Malignant Pleural Effusion in detail for pg

MALIGNANT PLEURAL EFFUSIONS
Dr. Gautam Ram Karthik M
PG Resident
ITM

• A malignant pleural effusion is diagnosed by detecting exfoliated
malignant
cells in pleural fluid or demonstrating these cells in pleural tissue
obtained by
percutaneous pleural biopsy, thoracoscopy, thoracotomy, or at
autopsy.
• Second leading cause of exudative pleural effusions after
parapneumonic
effusions.
• MPE accounts 24% of all pleural effusions (and 42% of exudates)
MALIGNANT PLEURAL EFFUSIONS (MPE)

Pleural effusion of
pleura
• Malignant
Mesothelioma
MALIGNANT PLEURAL EFFUSIONS (MPE)
Pleural Effusions Related to Metastatic
Malignancies
• Lung carcinoma
• Breast carcinoma
• Lymphoma and leukemia
• Ovarian carcinoma
• Sarcoma ( including melanoma )
• Uterine and cervical carcinoma
• Stomach carcinoma
• Colon carcinoma
• Pancreatic carcinoma
• Bladder carcinoma

Lung Malignancy
• Pleural effusions occur with all the cell types of lung carcinoma but
most frequent with adenocarcinoma.
• Patients with lung cancer who have anti-p53 antibodies are more
likely to have pleural effusions.
• Patients with lung cancer and pleural effusion be classified as M 1a
which would make them a stage IV.
• The presence of a pleural effusion at the time of diagnosis
adversely affected prognosis
PLEURAL EFFUSIONS RELATED TO METASTATIC
MALIGNANCIES

Breast Carcinoma
• The second most leading cause of malignant pleural effusion.
• Pleural effusions were more common with lymphangitic spread
than without lymphangitic spread.
• Determination of steroid receptors in the effusion is useful in
planning therapy
MALIGNANCIES

Lymphomas
• Lymphomas, including Hodgkin's disease, are the third leading cause of
malignant pleural effusions.
• Most patients with Hodgkin's disease and pleural effusion have the nodular
sclerosis type.
• For Non-Hodgkin’s lymphoma, large cell lymphomas more frequently have
associated pleural effusion at the time of presentation than do small cell
lymphomas
• Non-Hodgkins Lymphoma more frequently present with Chylothorax than
Hodgkin’s Lymphoma
• The presence of a pleural effusion at the time of presentation does not
adversely affect complete remission or survival rates with non Hodgkin’s
lymphoma
MALIGNANCIES

• MPE have visceral, but not necessarily parietal pleural involvement.
• Spread through the blood-stream and initially invade the visceral
pleura
• Secondary dissemination to the parietal pleural occurs by tumour
seeding along adhesions or by exfoliated tumour cells floating in
the effusion, lymphangitic spread or even through direct extension
of tumours infiltrating adjacent structures (i.e. lung, chest wall,
mediastinum or diaphragm)
• A combination of increased fluid production due to fluid
extravasation from hyper-permeable parietal or visceral pleural
and/or tumour vessels and impaired lymphatic outflow underlie
MECHANISMS OF PLEURAL METASTASIS

PARAMALIGNANT EFFUSIONS
Paramalignant
effusions are pleural
effusions found in patients with
solid tumors without direct pleural
involvement and no evidence of
malignant cells in pleural fluid

• Dyspnea, chest pain and cough are the most common symptoms .
• To accommodate the volume of pleural fluid, thoracic cage has to
enlarge causing the hemidiaphragm to flatten/ evert, the chest
wall to expand and the mediastinum to shift contralaterally.
• Chest pain is usually dull rather than pleuritic.
• Constitutional symptoms eg: weight loss, malaise, anorexia
CLINICAL PRESENTATION

Plain radiograph
• Insensitive at distinguishing it from a
benign effusion.
• Bronchogenic Ca - demonstrable
pulmonary abnormalities besides the
effusion
• Lymphoma - hilar or mediastinal
adenopathy
• In cases where multiple nodular regions or
pleural thickening are present the
diagnosis may be evident
RADIOGRAPHIC FEATURES

COMPUTED TOMOGRAPHY
Signs suggestive of Malignancy
RADIOGRAPHIC FEATURES
Concurrent abnormalities frequently
reported :
• Lung masses, nodules, or infiltrates
• Mediastinal adenopathy
• Pericardial thickening
• Pericardial effusion
• Chest wall involvement
• Lymphangitic carcinoma
• Pleural nodularity
• Pleural rind
• Mediastinal pleural involvement
• Pleural thickening greater than 1 cm

