Journal of the Egyptian Nat. Cancer Inst., Vol. 16, No. 3, Septemper: 188-194, 2004Pleurodesis as a Palliative Treatment of Advanced Lung Cancer with Malignant Pleural Effusion
ISMAIL A. MOURAD, M.D.; ABDEL RAHMAN M. ABDEL RAHMAN, M.D.; SHERIF A. AZIZ, M.D.;NAGI M. SABER, M.D. and FOUAD A. FOUAD, M.D. The Department of Surgery, NCI, Cairo University.ABSTRACT
nosed exudative pleural effusion in adults and
Purpose: This study was conducted to evaluate the
for 28-61% of pleural effusion in hospitalized
success rate of management of advanced. Lung cancer
patients [1]. Pleural effusion is a common com-
patients with malignant pleural effusion comparing talc
plication in patients with malignancy occurring
powder with tetracycline for pleurodesis.
in 50-70% in the course of their illness [2]. Patients and Methods: We report 60 patients with
lung cancer associated with malignant pleural effusion
Carcinoma of any organ can metastasize to
treated in the department of surgery NCI, Cairo University,
the pleura, however, carcinoma of the lung is
between January. 1998 and February, 2003.
the commonest malignancy to invade the pleura
Patients were Divided Into Three Groups:
and produce malignant and paramalignant pleu-
• Group I: Pleurodesis using tetracycline (20 patients).
ral effusion [3].
• Group II: Pleurodesis using talc slurry (20 patients).
Lung cancer accounts for nearly 36% of all
• Group III: Pleurodesis using talc insufflation (20 patients).
cases with malignant pleural effusion, when
Good response to pleurodesis is defined as no pleural
carcinoma of the lung metastazise to the pleura,
fluid re-accumulation or minimal pleural fluid re accumu-lation not causing symptoms or requiring further aspiration
both visceral and parietal surfaces tend to be
involved. The mechanisms involved in the for-mation of the malignant pleural effusion are:
Results: There were 34 males and 26 females, mean
age was 54 years with range of 42-66 years, right sidedeffusion was present in 32 patients (53%) and left sided
crovascular permeability of the pleural vesselsand. actual invasion of the pleura by malignant
Pathological subtypes were adenocarcinoma in 32
patients, squamous cell carcinoma in 18 and undifferenti-
cells [4].
ated carcinoma in 10 patients. In group I, 12 patients(60%) showed good response to intra pleural tetracycline,
15 patients (75%) responded in group II, while 17 patients
type to involve the pleura because of it’s pe-
(85%) showed good response in group III. Post pleurodesis
ripheral location and spread by contiguity, fol-
complications included, fever, chest pain and empyema.
lowed by anaplastic and undifferentiated types,
Conclusion: It is concluded from this study that
while squamous cell carcinoma rarely produce
thoracoscopic talc insufflation was an effective, easy and
effusion [5].
low cost method for producing pleurodesis in patientswith recurrent malignant pleural effusion and proved tobe better than talc slurry and tetracycline.
The diagnosis of malignant pleural effusion
is usually straight foreword, the only difficulty
Key Words: Lung - Malignant - Effusion - Pleurodesis.
exists when a patient without a known primary
INTRODUCTION
cancer present with an exudate [6].
Malignant pleural effusion represents the
On plain chest roentgenogram, evidence of
majority of effusions in patients over 60 years,
underlying lung cancer is often seen, but may
accounting for nearly 50% of the newly diag-
be obscured by effusion [7]. Pleurodesis as a Palliative Treatment of Advanced Lung Cancer
Thoracentesis is a simple and essential step
injected through the chest tube [6]. It’s mecha-
in the diagnosis of malignant pleural effusion,
nism of action is not well known, the main side
cytological examination of aspirated pleural fluid
effects of tetracycline pleurodesis are fever
is the gold standard for diagnosis [6]. At least
(33%) and pain (31%) [14]. Unfortunately, the
250ml of the pleural fluid should be obtained,
commercial unavailability of tetracycline has
small amount often contains too few cells for
prompted consideration of alternative agents
adequate study and more than one thoracentesis
for induction of pleurodesis, of those, talc pow-
may be required to prove that this effusion is
der is the commonest used agent. The mecha-
malignant [8]. Chromosomal analysis of the cells
nism by which it causes pleural fibrosis is not
found in pleural space is sometimes useful is
well understood, it’s often assumed that adhesion
suspicious cases, but it doesn’t provide
caused by talc powder is caused by an inflam-
histopathological diagnosis [8]. Closed pleural
matory reaction. The dose of talc powder re-
biopsy using Abram’s needle is indicated when
quired for effective pleurodesis is between 5-
first thoracentesis failed to yield positive results
10gms [15]. The methods of administration of
talc powder are: At the time of thoracotomy,through thoracoscopy (Powderage) and through
fluid including pleural biopsy do not provide adiagnosis, pleuroscopy and biopsy under direct
Talc related complications are, pain, fever,
vision is probably the last choice with a diag-
surgical emphysema, pleural thickening and
nosic yield of 93-96% [9].
acute pneumonitis [12].
