Malignant pleural effusion

Scope
 Definition
 Causes
 Pathophysiology
 Clinical presentation
 Investigation
 Diagnosis
 Management
 Treatment
Definition
 Malignant Pleural Effusion
 Paramaliganant Pleural Effusion
Malignant Pleural Effusion
 Condition that found malignant cell or
pleural tissue in pleural fluid by fine
needle aspiration, needle biopsy or
Surgery
Malignant Pleural Effusion
 Condition that found malignant cell or
pleural tissue in pleural fluid by fine
needle aspiration, needle biopsy or
Surgery
 Most common of MPE is metastasis of
cancer
Paramaliganant pleural effusion
 Condition that cancer pts have pleural effusion but
fluid do not found malignant cell
 Causing by cancar metastasis, systemic response
or compilcations

of
Chemotherapy or Radiation or Surgery
Causes of MPE
Pathophysiology of MPE
 Direct result
 Indirect result
Direct result
 pleural metastasis with increasing permeability
 pleural metastasis with obstruction of pleural
lymphatic vessels
 mediastinal lymph node involvement with
decreased pleural lymphatic drainage
 bronchial obstruction (decrease pleural
pressure)
 Pericardial involvement
Direct result
 pleural metastasis with increasing permeability
 pleural metastasis with obstruction of pleural
lymphatic vessels
 mediastinal lymph node involvement with
decreased pleural lymphatic drainage
 bronchial obstruction (decrease pleural
pressure)
 Pericardial involvement
Lymphatic obstruction
 Postmortem studies, the presene of
pleural effusion is correlated with
metastases to lymph node
 complete blockage of lymphatics, the
rate of pleural fluid accumulation should
only be 15 ml/day
 Lymphatic obstruction would be
transudate , it is always an exudate
Direct result
 pleural metastasis with increasing permeability
 pleural metastasis with obstruction of pleural
lymphatic vessels
 mediastinal lymph node involvement with
decreased pleural lymphatic drainage
 brochial obstruction (decrease pleural
pressure)
 Pericardial involvement
Increasing permeability
 In series of Leckie and Tothrill,explain that the pts w
bronchogenic carcinoma w metastasis disease to the
pleural increased permeability of the pleura
 pts w bronchogenic had a secondary highest amount
of protein entering of plural space
 Due to the production of vascular endothelial growth
factor (VEGF)
 The madian level of VEGF in pleural effusions
secondary to malignancy is higher than that in pts w
effusion secondary to inflammatory disease
 The pleural fluid VEGF levels are also higher in
haemorrhagic MPE than in non-haemorrhagic MPE
Direct result
 pleural metastasis with increasing permeability
 pleural metastasis with obstruction of pleural
lymphatic vessels
 mediastinal lymph node involvement with
decreased pleural lymphatic drainage
 bronchial obstruction (decrease pleural
pressure)
 Pericardial involvement
Bronchial obstruction
 When neoplasms obs the mainstem
bronchus or a lobar bronchus, lung
distal to the obs becomes ateletatic
 Remaining lung must overexpand or
the ipsilateral hemithrox must
contract to compensate for the loss
volume of the atelectatic lung
 More negative pleural pressure to be
causes of pleural fluid to accumulate
Direct result
 pleural metastasis with increasing permeability
 pleural metastasis with obstruction of pleural
lymphatic vessels
 mediastinal lymph node involvement with
decreased pleural lymphatic drainage
 bronchial obstruction (decrease pleural
pressure)
 Pericardial involvement
Pericardial involvement
 When Pericardial effusion is caused
by such involvement and hydrostatic
pressure become elevated in the
systemic and pulmonary circulation
 Transudataive pleural effusion may
result
Indirect result
 Hypoprotenimia
 Postobstructive pneumonitis
 Pulmonary embolism
 Postradiation therapy
 Postchemotherapy
-Methotrexate
-Procabazine
-Cyclophosphamide
-Mitomycin
-Bleomycin
 Clinical presentation
 Dysnea (MC) 50%
 Weight loss 32%
 Malaise 21 %
 Anorexia 14%
Symptomatic Comparision MPE and benign PE
 Dull chest pain (34% vs 11%)
 Pleuratic chest pain( 24% vs 51%)
 Temperature elevation ( 37% vs 73%)
Investigation
 Chest radiograph
 CT scan
 Pleural fluid examination
Chest radiographs
 Pleural effusion varies from a few
milliliters to several liters,with the
fluid occupying the entre hemithorax
