Malignant pleural effusion (MPE) is an abnormal collection of fluid in the pleural space caused by the presence of malignant cells. It commonly occurs in advanced cancer and indicates poor prognosis. Treatment of MPE is palliative and aims to drain pleural fluid and prevent recurrence through pleurodesis. Chest tube drainage with chemical sclerosing agents like talc is the standard treatment and achieves a high rate of pleurodesis success. Thoracoscopy with talc poudrage is also effective at draining fluid and achieving pleurodesis. Treatment goals are to relieve symptoms and improve quality of life.

1. MALIGNANT PLEURAL
EFFUSION
DR. M. YIGAH

2. INTRODUCTION
Malignant Pleural Effusion (MPE) is the abnormal collection of exudative
fluid in the pleural space due to the presence of malignant cells in the pleural
space and/or the pleural membrane.
◦ It indicates an advanced or disseminated neoplasm.
◦ Affects 15 % of all cancer patients (Clive et al, 2016)
◦ An overall survival (OS) rate of 3–12 months after diagnosis of MPE (Neville et al 2010)

3. Anatomy of the pleura
Single layer of mesothelial cells
Parietal and visceral pleura
Pleural fluid –
◦ Lubricant
◦ Prevents the lung from collapsing

4. ANATOMYOF PLEURAL MEMBRANE

5. AETIOLOGY
Primary
◦ Malignant mesothelioma
Secondary (Metastatic)
◦ Lung cancer
◦ Breast cancer
◦ Lymphoma
◦ Gastrointestinal cancers – (Gastric,
colorectal ca )
◦ Gynaecological malignancy (Ovarian
cancers)
◦ Others
◦ Unknown primary tumor

6. EPIDEMIOLOGY
•Adult Population
• Both lung cancer and Breast cancer account for 50 - 65% of all malignant effusions.
• Lymphomas, tumours of the genitourinary tract and gastrointestinal tract account for a
further 25%.
• Tumors of unknown primary are responsible for 15% of all malignant pleural effusions.
• Paediatric Population
• Lymphomas or leukemias account for 50% of MPE
• Remaining 50% - mix of tumors such as neuroblastoma, Wilms tumor, and germ cell
neoplasms.

7. OUTLOOK INGHANAAND NIGERIA
Ghana (NCTC)
◦ Breast cancer (84%),
◦ Ovarian cancer (10%),
◦ Endometrial carcinoma (3%),
◦ Fallopian tube cancer (3%)
(Sereboe et al, 2005)
Nigeria (University of Benin Teach. Hosp.)
◦ Breast cancers
◦ Bronchogenic cancer
◦ Cervical cancer
◦ Renal cell cancer
◦ Others
(Omoregbee & Stanley Okugbo, 2021)

8. Pathogenesis
The spread of tumors involves a series of sequential steps called Invasion-Metastasis Cascade.
The predilection sites of metastatic tumor depends on
◦ Anatomic factors
◦ Biochemical factors
Mode of spread to the pleura
◦ Contiguous spread of tumors from neighbouring structures – breast cancers, lung cancers etc.
◦ Haematogenic dissemination – usually the sarcomas
◦ Lymphogenic dissemination - usually the carcinoma
Most tumor seedlings spread to the visceral pleura first before disseminating to
the parietal pleura.

9. PATHOGENESIS
Tumor cells that show tropism toward the pleura express CD44 receptors that bind to hyaluronan on
mesothelium
Tumor cells that implant on the pleura produce growth factors which
◦ Initiate an inflammatory reaction – IL-1, IL-2, TNF and INF
◦ stimulate angiogenesis - Angiopoietin 1 and 2
◦ increase vascular and mesothelial permeability – VEGF, EGF, matrix metalloproteinases (MMP), chemokine.
Tumors can also infiltrate and block the pleural lymphatics thereby impairing the absorption of
pleural fluid.

10. PATHOGENESIS
Not all primary or metastatic lesions to the pleura provoke an effusion.
◦ 55–60% of pleural metastases – Wet Pleural Carcinosis
◦ “WET” pleural carcinosis has a worse prognosis than to “DRY” pleural carcinosis.
Neoplastic lesions in the pleura can also incite an effusion indirectly – Para-malignant Pleural Effusion
◦ There is no direct pleural involvement and no evidence of malignant cells in pleural fluid.

