malignant pleural effusion

1. Malignant Pleural
Effusions (MPE)
Dr Kamal Bharathi. S

2. Malignant Pleural Effusions
 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 22% of all pleural effusions (and 42% of exudates)

3. Malignant Pleural Effusions
Pleural effusion of pleura
 Malignant Mesothelioma
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

4. Pleural Effusions Related to Metastatic
Malignancies
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

5. Breast Carcinoma
 The second most leading cause of malignant pleural effusion.
 Pleural effusions were more common with lymphangitic spread than without
lymphangitic spread.
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.
 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
Leukemia:
 MCC of pleural effusion in patients with CML and ALL is as a side-effect from the
tryrosine-kinase inhibitor dasatinib.

6. Mechanisms of Pleural Metastasis
 MPE have visceral, but not necessarily parietal pleural involvement.
 It is believed pleural metastases develop when tumors embolize to peripheral
lung and invade visceral pleura first then to parietal.
 Direct invasion from adjacent tumors in the lung, breast or chest wall .
 Hematogenous and lymphatic spread to pleura.
 Combination of increased fluid extravasation from hyperpermeable vessels
(due to VEGF produced by the tumor) and impaired lymphatic outflow-
development of MPE.

8. Pathophysiologic Features
Direct Result
 Pleural metastases with
increased permeability
 Pleural metastases with
obstruction of pleural
lymphatic vessels
 Mediastinal lymph node
involvement with decreased
pleural lymphatic drainage
 Thoracic duct interruption
(chylothorax)
 Bronchial obstruction
(decreased pleural pressures)
 Pericardial involvement.
Indirect Result
 Hyponatremia
 Postobstructive
pneumonitis
 Pulmonary embolism
 Postradiation therapy

9. Para-Malignant effusions
 Can develop in cancer patients without tumor involvement of the pleura.

10. Clinical Presentation
 Dyspnea, 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: anorexia, weight loss, or tumor fever.

11. Radiographic features
Plain radiograph
 Insensitive at distinguishing it from a benign effusion.
 In cases where multiple nodular regions or pleural thickening are present the
diagnosis may be evident

12. CT
number of features are recognised, including:
a) circumferential pleural thickening
b) nodular pleural thickening
c) parietal pleural thickening greater than 1 cm
d) mediastinal pleural involvement
e) pleural calcification generally suggests a benign process
In many cases the primary malignancy will be
visible (e.g. breast cancer, bronchogenic cancer)
and/or evidence of pulmonary or bony
metastases will be visible.
Left-sided effusion and multiple pleural
nodules. Pleural biopsy showed
adenocarcinoma

13.  showing pleural calcification (left, black arrow) and a nodule (black arrow) in the right lower lobe
with a minimal right-sided effusion. Fine needle aspiration and immunohistochemistry from the
nodule confirmed adenocarcinoma

14.  (left) showing right moderate pleural effusion (black arrow) and mediastinal
lymphadenopathy (white arrow). Thoracocentesis suggested a chylothorax (triglyceride
150 mg/dl and cholesterol of 45 mg/dl, right) and mediastinoscopic biopsy confirmed
lymphoma.

15. • showing right moderate pleural effusion (black arrow) and a large right
lower lobe mass (red arrow).

16. FDG-PET:
 More sensitive than conventional imaging in diagnosing malignant pleural
disease and distinguishing them from benign processes
PET/CT image demonstrating metastatic
lung cancer, evident as bright areas
(in yellow) at the left base and the right
hilum.

17. Medical Approaches for Diagnosis and
Management

18. 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.
 There are no absolute contraindications to performing thoracentesis.
 Relative contraindications include a minimal effusion ( <1 cm in lateral
decubitus view), bleeding diathesis, anticoagulation, and mechanical
ventilation.
 Serum creatinine levels of > 6.0 mg/dl are at a considerable risk of bleeding

19.  patient with massive left-sided pleural effusion (left). Subsequent to
intercostal tube drainage, the patient developed re-expansion pulmonary
edema (right). The patient was managed with diuretics and oxygen and
recovered at 48 hours.

20. Pleural fluid analysis

21. Closed pleural biopsy
• Abrams or Cope needle
• lower sensitivity due to the lower early
stage and distribution of tumor

22. Tumor markers in pleural fluid
 Possibility of diagnosing MPE when increased levels of tumor markers are
found in the pleural fluid.
 First, measurement of pleural CEA is a diagnostic tool for confirming MPE and
is useful for the differential diagnosis between malignant pleural
mesothelioma and metastatic lung cancer.
 A high level of pleural CEA seems to rule out malignant mesothelioma.
 Second, 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
 Mesothelin and fibulin-3 – to detect pleural mesothelioma at an earlier stage.

23. Medical thoracoscopy & VATS
 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:
a) the evaluation of exudative effusions of unknown.
b) to rule out cause, staging of malignant mesothelioma or lung cancer, & treatment
of malignant or other recurrent effusions.
c) talc pleurodesis.
d) Another purpose may be biopsy of the diaphragm, lung, mediastinum, or
pericardium.
e) Thoracic surgery backup should be available.

24.  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- pleural fluid cytology alone.
 Port side radiation post procedure in patients with mesothelioma to decrease the
risk of tract tumor seeding with malignant cells.

