Case Presentation - Malignant Pleural Effusion Edited

• No greater opportunity, responsibility, or
obligation can fall to the lot of a human being

than to become a physician. In the care of
the suffering, [the physician] needs technical
skill, scientific knowledge, and human
understanding. . . . Tact, sympathy, and
understanding are expected of the physician,
for the patient is no mere collection of
symptoms, signs, disordered functions,
damaged organs, and disturbed emotions.
[The patient] is human, fearful, and hopeful,
seeking relief, help, and reassurance.
• –Harrison's Principles of Internal Medicine,
1950
Malignant Pleural Effusion
Christian Gallardo, MD
Objectives
• To discuss a case of Pleural effusion and
its approach.
• To discuss the approach to Transudative
and Exudative Pleural Effusion using the
Light’s Criteria.
• To discuss the Diagnosis and Treatment
strategies for Malignant Mesothelioma
General Data
• F.E.
• 74/M
• Las Pinas
• Roman Catholic
Chief Complaint
Difficulty of
Breathing
History of Present Illness
2 ●
●
Cough, non productive
No Hemoptysis
No Colds
weeks
●
No Fever
●
No Chest Pain
●
No DOB
●
No Orthopnea, No PND
PTA
●
No Consult done
●
No Medications taken
●
Still with non productive cough
●
Chest pain, G4/10
1 week
●
pricking in character,
●
radiating to the shoulder, < 1 minute,
precipitated by breathing
●
No Orthopnea, No PND
●
No Hemoptysis
PTA
●
No swelling of the legs
●
Consulted
●
Medications:
●
Cefixime 200mg BID
●
Ambroxol 75mg OD
C
Few ●
Persistence of increased
severity of chest pain and non
productive coughing
O
N
Hours Difficulty of Breathing
●
●
Fever, One episode, Low S
Grade (38C)
U
PTA
●
No chills
●
No colds
L
T
Past Medical History
• Hypertension Stage II
• Maintained on Losartan 50mg/tab 1 tab OD
• Type 2 DM
• Maintained on Metformin 500mg/ tab 1 tab OD
• CAD
• Maintained on Clopidogrel 75mg/tab 1 tab OD
Trimetazidine 35mg 1 tab TID
Simvastatin 40mg OD HS
• S/P Coronary Angiogram (7/26/2008) - UPHR
• S/P PTCA of LAD (7/26/2008) - UPHR
• S/P IABP Insertion R Femoral Artery (7/26/2008) -UPHR
• S/P ORIF Right Forearm (1994) - UPHR
• S/P Cholecystectomy (1982) - ?
Family Medical History
• (-) Hypertension
• (-) DM
• (-) Bronchial Asthma
• (-) Heart Disease
• (-) Thyroid disease
• (-) Blood Dyscrasia
• (-) Cancer
Personal and Social History
• (-) Non smoker
• (-) Alcoholic beverage drinker
• Retired Office Employee
Review of Systems
• General: (+) Weight Loss 20% for 2 months
• HEENT: (-) blurring of visions, (-) sorethroat
• Gastroenterology: (-) abdominal pain, (-) diarrhea, (-)
constipation, (-) melena, (-) hematochazia
• GUT: (-) dysuria, (-) oliguria (-)anuria
• Endocrinology: (-) polyuria, polydipsia, polyphagia,
• Musculoskeletal: (-) myalgia
• Hematology: (-)easy brusability
• Neurology: (-) neuropathy, (-)seizures
Physical Examination
• General:
• conscious, coherent, not in respiratory distress
• Vital Signs:
• BP: 110/70mmHg RR:24 cpm
• CR: 101 bpm, regular T: 38. 1 C
• Skin:
• Good skin turgor, no rashes, no jaundice
• HEENT:
• Anicteric sclera, pink palpebral conjunctivae, no
tonsillopharyngeal congestion, no nasoaural
discharge, no cervicolymphadenopathy, JVP at
9 cm
Physical Examination
• Chest and Lung:
• Symmetrical chest expansion, no lagging, no
retractions, dull at percussion at left base,
decreased breath sounds at left base,
decreased tactile and vocal fremitus at left
base, fine crackles at left base
• Heart:
• Adynamic precordium, normal rate, regular rhythm, PMI at 6 th
ICS at MCL, normal S1 and S2, (-) S3 and S4, no murmurs.
• Abdomen:
• Flat, soft, normoactive bowel sounds, non-tender. Liver span:
8 cm, Intact Traube’s space, No Organomegaly
• Extremities:
• Full pulses, no edema, extremities with full range of motion
Neurological Examination
• Oriented to time, person and place, (-) dysmetria
• (-) dysdiadochokinesia, can do FTNT, (-) nystagmus
• Cranial Nerves:
• I: can smell
• II: 2-3mm PERTL, Fundoscopy: (+) ROR, Clear
Media, Distinct Cup borders, CDR: 1:3, AVR: 2:3, No
exudates, No Hemorrhage
• III, IV, VI: Full EOM
• V: (+) bilateral corneal reflex, good masseter tone
• VII: (-) facial asymmetry
• VIII: can hear
• IX, X: (+) gag Reflex
• XI: can equally shrug shoulder
• XII: no tongue deviation
Neurological Examination
5/5 5/5 100% 100% ++ ++
100% ++ ++
5/5 5/5 100%
5/5 5/5
100% 100%
++ ++
100%
5/5 5/5
100%
++ ++
• (-) Babinski (-) Brudzinski

