease. 2015 Jun:7(6):964-80. doi: 10.3978/j.issn.2072-1439.2015.02.19. Epub [PubMed PMID: 26150910]
Huggins JT, Doelken P, Sahn SA. The unexpandable lung. F1000 medicine reports. 2010 Oct 21:2():77. doi: 10.3410/M2-77. Epub 2010 Oct 21 [PubMed PMID: 21173837]
Hallifax RJ, Talwar A, Wrightson JM, Edey A, Gleeson FV. State-of-the-art: Radiological investigation of pleural disease. Respiratory medicine. 2017 Mar:124():88-99. doi: 10.1016/j.rmed.2017.02.013. Epub 2017 Feb 17 [PubMed PMID: 28233652]
Huggins JT, Maldonado F, Chopra A, Rahman N, Light R. Unexpandable lung from pleural disease. Respirology (Carlton, Vic.). 2018 Feb:23(2):160-167. doi: 10.1111/resp.13199. Epub 2017 Oct 24 [PubMed PMID: 29064169]
Bertolaccini L, Viti A, Paiano S, Pomari C, Assante LR, Terzi A. Indwelling Pleural Catheters: A Clinical Option in Trapped Lung. Thoracic surgery clinics. 2017 Feb:27(1):47-55. doi: 10.1016/j.thorsurg.2016.08.008. Epub [PubMed PMID: 27865327]
Masoud HH, El-Zorkany MM, Ahmed AA, Assal HH. Pleural Space Elastance and Its Relation to Success Rates of Pleurodesis in Malignant Pleural Effusion. Tuberculosis and respiratory diseases. 2021 Jan:84(1):67-73. doi: 10.4046/trd.2020.0081. Epub 2020 Nov 9 [PubMed PMID: 33161689]
Choi WI. Pneumothorax. Tuberculosis and respiratory diseases. 2014 Mar:76(3):99-104. doi: 10.4046/trd.2014.76.3.99. Epub 2014 Mar 29 [PubMed PMID: 24734096]
Dugan KC, Laxmanan B, Murgu S, Hogarth DK. Management of Persistent Air Leaks. Chest. 2017 Aug:152(2):417-423. doi: 10.1016/j.chest.2017.02.020. Epub 2017 Mar 4 [PubMed PMID: 28267436]
Lazarus DR, Casal RF. Persistent air leaks: a review with an emphasis on bronchoscopic management. Journal of thoracic disease. 2017 Nov:9(11):4660-4670. doi: 10.21037/jtd.2017.10.122. Epub [PubMed PMID: 29268535]
Lois M, Noppen M. Bronchopleural fistulas: an overview of the problem with special focus on endoscopic management. Chest. 2005 Dec:128(6):3955-65 [PubMed PMID: 16354867]
Level 3 (low-level) evidenceKeshishyan S, Revelo AE, Epelbaum O. Bronchoscopic management of prolonged air leak. Journal of thoracic disease. 2017 Sep:9(Suppl 10):S1034-S1046. doi: 10.21037/jtd.2017.05.47. Epub [PubMed PMID: 29214063]
Bielsa S, Martín-Juan J, Porcel JM, Rodríguez-Panadero F. Diagnostic and prognostic implications of pleural adhesions in malignant effusions. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2008 Nov:3(11):1251-6. doi: 10.1097/JTO.0b013e318189f53d. Epub [PubMed PMID: 18978559]
Level 2 (mid-level) evidenceRodriguez-Panadero F, Janssen JP, Astoul P. Thoracoscopy: general overview and place in the diagnosis and management of pleural effusion. The European respiratory journal. 2006 Aug:28(2):409-22 [PubMed PMID: 16880371]
Level 3 (low-level) evidenceMishra EK, Clive AO, Wills GH, Davies HE, Stanton AE, Al-Aloul M, Hart-Thomas A, Pepperell J, Evison M, Saba T, Harrison RN, Guhan A, Callister ME, Sathyamurthy R, Rehal S, Corcoran JP, Hallifax R, Psallidas I, Russell N, Shaw R, Dobson M, Wrightson JM, West A, Lee YCG, Nunn AJ, Miller RF, Maskell NA, Rahman NM. Randomized Controlled Trial of Urokinase versus Placebo for Nondraining Malignant Pleural Effusion. American journal of respiratory and critical care medicine. 2018 Feb 15:197(4):502-508. doi: 10.1164/rccm.201704-0809OC. Epub [PubMed PMID: 28926296]
Level 1 (high-level) evidenceSoni NJ, Franco R, Velez MI, Schnobrich D, Dancel R, Restrepo MI, Mayo PH. Ultrasound in the diagnosis and management of pleural effusions. Journal of hospital medicine. 2015 Dec:10(12):811-6. doi: 10.1002/jhm.2434. Epub 2015 Jul 28 [PubMed PMID: 26218493]