Other methods of pleurodesis are intrapleural
to confirm the diagnosis with high diagnostic
yield approaching 100%, while the yield of
Laser pleurodesis and pleural abrasions.
pleural fluid cytology alone is 25% and that ofcombined pleural fluid cytology and closed
The aim of this work is to evaluate the pal-
pleural biopsy is 40% [10]. Patients with malig-
liative effect of management of malignant pleu-
nant pleural effusion have significantly short
ral effusion comparing talc powder (either
survival and the treatment is usually palliative
through thoracoscopic insuffilation or injection
[11], it should be remembered that not all ma-
through chest tube) versus tetracycline for pleu-
lignant pleural effusion require treatment, the
criteria for instituting therapy for malignant
PATIENTS AND METHODS
effusion are based on the frequency and patternof reacumulation in addition to the degree of
Sixty patients with malignant pleural effu-
sion from lung primaries underwent pleurodesisusing thoracoscopic talc insuffilation, talc slurry
Pleurodesis is the process by which fibrosis
and tetracycline as a palliative treatment for
is induced between the visceral and parietal
recurrent malignant pleural effusion between
pleurae in order to obliterate the pleural space.
It is the most commonly used method for palli- ation of malignant pleural effusion [12].
A variety of agents could be used to induce
• Full history taking and full clinical examina-
pleurodesis and are classified into two broad
categories according to their modes of action,
• Chest radiographs, posteroanterior and lateral
cytostatic agents (that control the effusion by
reducing the tumor volume) and sclerosants
(which produce a chemical pleurisy that lead
• Documented malignant pleural effusion of
to formation of adhesions and subsequent oblit-
eration of the pleural space) [13]. Patients were Divided Into 3 Groups:
broad spectrum antibiotic can be used with a
Group I: Included 20 patients subjected to pleu-
dose of one gram in 50ml of normal saline
Group II: Included 20 patients in whom talc
powder slurry was the method usedfor pleurodesis.
Sixty patients with malignant pleural effu-
sion were included in this study. There were
Group III: Included 20 patients, in whom tho-
Thirty-four males and twenty six females, the
mean age was 54 years with range between 42-
66 years, right sided effusion was present in 32patients (53%) and left sided effusion in 28
adenocarcinoma in 32 patients, squamous cell
in 18 and undifferentiated carcinoma in 10
- Chest tube insertion to drain the pleural
effusion and after complete evacuation, 20-
Table (1) shows the success rate of different
25mg/kg of tetracycline is diluted in 50ml nor-
types of pleurodesis. In group I twelve patients
mal saline and instilled in the chest tube.
(60%) showed good response to intrapleuraltetracycline. Eight patients (40%) showed treat-
ment failure i.e. there were rapid reaccumulation
The patients were premediacted with atro-
of the pleural fluid. Treatment related compli-
cations developed in 6 patients (30%).
After insertion of the chest tube and the
output is less than 50ml/24hrs, 5-10gm of puri-fied talc powder was mixed with 100ml normal
saline and 10ml of 2% lidocaine to form sus-
(75%) and treatment failure developed in 5.
pension which was instilled into the chest tube,
Complications were observed in 3 patients.
Figs. (2,3) show massive right sided pleuraleffusion before and one month following talc
Ten cc of 2% xylocain is ingected locally at
the site of port introduction, General anaesthesia
good response to intrapleural talc insuffilation,
Zero angled telescope was used, suctioning
the remaining 3 patients failed to respond to
the pleural effusion, a powder blower was filled
treatment. Figs. (4,5) show massive left sided
with 5-10gm of purified talc powder and insuf-
pleural effusion befor and one month after
flated into the pleural cavity followed by re-
thoracoscopic talc powder insuffilation. Four
moval of the chest tube when daily output was
patients developed postoperative complications.
Table (2) presents the complication rate ofdifferent types of pleurodesis.
