**8. Treatment**

The aims of the treatment include drainage of pleural space, apposition of the visceral and pleural surfaces with complete expansion of the lung, and obliteration of the pleural surface with dispersion of a sclerosing agent throughout the pleural space [78]. Treatment options for malignant pleural effusion (MPE) are varied and often tailored to the clinician's specialty and expertise, the patient's physical performance status, hospitalization status, and individual desires [78].

Selection of optimal treatment for each individual patient requires a careful assessment of the benefits and the risks of the treatment. Primary treatment targets should involve palliation or elimination of dyspnea, improvement of a patient's overall quality of life in order to restore daily activities, and implementation of oncological therapies [102]. Treatment options include repeat thoracentesis, tube thoracostomy with drainage and sclerosis with chemical sclerosant agents, chronic indwelling pleural catheter, pleuroperitoneal shunt, intrapleural or systemic chemotherapy, thoracoscopy with drainage and talc insufflation, and pleurectomy [78].

Lung re-expansion is necessary for a successful pleurodesis. A failure of the lung to expand completely after removal of fluid is suggestive of a trapped lung [114]. Radiographic appear‐ ance of lung re-expansion can determine an adequate timing for pleurodesis; the amount of pleural fluid drainage is not particularly significant in the timing and outcome of pleurodesis. After pleurodesis, the chest tube can be removed once the pleural fluid drainage is less than 150 ml/day [115, 116]. Failure of pleurodesis may be due to incomplete drainage of the effusion, unequal distribution of a sclerosing agent within the pleural cavity, or trapped lung syndrome

Management of Malignant Pleural Effusion http://dx.doi.org/10.5772/54441 95

Pleurodesis is performed by mixing the sclerosing agent of choice with 50–100 mL of sterile saline and then instilling it into the pleural cavity through the chest tube or small-bore catheter. The chest tube is clamped for 1–2 h and then reconnected to suction. No benefit in distribution

A number of antineoplastic and non-antineoplastic agents are used for pleurodesis. Sterilized asbestos-free talc consistently produces the highest success rates regardless of how it is implemented. Talc can be applied as poudrage or slurry. Poudrage is insufflation of talc powder after evacuation of fluid, while slurry is instillation of talc solution through the chest tube after tube thoracostomy and evacuation of an effusion [120]. Walker et al. reported success with the use of talc in 93% (153/165) of patients with MPE [120] Viallat et al. reported a 79% success rate in patients with malignant mesothelioma and an 89% success rate in patients with other malignancies underlying pleural metastasis [121]. Kılıc et al. reported that the success rates with talc insufflation by VATS were 81% in patients with pleural malignant mesothelioma and 91% in those with other malignancies, defined by a reacculumation ratio in 90 days of 19%

The video-assisted thoracoscopic talc poudrage with talc slurry via chest tube in patients with MPE has shown similar efficacy [30-day outcome: 78% for poudrage and 71% for slurry). Respiratory complications seem to be slightly higher after talc insufflations (i.e., insufflation 14% vs slurry 6%) [123]. Talc is usually well tolerated, and its most common side effects are pleuritic chest pain and fever. Acute respiratory distress syndrome has been reported with talc

Tetracycline was commonly used in the past in association with tube thoracostomy. Instillation of the tetracycline solution provides a faster pleurodesis and pleural symphysis than chest tube drainage alone; however, it may cause significant pain. Doxycycline is an available alternative

Bleomycin, an antineoplastic agent, is used in pleurodesis as a sclerosing agent. The precise mechanism of action of bleomycin and other antineoplastic agents is not fully understood, but the optimal dose is 1IU/kg (average 60 IU). In a study on 199 patients with malignant pleural effusion, bleomycin achieved a 54% (108 patients) complete response rate [120]. In the same study, 24% of patients had chest pain, 24% had fever, and 11% suffered from nausea. He‐ moptysis, rashes, and diarrhea were also reported. Other rare side effects of bleomycin include alopecia and pulmonary fibrosis. Diacon et al. compared bleomycin with talc poudrage. The

of sclerosant or outcome or has been shown from rotating the patient [118, 119].

[17].

(6/31) and 9% (2/24), respectively [122].

pleurodesis, which correlates with higher doses [124-126].

to tetracycline and is felt to have roughly equal effectiveness [127].