• (-) Nuchal Rigidity
Salient Features
• Male
• 74 years old
• Cough, non productive
• Chest Pain, pricking in character
• Shortness of Breath
• Hypertensive and Diabetic
• Known with CAD
• Non- Smoker
• Chest and Lung:
• Symmetrical chest expansion, no lagging, no
retractions, dull at percussion at left base, decreased
breath sounds at left base, decreased tactile and
vocal fremitus at left base, fine crackles at left base
Differential Diagnosis
Dyspnea
Cardiac Pul monary
Pleural Effusion
Acute Coronary Syndrome Congestive Heart Failure

Pneumonia PTB
PulmoMalignancy
Embolism
Admitting Impression
• Pleural Effusion Probably secondary to
• Parapneumonic process
• PTB
• Malignancy
• HCVD, Congestive Heart Failure NYHC I
Secondary to CAD
• S/P AMI
• S/P PTCA
• DM Type 2
Chest Xray Cardiomagaly
CBC Course in the Wards
Atheromatous Aorta
Hematocrit 31Effusion,
•Pleural Left
1 st
Hospital
12 lead ECG Day VS: 110/70 CR: 104 RR: 23 T: 38.1
Sinus Tachycardia
Serum
Left Lateral Sodium
Hemoglobin 113 135 mmol/L
• Venoclysis
PresenceLeft Atrial Enlargement
of Shifting Density Towards
WBC • Diagnostics
14.5Complete Right Bundle
Serum
Decubitus Potassium 4.5mmol/L
the• Dependent Portion of the Right
Cardiac Enzymes were not Requested
Segmenters 86 Branch Block of Pleural
Serum BUN •Hemithorax, 4.5
Therapeutics
Suggestive
mmol/L
Lymphocytes Fluid
• 1.06
Anterior Wall Myocardial
Serum Creatinine Paracetamol
68 umol/L
Infarction,
+ tramadol (Dolcet)
Old
• 2. Salbutamol + Ipratropium Br
SGPT
Monocytes 07 49 U/L
(Combivent) q 8 hrs.
CBG
Eosinophils • 3.01
Ambroxol 75mg 1 tab OD
112 mg/dL
• 4. Paracetamol 500mg 1 tab q 4 hrs
Platelet Count 373
for fever
• 5. Paracetamol 300mg 1 ampule Q4
hrs for fever
Anatomy of Pleura
• The pleura
• Serous membrane that covers the lung
parenchyma, the mediastinum, the
diaphragm, and the rib cage.
• Visceral pleura
• Covers the lung parenchyma, not only
at its points of contact with the chest
wall, diaphragm, and mediastinum but
also in the inter-lobar fissures.
Light, Richard. Pleural Diseases.

5th Edition. 2007©
Anatomy of Pleura
• Parietal pleura
• Lines the inside of the thoracic cavities.
• Subdivided
• Costal
• Mediastinal
• Diaphragmatic
• The visceral and the parietal pleura meet
at the lung root.

5th Edition. 2007©
Anatomy of Pleura
• Pleural fluid
• Normally present between the parietal
and the visceral pleura.
• Acts as a lubricant and
• Allows the visceral pleura covering the
lung to slide along the parietal pleura
lining the thoracic cavity during
respiratory movements.

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Physiology of Pleural Fluid
• It is believed that the fluid that normally
enters the pleural space originates in the
capillaries in the parietal pleura
• Human beings
• Amount of pleural fluid formed daily in a
50-kg individual = approximately 15 mL
• The mean lymphatic flow from one
pleural space = 0.40 mL/kg/hour

5th Edition. 2007©
• Pleural fluid accumulates when the rate of
pleural fluid formation exceeds the rate of
pleural fluid absorption.
• Normally, there should be a small amount
(0.01 mL/kg/hour) of fluid constantly enters
the pleural space from the capillaries in the
parietal pleura.

5th Edition. 2007©
• Almost all of this fluid is removed by the
lymphatics in the parietal pleura, which
have a capacity to remove at least 0.20
mL/kg/hour.
• Note that the capacity of the lymphatics to
remove fluid exceeds the normal rate of
fluid formation by a factor of 20.

5th Edition. 2007©
The most common cause of increased
pleural fluid formation is increased interstitial
fluid in the lung. The amount of edema in the
lung exceeds 5 g/gram of dry lung weight,
pleural fluid accumulates, irrespective of
whether the edema is due to high-protein or
low-protein fluid

5th Edition. 2007©
Radiologic Signs
• When more fluid accumulates, it spills over into
the posterior costophrenic angle and obliterates
that sinus as viewed in the lateral projection.
• The normally sharp posterior costophrenic angle
is obliterated by a shallow, homogeneous shadow
whose upper surface is meniscus-shaped.

