Management of malignant pleural effusions.
ABSTRACT Malignant pleural effusions are a common clinical problem in patients with primary thoracic malignancy and metastatic malignancy to the thorax. Symptoms can be debilitating and can impair tolerance of anticancer therapy. This article presents a comprehensive review of pharmaceutical and nonpharmaceutical approaches to the management of malignant pleural effusion, and a novel algorithm for management based on patients' performance status.
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ABSTRACT: Malignant pleural effusion (MPE) and ascites (MA) negatively impact quality of life of palliative patients. Treatment options are limited. This study's purpose is to examine the experience with indwelling tunneled catheters (ITCs) for management of MPE/MA in children with advanced cancer. Children with MPE/MA who underwent ITC insertion (2007-2012) were retrospectively reviewed. Clinical, procedural, complication and outcome details were analyzed. PleurX® ITCs (n = 12) were inserted in eight patients (5-18 years) with sarcoma (11 MPE, 1 MA), achieving symptom relief and facilitating discharge home post ITC (median 2 days). Median survival following ITC was 51 days. There were two major complications: pain (n = 1), late site infection (n = 1), and five minor complications. Drainage ceased in four patients (pleurodesis/tumor progression). At time of death, six ITCs (five patients) were still in situ. ITC appears to be a safe, effective treatment for MPE/MA in advanced pediatric cancer, achieving symptomatic relief and discharge home. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.Pediatric Blood & Cancer 12/2013; · 2.35 Impact Factor
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ABSTRACT: Malignant pleural effusions (MPEs) are the second leading cause of exudative pleural effusions after parapneumonic effusions. In the vast majority of cases, a MPE signifies incurable disease associated with high morbidity and mortality. Considerable advances have been made for the diagnosis of MPEs, through the development of improved methods in the specialized cytological and imaging studies. The cytological or histological confirmation of malignant cells is currently important in establishing a diagnosis. Furthermore, despite major advancements in cancer treatment for the past two decades, management of MPE remains palliative. This article presents a comprehensive review of the medical approaches for diagnosis and management of MPE.Tuberculosis and Respiratory Diseases 05/2014; 76(5):211-217.
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ABSTRACT: A consensus has not yet been reached for the ideal moment to carry out pleurodesis in patients with malignant pleural effusion among the majority of centres, especially those which don't specialise in oncologic treatment. The PET (positron emission tomography)/CT (computed tomography) used in the staging of patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) has caused controversy when used in the evaluation of therapeutical response and in detection of recurrence in patients with pleurodesis. For not distinguishing between inflammatory and neoplasic processes while using PET or CT, suspicion of pleural involvement can result in the indication for invasive diagnostic procedures or inadequate exchange of therapy. In such cases, the hypothesis of the inflammatory process must be included in the differential diagnoses for positive findings with the PET/CT in patients with NSCLC who have undergone pleurodesis, independently of time since the procedure. The reports of two patients with NSCLC have been presented in order to illustrate situations in which pleurodesis has been performed at the moment of diagnosis, outside of a cancer centre.ecancermedicalscience 01/2014; 8:452.
Mateen H. Uzbeck · Francisco A. Almeida · Rodolfo C.
Morice · Carlos A. Jimenez · Georgie A. Eapen
Department of Pulmonary Medicine, MD Anderson
Cancer Center, Houston, Texas, USA
Mona G. Sarkiss
Department of Anesthesia, MD Anderson Cancer
Center, Houston, Texas, USA
Marcus P. Kennedy ()
Cork University Hospital, Wilton, Cork, County Cork,
Republic of Ireland.
Adv Ther (2010) 27(5): 14.
Management of Malignant Pleural Effusions
Mateen H. Uzbeck · Francisco A. Almeida · Mona G. Sarkiss · Rodolfo C. Morice · Carlos A. Jimenez ·
Georgie A. Eapen · Marcus P. Kennedy
Received: February 24, 2010 / Published online:
© Springer Healthcare 2010
Malignant pleural effusions are a common
clinical problem in patients with primary
thoracic malignancy and metastatic malignancy
to the thorax. Symptoms can be debilitating
and can impair tolerance of anticancer therapy.