#### **8.1. Therapeutic thoracentesis**

Therapeutic thoracentesis must be performed in all symptomatic patients with MPE. Up to 50% of patients may not have significant symptom relief due to comorbid conditions, gener‐ alized deconditioning from their malignancy, or incomplete re-expansion of the lung. Trapped lung may result from pleural-based malignancy or metastasis, pleural loculations, or bronchial obstruction with post-obstruction collapse [15]. A total of 98%–100% of patients will have reaccumulation of pleural fluid and recurrence of associated symptoms within 30 days of thoracentesis [103,104]. Therefore, recurrent thoracentesis may be a viable therapeutic approach for patients who have limited life expectancy or who are poor candidates for more definitive but invasive interventions [14].

Massive pleural effusions should be drained in a controlled fashion, avoiding evacuation of more than 1.5 l at one time or should be slowed down to about 500 ml/h. A massive evacuation of pleural fluid and rapid re-expansion of the lung can cause discomfort, bothersome cough, and hypotension. Reexpansion pulmonary oedema is a rare complication after rapid drainage of pleural effusion [105]. The mechanism of oedema progression is not fully clarified, but it is believed that it is mostly related to mechanical forces causing vascular stretching or injury, and increasing capillary permeability rather than the absolute level of negative pleural pressure [106].

#### **8.2. Tube thoracostomy and pleurodesis**

The aim of tube thoracostomy in MPE is primarily to drainage of the pleural cavity and demonstration of lung re-expansion before instillation of a chemical sclerosant. Typically a large bore chest tube is used though smaller bore tubes [10-14F) have been used for chemical pleurodesis [107-109]. Large bore chest tubes are associated with greater patient discomfort but have traditionally been used because of the concern of obstruction of smaller bore tubes by fibrin plugs. However, several randomized trials have compared small versus large bore chest tubes without significant difference in pleurodesis outcome [107, 110, 111].

Simple small bore drainage catheters have been used effectively. Gravity drainage of the pleural fluid can be accomplished and pleurodesis can be achieved with several agents. In one study, small-bore catheters yielded outcomes equivalent to patients receiving chest tube after diagnos‐ tic thoracoscopy, and in addition, they were more comfortable [107]. Additional small studies have been performed with early success using bleomycin or talc sclerotherapy [110, 112, 113].

An earlier randomized trial noted that pleurodesis following rapid drainage (median chest tube duration, 2 days) was equivalent to pleurodesis performed after drainage was less than 150 mL/day (median chest tube duration, 7 days). In summary, drainage of MPE using small bore catheter drainage and rapid pleurodesis achieves results similar to prolonged drainage prior to pleurodesis [78].

Lung re-expansion is necessary for a successful pleurodesis. A failure of the lung to expand completely after removal of fluid is suggestive of a trapped lung [114]. Radiographic appear‐ ance of lung re-expansion can determine an adequate timing for pleurodesis; the amount of pleural fluid drainage is not particularly significant in the timing and outcome of pleurodesis. After pleurodesis, the chest tube can be removed once the pleural fluid drainage is less than 150 ml/day [115, 116]. Failure of pleurodesis may be due to incomplete drainage of the effusion, unequal distribution of a sclerosing agent within the pleural cavity, or trapped lung syndrome [17].

agents, chronic indwelling pleural catheter, pleuroperitoneal shunt, intrapleural or systemic chemotherapy, thoracoscopy with drainage and talc insufflation, and pleurectomy [78].

Therapeutic thoracentesis must be performed in all symptomatic patients with MPE. Up to 50% of patients may not have significant symptom relief due to comorbid conditions, gener‐ alized deconditioning from their malignancy, or incomplete re-expansion of the lung. Trapped lung may result from pleural-based malignancy or metastasis, pleural loculations, or bronchial obstruction with post-obstruction collapse [15]. A total of 98%–100% of patients will have reaccumulation of pleural fluid and recurrence of associated symptoms within 30 days of thoracentesis [103,104]. Therefore, recurrent thoracentesis may be a viable therapeutic approach for patients who have limited life expectancy or who are poor candidates for more

Massive pleural effusions should be drained in a controlled fashion, avoiding evacuation of more than 1.5 l at one time or should be slowed down to about 500 ml/h. A massive evacuation of pleural fluid and rapid re-expansion of the lung can cause discomfort, bothersome cough, and hypotension. Reexpansion pulmonary oedema is a rare complication after rapid drainage of pleural effusion [105]. The mechanism of oedema progression is not fully clarified, but it is believed that it is mostly related to mechanical forces causing vascular stretching or injury, and increasing capillary permeability rather than the absolute level of negative pleural