Altmann ES, Crossingham I, Wilson S, Davies HR. Intra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema. The Cochrane database of systematic reviews. 2019 Oct 30:2019(10):. doi: 10.1002/14651858.CD002312.pub4. Epub 2019 Oct 30 [PubMed PMID: 31684683]
Level 1 (high-level) evidenceOkur E, Baysungur V, Tezel C, Ergene G, Okur HK, Halezeroglu S. Streptokinase for malignant pleural effusions: a randomized controlled study. Asian cardiovascular & thoracic annals. 2011 Jun:19(3-4):238-43. doi: 10.1177/0218492311410874. Epub [PubMed PMID: 21885549]
Level 1 (high-level) evidenceKrenke R, Nasilowski J, Korczynski P, Gorska K, Przybylowski T, Chazan R, Light RW. Incidence and aetiology of eosinophilic pleural effusion. The European respiratory journal. 2009 Nov:34(5):1111-7. doi: 10.1183/09031936.00197708. Epub 2009 Apr 22 [PubMed PMID: 19386682]
Level 2 (mid-level) evidenceLi WJ, Lin ZD, Wang JL. A narrative review of malignant eosinophilic pleural effusion: incidence, etiology and prognostic significance. Annals of palliative medicine. 2021 Feb:10(2):2314-2322. doi: 10.21037/apm-20-1742. Epub 2021 Jan 22 [PubMed PMID: 33549025]
Level 3 (low-level) evidenceTakeuchi E, Okano Y, Machida H, Atagi K, Kondou Y, Kadota N, Hatakeyama N, Naruse K, Shinohara T. Eosinophilic pleural effusion due to lung cancer has a better prognosis than non-eosinophilic malignant pleural effusion. Cancer immunology, immunotherapy : CII. 2022 Feb:71(2):365-372. doi: 10.1007/s00262-021-02994-5. Epub 2021 Jun 25 [PubMed PMID: 34170380]
Lending G, El Ghani YA, Kaykov E, Svirsky B, Cohen HI, Altman E. Hemorrhagic Malignant Pleural Effusion: Diagnosis, Survival Rate, and Response to Talc Pleurodesis. Indian journal of surgical oncology. 2021 Mar:12(1):54-60. doi: 10.1007/s13193-020-01099-2. Epub 2020 Nov 14 [PubMed PMID: 33814832]
Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, Calverley PM, Gift AG, Harver A, Lareau SC, Mahler DA, Meek PM, O'Donnell DE, American Thoracic Society Committee on Dyspnea. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. American journal of respiratory and critical care medicine. 2012 Feb 15:185(4):435-52. doi: 10.1164/rccm.201111-2042ST. Epub [PubMed PMID: 22336677]
Ambrosino N, Serradori M. Determining the cause of dyspnoea: linguistic and biological descriptors. Chronic respiratory disease. 2006:3(3):117-22 [PubMed PMID: 16916005]
Johnson MJ, Bland JM, Oxberry SG, Abernethy AP, Currow DC. Opioids for chronic refractory breathlessness: patient predictors of beneficial response. The European respiratory journal. 2013 Sep:42(3):758-66. doi: 10.1183/09031936.00139812. Epub 2012 Dec 20 [PubMed PMID: 23258776]
Level 2 (mid-level) evidenceHui D, Maddocks M, Johnson MJ, Ekström M, Simon ST, Ogliari AC, Booth S, Ripamonti C, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of breathlessness in patients with cancer: ESMO Clinical Practice Guidelines(†). ESMO open. 2020 Dec:5(6):e001038. doi: 10.1136/esmoopen-2020-001038. Epub [PubMed PMID: 33303485]
Level 1 (high-level) evidenceJohnson MJ, Yorke J, Hansen-Flaschen J, Lansing R, Ekström M, Similowski T, Currow DC. Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness. The European respiratory journal. 2017 May:49(5):. pii: 1602277. doi: 10.1183/13993003.02277-2016. Epub 2017 May 25 [PubMed PMID: 28546269]
Level 3 (low-level) evidenceNishino T. Dyspnoea: underlying mechanisms and treatment. British journal of anaesthesia. 2011 Apr:106(4):463-74. doi: 10.1093/bja/aer040. Epub 2011 Mar 4 [PubMed PMID: 21378105]