FDG-PET:
• More sensitive than conventional
imaging in diagnosing malignant
pleural disease and distinguishing
them from benign processes
NUCLEAR IMAGING

PLEURAL FLUID ANALYSIS
The first diagnostic step in determining pleural effusion characteristics.
Routinely analyzed for total and differential cell counts, proteins, lactate
dehydrogenase (LDH), glucose, and pH, as well as subjected to
microbiological and cytological examinations.
Always categorized as exudates, a few are transudates.
DIAGNOSIS

TUMOR MARKERS IN PLEURAL FLUID
• Possibility of diagnosing MPE when increased levels of tumor markers are found in
the pleural fluid.
• A high level of pleural CEA seems to rule out malignant mesothelioma.
• CA 15-3, CA 19-9, and CYFRA 21-1 are highly specific but insufficiently sensitive to
diagnose MPE, and the combination of two or more tumor markers appears to
increase the diagnostic sensitivity.
• Vascular endothelial growth factor (VEGF) as a diagnostic biomarker of MPE
DIAGNOSIS

DIAGNOSIS
• the use of tumor markers for the diagnosis of pleural malignancy is
not recommended. One possible use of pleural fluid tumor markers
is to use high levels to select patients for more invasive studies
• Patient selection for more invasive procedure/ Thoracoscopy
• a symptomatic period of more than 1 month,
• the absence of fever,
• the presence of serosanguineous pleural fluid, and
• chest CT scan suggestive of pleural malignancy

Dixit, et al.: Malignant pleural effusion ; Lung India 20
17
DIAGNOSIS

Dixit, et al.: Malignant pleural effusion ; Lung India 20
17

CLOSED PLEURAL BIOPSY
• Abrams or Cope needle
• lower sensitivity due to the lower early
stage and distribution of tumor
DIAGNOSIS

MEDICAL THORACOSCOPY
• Medical Thoracoscopy (pleuroscopy) - advantage that it can be performed under
local anaesthesia or conscious sedation.
• MT into VATS has allowed for an even greater range of therapeutic solutions
• MT is primarily a diagnostic procedure.
Indication:
• the evaluation of exudative effusions of unknown.
• to rule out cause, staging of malignant mesothelioma or lung cancer, &
treatment of malignant or other recurrent effusions.
• Talc pleurodesis.
• Another purpose may be biopsy of the diaphragm, lung, mediastinum, or
pericardium.
• Thoracic surgery backup should be available.
DIAGNOSIS

MEDICAL THORACOSCOPY
Mortality rate related to MT alone is approximately 0.34%
Major complications:
a) empyema,
b) hemorrhage,
c) port site tumor growth (mesothelioma),
d) bronchopleural fistula,
e) postoperative pneumothorax or air leak
f) pneumonia were reported in 1.8% of cases
• VATS and MT is an invaluable diagnostic tool for the diagnosis of
pleural mesothelioma
• Port side radiation post procedure in patients with mesothelioma to
decrease the risk of tract tumor seeding with malignant cells.
DIAGNOSIS

BRONCHOSCOPY
• The diagnostic yield of bronchoscopy is low in patients with
undiagnosed pleural effusions.
Indicated when,
Endobronchial lesions are suspected, hemoptysis, atelectasis,
pulmonary infiltrates or large effusions without contralateral
mediastinal shift
DIAGNOSIS

MANAGEMNET OF MALIGNANT PLEURAL EFFUSION

MPE : PROGNOSIS ?

Condition Value (%) level of Functional Capacity
Able to carry on normal activity and to
work; no special care needed
100% No complaints; no evidence of disease
90%
Able to carry on normal activity; minor signs or
symptoms of disease
80%
Normal activity with effort; some signs or symptoms of
disease
Unable to work; able to live at home and
care for most personal needs; varying
amount of assistance needed
70%
Cares for self; unable to carry on normal activity or to
do active work
60%
Requires occasional assistance but is able to care for
most personal needs
50%
Requires considerable assistance and frequent medical
care
Unable to care for self; requires equivalent
of institutional or hospital care; diseases
may be progressing rapidly
40% Disabled; requires special care and assistance
30%
Severely disabled; hospital admission indicated
although death not imminent
20%
Very sick; hospital admission necessary; active
supportive treatment necessary
10% Moribund; fatal processes progressing rapidly
0% Dead
ECOG
0
1
2
4
3
5
Karnofsky Performance Scale (KPS)
MEDIAN SURVIVAL
KPS >70 – 13.2 months
KPS <30 – 1.1 months
CHEST 2000; 117:73–78