11. PARA-MALIGNANT EFFUSION

12. Clinical Presentation
Clinical features
Asymptomatic – 25% of cases (incidental)
Dyspnoea and Cough
Chest pain – dull ache (rather than pleuritic)
Constitutional symptoms - weight loss, malaise and anorexia
Local symptoms of tumor
PMH – Any history of malignancy, heart failure, renal disease and pneumonia, TB
Drugs - Methotrexate or Amiodarone
Social – Occupational exposures e.g. asbestos, Smoking history

13. Physical examination
General
◦ Ill-looking, weight loss, pallor, peripheral lymph nodes
Respiratory system
◦ Increased respiratory rate and use of accessory muscles of respiration
◦ asymmetrical chest expansion or even bulging of the intercostal spaces.
◦ Stony dull percussion, Decreased tactile fremitus & Decreased breath
sounds
◦ Trachea may deviate if there is an associated mediastinal shift

14. Chest x-ray
• 80% - moderate to large pleural effusion (500 – 2000ml)
• 10% - mild effusion (< 500ml)
• 10% - massive pleural effusion (occupying the entire
hemithorax)
• Important to request for at least 2 views – PA, Lateral
• Features of MPE on an Erect CXR
• Blunting of the costophrenic angle
• blunting of the cardiophrenic angle
• fluid within the horizontal or oblique fissures
• Presence of a meniscus

15. Lateral Decubitus Chest Xray
◦ Very good at detecting small volumes of
fluid.
◦ Very good for very sick patients (ICU)
Massive Pleural Effusion
◦ Complete homogenous opacification of the
hemithorax
◦ immediate therapeutic thoracentesis

16. ULTRASOUND
Available, portable and cheap
Diagnostic purposes
◦ Identify and quantifying small volumes of
effusion.
◦ Pleural thickening > 1cm
◦ Diaphragmatic nodularity or thickening >7 mm,
◦ pleural nodularity/irregularity
Therapeutic purposes
◦ Safe thoracocentesis or chest tube insertion

17. CT Scan
Gold standard of pleural imaging
Features
◦ Loculation,
◦ Parietal Pleural thickening (>1cm)
◦ Circumferential pleural thickening
◦ Nodular Pleural Thickening
◦ Lymph node involvement
It should be done for all MPE of unknown
origin
Can be used to biopsy lesions

18. PET-CT SCAN
Useful for early detection pleural metastases
(Very sensitive) but relatively low specificity
High degree of accuracy in distinguishing
benign from malignant effusion
Hypermetabolism can be seen in either the
pleura or pleural effusion

19. MRI
Good value in delineating malignancy in
the pleural space
better than chest CT for determining
chest wall or diaphragmatic invasion.

20. PLEURAL FLUIDANALYSIS
Samples are obtained by Thoracocentesis (blindly or USG-guided)
A minimum of 50ml is needed for analysis
Larger volumes of 100-200ml are needed for cell block and molecular
testing
Test to run
◦ Total and differential cell count,
◦ chemical analysis (total protein, lactate dehydrogenase (LDH), pH, glucose,
albumin),
◦ microbiological study
◦ Cytological analysis

21. PLEURAL FLUIDANALYSIS
Pleural White Cell Count and Differential
◦ Most MPE are exudates (WBC ≥ 10 X 109/L) – Infective pathology and occasionally
malignancy
◦ Eosinophilic effusion (12-24% of pleural white cell count) –suggestive of
malignancy, parapneumonic TB
◦ Lymphocyte predominant fluid (>50% cells are lymphocytes) – > 90% chance of
Malignancy or TB
◦ High consideration for biopsy

22. PLEURAL FLUIDANALYSIS
Biochemical Analysis
Light criteria has little diagnostic value in MPE
For MPE – other biochemical analysis
◦ Low glucose (<60 mg/dL)
◦ low pH (<7.20)
◦ High Pleural Fluid Amylase – is commonly caused by neoplasm
◦ Adenosine deaminase (ADA) – used to differentiate TB from other causes including
MPE

23. PLEURAL FLUID ANALYSIS
Cytology
◦ The frequency of positive pleural fluid cytologic tests is dependent on the tumor type and number of
specimens
◦ Most patients with adenocarcinomas have positive cytology but it is 25% of patients with Hodgkin
disease.
◦ More separate specimen increase chance of detecting malignant cells
◦ Immunohistochemical stains of malignant cells are used to confirm a diagnosis and to specify tumor type.
◦ Cytology can provide enough DNA to assess mutational analysis for epidermal growth factor receptor
(EGFR)

24. CYTOLOGY
Clumps of neoplastic cells with
Pleomorphism
binucleations, anisokaryosis, nuclear hyperchromasia
increased nuclear/cytoplasmic ratio,
prominent and large nucleoli
cytoplasmic vacuoles