5th Edition. 2007©
Course in the Wards
• Levofloxacin 750mg 1 tablet OD
• Patient’s Meds:
• 1. Essentiale Forte 1 Tab TID
• 2. Losartan 50mg 1 tab OD
• 3. Clopidogrel 75mg 1 tab OD
• 4. Digoxin 0.25 mg 1 tab OD
• 5. Metformin 500mg 1 tab OD
• 6. Simvastatin 40mg 1 tab OD
HS
• 7. Vit B Complex 1 Tab OD
• 8. Trimetazidine 35mg 1 tab OD
Course in the Wards
• 02 saturation: 97%-98% at 2
lpm via nasal cannula
• Sputum AFB for 3 collection
Sputum AFB x 3 Collection Negative for Acid Fast
• Sputum
BacilliGS/CS
Sputum GS/CS Gram Stain:
Pus Cells: < 25/OIF
Epithelial: < 25/OIF
Gram Positive cocci single
and Pair
Gram Negative Short Rods:
Few
Couse in the Wards
2nd Hospital Day
• Levodropropizine (Levopront)
1 tspFree
Chest Mapping Ultrasound TIDfluid
POin both pleural
cavities, more in the left.
Approximate Volume in
24cc in the right and 818cc
• Chestin UTZ with Mapping
the left
Ultrasound
• Ultrasound is more accurate than plain
chest radiography for estimating pleural
fluid volume and aids thoracentesis.
• In a series of 320 patients, Yang et al
found that pleural effusions with complex
septated, complex non-septated, or
homogeneously echogenic patterns are
always exudates, whereas hypoechoic
effusions can be either transudates or
exudates.
BTS guidelines for the investigation of a unilateral pleural

effusion in adults, Thorax 2003;58(Suppl II):ii8–ii17
Course in the Wards
3rd Hospital Day • No Difficulty of Breathing, No
chest pain
• VS Stable
• Refered to Cardio Service for CP

Clearance
• Started on HR (Rimactazid)
300mg 1 Tab OD and Ethambutol
400mg/tab 1 tab BID
• Tramadol tablet was started

Course in the Wards
4th Hospital Day  With Epigastric discomfort after
Color takingYellowish
HR (Rimactazid), No Difficulty
Character of Breathing,
Hazy No Chest Pain
RBC Stain
 VS Stable
1894 cells/ CU MM
Gram Pus Cells: (+1)
WBC Red
256Blood Cells:
cells/ CU MMFew
No Bacterial Organism
Differential
Repeat CXR Count • All
PostSeen Lymphocytes
thoracentesis
Decrease in the seen
Volume of
• TeaPleural Effusion on the
Culture and Sensitivity No colored
Growth
Left pleural
after
Following 48 hrsfluid of 850 cc
Thoracentesis
• Repeat CXR: Pneumothorax

Marginal Pneumothorax L 10%
on the Left
• O2 increased at 5 lpm
Exudative VS Transudative
●
Systemic factors influencing
the formation or absorption of
Trans pleural fluid are altered so
that pleural fluid accumulates
udativ ●
Left ventricular failure,
ascites, and decreased
e serum oncotic pressure with
hypoproteinemia.
●
Pleural surfaces or the
capillaries in the location
Exud where the fluid originates are

altered such that fluid
accumulates
ative ●
Pleural malignancy, para-
pneumonic effusions, and
pulmonary embolism

5th Edition. 2007©
Light, Richard. Pleural Diseases. 5th
Edition. 2007©
Edition. 2007©
Edition. 2007©
Edition. 2007©
Patient with Abnormal Chest Xray
Suspected Pleural fluid
Algorithm for
distinguishing
transudative
from exudative
pleural effusions

5th Edition. 2007©
Yes Algorithm for
distinguishing
transudative
from exudative
pleural effusions
Suspected Pleural fluid

Edition. 2007©
Pleural Fluid Protein Patient’s Light’s
Values Criteria
Is/ the Light’s
Pleural Protein 19.6Criteria for
0.34
Serum Proteindiagnosing an
56.7 Exudative
Transudative
Pleural
Pleural LDHPleural
/ Effusion215 Fulfilled
Effusion ?
0.53
Serum LDH 399
Pleural LDH > 2/3rd the 215 215< 412
upper limits of N serum LDH (N: 313 -618)
Light’s Criteria
• Light criteria have an overall diagnostic
accuracy of 93% but commonly misclassify
effusions (approximate diagnostic
accuracy, 65%) when any 1 of the 3
criteria has a value near its cutoff point.
• Light criteria can be effectively used to
categorize effusions as exudates because
they are associated with the increased
permeability of pleural membranes or the
breakdown of intrapleural cells, allowing
high–molecular weight constituents to
concentrate in the pleural space.
Heffner, J and Klein, J. Recent Advances in the
Diagnosis and Management of Malignant Pleural
Effusion, Mayo Clin Proctocol, 2008;83(2):235-250
Light’s Criteria
• For many years, a pleural fluid protein
level of 3.0 g/dL was used to separate
transudates from exudates, with exudative
pleural effusions characterized by a
protein level above 3.0 g/dL (13,14).
• Light's criteria identified 98% of the
exudates correctly, but they were less
accurate in identifying transudates,
misclassifying 19 of 112 (17%)

5th Edition. 2007©
Pleural Fluid Findings Suggestive
of Malignant Pleural Effusion (MPE)

Pleural Fluid Findings Suggestive
of Malignant Pleural Effusion (MPE)