MEDIAN SURVIVAL
Low risk – 319 days
Moderate risk - 130
days
High risk - 44 days
Clive AO, et al. Thorax 2014;69:1098–1104

GOAL OF MANAGEMENT
Survival?
Palliation of Dyspnoea

• MPE whether primary or metastatic - advanced incurable disease
with poor prognosis.
• Median survival following diagnosis ranges from 3 to 12 months.
Lung cancers have shortest and Ovarian cancer longest
• Management should include measures to control the symptoms
arising from the pleural disease as well as underlying malignancy.
• Therapeutic thoracentesis may be adequate to allow time to assess
respond to systemic therapy.
• Lung cancers with EGFR mutations, Lymphoma, Small Cell
Carcinoma of lung respond well to chemotherapy.

Ideal therapy for MPE:
• Complete fluid control
• Improved symptoms
• Quality of life
• Minimally invasive
• Reduced hospital stay
The 2 primary modes of treatment to control the accumulation of
pleural fluid are
• insertion of an INDWELLING PLEURAL CATHETER or
• creation of a PLEURODESIS.

THERAPEUTIC THORACENTESIS
• The first step in the management of newly diagnosed MPE
• Only the patients who are dyspeic and whose dypnea improves after
thoracocentesis are candidates for fluid removal
• If the patient remains symptomatic despite large-volume
thoracentesis, causes such as lymphangitic spread, pulmonary
embolism, or malignant airway obstruction should be suspected
and investigated appropriately.
• To prevent reexpansion pulmonary edema, the amount of fluid
removed by thoracentesis should be assessed by patient symptoms
(cough, chest discomfort) and limited to 1.5 L on a single occasion.

SYSTEMIC CHEMOTHERAPY
• The presence of a malignant pleural effusion usually indicates
disseminated tumor therefore the only hope is prolonged
palliation with systemic chemotherapy.
Points to remember:
• Anti-VEGF antibody (Bevacizumab) + standard first-line
chemotherapy, provides survival advantage in NSCLC. It is important
not to attempt pleurodesis in these patients because angiogenesis
is necessary for pleurodesis and angiogenesis will be inhibited by
anti-VEGF drugs.
• Pleural effusions should be aspirated before chemotherapy is given
because the antineoplastic drugs may accumulate in the pleural

INTRAPLEURAL CHEMOTHERAPY
• Combined RT, Intrapleural Chemotherapy, Systemic Chemotherapy
• Staphylococcus aureus superantigen (SSAg), a powerful T-cell
stimulant.
• Rituximab
• Interferon-gamma, tumor necrosis factor, interleukin-2, cisplatin
have all been tried in small numbers of patients with results that are
not particularly impressive.
Cisplatin 60mg/m2
- Day 1
Gemcitabine 1000 mg/m2
- Days 1, 8, 15 every 4 weeks for three times
Radiotherapy – 7020 Gy/ 39 #
Postradiation Chemotherapy – Docetaxel 60mg/ m2
weekly fro 3 – 6 times

INDWELLING PLEURAL CATHETER
• The PleurX catheter is a 15.5 F silicone
rubber catheter, 66 cm in length, with
fenestrations along the proximal 24 cm
• Inserted using the Seldinger technique
under local anesthesia.
• The catheter is maintained in place with a
chest wall tunnel 5 to 8 cm in length.
• The valve prevents fluid or air from passing
in either direction through the catheter
unless the catheter is accessed with the
matched drainage line.

INDWELLING PLEURAL CATHETER
• If the patient is dyspneic and if the dyspnea is relieved by a
therapeutic thoracentesis, outpatients who receive home health care
or who have strong family support are ideal candidates for IPC.
• Long-term IPCs may lead to spontaneous pleurodesis in 40 58% of
−
patients with IPC. Therefore, sclerosants can be instilled through the
catheter if spontaneous pleurodesis does not occur after several
weeks of drainage.

COMPLICATIONS OF INDWELLING PLEURAL CATHETER
.

1. IPC-related pleural infection CRPI :
• Cutaneous flora, including Staphylococcus spp (especially S. aureus),
followed by Pseudomonas aeruginosa and Enterobacteriaceae.
• typically occurs at least 6–8 weeks after insertion
• Managed with Antibiotics
• CRPI can be categorized under 3 different forms
• Cellulitis
• Empyema
• Tunnel Infections
.