This article presents a comprehensive review
of pharmaceutical and nonpharmaceutical
approaches to the management of malignant
pleural effusion, and a novel algorithm for
management based on patients’ performance
Keywords: lung cancer; management; pleural
effusion; pleurodesis; pleuroscopy; thoracentesis
With an estimated annual incidence of
150,000 to 175,000 cases per year in the US
and 40,000 per year in the UK,1,2 malignant
pleural effusions (MPEs) are a common
clinical problem in the setting of cancer.
The presence of malignant cells in the
pleural fluid is often indicative of advanced
disease associated with high morbidity and
mortality and precludes the possibility of a
curative treatment approach.2 In many parts
of the world, chest tube thoracostomy with
subsequent chemical pleurodesis remain
standard management of this protracted and
often devastating condition. This option
is less than optimal given the associated
morbidity. Modalities such as pleuroscopy
with sclerotherapy and the increasing use
of long-term indwelling pleural catheters
have shown to be efficacious, cost effective,
and patient friendly,3-5 and may indicate a
paradigm shift in the management of this
debilitating condition. In this paper we
review the current evidence for the available
management options for MPE and present an
algorithm to aid clinical decision making as
to the most appropriate modality.
2 Adv Ther (2010) 27(5): 14.
Almost any cancer can produce an MPE. The
most common etiologies of MPE are lung cancer in
men and breast carcinoma in women, with these
two malignancies accounting for approximately
75% of all MPEs.6,7 Other malignancies associated
with MPE include lymphoma, ovarian cancer,
gastrointestinal cancer, and mesothelioma in
the order of decreasing frequency with about 7%
occurring in the setting of an unknown primary
cancer.6,7 Pleural effusions presenting in the setting
of an underlying cancer that fail to demonstrate
evidence of malignancy in the fluid and pleural
surface are described as paramalignant pleural
effusions. These effusions may be secondary to
local or systemic tumor effects, cancer therapy
complications, or concurrent nonmalignant
Pleural malignancies may arise from tumor
emboli to the visceral pleura5 or direct extension
from neighboring structures and hematogenous
metastasis to parietal pleural,5,7 (Figure 1), but
the exact mechanism of malignant pleural fluid
accumulation is not entirely understood. The
mere presence of pleural metastasis does not
appear to be sufficient for its pathogenesis. In
fact, only about 60% of patients with proven
pleural metastases develop pleural effusions.8,9 A
diagram highlighting the different mechanisms
of impaired transpleural flow that can result in
the accumulation of pleural fluid in the setting
of malignancy is presented in Figure 2.
Many hypotheses exist regarding the
pathogenesis of MPE in cancer. Indeed, the
accumulation of excess pleural fluid associated
with cancer may be the result of a number
of separate factors in an individual patient.9
Postmortem studies have demonstrated a strong
relationship between carcinomatous infiltration
of the mediastinal lymph nodes and the
occurrence of pleural effusion.8,10 This finding
suggests an important role of the impaired
lymphatic drainage in the pathogenesis of MPE.
However, if this was to be the only mechanism,
one would expect MPEs to be transudative,
but instead, the majority of these effusions are
exudates.9 There is also some evidence that the
upregulation of vascular endothelial growth
factor (VEGF) may play a significant role in the
pathogenesis of MPEs.11,12
Tumour seeding from visceral to parietal pleura
Direct extension from neighboring structures
Hematogenous metastasis to parietal pleura
Tumour emboli to visceral pleura
Figure 1. Pleural involvement in malignancy.
Adv Ther (2010) 27(5): 14.3
Typically, patients present with progressive
exertional dyspnea.5 Cough and chest pain may
also be troubling symptoms. However, some
patients may have no respiratory symptoms
at the time a pleural effusion is noted on
an imaging study. The history and physical
examination should be carried out in the
same manner as in the evaluation of any other
pleural effusion. Posteroanterior and lateral
chest radiographs should be obtained in all
patients with suspected pleural effusion. Lateral
decubitus radiograph may be necessary when the
presence and/or volume of the effusion are in
doubt. However, because other conditions may
be confused with a pleural effusion on x-rays,
other imaging studies may be necessary, such as
ultrasound (Figure 3) or computed tomography
Figure 2. Mechanisms of impaired transpleural flow that can result in the accumulation of pleural fluid in the setting of
malignancy. VEGF, vascular endothelial growth factor.