The aim of tube thoracostomy in MPE is primarily to drainage of the pleural cavity and demonstration of lung re-expansion before instillation of a chemical sclerosant. Typically a large bore chest tube is used though smaller bore tubes [10-14F) have been used for chemical pleurodesis [107-109]. Large bore chest tubes are associated with greater patient discomfort but have traditionally been used because of the concern of obstruction of smaller bore tubes by fibrin plugs. However, several randomized trials have compared small versus large bore

Simple small bore drainage catheters have been used effectively. Gravity drainage of the pleural fluid can be accomplished and pleurodesis can be achieved with several agents. In one study, small-bore catheters yielded outcomes equivalent to patients receiving chest tube after diagnos‐ tic thoracoscopy, and in addition, they were more comfortable [107]. Additional small studies have been performed with early success using bleomycin or talc sclerotherapy [110, 112, 113].

An earlier randomized trial noted that pleurodesis following rapid drainage (median chest tube duration, 2 days) was equivalent to pleurodesis performed after drainage was less than 150 mL/day (median chest tube duration, 7 days). In summary, drainage of MPE using small bore catheter drainage and rapid pleurodesis achieves results similar to prolonged drainage

chest tubes without significant difference in pleurodesis outcome [107, 110, 111].

**8.1. Therapeutic thoracentesis**

94 Principles and Practice of Cardiothoracic Surgery

definitive but invasive interventions [14].

**8.2. Tube thoracostomy and pleurodesis**

pressure [106].

prior to pleurodesis [78].

Pleurodesis is performed by mixing the sclerosing agent of choice with 50–100 mL of sterile saline and then instilling it into the pleural cavity through the chest tube or small-bore catheter. The chest tube is clamped for 1–2 h and then reconnected to suction. No benefit in distribution of sclerosant or outcome or has been shown from rotating the patient [118, 119].

A number of antineoplastic and non-antineoplastic agents are used for pleurodesis. Sterilized asbestos-free talc consistently produces the highest success rates regardless of how it is implemented. Talc can be applied as poudrage or slurry. Poudrage is insufflation of talc powder after evacuation of fluid, while slurry is instillation of talc solution through the chest tube after tube thoracostomy and evacuation of an effusion [120]. Walker et al. reported success with the use of talc in 93% (153/165) of patients with MPE [120] Viallat et al. reported a 79% success rate in patients with malignant mesothelioma and an 89% success rate in patients with other malignancies underlying pleural metastasis [121]. Kılıc et al. reported that the success rates with talc insufflation by VATS were 81% in patients with pleural malignant mesothelioma and 91% in those with other malignancies, defined by a reacculumation ratio in 90 days of 19% (6/31) and 9% (2/24), respectively [122].

The video-assisted thoracoscopic talc poudrage with talc slurry via chest tube in patients with MPE has shown similar efficacy [30-day outcome: 78% for poudrage and 71% for slurry). Respiratory complications seem to be slightly higher after talc insufflations (i.e., insufflation 14% vs slurry 6%) [123]. Talc is usually well tolerated, and its most common side effects are pleuritic chest pain and fever. Acute respiratory distress syndrome has been reported with talc pleurodesis, which correlates with higher doses [124-126].

Tetracycline was commonly used in the past in association with tube thoracostomy. Instillation of the tetracycline solution provides a faster pleurodesis and pleural symphysis than chest tube drainage alone; however, it may cause significant pain. Doxycycline is an available alternative to tetracycline and is felt to have roughly equal effectiveness [127].

Bleomycin, an antineoplastic agent, is used in pleurodesis as a sclerosing agent. The precise mechanism of action of bleomycin and other antineoplastic agents is not fully understood, but the optimal dose is 1IU/kg (average 60 IU). In a study on 199 patients with malignant pleural effusion, bleomycin achieved a 54% (108 patients) complete response rate [120]. In the same study, 24% of patients had chest pain, 24% had fever, and 11% suffered from nausea. He‐ moptysis, rashes, and diarrhea were also reported. Other rare side effects of bleomycin include alopecia and pulmonary fibrosis. Diacon et al. compared bleomycin with talc poudrage. The response to bleomycin was 59% whereas it was 87% for talc poudrage [128]. The disadvantages of bleomycin are its lower success rate and higher cost compared with tetracycline and talc.

malignant effusions.Afterthe initialtherapeutic thoracentesis, chemotherapymustbe adminis‐ tered and pleurodesis, can be delayed until systemic treatment becomes ineffective [135].