Why Transudative?
• Malignant pleural effusions were
transudative in 1.5% of malignant
mesotheliomas, 6.8% of metastatic
diseases, and 11.1% of
paramalignant effusions. Cytological
examination of pleural fluid in
patients with unexplained
transudative effusion is essential to
rule out malignant processes.
Gonlugur, T., Gonlugur, M. Transudates in Malignancy: Still a Role for

Pleural Fluid: Ann Acad Med Singapore 2008;37:760-3
Why Transudative?
• Transudative malignant effusions
are generally due to early stages of
mediastinal node involvement,
atelectasis, or concomitant
congestive heart failure.
Gonlugur, T., Gonlugur, M. Transudates in Malignancy: Still a Role for

Pleural Fluid: Ann Acad Med Singapore 2008;37:760-3
Gross Apperance of Pleural Fluid
• Most transudative and many exudative
pleural effusions
• Clear, straw colored, nonviscid, and
odorless
The• appearance of the pleural fluid and
Blood tinged
any odour should be noted. [C]
• Pleural fluid RBC count is between
5,000 and 10,000/mm
A pleural fluid haematocrit is helpful in
3
Turbid pleural
the •diagnosis fluid
of haemothorax.
• increased cellular content or increased
lipid contenteffusion in adults, Thorax 2003;58(Suppl II):ii8–ii17

5th Edition. 2007©
Gross Appearance of Pleural
Effusion
• Turbid pleural fluid that clears with
centrifugation
• Pleural infection
• Turbidity persists after centrifugation,
• Chylothorax or a pseudochylothorax
• Chocolate sauce or anchovy paste
• Amebiasis with a hepatopleural fistula
• High viscosity
• Suggestive of malignant mesothelioma;
2nd to an elevated pleural fluid
hyaluronic acid level
5th Edition. 2007©
RBC Count
• Bloody
• Hematocrit should be obtained on the
fluid
• Hct > 1%
• Malignant pleural disease,
• Pulmonary embolus
• Traumatically induced pleural
effusion
• Hct >50% of that of the peripheral blood
• Hemothorax - consider performing a
tube thoracostomy
5th Edition. 2007©
WBC Count
• Pleural fluid WBC count is of limited
diagnostic use.
• Most transudates
• Have WBC counts below 1,000/mm3,
• Most exudates
• Have WBC counts above 1,000/mm3
• Parapneumonic effusions
• Pleural fluid WBC counts above
10,000/mm3

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Neutrophils
• Predominate in pleural fluid resulting from
acute inflammation as with pneumonia,
pancreatitis, pulmonary embolization,
subphrenic abscess, and early
tuberculosis
• Interleukin (IL-8) appears to be one of the
primary chemotaxins for neutrophils in the
pleural space
• The significance of neutrophils in an
exudative pleural effusion is that they
indicate acute inflammation of the pleural
surface.
5th Edition. 2007©
Lymphocytes
• Probably has a malignant disease,
tuberculous
Differential cell counts pleuritis,
on the or a pleural
pleural fluid effusion
after CABG surgery
• Almost
Pleural all of the is
lymphocytosis effusions
common secondary
in to
tuberculosis,
malignancy but only two thirds of the
and tuberculosis.
effusions secondary to malignant disease
had predominantly small lymphocytes

5th Edition. 2007©
Protein Measurements
• The pleural fluid protein levels
• Generally higher in exudative pleural
effusions than in transudative pleural
effusions.
• Pleural fluid protein levels
• Not useful in separating the various
types of exudative effusions, however,
because the protein level in most
exudates is elevated to a comparable
degree

5th Edition. 2007©
Glucose Level
• Low pleural fluid glucose level (<60 mg/dL)
indicates
• Parapneumonic effusion
• malignant disease
• rheumatoid disease
• tuberculous pleuritis
• The lower the pleural fluid glucose level,
the more likely that one is dealing with a
complicated parapneumonic pleural
effusion.

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Lactic Acid Dehydrogenase
Measurement
• The higher the LDH, the more inflamed the
pleural surfaces
• All Effusions with elevated pleural fluid
LDH levels
• Seen in most malignant effusions

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pH Measurements
• Transudative PE,
• Pleural fluid pH is usually higher than the
pH simultaneous blood pH
• Active transport of bicarbonate from the
pH shouldbloodbe
intoperformed
the pleural in space all non-
• purulent effusions.[B]
Exudative PE
• Pleural fluid pH falls substantially below
In an infected effusion a pH of <7.2
that of
indicates the
the arterial
need for tube pH drainage.
• If the pleural fluid pH is below 7.0,
• Complicated parapneumonic effusion
• Therapeutic thoracentesis or tube

thoracostomy Light, Richard. Pleural Diseases.
5th Edition. 2007©
Tests for Diagnosing Pleural
Tuberculosis
• Adenosine Deaminase Measurement
• Higher in tuberculous pleural effusions
than in other exudates
• Cutoff level of between 40 and 45 U/L is
used with levels above this being
indicative of tuberculosis
• The higher the level, the more likely
the patient is to have tuberculosis