and shifting the mediastinum to the
contralateral side
 Most common
cause of
massive
pleural
effusion
 Series:
(entire hemithorax)
67%
(>2/3 hemithorax)
55%
Chest radiographs
 Almost All pts w plural effusion secondary
to bronchogenic carcinoma have pulmonary
abnormality beside the effusion
 Almost all pts w plural effusion secondary
to lymphoma have mediastinal lymph node
involvement , but not always evident in
CXR
 The chest radiographs of patient with
pleural effusions due to malignant tumors
other than lung carcinoma or lymphoma
often reveal only a pleural effusion
 Underdiagnosis for CXR
CT scan
 Useful in indicating whether the effusion
has a benign or malignancy etiology
 Yilmaz et al reported the following
suggestive of malignancy
 Pleural nodularity
 Pleural rind
 Mediastinal pleural invovlement
 Pleural thickening > 1 cm
But this series are more large %
mesothelioma,which are more likely to have
abnormality of the pleural surfaces
CT scan
 Concurrent abnormalities are
frequently present in the pts with
documented MPE
 The incidence of concurrent abnormailty
 Percardial effusion 3%
 Pericardial thickinening 14%
 Mediastinal adenopathy 43 %
 Chest wall involvement 12 %
 Lymphangitic carcinoma 7 %
 Suspeciuos lung masses, nodules or infiltrate 53 %
Pleural fluid
 Can be found in serous,serosanguinous and
bloody fluids but most common is
serosanguinous or bloody fluid
(RBCs>100,000 /mm3)
 Most common is the exudate with protein
and lactate dehydrogenase-rich
 If be transudate, be considered to lymphatic
obstruction or bronchial obstruction or with
condition of heart failure
 Most pleural effusions thet meet exudate
criteria by the LDH but not by the protien
level are malignant pleural effusion
Pleural fluid
 WBC count is varible between 1,000-
10,000 cell/mm3
 Predominant cell in the pleural fluid
differential white cell count
 Lymphocyte ~45 %
 Monocyte ~40 %
 Polymorphonuclear leukocyte ~15%
 Pleural fluid Eosinophilia ~>10%(old)
 Pleural fluid Eosinophilia not associated with
pleural air,blood or malignancy
Pleural fluid
 Pleural fluid glucose level <60 mg/dl in
appoximately 15-20% of MPE
 Low pleural fluid glucose level in
association with MPE with indicates that the
pts high tumor burden in pleural space
 Cytology and pleural biospy are more likely
positve in pts with low-glucose pleural
effusion
 Pts w low-glucose pleural effusion have
indicated worsen prognosis
 Caused by impaired glucose transfer from
blood to pleural space or Increased glucose
Pleural fluid
 1/3 of pts with malignant pleural effusion have a
pleural fluid pH below 7.3
 Short survival than individuals with mPE and a pH
level above than 7.3
 Caused by acid production by the pleural fluid or
pleura and a block the movement of the carbon
dioxide out of the pleural space
 Appoximately 10% of MPE have an elevated pleural
fluid amylase level. Usually primary tumor is not in
the pancreas when analysis isoenzymes has
demonstrated that amylase is the salivary isoenzyme
rather than pancreatic isoenzyme.
Diagnosis
 Cytologic Examination
 Immunohistrochemical test
 Tumor markers
 Pleural biopsy
 Observation,Thoracoscopy or an Open
Thoracotomy
Cytologic Examination
 The Easiest way to estabish the diagnosis
 Percentage of cases in which cytologic study
establishes the diagnosis of MPE range from 40-87%
 Three separate pleural fluid specimen from MPE
should expect a positve diagnosis is approximately
80%
 Incidence of positve result depends on the primary
tumor , Most case metastatic adenocarcinoma
diagnosed by fluid cytology. Positive results are
uncommon with squamous cell carcinoma because the
pleural effusion are usually due to bronchial
obstruction or lymphatic blokade
 With lymphoma,the cytologic test positve ~25% in
HKL and NHKL~50-60%
 Can identified the histological type, but not identified
the primary site of tumor
Immunohistochemical tests
 Using a monoclonal antibodies to
distinguish malignant or benign antigen
 Metastic adenocarcinoma tend to positive
Carcinoembyonic antigen (CEA), MOC-3,1 ,
B72.3 , Ber-ER4,BG-8
 Malignant mesothelial cell and benign
mesothelial cell stain positive with calrinin
and cytokeratin
 Use in unkonwn primary
Tumor marker
 Tumor marker evaluated have
included CEA,CA15-3,19-9 etc.