West N, Popkess-Vawter S. The subjective and psychosocial nature of breathlessness. Journal of advanced nursing. 1994 Oct:20(4):622-6 [PubMed PMID: 7822595]
Level 3 (low-level) evidence. Dyspnea. Mechanisms, assessment, and management: a consensus statement. American Thoracic Society. American journal of respiratory and critical care medicine. 1999 Jan:159(1):321-40 [PubMed PMID: 9872857]
Level 1 (high-level) evidenceLaviolette L, Laveneziana P, ERS Research Seminar Faculty. Dyspnoea: a multidimensional and multidisciplinary approach. The European respiratory journal. 2014 Jun:43(6):1750-62. doi: 10.1183/09031936.00092613. Epub 2014 Feb 13 [PubMed PMID: 24525437]
Deshpande PR, Rajan S, Sudeepthi BL, Abdul Nazir CP. Patient-reported outcomes: A new era in clinical research. Perspectives in clinical research. 2011 Oct:2(4):137-44. doi: 10.4103/2229-3485.86879. Epub [PubMed PMID: 22145124]
Level 3 (low-level) evidenceDorman S, Byrne A, Edwards A. Which measurement scales should we use to measure breathlessness in palliative care? A systematic review. Palliative medicine. 2007 Apr:21(3):177-91 [PubMed PMID: 17363394]
Level 1 (high-level) evidenceMuller JP, Gonçalves PA, Fontoura FF, Mattiello R, Florian J. Applicability of the London Chest Activity of Daily Living scale in patients on the waiting list for lung transplantation. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2013 Jan-Feb:39(1):92-7 [PubMed PMID: 23503491]
Level 2 (mid-level) evidenceSimon ST, Bausewein C, Schildmann E, Higginson IJ, Magnussen H, Scheve C, Ramsenthaler C. Episodic breathlessness in patients with advanced disease: a systematic review. Journal of pain and symptom management. 2013 Mar:45(3):561-78. doi: 10.1016/j.jpainsymman.2012.02.022. Epub 2012 Aug 24 [PubMed PMID: 22921180]
Level 1 (high-level) evidenceBooth S, Wade R. Oxygen or air for palliation of breathlessness in advanced cancer. Journal of the Royal Society of Medicine. 2003 May:96(5):215-8 [PubMed PMID: 12724429]
Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. The Cochrane database of systematic reviews. 2016 Oct 20:10(10):CD007354 [PubMed PMID: 27764523]
Level 1 (high-level) evidenceHaywood A, Duc J, Good P, Khan S, Rickett K, Vayne-Bossert P, Hardy JR. Systemic corticosteroids for the management of cancer-related breathlessness (dyspnoea) in adults. The Cochrane database of systematic reviews. 2019 Feb 20:2(2):CD012704. doi: 10.1002/14651858.CD012704.pub2. Epub 2019 Feb 20 [PubMed PMID: 30784058]
Level 1 (high-level) evidencePrado BL, Gomes DBD, Usón Júnior PLS, Taranto P, França MS, Eiger D, Mariano RC, Hui D, Del Giglio A. Continuous palliative sedation for patients with advanced cancer at a tertiary care cancer center. BMC palliative care. 2018 Jan 4:17(1):13. doi: 10.1186/s12904-017-0264-2. Epub 2018 Jan 4 [PubMed PMID: 29301574]
Potter J, Shields S, Breen R. Palliative Sedation, Compassionate Extubation, and the Principle of Double Effect: An Ethical Analysis. The American journal of hospice & palliative care. 2021 Dec:38(12):1536-1540. doi: 10.1177/1049909121998630. Epub 2021 Mar 4 [PubMed PMID: 33657860]
Jacobs JM, Shaffer KM, Nipp RD, Fishbein JN, MacDonald J, El-Jawahri A, Pirl WF, Jackson VA, Park ER, Temel JS, Greer JA. Distress is Interdependent in Patients and Caregivers with Newly Diagnosed Incurable Cancers. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2017 Aug:51(4):519-531. doi: 10.1007/s12160-017-9875-3. Epub [PubMed PMID: 28097515]