Figure 3. A 73-year old female with non-small cell lung
cancer (NSCLC). Transthoracic ultrasound image displays
a right-sided malignant pleural effusion.
4 Adv Ther (2010) 27(5): 14.
(CT).5 Ultrasound is in fact more sensitive
than radiography and can detect as little as
5 mL of pleural fluid and is superior to CT for
characterization of collections for the presence of
septations and loculations.13 Once the presence
of a clinically significant pleural effusion has
been established, a diagnostic thoracentesis
is indicated. Since a significant portion of
patients with MPE are dyspneic, a therapeutic
thoracentesis is almost always performed at
the same time. A large volume thoracentesis
is also important to establish if fluid drainage
will lead to symptom(s) improvement. In this
case, if or when the pleural effusion recurs, one
of the more definitive therapeutic options that
will be discussed below should be considered. In
patients with a known underlying malignancy,
it is our practice not only to obtain the usual
tests to differentiate a transudate from an
exudate (total protein and lactate dehydrogenase
both in the fluid and in the serum) but also to
obtain total and differential cell count, glucose
level, cholesterol and triglycerides, cytological
analysis, hematocrit (if fluid is grossly bloody),
and cultures. It is important to keep in mind
that 2% to 5% of MPEs are transudates.14,15 The
yield of cytological examination in establishing a
diagnosis of cancer is quite variable (62% to 90%)
and a second thoracentesis may be considered
depending on the availability of thorascopy.2 Its
sensitivity may be as low as 10% for effusions due
to mesothelioma and over 70% for metastatic
adenocarcinomas.13 Recent data suggests that at
least 50 mL of pleural fluid should be studied in
order to provide optimal cytological analysis.16,17
If lymphoma is suspected, flow cytometry should
also be performed.5 Pleural fluid mesothelin
measurement, where available, appears to be
a promising tumor marker in the diagnosis
of mesothelioma-related pleural effusions.18
However, other tumor marker measurements are
not indicated at this time. If pleural fluid analysis
is negative for malignancy, thoracoscopy should
be the next procedure of choice among patients
in whom cancer is suspected;2,5,13 its sensitivity
for pleural malignancy is generally >90%.2,19,20
Despite recent advances in cancer therapy,
the prognosis of patients with MPE remains poor.
The median survival after a malignant effusion
diagnosis is between 4 and 9 months.21
THERAPEUTIC OPTIONS FOR MPE
Deciding on therapeutic options for MPE
should take into account the etiology, prognosis,
symptoms, and the patients’ overall performance
status. Although MPE secondary to breast cancer,
small cell lung carcinoma, and lymphoma may
respond to systemic chemotherapy and radiation,2
most malignant effusions also require local
palliative therapy. The local treatment options
include frequent thoracentesis, placement of
nontunneled or tunneled drainage catheters,
tube thoracostomy or thoracoscopic pleurodesis,
pleuroperitoneal shunting, pleurectomy, and
decortication (Table 1).
A flow diagram for the different management
options for MPE developed and used in our
institution is given in Figure 4.
Thoracentesis is typically the first step in
the management of a newly diagnosed pleural
effusion. As discussed previously, the initial
thoracentesis usually has a diagnostic and
therapeutic role and can segregate patients into
responders, where repeated fluid evacuation
may be a therapeutic option and nonresponders,
where due to coexisting morbidities or the
presence of non re-expandable lung the
Adv Ther (2010) 27(5): 14.5
removal of fluid does not have significant
impact on symptoms and additional procedures
may have a limited role. In patients who are
unable to undergo invasive procedures or who
have advanced disease with <30 days to live,
repeated thoracentesis along with opiods to
palliate dyspnea may be an option especially
as it can be performed on an outpatient
basis avoiding prolonged hospitalizations.