5th Edition. 2007©
Course in the80%
Repeat CXR Wards
Pnumothorax
6th Hospital
RepeatDay
CXR after 6 hrs
 Shortness ofComplete Reexpansion
Breathness of pain
with epigastric
Post CTT  VS Stable the Left Lung with
Resoption of the Pleural
12 lead ECG FiudTachycardia
Sinus Along the Left
 Repeat CXR:Costophrenic Area
Complete
 Pneumothorax 80%
Right Bundle
Branch Block
Ultrasound of Abdomen Negative Sonographic
Anterior
 Clopidogrel Wall Myocardial
discontinued
Study of the Kidneys,
Infaraction, Old
Ureters and Urinary
 Stat CTT:Bladder. Normal
400cc drained, sized
blood tinge, (+)
Prostrate Glands;
fluctuations
Negative for Mass
 O2 at 5 lpm via nasal cannula
 Post CTT: Reexpansion of L Lung
 ICU Transfer
Pneumothorax
• Air in the pleural space, that is, air
between the lung and the chest wall
• Spontaneous pneumothoraces
• Ooccur without antecedent trauma or
other obvious cause
• Traumatic pneumothoraces
• Occur from direct or indirect trauma to
the chest.
• Iatrogenic pneumothorax
• An intended or inadvertent consequence of
a diagnostic or therapeutic maneuver

5th Edition. 2007©
Complications of Pneumothorax
• The most common complication of
thoracentesis is pneumothorax.
• When three different series involving 459
patients are combined, 51 of the patients
(11%) developed a pneumothorax and
chest tubes were necessary in 9 (2%).
• In a more recent report, the incidence of
pneumothorax was 4% in a series of 506
thoracenteses and 2% received a chest
tube (18).

5th Edition. 2007©
Complications of Pneumothorax
• Thoracentesis is probably the third leading
cause of iatrogenic pneumothorax.
• Incidence: 5%
• Approximately 20% to 50% of those
with a pneumothorax requiring a
chest tube
• The incidence of pneumothorax can be
decreased if the thoracentesis is
performed by experienced
interventional radiologists with
ultrasound guidance.
5th Edition. 2007©
Indication for Chest Drain
Insertion
BTS guidelines for the insertion of a chest drain. D Laws, E Neville, J

Duffy, on behalf of the British Thoracic Society Pleural Disease
Group, a subgroup of the British Thoracic Society Standards of Care
Committee, Thorax 2003;58(Suppl II):ii53–ii59
Course in the Wards
8th Hospital Day  (-) DOB, comfortable
 VS Stable
 Decreased Breath Sounds at L
 CTT output: 500mL/day
 Clopidogrel Resumed
 Decreased O2 at 2 lpm
 Tramadol was given for pain

Course in the Wards
 VS Stable

Cell Cytology of Pleural Reddish Fluid and a
Fluid volume approximately
600ml for cell cytologic
 CTT output: 350cc/day
Evaluation
Chronic Inflammatory
 Cell Cytology
Pattern with Reactive
Mesothelial Hyperplasia
Repeat Pleural Fluid

Cytology: Atypical
Mesothelial Cells
Cytology Cytologic Examinations
• The nuclei of malignant cells may exceed
Malignant effusions can be diagnosed by pleural
50 µm in diameter, in contrast with
fluid cytology alone in only 60% of cases.
mesothelial cell nuclei, which rarely
exceed 20 µm in diameter.
If the first pleural cytology specimen is negative,
• Small lymphocytes, by comparison, have a
this should be repeated a second time. [B]
diameter of approximately 10 µm.
Mesotheliomas
Both cell• blocks and fluidtend to have
smears true papillary
should be
prepared for aggregation,
examinationmultinucleation with atypia,
and, if the fluid has
and cell-to-cell
clotted, it needs to be fixedapposition, whereas
and sectioned as a
histological adenocarcinomas
section. [B] tend to have acinus-like
structures and balloon-like vacuolation
5th Edition. 2007©
Course in the Wards
 VS Stable
 Immunohistochemical Staining
 CEA, CK 7, Calretenin, CK
20
Course in the Wards
 VS Stable

Bone Scintigraphy No Evidence of Bone
Metastasis
 Bone Scan
 Contemplated Pleurodesis if
CTT output is < 100cc/day
Course in the Wards
Non-Contrast and Bilateral Pleural Effusion,
Contrast CT
15th Hospital Day Larger Amount on the Left
 (-) DOB, comfortable
side
 VS Stable
 The Tip
Decreased of theSounds at L
Breath
Thoracotomy Tube is in
the Left Major Fissure
Small Amount of Fluid
Collections in the
Pericardial Sac
 CT Scan of Chest
Ground Glass Opacity in
the Left
 Pleurodesis <Lower Lobe
done
Secondary to Compressive
 Doxurubicin
Atelectasis or infiltrates
Prerequisites for Pleurodesis
• Significant symptoms that are relieved when
pleural fluid is evacuated
• Evidence of complete re-expansion of the
lung without evidence of bronchial
obstruction or fibrotic-trapped lung
• Daily tube drainage is less than 150 mL/day
• Reserved for those cases where there is no
other therapeutic alternative, or when this
has already failed
• If the patient undergoing pleurodesis is
receiving corticosteroid therapy
5th Edition. 2007©
CT Scan
CT Scan • Useful in distinguishing empyema with air
fluid levels from lung abscess
CT scans• for pleural
Identify effusion
pleural shouldwhich
thickening, be suggests
performed with contrast
that the enhancement.
patient has an exudative [C]
effusion.
• In one study, 36 of 59 exudative effusions
In cases of difficult
(61%) drainage, CT scanning
had associated pleural thickening,
should be used to delineate
whereas only 1 the size
of 27 and
transudates (4%)
had associated
position of loculated pleural
effusions. [C]thickening (45).
• An added bonus with CT is the clear
CT scanning demonstration
can usuallyofdifferentiate
bone pathology such as
between
benign andmetastases
malignantorpleural
tuberculosis.
thickening.
5th Edition. 2007©
Course in the Wards
 VS Stable
 CTT removed
Course in the Wards
 VS Stable
 Discharged
 Home Medications:
 HR (Rimactactazid) 300mg/tab 1
tablet OD
 E 400mg/tab 1 tablet BID before
meals
 Ipratropium + Salbutamol beulization
every 8 hrs.
 Lactulose 15 ml OD HS
 Pantoprazole 40mg/tab 1 tab OD HS