 Some the benign and malignant is
overlap
Pleural biopsy
 The percentge of positive plural biopsy in
pts MPE range from 39% to 75%
 Plueral biospy is lower diadnosis yield than
of pleural fluid cytologic examination
 Because ~ 50% of MPE is not involved
costal parietal pleura
 If the cytology is negative and
thorocoscopy in unavailble or an outpatient
procedure is desired, consideration can be
give to perfrom needle biopsy of the pleura
 Alternative to use CT-quided cutiing-needle
biopsy
Thoracoscopy and Open
Thracotomy
 Establish the diagnosis of malignancy
in ~90%
 If Thoracoscopy is not available, an
alternative appoach is to perfrom a
thoracotomy with open biopsy of the
pleura or to perfrom needle biopsy
mangement
mangement
teatment
 Systemic chemotherapy
 Intrapleural chemotherapy
 Mediastinal Radiation
 Symtomatic treatment
 Repeated thoracenteses
 Indewelling pleural Catheter
 Pleurodosis
 Pleuroperitoneal shunt
 Pleurectomy
Systmic chemotherapy
 Cisplatin,ifosfamide,irinotecan for NSCLC and pleural
effusion
-Complete disappearance of effusion 30%
-Partial resolution 21%
-mean survival of 362 days
 1st Chemotherapy+ bevacizumab(anti-VEGF antibody)
-because angiogensis is necessary for pleurodosis
-statistically and clinically significant surrival
adventage in pts w NSCLC
 Metastasic breast CA,lymphoma
Intrapleural chemotherpy
 Intrapleural chemotherapy decreased the number of
tumor cells in the pleural space, the rate of plural fluid
fromation should be decrease.
 One study use cisplatin and gemcitabine by
intrapleural chemotheray in NSCLC found that overall
respone rate was 55%(complete 7%&partial 48%)
 Staphylococcus aureus superantigen(SSAg)(T-cell
stimulant)
- the effusion is complete controlled in some pts and
meadian surrival was 7 month
 Rituximab ,monoclonal antibody directed agianst the CD
20 antigen of B-cell is effective in controlling Non-
Hodgkin’s lymphoma
 Intreferon-gramma,tumor necrosis factor,interleukin-2
Mediastinal Radiation
 Chylothrox, the throracic duct
involved
 Tumor type that resistant the
chemotherapy
 Lymphoma,metastasic Carcinoma
Symtomatic treatment
 Symtomatic MPE with chest pain and
shortness of breath
-Suffiient analgestics should be control
the pain (not worry about narcotic
addiction)
 Symtomatic MPE with dyspnea
- Should be given opiates or oxygen,or
both
Repeated thoracenteses
 Temporary Supportive treatment for
dyspnea
 Recurrent for 1-3 day, After tapping
 Compilcation
 Pneumothorax tumor implantation
 Tapping lung syndrome
Indwelling pleural Catheter(Pleurx)
 Pts with recurrent pleural effusion to fluid drained without having
to return to the hosipital
 Applied with local anesthasia by pulmonologists,radiologists and
Surgeons
 Place in chest wall tunnel 5 to 8 cm in length
 Has a spacial valve on distal end to prevent gas or fluid passing in
ether direction
 Draining the fluid though an external tube into vaccum bottles
 Tremblay and Michaud reported that tunneled cathete insertion
resulted in complete symptom control in 38.8%,patrial control
3.6%,no control inb 3.6%
 Spontaneous pleurodesis ocurred after 43% of the procedures
 Be considered as the first-line treatment option in mangement of
pts w MPE
 Pleural fluid production of > 1,000 ml fluid/week after place it for
7-14 days have attempt at chemical pleurodosis through the pleual
catheter.
Morbidty of Pleur X
 Fever
 Pneumothorax
 Misplacement of the catheter
 Reexpansion pulmonary edema
Compilcation (prolonged use)
 Empyema
 Tumor seeding of catheter tract
 Loculation of the plural effusion
Pleurodesis
 Pts w MPE are not candidates for tunneled
catheter or systemic chemotherapy and do
not have a chylothrox
 Procedure consider for pts whom systemic
chemotherapy or mediastinal radiation
failed
 Use in symtomatic MPE: only dyspnea is
likely to be relived with pleurodesis
 Not to improve duration of pts’ life, but also
improve the quality of life
Pleurodesis
 Before Pleurodesis should mediastinal CXR,
if the mediastinum shifted toward the side
of the pleural effusion, the plural pressure
is more negative on side of effusion
 Should bronchoscopy to r/o neoplastic
bronchial obstruction. If found,should be
considered to relief by radiotherapy,laser
therapy or an endotrachial stent
 Symtomatic pts with relieved by
thoracentesis should be considered to use
PleurX,Pleuroperitoneal shunt
Technique of Pleurodesis
 Tube thoracostomy w sclerotherapy
 Surgery
 Thoracoscopy w Pleurodesis
 Open thoracoscopy w Pleurodesis
Pleuroperitoneal shunt
 Use in condition of tapping lung syndrome
-Trappinng lung syndrome-
The prolonged accumulation of pleural secretion to from
fibrin debris or adhesion make lung no full expansion
 Is a device consist of two catheter connected with
pump chamber(1.5ml)
Two-one way valves in pump chamber control only flow
from the pleural space to peritoneal cavity
 On evidence of peritoneal tumor seeding but can be
found the tumor seeding on surgical site
Pleurectomy
 Major- risk operation(10-20)%
 Use in pts that expected life longer
than 6 months
 No response for pleurosis
 Breast CA