Chi-square test was used to compare inde-
Although the success rate of talc insufflation
is higher than that of talc slurry (85% versus
After discharge all patients were followed-
75%), and the success rate of talc slurry is better
up every 2 weeks in the 1st month by chest
than tetracycline pleurodesis (75% versus 60%),
radiograph and then monthly interval till death.
but these differences is not statistically signif-icant (p value = 0.2).
fluid reaccumulation during the follow-up period
Also the complication rate of tetracycline
or pleural fluid reaccumulation not causing
pleurodesis was higher than that of talc powder
symptoms or requiring further aspiration for
pleurodesis, yet this difference is not statistically
Pleurodesis as a Palliative Treatment of Advanced Lung Cancer
Fig. (2): Massive right sided effusion.
Fig. (3): One month following talc slurry.
Fig. (4): Massive left sided effusion.
Fig. (5): One month post thoracoscopic talc insufillation.
Table (1): Results of different types of pleurodesis.
Table (2): complication rate of different types of pleurodesis. DISCUSSION
The use of thoracoscopy in talc pleurodesis
helps in lysis of adhesions when necessary,
insures equal distribution of talc over the pleural
tients with malignant pleural effusion may live
surfaces and assesses the effect of positive
for months or even years. The quality of life
pressure ventilation on trapped lung to look for
for such patients is therefore of much importance
it’s ability to re-inflate. These advantages con-
and the aim of treatment should be beside the
tributes to the high success rate of thoracoscopic
management of the primary disease, is to relieve
talc powderage if compared with the results
symptoms, and to decrease the discomfort of
the patient. The necessity for repeated aspira-tions to relieve dyspnea is both physically and
psychologically traumatic to the patient and a
success rate after using talc slurry in 28 pateints
burden to the physician [16].
with malignant pleural effusion. compared with75% response rate in our study. The procedure
was well tolerated without any side effects [15].
become the preferred treatment for symptomaticmalignant pleural effusion. Many sclerosing
The results obtained by Shedbalker et al.
agents have been tried for creating pleural sym-
(1971), were comparable to the results of this
phasis with variable degrees of success. In this
study. They used talc. Slurry in 28 patients with
study, sixty patients were available for follow-
complete success in 20 patients (71.4%), partial
up, in group I (pleurodesis by tetracycline) 12
patients (60%) showed good response, in group
II (pleurodesis by talc slurry) 15 patients (75%)
These low results were contributed by the
showed good response while in group III (pleu-
authors to be due to clumping of talc over the
rodesis by talc insuffilation) 17 patients (85%)
pleural surfaces [19].
Erickson et al. (2002), showed response rate
The success rate of thoracoscopic talc pow-
to tube thoracostomy of 77% compaired to100%
derage achieved in this study is the same as that
success rate following thoracoscopic talc pow-
obtained by Weissberg 1993 who reported a
derage [20].
success rate of 84.5% after performing thoraco-scopic talc pleurodesis in 169 patients with
malignant pleural effusion [9].
thoracoscopic talc powderage is that in talcslurry, talc is injected into the pleural cavity
after making sure that the lung is fully expanded,
rate after performing thoracoscopic talc insuf-
in contrast to the thoracoscopic talc powderage
flation in 14 patients with malignant pleural
in which talc is insuffilated before inflation of
effusion [6].
the lung takes place, thus the risk of non inflationof the lung as a cause of failure of thoracoscopic
Brungel et al. (2002), achieved success rate
talc powderage can be abolished if talc slurry
of 95.6% following thoracoscopic talc pleurod-
esis, with failure in 2 patients out of 46 [17]. Cardillo et al. (2002) reported success rate of
The results obtained after the use of sclero-
93% (558 out of 600) after thoracoscopic talc
sants other than talc are generally lower. Bayly
pleurodesis [18].
et al. (1978), reported a success rate of tetracy-
Pleurodesis as a Palliative Treatment of Advanced Lung Cancer
cline pleurodesis of 67% in 12 patients with
Cardillo et al. (2002), reported this compli-
malignant pleural effusion [21], which is com-
cation in 3.1% of patients following thoraco-
parable to our results. Tag El Dien et al. (1985),
scopic talc powderage [18].
reported a success rate of 60% after tetracyclinepleurodesis in 12 patients with malignant pleural
effusion [14].
available in Egypt, we have not used talc as asclerosant except in patients with malignant
pleural effusion, as the life expectancy of such
powder as a pleural sclerosant is its easy use
patients is much less than the latent period
and a fewer side effects other than fever and
needed for the development of asbestos-related
neoplasia. There has been some concern aboutthe use of talc pleurodesis in patients with
benign disease, as respiratory functions may be
mended by many authors, Hartman et al. (1993),
reported that the intrapleural administration of3-6gms of aerosolized talc controlled the pleural
Lang and associates (1988), observed only
effusion in 95% of patients in their series.