The optimal amount of fluid that should
be removed remains controversial, with the
consensus statement by the American Thoracic
Table 1. Treatment options for malignant pleural effusions (MPEs).
Continuous outpatient care
Repeat intervention required
Cost per procedure
Figure 4. Algorithm for the management of malignant pleural effusions (MPEs) based on patient’s performance status.
Lighter grey boxes represent virtual multimodality evaluation. *Patients with chemoradiosensitive tumors on initial
treatment (lymphoma, breast cancer, small cell lung cancer, germ cell, ovarian, prostate, and thyroid neoplasms) could
obtain palliation with therapeutic thoracentesis while waiting on systemic treatment results. **The 60-day time point for
reaccumulation is our institution’s cut-off and based on unpublished data. CXR=chest x-ray; ECOG PS=Eastern European
Cooperative Oncology Group Performance Status; r/o=rule out; TT=therapeutic thoracentesis.
Management of Malignant Pleural Effusions (MPE)*
CXR after initial
after intitial TT
0, 1 or 2
60 days or less
of MPE 60 days or less
(if more than 60 days then TT)
after intitial TT
3 or 4
after intitial TT
0, 1 or 2
after intitial TT
3 or 4
No lung re-expansion
R/o endobronchial obstruction
No lung re-expansion
No symptomatic improvement
R/o endobronchial obstruction
to consider according to
Other pailiative modalities
if deem appropriate
Estimate life expectancy
pleural catheter if
contraindicated perform TT
Estimate lafe expectancy
Life expectancy 30 days or more
Palliative modalites to consider
according to patients needs
Chest tibe Pleurodesis
Indwelling Pleural Catheters
Indwelling pleural catheter
Chemical pleurodesis if
chest tube is in place
Failure to obtain palliation
Modalites used seldom
Life expectancy <30 days
Life expectancy 30 days or more
Life expectancy <30 days
causes to explain
6 Adv Ther (2010) 27(5): 14.
Society and the European Respiratory Society
recommending not more than 1.0-1.5 L of fluid
to be slowly evacuated in one sitting and that
drainage should be discontinued if the patient
develops symptoms of dyspnea, cough, or chest
discomfort.22 However, in recent studies the risk
of re-expansion pulmonary edema was shown to
be unrelated to the amount drained, and it has
been suggested that no upper limit is necessary.23
In our experience, patients with radiographic
evidence of contralateral mediastinal shift from
large pleural effusions may safely tolerate the
removal of 2.0-2.5 L of fluid in one sitting as
long as there are no procedure-related symptoms
of chest pain, cough, or dyspnea. However, large
volume pleural fluid drainage during a single
procedure should be approached cautiously,
especially when radiological studies reveal a
centered or ipsilaterally shifted mediastinum.5
Ultrasound-directed thoracentesis is increasingly
being accepted as the standard of care and we
routinely use ultrasound for all our diagnostic and
therapeutic pleural procedures. A recent meta-
analysis shows reduced pneumothorax rates with
the use of real-time ultrasound guidance.24 Other
complications related to thoracentesis include
vasovagal reactions, cough, chest pain, and
hemothorax. Pneumothorax can result from an
accidental disruption of the visceral pleura, from
the introduction of air along the needle/catheter
tract, or due to the presence of nonre-expanding
lung.5 If the patient remains symptomatic
despite adequate re-expansion, causes such as
lymphangitic spread, pulmonary embolism,
or malignant airway obstruction should be
suspected and investigated appropriately. In
nearly all patients the fluid reaccumulates
within 30 days of thoracentesis.25 Therefore,
for patients with limited life expectancies,
poor performance status, or those in whom
pleural fluid reaccumulation is slow, repeated
therapeutic thoracentesis is a viable option.