Cocker F, Joss N. Compassion Fatigue among Healthcare, Emergency and Community Service Workers: A Systematic Review. International journal of environmental research and public health. 2016 Jun 22:13(6):. doi: 10.3390/ijerph13060618. Epub 2016 Jun 22 [PubMed PMID: 27338436]
Level 1 (high-level) evidenceMystakidou K, Parpa E, Tsilika E, Athanasouli P, Pathiaki M, Galanos A, Pagoropoulou A, Vlahos L. Preparatory grief, psychological distress and hopelessness in advanced cancer patients. European journal of cancer care. 2008 Mar:17(2):145-51. doi: 10.1111/j.1365-2354.2007.00825.x. Epub [PubMed PMID: 18302651]
Quek JC, Tan QL, Allen JC, Anantham D. Malignant pleural effusion survival prognostication in an Asian population. Respirology (Carlton, Vic.). 2020 Dec:25(12):1283-1291. doi: 10.1111/resp.13837. Epub 2020 May 11 [PubMed PMID: 32390227]
Clive AO, Kahan BC, Hooper CE, Bhatnagar R, Morley AJ, Zahan-Evans N, Bintcliffe OJ, Boshuizen RC, Fysh ET, Tobin CL, Medford AR, Harvey JE, van den Heuvel MM, Lee YC, Maskell NA. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax. 2014 Dec:69(12):1098-104. doi: 10.1136/thoraxjnl-2014-205285. Epub 2014 Aug 6 [PubMed PMID: 25100651]
Level 2 (mid-level) evidencePsallidas I, Kanellakis NI, Gerry S, Thézénas ML, Charles PD, Samsonova A, Schiller HB, Fischer R, Asciak R, Hallifax RJ, Mercer R, Dobson M, Dong T, Pavord ID, Collins GS, Kessler BM, Pass HI, Maskell N, Stathopoulos GT, Rahman NM. Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis. The Lancet. Oncology. 2018 Jul:19(7):930-939. doi: 10.1016/S1470-2045(18)30294-8. Epub 2018 Jun 13 [PubMed PMID: 29908990]
Level 1 (high-level) evidenceFiorelli A, Ricci S, Feola A, Mazzella A, D'Angelo L, Santini M, Di Domenico M, Di Carlo A. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in diagnosis of pleural effusion of malignant origin. Interactive cardiovascular and thoracic surgery. 2016 Apr:22(4):411-8. doi: 10.1093/icvts/ivv378. Epub 2016 Jan 13 [PubMed PMID: 26769731]
Dipper A, Maskell N. Prognostication in malignant pleural effusion: One size does not fit all. Respirology (Carlton, Vic.). 2020 Dec:25(12):1229-1230. doi: 10.1111/resp.13916. Epub 2020 Jul 30 [PubMed PMID: 32734601]
Schwalk AJ, Ost DE, Saltijeral SN, De La Garza H, Casal RF, Jimenez CA, Eapen GA, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Elamin Y, Zhang J, Roth JA, Swisher S, Heymach JV, Grosu HB. Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations. Chest. 2021 Mar:159(3):1256-1264. doi: 10.1016/j.chest.2020.10.081. Epub 2020 Nov 17 [PubMed PMID: 33217413]
Khera N. Reporting and grading financial toxicity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014 Oct 10:32(29):3337-8. doi: 10.1200/JCO.2014.57.8740. Epub 2014 Sep 8 [PubMed PMID: 25199760]
Kheir F, Akulian J, Gesthalter YB. Indwelling Tunneled Pleural Catheters. American journal of respiratory and critical care medicine. 2019 Dec 1:200(11):P20-P21. doi: 10.1164/rccm.20011P20. Epub [PubMed PMID: 31774312]
Liu L, Zhan P, Zhou X, Song Y, Zhou X, Yu L, Wang J. Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods. PloS one. 2015:10(3):e0117032. doi: 10.1371/journal.pone.0117032. Epub 2015 Mar 18 [PubMed PMID: 25785456]
Ren S, Terman DS, Bohach G, Silvers A, Hansen C, Colt H, Sahn SA. Intrapleural staphylococcal superantigen induces resolution of malignant pleural effusions and a survival benefit in non-small cell lung cancer. Chest. 2004 Nov:126(5):1529-39 [PubMed PMID: 15539723]