Management of Malignant Pleural Effusion http://dx.doi.org/10.5772/54441 97

Administration of chemotherapeutic agents directly into the pleural space has the potential to control the underlying malignancy and/or the MPE by producing high drug concentrations localized at the malignancy site while minimizing systemic toxicity [138]. Ideal agents would have a slow clearance rate from the intrapleural cavity, allowing greater exposure of cancer cells to the cytotoxic agent. Doxorubicin hydrochloride, cisplatin, cytarabine, mitomycin C,

Several studies have investigated the intrapleural use of several active cytokines. Interleukin-2 and interferon-β have been used. Their success varies but, in general, the results were poorer than that of talc [137, 138]. Staphylococcus aureus superantigen (SSAg) is one of the newer agents. Given current indwelling methods allowing chronic access to the pleural cavity, intrapleural chemotherapy remains a potential mechanism of drug administration, however,

Tube thoracostomy and drainage with instillation of sclerosing agents is the most common treatment used for malignant pleural effusion. Chest tube drainage and pleurodesis does not allow lysis of adhesions to drain loculated effusions, which are often the reason for failure. The video-thoracoscopic approach allows for breaking of fibrin bridges and consequent locula‐ tions, insufflating talc uniformly on pleural surfaces, and full re-expansion of the lung [139]. The video-assisted thoracoscopy (VATS) should replace conventional instillation of talc slurry through tube thoracostomy as a procedure of choice to achieve pleurodesis. VATS pleurodesis offers reasonable palliation of MPE with low morbidity and rapid recovery. It is a safe and effective approach with an efficacy ranging from 88 to 97.5% [139, 140]. The VATS seems to be superior to simple chest tube drainage in management of MPE (92.3% vs 59.3%), with remission rates of 88.5 and 44.4% respectively [42,43]. In a series of 148 patients (VATS pleurodesis in 82 patients and tube thoracostomy with pleurodesis in 66 patients), VATS demonstrated longer

Thoracoscopic mechanical pleurodesis is a parietal pleura abrasion causing inflammation and adhesion of the parietal and visceral pleurae as a result of the healing process. Abrasion of the parietal pleura is initiated to yield uniform oozing. An injury to the visceral pleura should be avoided to reduce the risk of parenchymal injury, which would cause long-lasting postoper‐ ative air leak. Its efficacy was re-evaluated in a series of breast cancer patients (n=87) with MPE. Thoracoscopic mechanical pleurodesis and talc pleurodesis demonstrated similar success rates

A VATS pleurectomy can provide excellent pleurodesis with less postoperative discomfort and pulmonary dysfunction compared to thoracotomy. Another benefit of VATS pleurectomy is a reduction of chest pain in patients with malignant tumors of the pleura and lung disease. In addition, it carries a lower risk of postoperative morbidity, less discomfort, and a better

and 5-FU are some of the agents used.

recurrence-free survival and improved quality of life [142].

further studies are required.

(92 and 91%, respectively) [143].

quality of life in terminally ill patients [144].

**8.6. Thoracoscopy**

Other agents tested for use for pleurodesis include cisplatin, cytarabine, doxorubicin, 5-FU, binterferon, mitomycin C, and Corynebacterium parvum; however, these agents are not commonly used because of their high cost, adverse effects, and low efficacy [129].

#### **8.3. Chronic indwelling pleural catheter**

In patients not suitable for pleurodesis, or with recurrent MPE after pleurodesis, chronic intermittent drainage via a subcutaneous tunneled pleural catheter on an outpatient basis has been shown to relieve dyspnea effectively without serious complications [78,130]. A limited number of studies focused on the use of a chronic indwelling pleural catheter in patients with MPE. Putnam et al. summarized their experience with 100 consecutive patients with MPE treated with a chronic indwelling pleural catheter [78]. They concluded that placement of an indwelling pleural catheter was safe, effective and cost-effective. Hospitalization was only one day for patients treated with the pleural catheter, in contrast to 7 days with tube thoracostomy and sclerosis with doxycycline [12].

