Author: John E Heffner, MD

Section Editor: Fabien Maldonado, MD

Deputy Editor: Geraldine Finlay, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Dec 2019. | This topic last updated: Jan 18, 2019.

INTRODUCTION

Malignant pleural effusions (MPE) and paramalignant pleural effusions are common
problems for patients with cancer [1,2]. Malignant pleural effusion can be caused by
metastatic disease, lymphoma and other, hematologic malignancies, or primary pleural
malignancy (eg, mesothelioma). Paramalignant pleural effusions result from tumor effects
that indirectly act on the pleural space such as by bronchial obstruction, mediastinal lymph
node infiltration, thromboembolism, or superior vena cava syndrome; pleural fluid cytology
and pleural biopsy are negative by definition because cancer cells have not invaded
pleural membranes. MPEs, on the other hand, have infiltration of cancer cells into pleural
tissue that may result in positive fluid cytology and/or pleural biopsy for cancer.

When clinicians encounter a patient with an MPE, they frequently ask:

● What is the prognosis?

● Should the effusion be treated?
● What are the treatment options?
● How do I know which option is best?

The diagnosis of pleural effusions, including MPEs, and the management of refractory
nonmalignant pleural effusions, are discussed in detail separately. (See "Diagnostic
evaluation of a pleural effusion in adults: Initial testing" and "Management of refractory
nonmalignant pleural effusions".)

PROGNOSIS
The prognosis of patients with an MPE depends on a variety of factors, such as age,
performance status, tumor type, tumor stage, comorbidities, composition of the pleural
fluid, and responsiveness of the underlying cancer to antitumor therapy. Overall,
observational studies demonstrate that mortality is higher for patients with an MPE as
compared with those with metastatic cancer without a malignant effusion. As examples:

● Among patients with advanced non-small-cell lung cancer with distant metastases,
one study demonstrated that the presence of a malignant effusion was an
independent predictor of a lower overall survival at one and two years (hazards ratio
[HR] 1.36, 95% CI 1.30-1.43) [3].

● The median survival among 417 patients identified in a systematic review was four
months after the recognition of an MPE, although some patients may have a
prolonged survival [4].

● A series of 278 patients referred to a thoracic surgery clinic for management of an

MPE found a median postoperative survival of 211 days [5].

● A series of 789 patients from three centers who presented with their first episode of
an MPE varied in median survival based on the underlying tumor type [6]. Median
survivals ranged from 74 days for patients with lung cancer to 339 days for patients
with mesothelioma (table 1).

Multiple factors have been examined to predict survival of patients with MPEs to assist in
selecting an appropriate approach to management. The largest series with prospective
data collection that assessed prognostic factors derived and validated a risk stratification
system called the LENT score (pleural fluid lactate dehydrogenase, Eastern Cooperative
Oncology Group [ECOG] performance score, blood neutrophil–to-lymphocyte ratio, and
tumor type) (table 2) [6]. The four factors combined into the LENT score had greater
prognostic value than individual factors and identified patients with the lowest one, three,
and six month survivals. The receiver operating curve area, however, ranged from 0.77 to
0.85 for prediction of survival at one-month and six-month respectively, so uncertainty
regarding prognosis remains when applying the LENT score or other prognosticators to
individual patients.

The importance of tumor type in influencing survival at least partly derives from the
responsiveness to therapy of the underlying tumor. As an example, patients with a
lymphoma or breast cancer that is responsive to chemotherapy are more likely to have
prolonged survival compared to those with an effusion due to non-small cell lung cancer.
Additional studies suggest that MPEs due to epidermal growth factor receptor (EGFR)
mutant non-small cell lung cancer may respond to EGFR-tyrosine kinase inhibitor therapy
[7] although most patients become resistant to this therapy after a year.

INDICATIONS FOR TREATMENT

The decision to use a pleural intervention to treat a malignant effusion depends upon the
presence of respiratory symptoms of which dyspnea is the most common and prominent.
Some tumor types, such as breast or ovarian cancer or lymphomas, may respond to
therapy directed at the underlying tumor with resolution of the effusion.

● Asymptomatic MPEs do not need to be treated as long as they remain asymptomatic,

although nearly all malignant effusions eventually become symptomatic.

● Symptomatic malignant effusions that do not respond to treatment of the underlying

tumor require consideration of palliative therapy directed at the pleural space.

Because successful management of an MPE is palliative and without survival benefit,

clinicians should focus on patient-centered goals of therapy, which include sustained
symptom relief, improvement in quality of life, patient and family acceptability of an
intervention, affordability, and preference for less invasive procedures and attendant
complications that take patients from home and disrupt the course of their remaining life
[8,9]. Although no specific approach to the management of an MPE prolongs survival,
misguided strategies can worsen symptoms and shorten survival [2]. This approach is
supported by the American Thoracic Society (ATS), Society of Thoracic Surgeons (STS),
and Society of Thoracic Radiology (STR) clinical practice guideline [10].

TREATMENT OPTIONS

Approaches to the management of an MPE are shown in the figure (table 3) [1,2]. Patients
who have symptoms caused by an MPE should initially undergo therapeutic thoracentesis
to drain the fluid, preferably under the guidance of ultrasound. In most circumstances, if
feasible, large volume thoracentesis with manometry is advised to ascertain the response
of the patient’s symptoms to pleural fluid removal and to assess whether or not the lung is
expandable. An initial thoracentesis does not decrease the effectiveness of subsequent
procedures to produce pleurodesis. The rate of reaccumulation of the pleural effusion,
functional status, pulmonary elastance, responsiveness of the pleural effusion to systemic
antitumor therapy and/or radiation directed at the underlying tumor, the patient's
prognosis, the severity of the patient's symptoms, institutional resources and expertise
with various therapies, and patient preferences should guide the subsequent management
choices [2]. These recommendations are for the most part in keeping with the European
Respiratory Society/European Association of Cardiothoracic Surgery (ERS/EACTS) and
the ATS/STS/STR guidelines [10,11]. (See 'Antitumor therapy' below.)

Slow reaccumulation — Patients whose MPE reaccumulates slowly (eg, more than one
month) may be managed with repeat therapeutic thoracentesis. This is particularly
appropriate if patients also have a short (<2 to 3 months) expected survival and poor
performance status [12].

Thoracentesis — Multiple repeat therapeutic thoracentesis is a simple approach to

managing MPEs that reaccumulate slowly. Briefly, topical analgesia is administered and
then a catheter is percutaneously advanced under ultrasound guidance into the pleural
space using sterile conditions. A large volume of pleural fluid is then drained. The
procedure can be performed at the bedside or in an office setting with appropriate
monitoring. Additional details about the technique of thoracentesis are provided
separately. (See "Ultrasound-guided thoracentesis".)