Frequent repeated thoracenteses may trigger
fluid loculation by inducing local cytokines and
fibrin, which can make further thoracenteses
difficult, and can also complicate future modes
Indwelling Tunneled Pleural Catheter
The US Food and Drug Administration
approved the use of the only commercially
available indwelling tunneled pleural catheter
(IPC [Pleurx; Denver Biomedical, Golden, CO,
USA]) in 1997. Ever since, several studies have
demonstrated its safety and efficacy in the
treatment of MPEs.26-29 The IPC placement with
intermittent outpatient drainage is our preferred
method of treatment for the majority of patients
with recurrent MPEs. The IPC is a 15.5 Fr silicone
catheter and 66 cm in length (Figure 5A). It has
fenestrations at its distal 24 cm. A safety valve
at its proximal end prevents passage of air or
fluid through the catheter unless the matched
drainage line is attached. The IPC has a polyester
cuff situated 14 cm from the proximal end and
lies within the subcutaneous tract (tunnel).
This cuff anchors the catheter in position and
it is believed to form a barrier to infection.26
Placement is simple and is generally performed
on an outpatient basis with local anesthesia. The
IPC is generally placed at the anterior or mid
axillary line. Once the pleural fluid is identified
with a “finder” needle, a soft tipped guidewire
is inserted through this needle into the pleural
space and the needle is removed (Figure 5B,C).
Two separate small incisions (0.5-2.0 cm) are
made, one at the site of the guidewire and one
approximately 5-7 cm inferiorly (Figure 5C). A
trocar attached to the distal end of the IPC guides
the catheter and creates a subcutaneous tunnel
starting at the inferior incision (Figure 5D). Once
the IPC comes out of the superior incision, the
polyester cuff is placed within 1 cm of the inferior
Adv Ther (2010) 27(5): 14.7
Figure 5. Indwelling pleural catheter. (A) Indwelling tunneled pleural catheter (IPC) with its fenestrations (black arrows),
safety valve (in circle), and polyester cuff (white arrow). (B) A syringe attached to the “finder” needle is used to identify
the pleural fluid. (C) Soft tipped guide wire in place after removal of the finder needle and the two separate small incisions
(0.5-2.0 cm) to create the subcutaneous tunnel. (D) Trocar attached to the distal end of the IPC, creating the subcutaneous
tunnel starting at the inferior incision. (E) Dilator with a peel-away sheath being placed over the guide wire using a modified
Seldinger technique. (F) IPC introducer being peeled away.
8 Adv Ther (2010) 27(5): 14.
incision. The trocar is removed and a dilator with
a peel-away sheath is placed over the guidewire
using a modified Seldinger technique (Figure 5E).
The dilator and wire are removed and the IPC is
threaded through the peel-away introducer into
the pleural space (Figure 5F). The introducer is
then removed and the incisions are sutured.
Initial drainage is performed immediately after
the procedure, and then subsequently the IPC
is drained using a dedicated vacuum bottle on a
daily basis or every other day.
We favor this modality of treatment for the
majority of our patients because of its minimally
invasive outpatient approach. It is less onerous
for patients with poor performance status and
rarely interferes with ongoing active cancer
treatments. Pleurodesis has been reported to
occur in 40% to 70% of patients, and it may
occur in as little as 7 days.22,28,30 Tremblay and
Michaud28 reported their experience of 250
IPCs. Lack of symptom control occurred in <4%
of patients. Complication rates were relatively
low. Infection was reported in <5% of cases
and symptomatic loculations in 8%. Using the
same database, they reported that in patients
that could otherwise tolerate other pleurodesis
modalities, such as talc slurry or poudrage, 70%
achieved pleurodesis with the IPC.30 In Warren
et al.’s retrospective analysis of 231 IPCs placed,29
the incidence of infection was only 2%, and
pleurodesis was achieved in about 54% of cases.
A recent retrospective cohort of 311 patients
with MPEs treated with IPC demonstrated that
pleurodesis was an independent predictor of
survival.31 Whether IPC induced pleurodesis or
pleurodesis per se (independent of treatment
modality) is responsible for this finding is unclear.
Unfortunately, no randomized controlled studies
have been performed to compare IPC and
talc pleurodesis, which remains the preferred
method of treatment of MPEs by many. Some
have attempted the injection of sclerosing
agents through the IPC such as bleomycin
or doxycycline, but no studies on the use of
sclerosing agents with IPC have been reported.