25. a) Candle wax metastatic nodules on the pericardium of a 70-year-old patient with a pleural effusion
from breast adenocarcinoma. Note the diffuse invasion of the parietal pleura
b) Invasion of the parietal pleura from Hodgkin’s lymphoma as discovered during thoracoscopy in a 39-
year-old patient with a pleural effusion. In addition to the nodule, there is diffuse invasion of the parietal
pleura as well as a mass within the mediastinum

26. a) A peripheral lung adenocarcinoma in a 46-yearold male, nonsmoker, presenting as an
“undiagnosed” pleural effusion. Note the satellite nodule on the visceral pleura and the
invasion of the parietal pleura
b) tumor nodules and whitish areas with pleural thickening on the parietal pleura- diffuse
malignant mesothelioma

27. (A) showing right-sided hydropneumothorax following thoracocentesis and lung
entrapment due to a thick visceral pleural peel. The computed tomography image.
(B) shows a large intra-bronchial mass, loculated effusion
and ipsilateral mediastinum

28. Bronchoscopy
 The diagnostic yield of bronchoscopy is low in patients with undiagnosed
pleural effusions.
Indicated when,
 Endobronchial lesions are suspected because of hemoptysis, atelectasis, or
large effusions without contralateral mediastinal shift.
Left complete
lung collapse
Left main
bronchus
endobronchial
hamartoma.

29. Management of malignant effusion
 MPE whether primary or metastatic- advanced incurable disease with poor
prognosis.
 Median survival of 4-6 months. Among lung cancers have shortest and longest
(9-12 months) if due to other causes.
 Management should include measures to control the symptoms arising from
the pleural disease as well as underlying malignancy.
 Therapeutic thoracocentesis 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.

30. Management of malignant effusion
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.

31. 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.

32. 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 space and lead to
increased systemic toxicity. But not in the case of pemetrexed.

33. lntrapleural
Chemotherapy
 Results are mostly
disappointing.

34.  Staphylococcus aureus superantigen, 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.

35. 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.

36. 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 include infections, clogging of the catheter, or other rare
events, such as empyema or tumor spread along the catheter track.

39. 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.

40. Complications of indwelling pleural
catheter
IPC-related pleural infection:
 Cutaneous flora, including Staphylococcus spp (especially S. aureus), followed
by Pseudomonas aeruginosa and Enterobacteriaceae.
 typically occurs at least 6–8 weeks after insertion.
Patient-related factors IPC-related factors Clinician-related factors
Underlying tumour
Ongoing chemotherapy
Immune status
Comorbidities
Skin diseases
Ability to adhere to
aseptic techniques
Drainage regimen
Drainage volume
Patients and carers
education
Manufacturers
Duration of IPC in situ
Insertion procedure
Expertise in after-care
Surveillance and audit
Dressing techniques
Infection control
bundles

41. Complications of indwelling pleural
catheter
a) Catheter tract metastasis:
 Treated effectively with simple
analgaesics and external beam
radiotherapy without the need to
remove the IPC.
 Prophylactic radiotherapy in
reducing postprocedural tract
metastases in mesothelioma
remains controversial.
CT images of a patient with mesothelioma who developed
catheter tract metastasis around his indwelling pleural
catheter (IPC), which was in place for 5 months

42. Complications of indwelling pleural
catheter
b)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.

43. Complications of indwelling pleural
catheter
c) Fracture of catheters on
removal:
 Spontaneous pleurodesis can
develop, which permits catheter
removal.
 IPC may be removed due to
cessation of drainage or
development of empyema or
severe pain.
 Removal of the catheter requires
freeing the cuff from the often
tight fibrinous adhesions.
the part distal to the cuff adhered tightly to underlying tissue
after freeing the cuff.

44. d) 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.
e) Cost of IPC
f) Nutrition and cell loss
g) Chest pain

45. Pleurodesis
 Pleurodesis is the obliteration of the pleural space by fusion of the visceral and parietal pleurae with fibrous
tissue.
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),
 Nitrates.

46.  It has been supposed that the ideal pleural sclerosing agent should be easily
administered, safe, inexpensive, and widely available.
 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.

48.  Pleuritic chest pain and fever are the most common side effects of sclerosant
administration.
 Lidocaine (3 mg/kg; maximum 250 mg) should be administered intrapleurally
just prior to sclerosant administration.
 Premedication should be considered to alleviate anxiety and pain associated
with pleurodesis.
 Patient rotation is not necessary after intrapleural instillation of sclerosant.
 The intercostal tube should be clamped for 1 h after sclerosant
administration.
 In the absence of excessive fluid drainage (>250 ml/ day) the intercostal tube
should be removed within 24-48 hr of sclerosant administration.

49. 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) showed a significant
association with the probability of failure.
The most likely cause of pleurodesis failure is the presence of trapped lung.
Before pleurodesis, the position of mediastinum should be evaluated.

50. 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.
 Failed pleurodesis: Lack of success as defined above

51. 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.

53. 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.

54. 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.

55. Gene therapy
 One approach is the intrapleural administration of replication-deficient
recombinant adenovirus (rAd)that has been genetically engineered to contain
the herpes simplex virus thymidine kinase gene (HSV tk). It is hoped that
delivery of rAd HSV tk directly into the pleural cavity of patients with
mesothelioma will transduce the tumour cells, enabling them to express viral
thymidine kinase and conveying sensitivity to the normally nontoxic antiviral
drug ganciclovir.
 A phase I dose escalation clinical trial ofadenovirus-mediated intrapleural HSV
tk-glanciclovirgene therapy demonstrated that the HSV tk gene iswell
tolerated and results in detectable gene transferwhen delivered at high
doses. Further development oftherapeutic trials for the treatment of
localizedmalignancy is warranted

56. Thank You…!!!