Reexpansion pulmonary edema (REPE) is rare following large volume thoracentesis

[13,14]. A safe threshold rate or volume of pleural fluid removal that will not cause
reexpansion pulmonary edema has not been identified. In our experience, it is generally
safe to continue to remove pleural fluid, as long as the procedure is terminated if the
patient develops anterior chest pain or the pleural pressure drops below -20 cm H2O [15].
If pleural pressure monitoring is not used, removal of pleural fluid beyond 1.5 L should be
accompanied by careful attention to the development of chest symptoms and
consideration of the relative merit of removing more fluid for greater symptom relief versus
the small potential risk of REPE. Cough is often noted during lung reexpansion and does
not correlate with development of REPE.
Repeated thoracentesis may induce pleural adhesions that can complicate thoracoscopic
pleurodesis if that procedure becomes indicated. The role for repeated thoracentesis has
decreased with the advent of tunneled pleural catheters, which avoid the need for frequent
clinic visits for pleural drainage. Other complications of therapeutic thoracentesis are the
same as those for diagnostic thoracentesis. (See "Ultrasound-guided thoracentesis",
section on 'Complications'.)

Rapid reaccumulation — A more aggressive intervention is required for most patients

because the MPE recurs rapidly (eg, less than one month) after an initial thoracentesis.
Options include indwelling pleural catheter drainage, pleurodesis by various techniques
(chest tube, thoracoscopic, pleuroscopic), pleurectomy, and pleuroperitoneal shunt.
Definitive procedures such as these generally result in fewer subsequent pleural
procedures and fewer pneumothoraces [16].

Indwelling pleural catheter — Placement of an indwelling pleural catheter (IPC; also

known as a tunneled pleural catheter) with intermittent outpatient drainage by the patient
or a patient attendant is our preferred initial step for most patients with recurrent malignant
effusions, especially in those with underlying expandable lung [17-22]. It is also the
preferred method in those with nonexpandable lung rather than chemical pleurodesis.

This method is preferred as primary therapy because it is the least invasive option and
requires little if any time in the hospital, as the catheter may be placed during an
outpatient procedure [12,23-30]. One randomized trial that compared inpatient treatment
of patients with malignant pleural effusions either by IPC or talc pleurodesis found that
patients with IPCs spent fewer effusion-related days in hospital than those who underwent
talc pleurodesis (1 versus 4 days) [31]. A meta-analysis of five trials that included 545
patients confirmed that compared with pleurodesis, IPCs resulted in a shorter hospital
length of stay and reduced frequency of repeat interventions without any survival benefit
[30]. However, IPCs did result in an increased risk of cellulitis. On the other hand,
pleurodesis by chest tube offers a greater probability of rapid resolution of the pleural
effusion although there is a likely probability of late failure after six months requiring
additional interventions [32]. Moreover, measures of quality of life or dyspnea do not differ
significantly between indwelling pleural catheter drainage alone as compared with chest
tube pleurodesis [19,30,31,33].
Indwelling pleural catheter drainage is indicated when there is irremediable lung
entrapment or endobronchial obstruction by tumor; in these patients, chemical pleurodesis
is contraindicated due to high failure rates when the lung is unable to expand against the
chest wall [34]. Indwelling pleural catheters may also improve symptoms following a failed
pleurodesis [35] or in those with nonexpandable lung.

Complications include bleeding, catheter blockage, catheter fracture on removal, and, in

particular, infection along the catheter tract or within the pleural space [19,20,30,36,37].
One study examined the cost-effectiveness of indwelling pleural catheters as compared
with pleurodesis and found that tunneled catheters were more cost-effective in patients
with survival less than three months while talc pleurodesis was more cost-effective in
those with longer survival [19]. These findings require validation in other studies that
include patients with a wide spectrum of underlying tumors and in different health care
settings. In general patients with infected IPCs can be treated with antibiotics without
removal of the catheter [10]. The catheter may need to be removed from patients whose
catheter infection fails to respond to antibiotics. (See "Diagnosis and management of
pleural causes of nonexpandable lung".)

The patient or a family member will need to be able to perform pleural fluid drainage via
the indwelling pleural catheter at home and maintain catheter sterility.

Indwelling pleural catheters provide a high degree of symptom relief, as demonstrated in a

retrospective analysis of 250 pleural catheter procedures (223 patients) [24]. Dyspnea
resolved following 39 percent of the procedures and improved in another 50 percent.
Additional observational studies have demonstrated that patients who chose indwelling
catheters as opposed to talc pleurodesis have fewer total hospital days, fewer effusion-
related hospital days, fewer subsequent procedures to control effusion-related symptoms,
and better quality of life within seven days of treatment [26,38]. One randomized study
found that indwelling pleural catheters, as compared with talc pleurodesis, had a lower
hospital stay, fewer admissions, and fewer reinterventions with a similar improvement in
dyspnea [22].

Two randomized trials have compared indwelling catheter drainage alone versus chest
tube drainage with talc pleurodesis in terms of outcomes such as palliation of dyspnea,
lung re-expansion, procedure related complications, and quality of life and found similar
results [19,20]. In the larger of two trials, 106 patients with MPEs were randomly assigned
to placement of an indwelling catheter or pleurodesis with talc slurry via a 12-French chest
tube placed over a guidewire [19]. No significant difference was found in post-procedure
dyspnea, chest pain, or quality of life scores between the groups. Twelve patients in the
talc group required additional pleural procedures compared with three in the indwelling
catheter group (OR 0.21, 95% CI 0.04-0.86). However, adverse events (eg, pleural or skin
infection, catheter blockage) were more common in the indwelling catheter group. One
multicenter study demonstrated a low incidence of infection (5 percent) from indwelling
pleural catheters with an overall mortality risk from infections of 0.29 percent [28]. Fifty-
four percent of the infections in this study could be treated with antibiotics without removal
of the chest catheter. Pleurodesis occurred in 62 percent of patients who experienced a
catheter-related infection [28]. Another prospective randomized trial comparing indwelling
catheter drainage alone with chest tube pleurodesis found no differences in
breathlessness or quality of life [31]. Indwelling pleural catheters appear to be relatively
safe in patients undergoing chemotherapy [39] and in those with MPEs due to
hematologic malignancies; the cumulative incidence of all complications of 13.6 percent
and cumulative incidence of all serious catheter related complications was 9.5 percent
[40]. (See 'Pleurodesis' below and 'Choosing among the options' below.)

Spontaneous pleurodesis may occur in approximately 27 percent to 70 percent after 2 to

12 weeks of indwelling pleural catheter drainage [41-44]. In one study, catheter drainage
achieved pleurodesis in 70 percent at a mean interval of 90 days after catheter placement
[41]. A randomized trial of 149 patients with MPEs treated with indwelling catheters
demonstrated that daily catheter drainage of 1 liter of fluid, as compared with every other
day drainage of 1 liter resulted in more frequent occurrence of spontaneous pleurodesis
(47 versus 24 percent, respectively) and a shorter median time to pleurodesis (54 versus
90 days) [45]. Another study reported higher rates of pleurodesis with lymphoma and
ovarian cancer, but reduced rates with gastrointestinal cancers and hydropneumothorax
[44]. When drainage ceases, the indwelling pleural catheter can be removed. However,
catheter removal is associated with fracture of the catheter in 10 percent with occasional
retention of a catheter fragment in the pleural space [46]. Among four patients with
retained catheter fragments, no complications were reported during a mean follow up of
459 days.
For those patients who do not develop a spontaneous pleurodesis after days to weeks of
drainage, a pleural sclerosant can be instilled through the catheter [17,47-49]. (See
"Chemical pleurodesis".)