Our limited experience has demonstrated that
the instillation of talc through the IPC already
in place is limited by frequent clogging of the
catheter. Talc poudrage followed by the placement
of IPC instead of tube thoracostomy has not
been studied. A recent phase 1 study on the
administration of interferon (IFN) beta through
IPC for mesothelioma has shown promising
results.32 The IPC has also been shown to be
successful for the treatment of trapped lung in
the setting of MPE33 and refractory chylothorax34
situations in which alternative options are
limited. In terms of cost, Putnam et al.27 reported
in 2000 a hospital charge advantage of IPC
treatment for outpatients vs. tube thoracostomy
and pleurodesis (US $3391±1753 vs. $7830±4497,
respectively). However, when hospital charges
were evaluated from insertion date until
death or last follow-up the difference was not
statistically significant (US $21,161±32,617 vs.
$32,252±56,682, respectively). Based on current
evidence, IPC is clearly a valuable option for the
management of MPE.
Chest Tube Thoracostomy
The therapy most widely used for pleurodesis
in the palliation of MPE is inpatient tube
thoracostomy. A variety of chest tubes can be
used for thoracostomy ranging traditionally from
a 28-32 Fr,2 and with emerging data, the use of
small bore catheters such as a 14 Fr plastic catheter
have proven to be successful.35,36 The procedure
is usually performed at the bedside under local
anesthesia with or without conscious sedation
and cardiopulmonary monitoring. The patients
generally require an inpatient stay averaging
5-7 days. Pleurodesis is attempted after a chest
Adv Ther (2010) 27(5): 14.9
x-ray can confirm complete lung re-expansion
and the absence of trapped lung. Premedication
with narcotic analgesics or conscious sedation or
both are often administered to reduce the pain
and discomfort associated with the instillation
of most sclerosing agents, and lidocaine may be
administered intrapleurally as a local anesthetic
prior to the sclerosant. The sclerosing agent of
choice is instilled into the pleural space via the
chest tube, typically in a solution of 50-100 mL
of sterile saline. The chest tube is then clamped
for 1-2 hours. The tube is then reconnected to
–20 cm H2O suction until the 24-hour output
is less than 150 mL at which point it can be
removed. In the meta-analysis by Tan et al.37
techniques such as rolling the patient after
instillation of the sclerosing agent, protracted
drainage of >24 hours and use of larger bore chest
tubes were not associated with any substantial
Medical Thoracoscopy or Video-Assisted
Thoracic Surgery (VATS)
Medical thoracoscopy (pleuroscopy) refers to
a minimally invasive procedure which allows
the pulmonologist to examine the pleural space
in a spontaneously breathing patient with local
anesthesia and under conscious sedation.38
It typically involves the insertion of a rigid or
semirigid pleuroscope through a single port
into the pleural space (although more ports
may be used depending on the indication and
complexity of pleural disease), evacuation of
pleural fluid, biopsy of parietal pleural lesions
if indicated, and insufflation of sclerosant into
the pleural space. The procedure is safe and well
tolerated. Complications include subcutaneous
emphysema, fever, and pain. Major complications
such as severe sepsis, pulmonary embolism,
massive bleeding, and shock are infrequent38 and
death is extremely rare as a direct complication
of the procedure.39
VATS is performed in an operating room
almost exclusively under general anesthesia with
a double lumen endotracheal tube allowing for
single lung ventilation. Multiple ports of entry
are usually used allowing for better visualization
of the entire parietal and visceral pleurae and
better manipulation of the lung to perform
biopsies, lobectomies, and pneumonectomies if
necessary. Depending on the type of sclerosant
used and expected outcomes, response rates of
60% to 100% have been recorded for chemical
pleurodesis via pleuroscopy and VATS.38
Both VATS and pleuroscopy can be
performed under local or regional anesthesia
in an awake or moderately sedated patient or
under general anesthesia with one or two lung
ventilations.40 Local anesthesia in the form of
intercostal nerve blocks performed at the level
of the incision and two interspaces above and
below provide adequate procedural analgesia.
Both paravertebral blocks with a single dose
of local anesthetics41 and thoracic epidural
anesthesia42 have been shown to provide
adequate intraoperative anesthesia with the
added advantage of postoperative analgesia.