25. PLEURAL FLUIDANALYSIS
Tumor Markers in Pleural Fluids
◦ Molecule that indicates the probable presence of cancer, its aetiology or its future behaviour.
◦ Common marker - Cytokeratin 19 fragment (CYFRA 21–1), CA 15–3, CA-125 and CEA
◦ CEA – lung cancer (59%), GI cancer – 71%
Utility in management
◦ High levels of TM with negative cytology may indicate need for confirmatory test with biopsy

26. PLEURAL BIOPSY
Indicated when cytology is negative, but MPE is still highly suspected
Contraindications –
◦ bleeding diathesis, anticoagulation,
◦ chest wall infection,
◦ lack of patient cooperation
Modalities
◦ Percutaneous Needle Biopsy (Blindly or CT Scan Guided)
◦ Thoracoscopy (Medical or Video assisted)

27. Abram pleural biopsy needle
CT Scan guided percutaneous
pleural biopsy
Sensitivity of about 80%
Specificity of 100%

28. Thoracoscopy
Directly biopsy abnormal or suspicious areas
Enables performance of all the necessary tests
to identify the origin of the malignant tumor
◦ (for example, hormone receptors in breast cancer)
Can be used to pass a chest tube

29. TREATMENT of MPE
Treatment is palliative
Length of survival depends on stage and type of primary tumor
Median survival is 3 to 12 months
◦ Lung cancer has the worst prognosis
◦ Gynaecological malignancies have a longer survival time
◦ Currently the survival time for Breast cancer - 15month

30. TREATMENT of MPE
Principles of treatment
◦ Address the effusion (evacuation and prevention of recurrence)
◦ Address the primary tumor
Treatment options for malignant pleural effusions are determined by
◦ Symptoms and performance status of the patient,
◦ The primary tumor type and its response to systemic therapy,
◦ Degree of lung re-expansion following pleural fluid evacuation

31. TREATMENT of MPE
Treatments options include
◦ Observation
◦ Therapeutic pleural aspiration (thoracocentesis) NO PLEURODESIS
◦ Intercostal tube drainage (tube thoracostomy) and pleurodesis
◦ Thoracoscopy and pleurodesis
◦ Placement of an indwelling pleural catheter.

32. TREATMENT of asymptomatic MPE
Observation
◦ For ASYMPTOMATIC patients with known tumor type
◦ The majority of these patients will become symptomatic in due course and
require further intervention.
◦ Repeated thoracocentesis will interfere with subsequent interventions

33. TREATMENT of symptomatic MPE
Therapeutic pleural aspiration (thoracocentesis)
◦ Provides transient relief of symptoms
◦ Avoids hospitalisation for patients with for frail or terminally ill patients
◦ A high rate of recurrence of effusion at 1 month hence is
◦ not recommended if life expectancy is >1 month.
◦ The volume to drain will be guided by patient symptoms (cough, chest discomfort) and
◦ Should be limited to 1.5 L on a single occasion

34. TREATMENT of symptomatic MPE
Chest tube drainage (Tube Thoracostomy) and Chemical Pleurodesis
◦ Preferred option for patients with MPE (EXCEPT for patients with very short life expectancy)
◦ Pleural fluid is drained with a Small-bore chest tube followed by chemical pleurodesis
◦ Pleurodesis is the artificial obliteration of the pleural space by chemically (sclerosants) or
physically (pleural abrasion) stimulating an inflammatory reaction between the two pleural
membranes
◦ It is to prevent recurrence.

35. CHESTTUBE
INSERTION
Educate the patient on procedure
Obtain consent
Tray – basic set, dressing materials, cleaning
agents
Chest tube (FR- 10-14) and under water
drainage seal

36. Positioning the Patient

37. Connect chest tube to underwater
drainage system
Confirm correct placement
◦ Pleural fluid flowing adequately
◦ Fluid oscillating in tube when not draining
◦ Improvement in symptoms
◦ Chest X-ray
Draining of pleural fluid
◦ maximum of 1.5 l on the first occasion
◦ Any remaining fluid - drained 1.5L 2hrly
◦ Remove tube if there is full lung expansion

38. Complications of chest tube thoracostomy
◦ Re-expansion pulmonary oedema
◦ Pneumothorax
◦ Subcutaneous emphysema
◦ Insertional –
◦ IC neurovascular injury,
◦ intraparenchymal lung placement
◦ Positional -
◦ Tube malposition, blockage or dislodgement
◦ Infection – surgical site infection, empyema