For those patients in whom continued drainage is preferred but is prohibited due to
catheter-related loculations, the instillation of an intrapleural fibrinolytic agent (tissue-
plasminogen activator, urokinase, or streptokinase) may be of benefit as suggested by a
multicenter uncontrolled observational study [50]. However, a randomized controlled trial
of the instillation of urokinase as compared with placebo in patients with malignant
effusions drained by standard chest tubes (not indwelling catheters) did not show benefit
[51]. More data are needed before intrapleural fibrinolytics can be recommended for
patients with loculated MPEs. (See 'Intrapleural fibrinolytic agents' below.)

Pleurodesis — The decision to undergo pleurodesis is often based upon an

anticipated survival of longer than three months and the patient's desire for an effective
therapy that can be carried out in a single definitive procedure, rather than the potential
inconvenience of having a long-term indwelling catheter that requires intermittent drainage
if spontaneous pleurodesis does not occur. (See 'Indwelling pleural catheter' above.)

The type of pleurodesis (chemical versus mechanical), sclerosing agent (talc versus
other), chest tube size (large- versus small-bore), choice of analgesic agent (opiate versus
nonsteroidal anti-inflammatory [NSAID]) varies considerably among centers and experts.
Based upon data derived from retrospective studies, a meta-analysis, and randomized
trials of patients with MPE, we prefer chemical pleurodesis using talc slurry via a small-
bore chest tube because the advent of bedside ultrasonography has allowed this
procedure to be performed by the bedside with optimization of drain placement within the
chest. While the ERS/EACTS prefer large-bore chest tubes, we prefer small-bore tubes
since they are also well tolerated by patients with treatment with opioid and/or NSAID
analgesia [11,12,52,53]. However, existing studies do not clearly demonstrate superiority
of talc slurry over talc poudrage or small versus large bore chest tubes in terms of
pleurodesis efficacy at three months [52,53]. So other approaches that use thoracoscopic
administration of talc by poudrage, talc slurry by large bore chest tubes, or performance of
thoracoscopic mechanical pleural abrasion followed by continued drainage with a large
bore chest tube appear to be effective options. Moreover, some clinicians routinely
perform pleurodesis during a thoracoscopic or pleuroscopic procedure that diagnoses the
pleural malignancy.
 Chemical pleurodesis — Chemical pleurodesis refers to obliteration of the pleural
space by the induction of pleural inflammation and fibrosis using a sclerosant (usually
talc). The sclerosant can be instilled via a small- or large-bore chest tube or indwelling
catheter (talc slurry) or it can be administered at the time of thoracoscopy (video assisted
thoracoscopy or pleuroscopy) or thoracotomy (talc insufflation/poudrage). We prefer
chemical pleurodesis via a small-bore chest tube rather than via thoracoscopy because
the former is as effective, less invasive, and better tolerated in our experience [54].
However, thoracoscopic chemical pleurodesis is an appropriate alternative in some
patients. Choosing among these options usually depends upon the medical
circumstances, goals and preferences of the patient, and institutional practice. As an
example, thoracoscopy may be preferred in those with a concomitant indication for
thoracoscopy or those in whom diagnosis of pleural malignancy is made during
thoracoscopy. In contrast, administration via a chest tube may be preferred in patients
with cardiopulmonary compromise who cannot tolerate thoracoscopy. (See "Talc
pleurodesis" and "Medical thoracoscopy (pleuroscopy): Diagnostic and therapeutic
applications".)

The introduction of sclerosant via small-bore chest tube or during video-assisted

thoracoscopy have similar efficacy in studies of patients with MPE due to a variety of
cancers, including malignant mesothelioma [54-57]. As an example, a randomized trial of
282 patients with MPE reported similar rates of radiographic recurrence at 30 days in
those in whom sclerosant was administered via a chest tube compared with thoracoscopic
administration (29 versus 22 percent) [54]. However, respiratory complications were less
common in those who received a sclerosant using a chest tube (6 versus 14 percent).

The technical aspects of chemical pleurodesis and the associated complications are
discussed in greater detail elsewhere. (See "Chemical pleurodesis" and "Talc
pleurodesis".)

Chest tube size — No convincing advantages derive from performing chemical

pleurodesis via a standard large-bore (eg, 24 French) as opposed to a small-bore chest
tube (eg, 12 French) [52,58]. However, in many but not all studies, large-bore chest tubes
cause more patient discomfort.

In a randomized trial of 320 patients with MPE, smaller chest tubes (12 French) were
associated with a similar rate of pleurodesis failure at three months when compared with
patients in whom large chest tubes were placed (24 French) (30 versus 24 percent) [52].
However, pain scores were significantly lower among patients with smaller chest tubes
(mean visual analogue score, 22 mm versus 27 mm), and although the complication rate
was higher with the insertion of smaller chest tubes it was not significantly different (24
versus 14 percent). Smaller and older studies have shown a similar lack of difference
between small and large-bore chest tubes in this population [58]. Methodologic flaws
including small sample size for group comparisons and uncertainty in some studies
whether the small bore chest tubes were inserted under imaging guidance limit the
interpretation of these studies.

Analgesia — The parietal pleural membrane contains a high percentage of pain

receptors such that the induction of inflammation by the intrapleural instillation of a
sclerosant is often intensely painful. NSAIDs and opiates are frequently prescribed by
clinicians for pain control. Animal studies had suggested that NSAIDs decrease the
efficacy of pleurodesis. In a randomized study of patients with MPE, a similar rate of
pleurodesis failure was noted in patients treated with opiates (10 to 20 mg oral morphine
four times daily) when compared with patients treated with NSAIDs (ibuprofen 800 mg
three times daily) (20 versus 23 percent) [52]. However, although pain scores were no
different between each group, twice as many patients who used NSAIDS required rescue
analgesia with intravenous morphine.

However, the choice of agent is typically individualized and dependent upon factors
including level of pain, known sensitivity to opiates or NSAIDs, history of gastrointestinal
bleeding, opiate drug abuse, liver or renal failure, and expected poor survival.

Sclerosing agent — Talc (slurry or poudrage) is typically the agent preferred by

many experts given its relative superiority for reducing the rate of MPE recurrence when
compared with other agents in patients with a variety of cancer cell types [53,59-63]. Talc
is also cheap and readily available. (See "Talc pleurodesis".)

In general, the success rate of talc in preventing recurrence at 30 days after pleurodesis
ranges between 60 to 90 percent [20,53,60,63,64]. It is difficult to determine success rates
at 30 days because many studies exclude those patients who die before the 30-day
assessment mark. If patients who die before 30 days after lung reinflation are included in
analyses, success rates of talc fall to 50 to 60 percent [54]. Moreover, the longer the
patient survives after pleurodesis the greater the probability of recurrence with one study
reporting that 50 percent of patients undergoing talc pleurodesis experiencing inadequate
fluid control at six months [54].

The tetracycline derivative doxycycline is an alternative sclerosant with reported success

rates of about 80 percent although an accurate assessment of effectiveness is limited by
the small number and low quality of existing studies [53,64-66]. Other sclerosing agents,
such as bleomycin, silver nitrate, and povidone-iodine, have also been used [67-71].