Noteworthy is that in an awake or moderately
sedated patient it is recommended that a high
FiO2 is delivered via a facemask to overcome the
shunt due to the loss in lung volume caused
by the unavoidable pneumothorax. If VATS is
planned to involve a more invasive or prolonged
procedure on the lung parenchyma than lung
biopsies or lobectomy, general anesthesia with
one lung ventilation using double lumen tube
or bronchial blockers is a more appropriate
Sclerosing Agents and Their Mode of Delivery
Pleurodesis may be performed at the bedside
using chest thoracostomy or thoracoscopically
10 Adv Ther (2010) 27(5): 14.
with pleuroscopy or VATS. The aim is to incite
chemical or mechanical irritation between
pleural layers resulting in inflammation
and fibrin deposition, which subsequently
results in pleural symphysis, preventing the
reaccumulation of fluid. A variety of agents have
been used as sclerosants for chemical pleurodesis,
some intended to cause an inflammatory
response and others that are supposed to act
as chemotherapeutic agents as well. This area
remains controversial with regards to the
sclerosing agent of choice and its method of
administration. Sterile asbestos-free talc is readily
available and relatively inexpensive. It can be
instilled into the pleural space via chest tube as
a suspension with sterile saline–talc slurry (TS)
or insufflated over the pleural surfaces during
thoracoscopy–therapeutic talc insufflation (TTI),
or poudrage. Talc consistently appears to be the
most effective agent. A 2004 Cochrane review43
compared the relative efficacy of different
sclerosing agents. Based on 10 studies with 308
patients who had pleurodesis for MPEs, it was
concluded that talc as slurry or poudrage was
the sclerosant of choice with a relative risk (RR)
of nonrecurrence of 1.34 (95% CI: 1.16, 1.55)
in favor of talc compared with bleomycin,
tetracycline, mustine, or tube drainage alone. In
the more recent meta-analysis by Tan et al.37 talc
was compared with other agents in nine studies
that included 341 patients. A modest reduction
in recurrence was found when talc was compared
with bleomycin (RR, 0.64; 95% CI: 0.34, 1.20).
Similar results were observed when talc was
compared with tetracycline (RR, 0.50; 95% CI:
The main advantages of TTI are that it allows
for complete fluid evacuation with visualization,
adhesion lysis when indicated, and more even
talc distribution during insufflations.38 Based on
the results of two small randomized controlled
trials,44,45 a preference for TTI “poudrage” over TS
“slurry” was demonstrated; however, subsequent
to these studies, Dresler et al.46 concluded from
their large randomized study with 501 patients
that there was no difference in freedom from
radiographic recurrence of MPE between the
two methods of talc delivery (TTI, 78%; TS,
71%) within 30 days. Respiratory complications
were greater with TTI in this study, although
symptoms of excess fatigue and pain were noted
among recipients of TS. Ad hoc subgroup analysis
revealed that patients with primary lung or
breast cancer had a higher success rate with TTI
(82%) than with talc slurry (67%). Our practice
is to consider clinically suitable patients with
good performance status (Eastern Cooperative
Oncology Group [ECOG] 0-2) who achieve
symptomatic relief with lung re-expansion after
initial thoracentesis, for pleurodesis with TTI as
the preferred modality of talc administration.5
The most common complications of
chemical pleurodesis are fever and pain.