39. TREAMENTOF SYMPTOMATIC MPE
3. Chest tube (Intercostal) drainage and Chemical Pleurodesis
Sclerosing agents for pleurodesis
◦ Mineral – Talc . (80 to 90% success rate and a high safety profile)
◦ Anti-neoplastic agent – (Bleomycin - 58% to 85% success rate)
◦ Antibiotics - (Tetracycline, Quinacrine)
◦ Antiseptic – (Povidone iodine, Silver Nitrate))
◦ Bacterial products - Corynebacterium parvum
◦ Cytokine – INF alpha-2b

40. STUDIES SUCCESS RATEOF
SCLEROSANT
1. Prospective study of 30 patients
(Benjamin Irene Omoregbee and Stanley Okugbo, 2021)
◦ Success rate of 93.4% Povidone group
◦ Success rate of tetracycline group was 93.3%
1. Tetracycline Pleurodesis for Malignant Pleural Effusion-A Review of 38 Cases
(Sereboe et al 2005)
◦ complete success - 61%
◦ Partially successful – 16%
◦ Failed pleurodesis - 23%

41. CHEMICAL Pleurodesis
Administration of talc
◦ Can be as aerosol during thoracoscopy with an atomizer (Talc poudrage)
◦ Can be instilled as a suspension via a chest tube (Talc slurry)

42. CHEMICAL Pleurodesis
Talc Slurry
◦ There must be complete re-expansion of the lungs radiographically.
◦ Instill lidocaine solution (3 mg/kg; maximum 250 mg) into pleural space.
◦ Instill 4-5 g sterile graded talc in 50 ml 0.9% saline.
◦ Clamp tube for 1-2 h.
◦ Remove intercostal tube within 24-48 hr, (In the absence of excessive fluid drainage
(<100ml/ day ).
◦ Patient rotation is NOT NECESSARY after intrapleural instillation of sclerosant

43. Pleurodesis
4. Thoracoscopy and pleurodesis
◦ Very useful in MPE of unknown origin (pleural
biopsy)
◦ Better drainage of pleural fluid (to dissect
adhesions)
◦ Chemical pleurodesis (talc poudrage)
◦ Better success rate than talc slurry
pleurodesis

44. CRITERIA FOR SUCCESSOR FAILUREOF
PLEURODESIS
Complete Successful pleurodesis
◦ Long term relieve of symptoms related to effusion
◦ No radiographic evidence reaccumulation until death
Partially successful pleurodesis
◦ Diminishing of symptoms related to effusion
◦ Partial reaccumulation of fluid ( should be < 50% of initial radiographic evidence).
◦ No need for further therapeutic thoracocentesis for the rest of the patient's life.
Failed Pleurodesis
◦ Lack of success as described above

45. CAUSESOF FAILUREOF PLEURODESIS
◦Trapped lung (thick visceral pleura)
◦Loculated MPE
◦Persistent air leak
◦Bronchial obstruction
◦pulmonary embolism,
◦atelectasis
◦Pleural carcinomatosis

46. Trapped lung
◦ Lung remain collapsed after drainage
◦ From adhesions or pleural
carcinomatosis.
◦ Treatment
◦ Long term indwelling catheter,
◦ pleuro-peritoneal shunt
◦ Decortication
Loculated MPE
◦ Multiple pockets of effusions
◦ Treatment
◦ Intrapleural fibrinolytics (streptokinase –
urokinase)

47. indwelling pleural catheter drainage
Indications
◦ Recurrent and symptomatic malignant effusions.
◦ MPE with trapped lung
Very short hospital stay
Limitations
◦ Higher rate of local complication– local cellulitis, tumor
seeding of tract
◦ It is expensive (buying the vacuum drainage bottle)

48. OTHER TREATMENT OF MPE
Pleuro-peritoneal shunt
◦ Another alternative for palliation when the lung cannot re-expand or pleurodesis is
unsuccessful
◦ Reserved primarily for patients with chylous effusions.
Parietal Pleurectomy
◦ Associated with substantial morbidity and mortality
◦ Nowadays not recommended with advent of pleurodesis and indwelling pleural
catheters

49. LENT SCORE

50. SUMMARY
Malignant Pleural Effusion is a hallmark concluding end of malignancy
Principles of Management
Identification and treat primary tumor
Evacuation of pleural fluid
Prevention of recurrence

51. REFERNCE
Malignant Pleural Effusion and Its Current Management: A Review (Kristijan et al 2019)
Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline
2010 (Roberts et al 2010)
Malignant Effusions (Mikhail Kiselevsky)
Murray Nadels Textbook of Respiratory Medicine Volume 2
Sabiston and Spencer Surgery of the Chest Volume 2
Textbook of Pleural Diseases (Hodder Arnold Publications) – 2nd Edition