mild restrictive impairment 22-35 years after
comparable results have also been obtained
talc pleurodesis for spontaneous pneumothorax,
after performing talc slurry [22]. Webb and
total lung capacity averaged 89% of the predict-
associates (1992), reported 100% success rate
ed value [26]. This complication needs long
of talc slurry, after using 5gms of talc and 3gms
follow-up period and was not studied in this
of thymol iodine in 50ml saline solution [15].
Many complication have been noticed after
the use of talc as a pleural sclerosant. The degree
Talc powder is the most effective pleural
of pain associated with talc has been variously
sclerosant. It has the best results among all
reported from non existing to severe. Walke-
chemical agents used. The administration of
Renard and colleagues (1994), reported a pleu-
talc during thoracoscopy (powderage), is better
ritic chest pain after thoracoscopic talc insuf-
than talc slurry. Thoracoscopy provides better
flation in 9 out of 131 patients (7%) with ma-
visualization of the pleural cavity, thus ensuring
lignant pleural effusion that responded to mild
equal distribution of talc, allows biopsy taking
analgesics [23]. In our study although all patients
if needed, cutting of adhesions if present and
complained of mild pain related to thoracoscopic
coagulation of any bleeding vessel. The least
procedure and intercostal tube drainage that
side effects were reported with thoracoscopic
responded to simple analgesics, only five pa-
talc powderage. Talc dusting during thoracoto-
tients (12.5%) experienced severe chest pain
my, although has a better results, carries the
which necessitates the use of strong analgesics.
risk of major operation and so, has no advantage
Fever following talc pleurodesis is common.
over the thoracoscopic talc powderage. Befor
Aelony and co workers (1991), noted tempera-
performing thoracoscopic talc powderage the
ture elevation varying from low to high grade
ability of the lung to reexpand should first be
in 21 out of 39 patients (54%) [24] which is
detected by noting relief of dyspnea and a ra-
comparable to 63% percent incidence noted in
diological evidence of re-inflation after a simple
the study of Lisa and collegues [11]. They stated
thracocentesis has been carried out. Also, a C.T.
that temperature elevation was not a predictor
of the chest to exclude pleural thickening and
of other complications such as respiratory failure
fiber-optic bronchoscopy to exclude endobron-
or empyema. The incidence of fever after the
chial lesion that will prevent lung areation are
use of talc pleurodesis is 5%, which is much
very important for proper selection of cases.
lower than that described in above mentioned
The procedure under local anesthesia is much
easier, well tolerated by the patient and hasfewer side effects.
incidence of empyema of 3% after performing
Any pateint with malignant pleural effusion,
thoracoscopic talc powderage in 163 patients
can get benefit of this procedure provided that
with malignant pleural effusion [25]. Two pa-
the effusion is drained completely and the lung
tients (5%) developed empyema in our study.
is fully expanded after evacuation of the effusion.
The difference in success and complication
pleural tetracycline in the management of malignant
rates of different types of pleural sclerosants
pleural effusion. Recent advances in chemotherapy,
did not reach a statistical significant value,
1985 proceedings of the 14th inter. Congress of che-motherapy. Koyto Japan.
however, there is a trend to use talc powder forpluerodesis in malignant pleural effusion pref-
15- Webb WR, Ozmen V, Moulder PV, Shabbang and
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Breaux J. Iodized talc pleurodesis or the treatment ofpleural effusions. J Thorac Cardiovasc Surg. 1992,
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1. INTRODUÇÃO Esta espécie é uma das mais antigas em uso popular, referidas desde a ancestralidade na fitoterapia chinesa. Essa marcante presença despertou o interesse da ciência e o ginseng caracteriza-se como uma das espécies mais estudadas em todo o mundo, constituindo-se num claro exemplo de fitoterápico com reconhecimento experimental e científico. Corresponde às raízes d
Nata a Rimini, ha intrapreso in giovane età gli studi musicali, diplomandosi poi a pieni voti in Canto e in Musica Vocale da Camera presso il Conservatorio Verdi di Milano, sotto la guida di Daniela Uccello; soprano con voce duttile ed estesa, ha saputo unire musicalità ed espressività teatrale, tanto da poter affrontare generi e stili diversi, specializzandosi nel repertorio barocco e sette