Studies differ regarding the influence of tumor type on the success rate of pleurodesis.
Some studies report no differences [72,73], but one retrospective study of 447 patients
undergoing talc pleurodesis by thoracoscopy demonstrated a lower success rate for
mesothelioma (76 percent) as compared with breast cancer (93 percent) [64]. The authors
also reported that pleurodesis success was negatively influenced by high intrapleural
tumor burdens, which is especially common in patients with mesothelioma. One meta-
analysis reviewed 62 randomized trials of pleurodesis and suggested that talc by
poudrage is the most effective sclerosing agent and mode of talc delivery into the chest
[53]. Extensive heterogeneity between studies and risk for bias, however, limited their
conclusions and the meta-analysis called for more and higher quality studies to establish
the ideal sclerosing agent.

Duration of chest tube drainage — No consensus exists regarding the duration

of chest tube drainage required to achieve pleurodesis after delivery of the sclerosing
agent. One study found that a shorter duration of chest tube placement of 24 hours as
compared with 72 hours did not decrease the likelihood of a successful pleurodesis
regardless of the rate of pleural fluid drainage [74]. We individualize management with a
goal of removing the chest tube after 24 hours of instillation of the sclerosant but may
maintain the chest tube in place for up to 72 hours for patients who have exceptionally
large volumes of ongoing drainage. For persistent large volume drainage, we then assess
the patient for complicating factors, such as chylothorax or entrapped lung.

Alternative approaches

Talc pleurodesis PLUS an indwelling catheter — Another option that may be

offered to patients with MPE who do not have evidence of lung entrapment is talc
pleurodesis combined with pleural fluid drainage with an indwelling pleural catheter. This
approach combines the efficacy and rapidity of pleurodesis with the safety and good
patient tolerance of indwelling catheters. Timing of talc insufflation varies:
● Some experts choose to drain the pleural fluid under thoracoscopic guidance, place a
tunneled pleural catheter, and insufflate sterile talc (5 g) at the time of indwelling
catheter placement. At the end of the procedure, a 24 gauge chest tube is placed
through the port created for the thoracoscope, attached to suction overnight and
removed 24 hours later. The indwelling catheter is drained three times a day on the
first postoperative day, twice on the second and third postoperative days, and then
once daily until the output is less than 150 mL per day. A chest radiograph is then
obtained and the tunneled catheter removed if no reaccumulation of pleural fluid is
noted. Details regarding the performance of thoracoscopy are provided separately.
(See "Medical thoracoscopy (pleuroscopy): Diagnostic and therapeutic applications".)

The combination of thoracoscopic talc pleurodesis and indwelling catheter placement

was assessed in a series of 30 patients [43]. All of the patients reported improved
dyspnea [43]. Successful pleurodesis was noted in 24 of the 26 patients who were
still alive at six months; the remaining two still required intermittent drainage using the
catheter. The indwelling catheter was removed at a mean of 16.6 days and a median
of 7.5 days following the procedure. Adverse effects included fever in two patients,
need for replacement of the indwelling catheter due to pleural loculations in one
patient, and an empyema in one patient. Another consecutive case series of 30
patients found that pleuroscopy combined with indwelling catheter placement as
compared with historical controls of conventional pleuroscopy had a similar success
rate for pleurodesis but shorter hospital stay, shorter time to pleurodesis, and better
control of symptoms in those patients who fail pleurodesis [75]. An uncontrolled study
of 29 patients found that patients were discharged after a median of two days and
had the catheter removed after a median of 10 days and only four of 29 patients had
a recurrence of pleural effusions [76].

● Other experts instill talc through an indwelling pleural catheter inserted as a same-day
procedure without overnight hospitalization. A randomized trial of 154 patients with
malignant pleural effusions compared indwelling pleural catheter drainage alone with
pleurodesis by talc instilled through an indwelling pleural catheter [77]. After initial
fluid drainage during catheter insertion, patients underwent three drainages daily
(limited to 1L of fluid removed with each drainage) at home over the subsequent 10
days. Patients who achieved full lung re-expansion (ie, no lung entrapment)
underwent randomization to continued drainage versus instillation of talc via the
 indwelling catheter (4 g in 50 mL normal saline slurry). Successful pleurodesis
occurred more frequently in patients treated by talc pleurodesis as compared with
indwelling pleural drainage alone at 35 days (43 versus 23 percent) and at 70 days
(51 versus 27 percent). No difference in adverse events or death was noted. Patients
treated by pleurodesis via the indwelling pleural catheter had improved symptom and
quality of life scores. The study was limited by the large number of run-in exclusions.
Among the 250 patients enrolled, 96 were excluded with 32 having lung entrapment,
23 were too ill to continue in the study, 41 had other reasons to be excluded.
Moreover, nearly 10 percent of those assigned to treatment groups were excluded
from the data analysis and the indwelling pleural catheters were inserted before a trial
of therapeutic thoracentesis to determine the rapidity of fluid re-accumulation, which
would bias the results toward positive study effects. In addition, the success rate for
pleurodesis was lower than in many studies that performed the procedure with
instillation of talc through a small-bore chest tube. The study does demonstrate,
however, the safety and relative efficacy of instilling talc via an indwelling pleural
catheter.

Pleurectomy — Radical total or subtotal pleurectomy (resection of visceral and

parietal pleura) and decortication (removal of fibrous pleural rind) can control malignant
pleural effusions in patients who have failed chemical pleurodesis. One observational
study reported pleurectomy in 19 patients with MPEs performed by single incision
thoracoscopic surgery [78]. Pleural effusions did not recur in 91 percent of patients and no
mortality or complications were observed.

It is rarely performed, however, for patients with malignant effusions that are not due to
mesothelioma because of the invasiveness of the procedure, long recovery time, and lack
of evidence of efficacy over less invasive palliative procedures to control the effusion.

Pleurectomy/decortication can be used as a primary therapeutic modality for patients with

malignant effusions due to mesothelioma, although it does not improve survival and is
associated with significant complications [79-81]. The management of malignant pleural
mesothelioma is discussed separately. (See "Initial management of malignant pleural
mesothelioma" and "Initial management of malignant pleural mesothelioma", section on
'Pleurectomy/decortication (P/D)'.)
Patients must be good surgical candidates and have a reasonably long expected survival,
because total radical pleurectomy/decortication requires a thoracotomy and is a major
surgical procedure associated with considerable morbidity and some mortality [82].
Subtotal pleurectomy/decortication can be accomplished thoracoscopically. Pleurectomy
is virtually always effective in obliterating the pleural space for control of an MPE.

Shunt — Pleuroperitoneal shunting is a rarely used option for patients who have
lung entrapment, malignant chylothorax, or have failed pleurodesis [83-85]. In general, we
prefer using an indwelling pleural catheter, rather than a pleuroperitoneal shunt, due to the
frequency of shunt-related problems and the less invasive nature of indwelling pleural
catheters. Pleuroperitoneal shunting, however, may have nutritional advantages for
patients with malignant chylothorax and high volumes of pleural fluid drainage because
shunting of nutrient-rich chyle to the peritoneal space allows its reabsorption. (See
"Etiology, clinical presentation, and diagnosis of chylothorax" and 'Indwelling pleural
catheter' above.)