CT images of a patient with mesothelioma who
developed catheter tract metastasis around his
IPC, which was in place for 5 months
.
2. Catheter tract metastasis:
• Treated effectively with simple
analgaesics and external beam
radiotherapy without the need to
remove the IPC.
• Prophylactic radiotherapy

3. Symptomatic loculations:
• facilitate pleural symphysis or
‘spontaneous pleurodesis’ in
approximately 40% of patients.
• Effusion that fails to evacuate
through a patent IPC.
• Intrapleural fibrinolysis
provides a feasible alternative.
.

4. Fracture of catheters on removal
5. Catheter blockage:
• The formation of dense fibrinous tissue around and within the IPC can
occasionally lead to blockage of some lumen.
• Saline flush and manipulation along the catheter may dislodge
occluding materials.
6. Cost of IPC
7. Malnutrition and Immunosuppression
.

Pleurodesis is defined as the symphysis between the visceral and parietal pleura that
prevents the accumulation of either air or liquid in the pleural space
SCLEROTIC AGENTS
• Talc (Poudrage or Slurry)
• Antibiotics (Tetracyclines, Minocycline, Doxycycline),
• Antimalarials (Quinacrine, Mepacrine),
• Antineoplastic Drugs (Bleomycin, 5-fluorouracil, Mitomicin, Thiotepa, Nitrogen
Mustard),
• 50% Glucose And Water,
• Immunomodulating Agents [Interferon alpha],
• Iodopovidone,
• Radioactive Colloidal Gold,
• Autologous Blood,
• Fibrin Glue,
• Biological Agents (Corynebacterium Parvum, Or BCG),
PLEURODESIS

PLEURODESIS
INDICATIONS
• Malignant Effusion
• Refractory Non malignant effusion
• Caused by chronic ambulatory Peritoneal Dialysis, Yellow Nail
Syndrome, Chylothorax, Lupus Pleuritis, CKD, & Heart Failure
• Pneumothorax
• Pleurodesis successfully prevented the recurrence of Primary & Secondary
Spontaneous Pneumothorax

PLEURODESIS
CONTRAINDICATIONS
• Trapped Lung
• Interstitial Pulmonary Fibrosis
• Endobronchial Obstruction
Pleural Manometry & Pleural Elastance >= 19 cm H2O/L of fluid
removed indicates a high likelihood of a unexpandable lung and
predicts Pleurodesis failure

PLEURODESIS
Ideal Pleural Sclerosing agent
• a high molecular weight and chemical polarity,
• low regional clearance,
• rapid systemic clearance,
• a steep dose-response curve
• well tolerated with minimal or no side effects.
• The choice of a sclerosing agent will be determined by the efficacy or success rate of
the agent, accessibility, safety, ease of administration, number of administrations to
achieve a complete response and cost
• Pleurodesis should be considered in patients with MPE who are not candidates for
the tunneled catheter or systemic chemotherapy and who do not have a
chylothorax.

Ann Intern Med. 1994;120:56-64
PLEURODESIS

European Respiratory Journal · September 2001
PLEURODESIS

PLEURODESIS
• Talc Pleurodesis - Best
• Talc is the most effective & frequently used sclerosing agent available for
Pleurodesis
• Talc is predominantly Hydrated Magnesium Silicate, and was first used for
Pleurodesis in 1935
• Particle size – Talc preparations with a high proportion of particles <5-10 μ in
diameter are associated with moe severe local and systemic inflammatory
responses and with a poorer outcome
• Silver Nitrate & Iodopovidone have also commonly being used
• RCT compared Silver Nitrate to Talc
Enrolled 60 pts with symptomatic Malignant Pleural Effusion who were randomly

Failure of Pleurodesis
• Pleural fluid glucose (< 60 mg/dl),
• Karnofsky performance status (< 70),
• Size of the effusion in chest radiographs (massive effusion),
• Pleural fluid pH (< 7.20),
• Presence of concomitant alterations in chest radiographs, and
• Pleural lactic acid dehydrogenase levels (> 600 U/l)
The most likely cause of pleurodesis failure is the presence of trapped lung.
Before pleurodesis, the position of mediastinum should be evaluated
PLEURODESIS

Definitions of Success or Failure of Pleurodesis (as per ATS guidelines)
Successful pleurodesis
 Complete success: Long-term relief of symptoms related to the
effusion,
with absence of fluid reaccumulation on chest radiographs until death
 Partial success: Diminution of dyspnea related to the effusion, with
only
partial reaccumulation of fluid (less than 50% of the initial radiographic
evidence of fluid), with no further therapeutic thoracenteses required
for the
remainder of the patient’s life.
PLEURODESIS