Course in the Wards
21th Hospital Day  Home Medications:
 Cefixime 200mg/tab 1 tablet BID PO
 Digoxin 0.25 mg/tab 1 tablet OD PO
 Clopidogrel 75mg/tab 1 tablet OD PO
 Losartan 50mg/tab 1 tablet OD PO

Immunochemical Staining
 Simvastatin 80 mg/ tab 1 tablet OD
CEA (-)
PO
CK 7 (+)
 Metformin 500mg/tab 1 tablet OD PO
CK20 (-) 1 tablet BID PO
 Trimetazidine
Calretenin Essentiale
(+)Forte 1 capsule BID PO
• Best markers for adenocarcinoma
• Carcinoembryonic antigen (CEA)
• MOC-31 (or B72.3, Ber-EP4, or BG8)
• Best markers for mesothelioma

• Calretinin and cytokeratin

5th Edition. 2007©
Final Diagnosis
• Malignant Pleural Effusion Secondary to
Mesothelioma
• HCVD, Congestive Heart Failure NYHC I
Secondary to CAD
• S/P AMI
• S/P PTCA
• DM Type 2, controlled
Clinical Manifestation of Pleural
Effusion
• Pleuritic chest pain
• Inflammation of the pleura, specifically,
the parietal pleura as the visceral
pleura does not have pain fibers.
• Dull, aching chest pain rather than pleuritic
chest pain
• Pleural malignancy
• Either pleuritic chest pain or dull, aching
chest pain
• The parietal pleura is probably involved
and that the patient - exudative pleural
effusion. Light, Richard. Pleural Diseases.
5th Edition. 2007©
Effusion
• A second symptom - dry, nonproductive
cough
• The mechanism is not clear, although it
may be related to pleural inflammation
• Lung compression by the fluid may
bring opposing bronchial walls into
contact, stimulating the cough reflex

5th Edition. 2007©
Effusion
• The third symptom is dyspnea.
• PE acts as a space-occupying process
in the thoracic cavity and therefore
reduces all subdivisions of lung
volumes
• Larger PE obviously cause a significant
reduction in lung volumes.

5th Edition. 2007©
Clinical Manifestations of Pleural
Effusion
• Tactile fremitus:
• Absent or attenuated because the fluid
absorbs the vibrations emanating from
the lung
• Much more reliable than percussion for
identifying both the upper border of the
pleural fluid and the proper site to
attempt a thoracentesis.

5th Edition. 2007©
Effusion
• Percussion:
• Dull or flat
• Dullness is maximum at the lung bases
where the thickness of the fluid is the
greatest
• If the dullness shifts as the position of
the patient is changed, one can be
almost certain that free pleural fluid is
present

5th Edition. 2007©
Effusion
• Breath Sounds:
• Auscultation over the pleural fluid
characteristically reveals decreased or
absent breath sounds
• Pleural rub.
• Coarse, creaking, leathery sounds
most commonly heard during the
latter part of inspiration and the early
part of expiration, producing a to-
and-fro pattern of sound

5th Edition. 2007©
Epidemiology – Malignant
Mesotehlioma
• There is widespread variation in the
incidence of malignant mesothelioma in
England: two Strategic Health Authorities
have 30 cases annually while two have
100 cases per year.
• Asbestos fibres are the cause of most
cases of mesothelioma. Evidence from two
British studies suggests that the proportion
of men with mesothelioma directly
attributable to occupational asbestos
exposure may be about 85%, and this is
consistent with evidence from studies in
other countries.
BTS statement on malignant mesothelioma in the UK, 2007
British Thoracic Society Standards of Care Committee
Mesothelioma
• Malignant mesothelioma will increase in
incidence over the next 5–10 years. It is
inexorably progressive with a very poor 5-
year survival and a median survival of 8–
14 months.
• Simian virus 40 (SV40), a DNA virus, has
been implicated as a cofactor in the
causation of malignant mesothelioma

Bruce W.S. Robinson, M.D., and Richard A. Lake, Ph.D.
Advances in Malignant Mesothelioma. New England Journal Medicine
2005;353:1591-603.
Mesothelioma
• Mesothelioma
• Fifth to seventh decades
• 70–80% of cases occur in men
• Between the ages of 20 to 40 years
usually have a history of childhood
exposure
• Typical presenting features are those of
chest pain, dyspnea or both
• Physical examination is usually
unremarkable except for signs of pleural
effusion and pleural thickening due to
tumour infiltration
Moore, J., Parker, R, Wiggins J. Review, Malignant Mesothelioma
Orphanet Journal of Rare Diseases 2008, 3:34 doi:10.1186/1750-
1172-3-34
2005;353:1591-603.
Pathophysiology
• Four principal processes by which
asbestos affects the pleura.
• First, asbestos fibers may irritate the
pleura.
• Shape of asbestos fibers
• Fibers penetrating the lung induce
disease manifested
• Scarring (plaques)
• Frank malignant process
(malignant mesothelioma).