Usually, the procedure is performed during thoracoscopy and under general anesthesia
but may be placed by interventional radiological techniques [84]. The shunt catheter
(Denver pleuroperitoneal shunt), has one or two one-way valves that allow unidirectional
flow from the pleural space and is inserted with one end in the pleural cavity and the other
through a subcutaneous tunnel into the peritoneum; the shunt pumping chamber is placed
in a subcutaneous pocket overlying the costal margin.

In the hands of experienced operators, placement of a pleuroperitoneal shunt is

reasonably safe, although shunt-related complications occur in about 15 percent [83]. The
major problems have been shunt failure, most commonly due to occlusion of the catheter
and infection. In a retrospective review of 160 patients who received a pleuroperitoneal
shunt for MPE, 12 developed shunt occlusion (requiring revision in 5 and replacement in
7); another 7 developed infection [83]. One patient developed malignant seeding on the
chest wall at the site of shunt insertion, but peritoneal seeding was not observed. It is not
known whether patients who have experienced shunt occlusion are at greater risk for
occlusion after a new shunt is placed.

Palliation of the pleural effusion is achieved in 73 to 90 percent of properly selected

patients [83].
Intrapleural fibrinolytic agents — Small case series report symptomatic benefit for
patients with loculated MPE after intrapleural instillation of urokinase or streptokinase to
break down fibrin adhesions and promote drainage [86-88]. The small size of these
studies does not support general recommendations for intrapleural fibrinolytic therapy,
which requires careful patient selection and monitoring [12]. A randomized controlled trial
of the instillation of urokinase as compared with placebo in patients with malignant
effusions drained by standard chest tubes did not show benefit and casts doubt on the
benefits of fibrinolytic therapy for patients with loculated MPEs [51].

Choosing among the options — Selection of an approach depends on local expertise

and practice patterns, individual patient clinical features, and patient preferences [89].
Some of the factors that guide the choice of an approach include the following:

● Indwelling pleural catheters require little if any time in the hospital; however, there is
more inconvenience related to the longer dwell time of the tube and slightly greater
risk of cellulitis at the insertion site. In addition, the patient or a family member needs
to be able to perform intermittent drainage at home. This option is ideal for patients
with a shorter anticipated duration of survival (less than six months), for patients who
prefer outpatient management and a less invasive intervention, and for patients who
have failed other modalities for pleurodesis. (See 'Indwelling pleural catheter' above.)

● Talc slurry instilled via small bore chest tube is a reasonable and cost-effective [90-
92] alternative for patients with an expected survival of more than six months. The
main disadvantage is initial pain with instillation and small but potentially serious risk
of respiratory complications. (See 'Pleurodesis' above.)

● Intrapleural doxycycline is somewhat less effective than talc and may be associated
with more pain. As a result, it would be used in settings where talc is not available.
(See 'Pleurodesis' above.)

● Video-assisted thoracoscopy with talc insufflation is a good choice for patients with
longer expected survival, particularly when a pleural malignancy has just been
identified during a diagnostic thoracoscopy or when lysis of adhesions or partial
decortication is needed to treat lung entrapment. (See 'Pleurodesis' above.)

● Combining thoracoscopic talc insufflation with insertion of an indwelling pleural

catheter that remains in place until pleural fluid no longer re-accumulates is
 undergoing investigation, but has not yet been compared with more standard
procedures in clinical trials. (See 'Talc pleurodesis PLUS an indwelling catheter'
above.)

● Pleurodesis is not indicated in the presence of irremediably entrapped or trapped lung

when a therapeutic thoracentesis does not improve dyspnea. Some patients with
entrapped or trapped lungs where partial pleural apposition can be achieved after
removal of pleural fluid may experience symptomatic relief with pleurodesis [66].
Other patients with a combination of a completely nonexpandable lung and recurrent
MPE are best managed with an indwelling pleural catheter. (See 'Indwelling pleural
catheter' above.)

● Pleuroperitoneal shunting is a rarely used option for patients who have failed
pleurodesis or have the combination of recurrent malignant effusion, lung entrapment,
and also the inability to perform intermittent drainage via an indwelling pleural
catheter at home.

Antitumor therapy — Antitumor therapy (ie, chemotherapy, protein kinase inhibitors,

monoclonal antibodies, and radiation) may benefit selected patients, but generally is not
adequate for most patients to control symptoms caused by an MPE. Whether definitive
treatment should be given in advance of anti-tumor therapy is unknown.

Systemic antitumor drug therapy — The response of MPEs to systemic

chemotherapy is disappointing for most malignancies. Exceptions include pleural effusions
due to underlying tumors that respond to chemotherapy, such as lymphoma, breast
cancer, small cell carcinoma of the lung, germ cell tumors, prostate cancer, and ovarian
cancer.

Preliminary phase I and II studies with nonsclerosant intrapleural chemotherapeutic

agents have shown a high rate of control of the malignant effusions, but have not directly
compared these agents to standard therapy [93-95]. Further randomized trials are needed
with comparisons to management with an indwelling pleural catheter alone, thoracoscopy,
and/or pleurodesis using traditional sclerosing agents.

Vascular endothelial growth factor (VEGF) has been suggested to be a critical cytokine in
the formation of malignant MPEs. Data suggest that some MPEs due to non-squamous
subgroup of non-small cell lung cancer (NSCLC) may respond to bevacizumab, a
recombinant monoclonal antibody directed against VEGF [96-98]. Also, patients with
epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer consistently
respond to EGFR-tyrosine kinase inhibitors [99,100]. Those with the EGFR mutation who
present with an MPE may experience control of their effusions as effectively with initiation
of EGFR-tyrosine inhibitor therapy alone as with the combination of EGFR-tyrosine kinase
inhibitors plus pleurodesis [7]. Unfortunately, most patients who present with EGFR
mutant non-small cell lung cancer without pleural effusions develop resistance to therapy
within one year [99] and then commonly follow a dramatic course with the rapid
development of an MPE. One study demonstrated control of these effusions by the
addition of bevacizumab to ongoing EGFR-tyrosine kinase inhibitor therapy [101].

Radiation therapy — Radiotherapy directed at the primary tumor may be helpful in

resolving MPEs when mediastinal lymph node disease predominates (eg, lymphoma).
Mediastinal radiation also may be effective for resolving paramalignant effusion in patients
with lymphomatous chylothorax.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Pleural
effusion".)

SUMMARY AND RECOMMENDATIONS

● Malignant pleural effusions (MPEs) can severely impair the quality of life of patients
with malignancy. Multiple palliative approaches are available to drain the effusion and
also to prevent its reaccumulation.

● The prognosis of patients with an MPE depends on a variety of factors, such as age,
performance status, tumor type, tumor stage, comorbidities, composition of the
pleural fluid, and responsiveness of the underlying cancer to antitumor therapy. (See
'Prognosis' above.)

● Asymptomatic patients with MPEs do not require treatment. Patients who have
symptoms due to an MPE should undergo an initial therapeutic thoracentesis. The
 patient's symptomatic response and the rate of reaccumulation of the pleural effusion
should be determined along with the patient's prognosis for duration of survival. (See
'Treatment options' above.)