Therapeutic options after failed Pleurodesis
• Talc pleurodesis fails in 30-50% of patients in which repeat pleurodesis
can be performed.
• But success rate will be lower than the first attempt.
• Repeated aspiration is appropriate for patients with short expected
survival.
• In terminally ill patients, narcotics and oxygen are more appropriate.
• The use of IPC is increasingly the preferred option.
• Surgical options such as decortication or pleurectomy are aggressive
and only used rarely in selected patients.
PLEURODESIS

Cumulative evidence proposes potential advantages of IPCs over talc pleurodesis
First, pleurodesis is only useful in patients with fully expanded lungs after fluid
evacuation. non-expandable (or ‘trapped’) lungs- not suitable.
Second, Pleurodesis failure progressively increased with prolonged survival.
By 6 months, talc pleurodesis had failed in approximately 50% of patients. 32% of all
patients required further pleural intervention.
Third, talc pleurodesis requires hospitalisation, often for 4–5 days.
Fourth, pleurodesis is known to provoke intense pleural and systemic inflammation,
with a median rise in C reactive protein of 360% from baseline. The resultant pain and
fever can be severe. Talc pleurodesis can cause hypoxaemia and, in severe cases, acute
respiratory failure.
CHOOSING BETWEEN IPC & PLEURODESIS

Wang et al. World Journal of Surgical Oncology (2020)
18:184

PLEURECTOMY
Parietal pleurectomy consists of stripping all of the parietal pleura
from the rib cage and the mediastinum.
Attempted in two different situations:
• The patient who undergoes a diagnostic thoracotomy for an
undiagnosed pleural effusion. If malignant disease is found, an
immediate parietal pleurectomy is useful to prevent recurrence of the
effusion.
• The symptomatic patient with a persistent pleural effusion and
trapping of the ipsilateral lung so that the sclerosing agents is
contraindicated.

PLEUROPERITONEAL SHUNT
Pleuroperitoneal stunt connects pleural and peritoneal cavities by
a one way valve pump chamber.
• It can be used as a alternative in patients with trapped lung or
following failed pleurodesis.
• The need for PPs decreased with advent of IPC, the pleuroperitoneal
shunt is recommended because the nutritional status of the patient is
preserved with this method.

CONCLUSIONS :
• Lung & Breast Cancer : most common causes of MPE
• MPE has poor prognosis (KPS)
• Asymptomatic patient with MPE : Observation
• Goal of management of MPE : to improve symptoms (dyspnoea)

CONCLUSIONS :
• Pleurodesis ONLY if near complete re-expansion of lung after thoracent
• Trapped Lung : ideal therapy Is IPC
• Thoracoscopy : Medical vs Surgical
• Factors to consider before management
• Expected survival
• Symptom relief
• Cost effectiveness

1. Management of Malignant Pleural Effusions ; Am J Respir Crit Care Med Vol 162. pp 1987–
2001, 2000
2. Thorax 2010;65(Suppl 2):ii32eii40. doi:10.1136/thx.2010.136994
3. Malignant pleural effusion: from bench to bedside ;
Ioannis Psallidas, Ioannis Kalomenidis, Jose M. Porcel, Bruce W. Robinson, Georgios
T. Stathopoulos
European Respiratory Review 2016 25: 189-198; DOI: 10.1183/16000617.0019-2016
4. Dixit, Ramakant; Agarwal, KC; Gokhroo, Archana1; Patil, Chetan B; Meena, Manoj; Shah,
Narender S2; Arora, Piyush Diagnosis and management options in malignant pleural
effusions, Lung India: Mar–Apr 2017 - Volume 34 - Issue 2 - p 160-166
doi: 10.4103/0970-2113.201305
5. Chalhoub M, Saqib A, Castellano M. Indwelling pleural catheters: complications and
management strategies. J Thorac Dis. 2018;10(7):4659-4666. doi:10.21037/jtd.2018.04.160
6. Iyer NP, Reddy CB, Wahidi MM, Lewis SZ, Diekemper RL, Feller-Kopman D, Gould MK,
Balekian AA. Indwelling Pleural Catheter versus Pleurodesis for Malignant Pleural
Effusions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2019 Jan;16(1):124-
131. doi: 10.1513/AnnalsATS.201807-495OC. PMID: 30272486.
REFERENCES :

THANK YOU
Etiology & Management of MPE – July 2021
Diagnosis of Pleural Effusion & Management of recurrent MPE – August 2004

Malignant Pleural Effusion in detail for pg

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