2005;353:1591-603.
Pathophysiology
• Second, asbestos fibers may sever or
pierce the mitotic spindle of cells and
thereby disrupt mitosis
• Third, asbestos induces the generation of
ironrelated reactive oxygen species that
cause DNA damage
• Fourth, asbestos induces phosphorylation
of the mitogen-activated protein (MAP)
kinases and of extracellular signal–
regulated kinases (ERK) 1 and 2

2005;353:1591-603.
Key Biologic Features of
Malignant Mesothelioma

2005;353:1591-603.
Suspected malignant
mesothelioma:
diagnostic algorithm

Diagnostics Imaging for Malignant
Mesothelioma
• Contrast-enhanced CT
• Primary imaging modality used for the
evaluation of suspected malignant
pleural disease.
• Malignant or inflammatory pleural
disease enhances strongly, and the
contrast allows differentiation between
thickened pleura, effusion and
underlying aerated or collapsed lung.

Mesothelioma
• CT features used to distinguish malignant
from benign pleural disease were
• (1) circumferential pleural thickening,
• (2) nodular pleural thickening,
• (3) parietal pleural thickening 1 cm,
• (4) mediastinal pleural involvement.
• Specificities:100%, 94%, 94% and 88%
respectively.
• Sensitivities: 41%, 51%, 36% and 56%
respectively.

Mesothelioma
• Magnetic resonance imaging (MRI)
• Limited role in the evaluation of malignant
mesothelioma
• MRI, with its ability to scan in any plane,
has been used to accurately assess
resectability prior to radical surgery
• 18F-fluorodeoxyglucose positron emission
tomography (FDG PET)
• May be useful in differentiating benign from
malignant pleural disease and might guide
choice of biopsy site.

Histopathological analysis
• Malignant mesothelioma
• EMA
• Calretinin
• WT1
• Cytokeratin 5/6
• HBME-1 (an anti–mesothelial cell
antibody) or
• Mesothelin (more than 85 percent of
epithelioid

2005;353:1591-603.
• Electrochemiluminescence and micro-
particle enzyme immunoassays of PF can
detect tumor markers none of the available
tumor markers has sufficient diagnostic
yield to be used in routine clinical practice.
• Groups of immunohistochemical markers
could lead to a diagnosis in approximately
80% of patients with malignant
mesothelioma.
Heffner, J and Klein, J. Recent Advances in the Diagnosis and

Management of Malignant Pleural Effusion, Mayo Clin Proctocol,
2008;83(2):235-250
Histopathological analysis

2005;353:1591-603.
Management of Malignant
Mesothelioma
• Treatment Strategy:
• Management of the pleural effusion.
• Indications for prophylactic radiotherapy to
intervention sites.
• Indications for chemotherapy.
• Immediate supportive care requirements.
• Compensation issues.
• Suitability for radical surgery.
• Suitability for clinical trial entry.
• Referral to the specialist multidisciplinary
team.
1172-3-34
Treatment Strategy: Surgery
• Extrapleural pneumonectomy (EPP) (or
pleuropneumonectomy)
• Eradicate all macroscopic disease,
ideally with good clearance margins.
• Operative mortality: 4–9%
• Significant complications: Over 60% of
patients
• A median survival of 19 months
following this radical operation with
adjuvant chemotherapy and
radiotherapy
Treatment Strategy: Surgery
• Debulking operation (cytoreductive
surgery)
• Less radical approach
• Can be performed by VATS or thoracotomy
• Has been reported to be effective in
preventing fluid recurrence
• May also be associated with increased
survival although, like EPP, it has not yet
been tested in a randomized trial

Treatment Strategy: Pleurodesis
• Early pleurodesis is a key aim for symptom
control and prevention of the development
of a trapped lung.
• Thoracoscopy is an extremely useful
diagnostic and therapeutic tool.
• Calibrated talc is the pleurodesis agent of
choice.
• Indwelling pleural catheters are useful for
symptom control in cases of trapped lung
or where chemical pleurodesis has failed.

• Talc is the most effective sclerosant available for
pleurodesis. [B]
• A small number of patients (<1%)may develop
acute respiratory failure following talc
administration. [B]
• Tetracycline ismodestly effective, has few severe
side effects, and is the preferred sclerosant to
minimise adverse event rates. [B]
• Bleomycin is an alternative sclerosant with a modest
efficacy rate but is expensive. [B]
• Pleuritic chest pain and fever are the most common
side effects of sclerosant administration. [B]
• Sterile talc
• Currently the most effective freely available
pleurodesis
• Dose of the talc should not exceed 4 g,
• Should be calibrated to avoid the rare
risk of the development of ARDS
• The intercostal tube should be clamped for
1 h after sclerosant administration and, in
the absence of excessive fluid drainage
(.250 ml/day), removed 24–48 h later.