● Management of patients who require treatment for recurrent symptomatic effusions

after initial thoracentesis:

• We suggest repeat outpatient therapeutic thoracentesis or an indwelling pleural

catheter rather than pleurodesis for patients with a short life expectancy (less
than two to three months) whose MPE reaccumulates slowly to produce
symptoms (eg, longer than one month) (Grade 2C). Use of large volume
thoracentesis and manometry may help detect expandable or nonexpandable
lung, and therefore guide future management. (See 'Thoracentesis' above.)

• For most patients with good performance status whose symptomatic MPE
reaccumulates sufficiently rapidly (eg, less than one month), we suggest
drainage via an indwelling pleural catheter or chemical pleurodesis by catheter or
by either thoracoscopy or pleuroscopy, rather than repeat therapeutic
thoracentesis (Grade 2C). (See 'Rapid reaccumulation' above.)

• Among those with rapid reaccumulation of the effusion, multiple factors

(particularly patient characteristics and preferences, clinician experience, and
agent availability) help determine the optimal management approach. When
choosing between indwelling catheter drainage and chemical pleurodesis,
patients with a relatively longer anticipated survival (eg, longer than two to three
months) may prefer chemical pleurodesis due to a desire for an effective
treatment that can be carried out in a single definitive procedure, rather than
living with the inconvenience of an indwelling catheter that requires intermittent
drainage. Other patients may prefer to avoid the longer hospitalization and
greater initial discomfort of pleurodesis via a chest tube (eg, local pain, low-grade
fever, and rarely respiratory distress) and choose indwelling catheter drainage,
which may allow catheter removal if spontaneous pleurodesis is achieved, or
instillation of talc via the catheter if pleural drainage persists for 10 days or more.
Some patients may choose to perform talc pleurodesis via an indwelling catheter
as soon as it is inserted to limit the duration of catheter insertion. Indwelling
pleural catheters (IPCs), rather than chemical pleurodesis may also be preferred
 in those with underlying expandable lung, although those with nonexpandable
lung may also be candidates for IPCs. (See 'Choosing among the options' above
and "Talc pleurodesis", section on 'Complications and safety' and "Chemical
pleurodesis", section on 'Complications'.)

• Systemic antitumor drugs and/or radiotherapy directed to the underlying cancer

may control the effusion in certain malignancies (eg, breast, lymphoma, ovarian,
prostate, small cell lung cancer, epidermal growth factor receptor (EGFR) mutant
non-small cell lung cancer. However, these therapies are generally not adequate
to control MPEs in patients with tumor types poorly responsive to systemic
therapy. (See 'Antitumor therapy' above.)

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REFERENCES

1. Heffner JE, Klein JS. Recent advances in the diagnosis and management of
malignant pleural effusions. Mayo Clin Proc 2008; 83:235.

2. Ferreiro L, Suárez-Antelo J, Valdés L. Pleural procedures in the management of

malignant effusions. Ann Thorac Med 2017; 12:3.

3. Morgensztern D, Waqar S, Subramanian J, et al. Prognostic impact of malignant

pleural effusion at presentation in patients with metastatic non-small-cell lung
cancer. J Thorac Oncol 2012; 7:1485.

4. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of survival for
patients with malignant pleural effusions. Chest 2000; 117:79.

5. Pilling JE, Dusmet ME, Ladas G, Goldstraw P. Prognostic factors for survival after
surgical palliation of malignant pleural effusion. J Thorac Oncol 2010; 5:1544.

6. Clive AO, Kahan BC, Hooper CE, et al. Predicting survival in malignant pleural
effusion: development and validation of the LENT prognostic score. Thorax 2014;
69:1098.
 7. Verma A, Chopra A, Lee YW, et al. Can EGFR-Tyrosine Kinase Inhibitors (TKI)
Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion
(MPE) in Lung Adenocarcinoma. Curr Drug Discov Technol 2016; 13:68.

8. Davies HE, Lee YC. Management of malignant pleural effusions: questions that
need answers. Curr Opin Pulm Med 2013; 19:374.

9. Basso SM, Mazza F, Marzano B, et al. Improved quality of life in patients with
malignant pleural effusion following videoassisted thoracoscopic talc pleurodesis.
Preliminary results. Anticancer Res 2012; 32:5131.

10. Feller-Kopman DJ, Reddy CB, DeCamp MM, et al. Management of Malignant
Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir
Crit Care Med 2018; 198:839.

11. Bibby AC, Dorn P, Psallidas I, et al. ERS/EACTS statement on the management of
malignant pleural effusions. Eur Respir J 2018; 52.

12. Roberts ME, Neville E, Berrisford RG, et al. Management of a malignant pleural
effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65
Suppl 2:ii32.

13. Feller-Kopman D, Berkowitz D, Boiselle P, Ernst A. Large-volume thoracentesis and

the risk of reexpansion pulmonary edema. Ann Thorac Surg 2007; 84:1656.

14. Feller-Kopman D, Walkey A, Berkowitz D, Ernst A. The relationship of pleural

pressure to symptom development during therapeutic thoracentesis. Chest 2006;
129:1556.

15. Doelken P, Huggins JT, Pastis NJ, Sahn SA. Pleural manometry: technique and
clinical implications. Chest 2004; 126:1764.

16. Ost DE, Niu J, Zhao H, et al. Quality Gaps and Comparative Effectiveness of
Management Strategies for Recurrent Malignant Pleural Effusions. Chest 2018;
153:438.

17. Saffran L, Ost DE, Fein AM, Schiff MJ. Outpatient pleurodesis of malignant pleural
effusions using a small-bore pigtail catheter. Chest 2000; 118:417.
18. Bazerbashi S, Villaquiran J, Awan MY, et al. Ambulatory intercostal drainage for the
management of malignant pleural effusion: a single center experience. Ann Surg
Oncol 2009; 16:3482.

19. Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs
chest tube and talc pleurodesis for relieving dyspnea in patients with malignant
pleural effusion: the TIME2 randomized controlled trial. JAMA 2012; 307:2383.

20. Demmy TL, Gu L, Burkhalter JE, et al. Optimal management of malignant pleural
effusions (results of CALGB 30102). J Natl Compr Canc Netw 2012; 10:975.

21. Sabur NF, Chee A, Stather DR, et al. The impact of tunneled pleural catheters on
the quality of life of patients with malignant pleural effusions. Respiration 2013;
85:36.

22. Boshuizen RC, Vd Noort V, Burgers JA, et al. A randomized controlled trial
comparing indwelling pleural catheters with talc pleurodesis (NVALT-14). Lung
Cancer 2017; 108:9.

23. van den Toorn LM, Schaap E, Surmont VF, et al. Management of recurrent
malignant pleural effusions with a chronic indwelling pleural catheter. Lung Cancer
2005; 50:123.

24. Tremblay A, Michaud G. Single-center experience with 250 tunnelled pleural

catheter insertions for malignant pleural effusion. Chest 2006; 129:362.

25. Warren WH, Kalimi R, Khodadadian LM, Kim AW. Management of malignant pleural
effusions using the Pleur(x) catheter. Ann Thorac Surg 2008; 85:1049.

26. Fysh ET, Waterer GW, Kendall PA, et al. Indwelling pleural catheters reduce
inpatient days over pleurodesis for malignant pleural effusion. Chest 2012; 142:394.