Other rare complications include local site
infection, empyema, arrhythmias, cardiac arrest,
myocardial infarction, and hypotension.2 The
incidence of respiratory complications including
acute respiratory distress syndrome (ARDS)
associated with talc pleurodesis varies.47,48 The
exact mechanism whereby talc induces acute
lung injury is still not fully understood, however
it is hypothesized that this toxicity may result
from the systemic absorption of small diameter
talc particles (size <15 microns) used in ungraded
or mixed talc preparations through the parietal
pleural pores, generating a systemic inflammatory
response.49 This hypothesis is given credence
by the observation that most cases of ARDS
after talc use are reported in the US, where talc
particles have the smallest mean diameter, and
by a recent European multicenter prospective
study of 558 patients with MPE, none of whom
developed ARDS after receiving large-particle talc
pleurodesis (mean size 24.4 microns).50
Adv Ther (2010) 27(5): 14.11
Despite being the most studied, most readily
available, and most cost-effective agent there
are doubts about talc being the most efficacious
agent and its added safety concerns demand
the continued search for an ideal sclerosing
agent. Animal studies have demonstrated that
transforming growth factor (TGF-B) induces
pleurodesis by stimulating the mesothelial cells
to produce collagen. This type of pleurodesis
is more efficacious compared to that induced
by talc, doxycycline, or bleomycin, it occurs
faster and since it does not require pleural
surface “chemical injury” the inflammatory
indices in the pleural fluid after the intrapleural
administration of TGF-B are much lower than
those after doxycycline or talc.51,52 A recent
study53 demonstrated a significantly higher
effective rate of pleurodesis with intracavitary
injections of recombinant adenovirus p53 agent
with cisplatin compared with the control group
of cisplatin alone over a 4-week period. The
treatment group also had a significantly higher
quality of life and there were no significant
side effects associated with the regimen. Based
on the principle that bacterial infection of
the pleural space can induce pleurodesis by
inflammation, a recent report54 postulated that
therapeutically administered lipoteichoic acid
T (LTA-T) from the bacterial cell wall might
produce a similar effect and achieve control
of MPEs. In this phase 1 study involving 13
patients with MPEs, a therapeutic dose range
of LTA-T with mild toxicity was established and
there was preliminary evidence of pleurodesis
efficacy suggesting a role for this agent in the
Thoracoscopic mechanical pleurodesis is
achieved by mechanical pleural abrasion of
parietal and visceral pleura to induce petechial
bleeding resulting in a diffuse inflammatory
response. In a series of malignant effusions
from breast cancer,55 mechanical pleurodesis
demonstrated similar success rates compared to
Pleuroperitoneal shunts transfer pleural fluid
from the pleural space into the peritoneal cavity
when manually pumped56,57 These shunts have
a niche in the palliation of chylous effusions
refractory to pleurodesis and have been used
in the management of patients who cannot
achieve successful pleurodesis because of nonre-
expandable lung or for patients who cannot
undergo surgery. The procedure is safe and
effective in the hands of experienced operators,
with palliation achieved in 80% to 90% of
properly selected patients. However the use of
these shunts has declined over time due to the
high incidence of shunt blockage due to clotting
reported in up to 25%,56 infected shunts, and
quality of life issues as the shunts can be
burdensome on the patients due to frequent
Major surgical procedures for the management
of MPE such as parietal pleurectomy, decortication,
or pleuropneumonectomy are associated with
high mortality rates. Surgery should be reserved
for patients with prolonged life expectancy,
significant symptoms, and who either failed other
treatments such as pleurodesis or are not suitable
for such treatments (complicated effusion with
Algorithm for the Management of MPE
Based on Patients’ Performance Status
An algorithm for the management options
for MPE that we use at our institution is
presented in Figure 4. This algorithm takes
12 Adv Ther (2010) 27(5): 14.
into account aspects of both cancer type and
response to treatment and the patient’s overall
clinical status.58 A thorough clinical history and
exam, information regarding prior thoracenteses
including the volume of fluid evacuated, lung
re-expansion, symptom relief, and interval
between repeated taps is pertinent and helps
guide further therapy.
MPE is an indicator of advanced disease
and carries a poor prognosis especially in the
setting of lung cancer. A palliative rather than a
curative approach is often needed and significant
importance should be given to factors such as
response to thoracentesis and lung re-expansion,
the patient’s life expectancy, and performance
status. Social factors, personal preferences, and
the availability of specific treatment modalities
also impacts the therapeutic options and help
tailor a management plan. In clinically suitable
patients, pleurodesis with asbestos-free graded
large particle talc, preferably via thoracoscopic
poudrage or the use of chronic IPC offer
efficacious, cost-effective, and minimally invasive
options for the management of MPE. Both the use
of novel compounds to block VEGF and the use
of gene therapy either alone or in combination
with other palliative modalities is promising.
All authors contributed to this paper and
declare they received no funding or sponsorship
in relation to this paper.
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