1172-3-34
• Success rates (complete and partial
response) for talc slurry range from 88% to
100% with a mean of 90%.
• In a recent randomised trial between talc
slurry (5 g) and bleomycin (60 units), 90%
of the talc group achieved a complete
response at 2 weeks compared with 79%
of the bleomycin group, which was
statistically insignificant.

Treatment Strategy: Radiotherapy
• Palliative radiotherapy provides pain relief
in about half of all patients.
• Palpable masses respond to radiotherapy
in about half of all patients.
• Breathlessness and superior vena caval
obstruction rarely respond to radiotherapy.
• Prophylactic radiotherapy may reduce
chest wall implantation following invasive
procedures, but may be most applicable
for patients with a better prognosis and
after more invasive procedures.

Treatment Strategy: Radiotherapy
• The current recommendation
• Patients of good performance status
(and therefore longer survival) who
have chest wall wounds should be
referred for radiotherapy promptly and
treated with a three-fraction schedule.

Treatment Strategy: Chemotherapy
• In general, palliative chemotherapy should
be considered for all patients with
performance status 0–2.
• The objective response rate that should be
expected is of the order of 20–40%, and
two randomised controlled trials have
shown significant differences in survival
between regimens, implying that
chemotherapy may extend the life
expectancy of some patients with
mesothelioma.

Treatment Strategy: Chemotherapy

Treatment Strategy:
Chemotherapy
• Until recently, all reviews of chemotherapy
for malignant mesothelioma reported poor
response rates (typically less than 15 to 20
percent) and, because of these low rates,
did not recommend a standard of care.
• In a multicenter phase 3 study involving 448
patients, those treated with pemetrexed plus
cisplatin had a longer overall median survival
(12.1 months) than those treated with cisplatin
alone (9.3 months) and had an objective
response rate (shrinkage of the tumor by at
least 50 percent) of 41 percent.
2005;353:1591-603.
New Approaches to Treatment for
Mesothelioma

2005;353:1591-603.
Key Points:
• The most common cause of increased
pleural fluid formation is increased
interstitial fluid in the lung.
• Light's criteria identified 98% of the
exudates correctly, but they were less
accurate in identifying transudates,
misclassifying 19 of 112 (17%).
• Pleural lymphocytosis is common in
malignancy and tuberculosis.
• Ultrasound is more accurate than plain
chest radiography for estimating pleural
fluid volume and aids thoracentesis.
Key Points:
• Thoracentesis is probably the third leading
cause of iatrogenic pneumothorax.
• CT features used to distinguish malignant
from benign pleural disease.
• Groups of immunohistochemical markers
could lead to a diagnosis in approximately
80% of patients with malignant
mesothelioma.
• Calibrated talc is the pleurodesis agent of
choice for Malignant Mesothelioma.
• Patients should be offered Surgery,
Radiotherapy and Chemotherapy depending
on the treatment strategy.

Case Presentation - Malignant Pleural Effusion Edited

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• No greater opportunity, responsibility, or

obligation can fall to the lot of a human being

5/5 5/5 100% 100% ++ ++

• (-) Babinski (-) Brudzinski

Cardiac Pul monary

Acute Coronary Syndrome Congestive Heart Failure

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

BTS guidelines for the investigation of a unilateral pleural

• Refered to Cardio Service for CP

• Tramadol tablet was started

• Repeat CXR: Pneumothorax

Exud where the fluid originates are

Light, Richard. Pleural Diseases.

Suspected Pleural fluid

Light, Richard. Pleural Diseases.

Suspected Pleural fluid

Light, Richard. Pleural Diseases. 5th

Light, Richard. Pleural Diseases.

BTS guidelines for the investigation of a unilateral pleural

BTS guidelines for the investigation of a unilateral pleural

Gonlugur, T., Gonlugur, M. Transudates in Malignancy: Still a Role for

Gonlugur, T., Gonlugur, M. Transudates in Malignancy: Still a Role for

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

• Therapeutic thoracentesis or tube

Light, Richard. Pleural Diseases.

 Post CTT: Reexpansion of L Lung

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

BTS guidelines for the insertion of a chest drain. D Laws, E Neville, J

 CTT output: 500mL/day

 Tramadol was given for pain

 Decreased Breath Sounds at L

Repeat Pleural Fluid

 CTT output: 400cc/day

 CTT output: 200cc/day

 Pantoprazole 40mg/tab 1 tab OD HS

 Digoxin 0.25 mg/tab 1 tablet OD PO

 Clopidogrel 75mg/tab 1 tablet OD PO

 Losartan 50mg/tab 1 tablet OD PO

• Best markers for mesothelioma

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

Light, Richard. Pleural Diseases.

BTS statement on malignant mesothelioma in the UK, 2007

Bruce W.S. Robinson, M.D., and Richard A. Lake, Ph.D.

Bruce W.S. Robinson, M.D., and Richard A. Lake, Ph.D.

Bruce W.S. Robinson, M.D., and Richard A. Lake, Ph.D.

BTS statement on malignant mesothelioma in the UK, 2007

BTS statement on malignant mesothelioma in the UK, 2007