27. Hunt BM, Farivar AS, Vallières E, et al. Thoracoscopic talc versus tunneled pleural
catheters for palliation of malignant pleural effusions. Ann Thorac Surg 2012;
94:1053.
28. Fysh ET, Tremblay A, Feller-Kopman D, et al. Clinical outcomes of indwelling pleural
catheter-related pleural infections: an international multicenter study. Chest 2013;
144:1597.

29. Rial MB, Lamela IP, Fernández VL, et al. Management of malignant pleural effusion
by an indwelling pleural catheter: A cost-efficiency analysis. Ann Thorac Med 2015;
10:181.

30. Iyer NP, Reddy CB, Wahidi MM, et al. Indwelling Pleural Catheter versus
Pleurodesis for Malignant Pleural Effusions. A Systematic Review and Meta-
Analysis. Ann Am Thorac Soc 2019; 16:124.

31. Thomas R, Fysh ETH, Smith NA, et al. 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; 318:1903.

32. Fortin M, Tremblay A. Pleural controversies: indwelling pleural catheter vs.

pleurodesis for malignant pleural effusions. J Thorac Dis 2015; 7:1052.

33. Freeman RK, Ascioti AJ, Mahidhara RS. A propensity-matched comparison of

pleurodesis or tunneled pleural catheter in patients undergoing diagnostic
thoracoscopy for malignancy. Ann Thorac Surg 2013; 96:259.

34. Pien GW, Gant MJ, Washam CL, Sterman DH. Use of an implantable pleural
catheter for trapped lung syndrome in patients with malignant pleural effusion. Chest
2001; 119:1641.

35. Thornton RH, Miller Z, Covey AM, et al. Tunneled pleural catheters for treatment of
recurrent malignant pleural effusion following failed pleurodesis. J Vasc Interv Radiol
2010; 21:696.

36. Bibby AC, Clive AO, Slade GC, et al. Survival in Patients With Malignant Pleural
Effusions Who Developed Pleural Infection: A Retrospective Case Review From Six
UK Centers. Chest 2015; 148:235.

37. Gilbert CR, Lee HJ, Skalski JH, et al. The Use of Indwelling Tunneled Pleural
Catheters for Recurrent Pleural Effusions in Patients With Hematologic
Malignancies: A Multicenter Study. Chest 2015; 148:752.
38. Lorenzo MJ, Modesto M, Pérez J, et al. Quality-of-Life assessment in malignant
pleural effusion treated with indwelling pleural catheter: a prospective study. Palliat
Med 2014; 28:326.

39. Hak CC, Sivakumar P, Ahmed L. Safety of indwelling pleural catheter use in patients
undergoing chemotherapy: a five-year retrospective evaluation. BMC Pulm Med
2016; 16:41.

40. Faiz SA, Pathania P, Song J, et al. Indwelling Pleural Catheters for Patients with
Hematologic Malignancies. A 14-Year, Single-Center Experience. Ann Am Thorac
Soc 2017; 14:976.

41. Tremblay A, Mason C, Michaud G. Use of tunnelled catheters for malignant pleural
effusions in patients fit for pleurodesis. Eur Respir J 2007; 30:759.

42. Abrão FC, Abreu IR, Cavalcanti MG, Pompa-Filho JF. Use of indwelling pleural
catheters for the definitive treatment of malignant pleural effusion. J Bras Pneumol
2017; 43:14.

43. Reddy C, Ernst A, Lamb C, Feller-Kopman D. Rapid pleurodesis for malignant

pleural effusions: a pilot study. Chest 2011; 139:1419.

44. Li P, Graver A, Hosseini S, et al. Clinical predictors of successful and earlier

pleurodesis with a tunnelled pleural catheter in malignant pleural effusion: a cohort
study. CMAJ Open 2018; 6:E235.

45. Wahidi MM, Reddy C, Yarmus L, et al. Randomized Trial of Pleural Fluid Drainage
Frequency in Patients with Malignant Pleural Effusions. The ASAP Trial. Am J
Respir Crit Care Med 2017; 195:1050.

46. Fysh ET, Wrightson JM, Lee YC, Rahman NM. Fractured indwelling pleural
catheters. Chest 2012; 141:1090.

47. Pollak JS. Malignant pleural effusions: treatment with tunneled long-term drainage
catheters. Curr Opin Pulm Med 2002; 8:302.

48. Pollak JS, Burdge CM, Rosenblatt M, et al. Treatment of malignant pleural effusions
with tunneled long-term drainage catheters. J Vasc Interv Radiol 2001; 12:201.
49. Ahmed L, Ip H, Rao D, et al. Talc pleurodesis through indwelling pleural catheters
for malignant pleural effusions: retrospective case series of a novel clinical pathway.
Chest 2014; 146:e190.

50. Thomas R, Piccolo F, Miller D, et al. Intrapleural Fibrinolysis for the Treatment of
Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter
Observational Study. Chest 2015; 148:746.

51. Mishra EK, Clive AO, Wills GH, et al. Randomized Controlled Trial of Urokinase
versus Placebo for Nondraining Malignant Pleural Effusion. Am J Respir Crit Care
Med 2018; 197:502.

52. Rahman NM, Pepperell J, Rehal S, et al. Effect of Opioids vs NSAIDs and Larger vs
Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients
With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial. JAMA 2015;
314:2641.

53. Clive AO, Jones HE, Bhatnagar R, et al. Interventions for the management of
malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev
2016; :CD010529.

54. Dresler CM, Olak J, Herndon JE 2nd, et al. Phase III intergroup study of talc
poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005; 127:909.

55. Debeljak A, Kecelj P, Triller N, et al. Talc pleurodesis: comparison of talc slurry
instillation with thoracoscopic talc insufflation for malignant pleural effusions. J
BUON 2006; 11:463.

56. Fysh ET, Tan SK, Read CA, et al. Pleurodesis outcome in malignant pleural
mesothelioma. Thorax 2013; 68:594.

57. Alar T, Ozcelik C. Single-incision thoracoscopic surgery of pleural effusions for

diagnosis and treatment. Surg Endosc 2013; 27:4333.

58. Caglayan B, Torun E, Turan D, et al. Efficacy of iodopovidone pleurodesis and

comparison of small-bore catheter versus large-bore chest tube. Ann Surg Oncol
2008; 15:2594.
59. Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database
Syst Rev 2004; :CD002916.

60. Tan C, Sedrakyan A, Browne J, et al. The evidence on the effectiveness of

management for malignant pleural effusion: a systematic review. Eur J Cardiothorac
Surg 2006; 29:829.

61. Steger V, Mika U, Toomes H, et al. Who gains most? A 10-year experience with 611
thoracoscopic talc pleurodeses. Ann Thorac Surg 2007; 83:1940.

62. Yildirim H, Metintas M, Ak G, et al. Predictors of talc pleurodesis outcome in patients

with malignant pleural effusions. Lung Cancer 2008; 62:139.

63. Spiegler PA, Hurewitz AN, Groth ML. Rapid pleurodesis for malignant pleural
effusions. Chest 2003; 123:1895.

64. Bielsa S, Hernández P, Rodriguez-Panadero F, et al. Tumor type influences the

effectiveness of pleurodesis in malignant effusions. Lung 2011; 189:151.