In a study by Pollak et al., the effectiveness of tunneled pleural catheter's in the treatment of malignant pleural effusions was assessed in 28 patients [130]. Dyspnea improved in 94% at 48th h and 91% on 30th day. Control of the MPE was achieved in 90% of patients. They concluded that the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis. Other authors concluded that placement of an indwelling catheter was the right procedure in subjects with evidence of a trapped lung [131]. With respect to potential complications of pleural catheters, infections and dislocations of the catheter are seen most often. However, serious complications are uncommon.

#### **8.4. Pleuroperitoneal shunt**

The pleuroperitoneal shunt was introduced in 1982 for the management of pleural effusions. Pleuroperitoneal shunts transfer fluid from the pleural space to the peritoneal cavity actively when manually pumped (Denver shunt) or passively (LeVeen shunt). Several series have shown that effective palliation can be achieved in up to 90% of cases [132, 133]. It is used for patients who have failed pleurodesis or systemic chemotherapy, are not surgical candidates, or have trapped lung. The major disadvantage of the pleuroperitoneal shunt is the length of time required to drain the pleural space. The volume of pumping chamber is only 1.5 to 2mL, which translates into the necessity for frequent and protracted pumping sessions, a major inconvenience for patients. Infection and shunt occlusion are the most significant complica‐ tions, occurring in up to 15% of cases [134].

#### **8.5. Systemic or intrapleural chemotherapy**

For the patients with chemosensitive tumors, including small cell lung cancer, lymphomas, and tumors of the breast, prostate, ovary, or thyroid, or those which have arisen from germ cells, systemic therapy can prove to be equally or more effective than local therapy for relieving malignant effusions.Afterthe initialtherapeutic thoracentesis, chemotherapymustbe adminis‐ tered and pleurodesis, can be delayed until systemic treatment becomes ineffective [135].

Administration of chemotherapeutic agents directly into the pleural space has the potential to control the underlying malignancy and/or the MPE by producing high drug concentrations localized at the malignancy site while minimizing systemic toxicity [138]. Ideal agents would have a slow clearance rate from the intrapleural cavity, allowing greater exposure of cancer cells to the cytotoxic agent. Doxorubicin hydrochloride, cisplatin, cytarabine, mitomycin C, and 5-FU are some of the agents used.

Several studies have investigated the intrapleural use of several active cytokines. Interleukin-2 and interferon-β have been used. Their success varies but, in general, the results were poorer than that of talc [137, 138]. Staphylococcus aureus superantigen (SSAg) is one of the newer agents. Given current indwelling methods allowing chronic access to the pleural cavity, intrapleural chemotherapy remains a potential mechanism of drug administration, however, further studies are required.

#### **8.6. Thoracoscopy**

response to bleomycin was 59% whereas it was 87% for talc poudrage [128]. The disadvantages of bleomycin are its lower success rate and higher cost compared with tetracycline and talc. Other agents tested for use for pleurodesis include cisplatin, cytarabine, doxorubicin, 5-FU, binterferon, mitomycin C, and Corynebacterium parvum; however, these agents are not

In patients not suitable for pleurodesis, or with recurrent MPE after pleurodesis, chronic intermittent drainage via a subcutaneous tunneled pleural catheter on an outpatient basis has been shown to relieve dyspnea effectively without serious complications [78,130]. A limited number of studies focused on the use of a chronic indwelling pleural catheter in patients with MPE. Putnam et al. summarized their experience with 100 consecutive patients with MPE treated with a chronic indwelling pleural catheter [78]. They concluded that placement of an indwelling pleural catheter was safe, effective and cost-effective. Hospitalization was only one day for patients treated with the pleural catheter, in contrast to 7 days with tube thoracostomy

In a study by Pollak et al., the effectiveness of tunneled pleural catheter's in the treatment of malignant pleural effusions was assessed in 28 patients [130]. Dyspnea improved in 94% at 48th h and 91% on 30th day. Control of the MPE was achieved in 90% of patients. They concluded that the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis. Other authors concluded that placement of an indwelling catheter was the right procedure in subjects with evidence of a trapped lung [131]. With respect to potential complications of pleural catheters, infections and dislocations of the catheter are

The pleuroperitoneal shunt was introduced in 1982 for the management of pleural effusions. Pleuroperitoneal shunts transfer fluid from the pleural space to the peritoneal cavity actively when manually pumped (Denver shunt) or passively (LeVeen shunt). Several series have shown that effective palliation can be achieved in up to 90% of cases [132, 133]. It is used for patients who have failed pleurodesis or systemic chemotherapy, are not surgical candidates, or have trapped lung. The major disadvantage of the pleuroperitoneal shunt is the length of time required to drain the pleural space. The volume of pumping chamber is only 1.5 to 2mL, which translates into the necessity for frequent and protracted pumping sessions, a major inconvenience for patients. Infection and shunt occlusion are the most significant complica‐

For the patients with chemosensitive tumors, including small cell lung cancer, lymphomas, and tumors of the breast, prostate, ovary, or thyroid, or those which have arisen from germ cells, systemic therapy can prove to be equally or more effective than local therapy for relieving

seen most often. However, serious complications are uncommon.

commonly used because of their high cost, adverse effects, and low efficacy [129].

**8.3. Chronic indwelling pleural catheter**

96 Principles and Practice of Cardiothoracic Surgery

and sclerosis with doxycycline [12].

**8.4. Pleuroperitoneal shunt**

tions, occurring in up to 15% of cases [134].

**8.5. Systemic or intrapleural chemotherapy**

Tube thoracostomy and drainage with instillation of sclerosing agents is the most common treatment used for malignant pleural effusion. Chest tube drainage and pleurodesis does not allow lysis of adhesions to drain loculated effusions, which are often the reason for failure. The video-thoracoscopic approach allows for breaking of fibrin bridges and consequent locula‐ tions, insufflating talc uniformly on pleural surfaces, and full re-expansion of the lung [139].

The video-assisted thoracoscopy (VATS) should replace conventional instillation of talc slurry through tube thoracostomy as a procedure of choice to achieve pleurodesis. VATS pleurodesis offers reasonable palliation of MPE with low morbidity and rapid recovery. It is a safe and effective approach with an efficacy ranging from 88 to 97.5% [139, 140]. The VATS seems to be superior to simple chest tube drainage in management of MPE (92.3% vs 59.3%), with remission rates of 88.5 and 44.4% respectively [42,43]. In a series of 148 patients (VATS pleurodesis in 82 patients and tube thoracostomy with pleurodesis in 66 patients), VATS demonstrated longer recurrence-free survival and improved quality of life [142].

Thoracoscopic mechanical pleurodesis is a parietal pleura abrasion causing inflammation and adhesion of the parietal and visceral pleurae as a result of the healing process. Abrasion of the parietal pleura is initiated to yield uniform oozing. An injury to the visceral pleura should be avoided to reduce the risk of parenchymal injury, which would cause long-lasting postoper‐ ative air leak. Its efficacy was re-evaluated in a series of breast cancer patients (n=87) with MPE. Thoracoscopic mechanical pleurodesis and talc pleurodesis demonstrated similar success rates (92 and 91%, respectively) [143].

A VATS pleurectomy can provide excellent pleurodesis with less postoperative discomfort and pulmonary dysfunction compared to thoracotomy. Another benefit of VATS pleurectomy is a reduction of chest pain in patients with malignant tumors of the pleura and lung disease. In addition, it carries a lower risk of postoperative morbidity, less discomfort, and a better quality of life in terminally ill patients [144].

#### **8.7. Pleurectomy**

Pleurectomy, which is a palliative debulking procedure, is used to reduce the size of the tumor. However, it can also be done to relieve the lung and provide pleurodesis as a result of severe adhesions between the lung and the chest cavity. A posterolateral thoracotomy provides adequate access to the pleura. The pleura is stripped from the apex to the diaphragm. Dissec‐ tion is continued in anterior, posterior, and apical aspects of the chest wall [144].

[3] Miserocchi G. Physiology and pathophysiology of pleural fluid turnover. Eur Respir

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[4] Cheng D, Rodriguez RM, Perkett EA, Rogers J, Bienvenu G, Lappalainen U, Light RW Vascular endothelial growth factor in pleural fluid. Chest 1999;116:760–765

[5] Bennett R, Maskell N Management of malignant pleural effusions. Curr Opin Pulm

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[11] Van den Toorn LM, Schaap E, Surmont VF, Pouw EM, van der Rijt KC, van Klaveren RJ. Management of recurrent malignant pleural effusions with a chronic indwelling

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The procedure has a low mortality rate (1.5 to 5%), and it is well tolerated in patients with multiple morbidities [145]. Most authors concluded that thoracotomy was not indicated in patients with malignant effusion because of the high complication rate and prolonged hospitalization [146]. Most authors now agree that VATS is the only surgical approach that can be used in these patients [135, 147].