65. Porcel JM, Salud A, Nabal M, et al. Rapid pleurodesis with doxycycline through a
small-bore catheter for the treatment of metastatic malignant effusions. Support
Care Cancer 2006; 14:475.

66. Robinson LA, Fleming WH, Galbraith TA. Intrapleural doxycycline control of
malignant pleural effusions. Ann Thorac Surg 1993; 55:1115.

67. Tabatabaei SA, Hashemi SM, Kamali A. Silver nitrate versus tetracycline in
pleurodesis for malignant pleural effusions; a prospective randomized trial. Adv
Biomed Res 2015; 4:178.

68. Andrade Neto JD, Terra RM, Teixeira RM, et al. Safety Profile of the Use of
Iodopovidone for Pleurodesis in Patients with Malignant Pleural Effusion. Respiration
2015; 90:369.

69. Rafiei R, Yazdani B, Ranjbar SM, et al. Long-term results of pleurodesis in malignant
pleural effusions: Doxycycline vs Bleomycin. Adv Biomed Res 2014; 3:149.
70. Ibrahim IM, Dokhan AL, El-Sessy AA, Eltaweel MF. Povidone-iodine pleurodesis
versus talc pleurodesis in preventing recurrence of malignant pleural effusion. J
Cardiothorac Surg 2015; 10:64.

71. Kahrom H, Aghajanzadeh M, Asgari MR, Kahrom M. Efficacy and Safety of

Povidone-iodine Pleurodesis in Malignant Pleural Effusions. Indian J Palliat Care
2017; 23:53.

72. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis
failure: analysis of primary data. Chest 2000; 117:87.

73. Barbetakis N, Asteriou C, Papadopoulou F, et al. Early and late morbidity and
mortality and life expectancy following thoracoscopic talc insufflation for control of
malignant pleural effusions: a review of 400 cases. J Cardiothorac Surg 2010; 5:27.

74. Goodman A, Davies CW. Efficacy of short-term versus long-term chest tube
drainage following talc slurry pleurodesis in patients with malignant pleural effusions:
a randomised trial. Lung Cancer 2006; 54:51.

75. Boujaoude Z, Bartter T, Abboud M, et al. Pleuroscopic Pleurodesis Combined With

Tunneled Pleural Catheter for Management of Malignant Pleural Effusion: A
Prospective Observational Study. J Bronchology Interv Pulmonol 2015; 22:237.

76. Krochmal R, Reddy C, Yarmus L, et al. Patient evaluation for rapid pleurodesis of
malignant pleural effusions. J Thorac Dis 2016; 8:2538.

77. Bhatnagar R, Keenan EK, Morley AJ, et al. Outpatient Talc Administration by
Indwelling Pleural Catheter for Malignant Effusion. N Engl J Med 2018; 378:1313.

78. Kara M, Alzafer S, Okur E, Halezeroglu S. The use of single incision thoracoscopic
pleurectomy in the management of malignant pleural effusion. Acta Chir Belg 2013;
113:270.

79. Nakas A, Martin Ucar AE, Edwards JG, Waller DA. The role of video assisted
thoracoscopic pleurectomy/decortication in the therapeutic management of
malignant pleural mesothelioma. Eur J Cardiothorac Surg 2008; 33:83.
80. Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus
pleurectomy/decortication in the surgical management of malignant pleural
mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg 2008; 135:620.

81. Rintoul RC, Ritchie AJ, Edwards JG, et al. Efficacy and cost of video-assisted
thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant
pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.
Lancet 2014; 384:1118.

82. Ohta Y, Shimizu Y, Matsumoto I, et al. Retrospective review of lung cancer patients
with pleural dissemination after limited operations combined with parietal
pleurectomy. J Surg Oncol 2005; 91:237.

83. Genc O, Petrou M, Ladas G, Goldstraw P. The long-term morbidity of

pleuroperitoneal shunts in the management of recurrent malignant effusions. Eur J
Cardiothorac Surg 2000; 18:143.

84. Khiatani V, Isaacson A, Yu H, Stavas J. Interventional radiologic placement of

Denver pleuroperitoneal shunt for refractory chylothorax. J Vasc Interv Radiol 2013;
24:1073.

85. Shimmyo T, Morita K, Mineshita M, et al. Pleuroperitoneal shunt for chylothorax and
chylopericardium in lung cancer: a case report. Ann Thorac Cardiovasc Surg 2011;
17:63.

86. Davies CW, Traill ZC, Gleeson FV, Davies RJ. Intrapleural streptokinase in the
management of malignant multiloculated pleural effusions. Chest 1999; 115:729.

87. Gilkeson RC, Silverman P, Haaga JR. Using urokinase to treat malignant pleural
effusions. AJR Am J Roentgenol 1999; 173:781.

88. Hsu LH, Soong TC, Feng AC, Liu MC. Intrapleural urokinase for the treatment of
loculated malignant pleural effusions and trapped lungs in medically inoperable
cancer patients. J Thorac Oncol 2006; 1:460.

89. Maskell NA. Treatment options for malignant pleural effusions: patient preference
does matter. JAMA 2012; 307:2432.
 90. Puri V, Pyrdeck TL, Crabtree TD, et al. Treatment of malignant pleural effusion: a
cost-effectiveness analysis. Ann Thorac Surg 2012; 94:374.

91. Olden AM, Holloway R. Treatment of malignant pleural effusion: PleuRx catheter or
talc pleurodesis? A cost-effectiveness analysis. J Palliat Med 2010; 13:59.

92. Van Meter ME, McKee KY, Kohlwes RJ. Efficacy and safety of tunneled pleural
catheters in adults with malignant pleural effusions: a systematic review. J Gen
Intern Med 2011; 26:70.

93. Jones DR, Taylor MD, Petroni GR, et al. Phase I trial of intrapleural docetaxel
administered through an implantable catheter in subjects with a malignant pleural
effusion. J Thorac Oncol 2010; 5:75.

94. Seto T, Ushijima S, Yamamoto H, et al. Intrapleural hypotonic cisplatin treatment for
malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-
institutional phase II trial. Br J Cancer 2006; 95:717.

95. Işık AF, Sanlı M, Yılmaz M, et al. Intrapleural hyperthermic perfusion chemotherapy
in subjects with metastatic pleural malignancies. Respir Med 2013; 107:762.

96. Marquez-Medina D, Popat S. Closing faucets: the role of anti-angiogenic therapies

in malignant pleural diseases. Clin Transl Oncol 2016; 18:760.

97. Masago K, Fujimoto D, Fujita S, et al. Response to bevacizumab combination

chemotherapy of malignant pleural effusions associated with non-squamous non-
small-cell lung cancer. Mol Clin Oncol 2015; 3:415.

98. Du N, Li X, Li F, et al. Intrapleural combination therapy with bevacizumab and

cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol
Rep 2013; 29:2332.

99. Jänne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-
cell lung cancer. N Engl J Med 2015; 372:1689.

100. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in

pulmonary adenocarcinoma. N Engl J Med 2009; 361:947.
101. Jiang T, Li A, Su C, et al. Addition of bevacizumab for malignant pleural effusion as
the manifestation of acquired EGFR-TKI resistance in NSCLC patients. Oncotarget
2017; 8:62648.

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