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Malignant Pleural Effusion: Prevalence. ~ 200,000 MPE / year in USA 1:4 Lung Cancer pt; 1:3 Breast; 9:10 Mesothelioma ~ 100,000 MPE from Lung Cancer / yr in Europe Pleural effusion is the first sign of cancer in 25% of patients with MPE. - PowerPoint PPT Presentation
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Malignant Pleural Effusion: Prevalence
• ~ 200,000 MPE / year in USA 1:4 Lung Cancer pt; 1:3 Breast; 9:10 Mesothelioma
• ~ 100,000 MPE from Lung Cancer / yr in Europe
• Pleural effusion is the first sign of cancer in 25% of patients with MPE
Light RW & Lee YCG. Textbook of Pleural Disease, 2nd ed. 2008
Malignant Pleural Effusions
• 95% MPM pts suffer from a pleural effusion
• Dyspnea most common presenting symptom
• Fear of ‘drowning to death’
Malignant Effusion: significant burden
Western Australia (population 2 million):
Year
2004
Tot
al B
ed D
ays
6500
7000
7500
8000
8500
9000
9500
10000
2005 2006 2007 2008 2003
~8,000 inpatient bed days per year
US$10 million inpatient costper year
Myths in Malignant EffusionsAlthough MPE common recent advances in
knowledge has shed light on many myths in
- Why symptoms develop
- Diagnostic workup and limitations
- Pleurodesis and its limitations
- Indwelling pleural catheters: pros and cons
Myth:
Patients with malignant effusions are breathless
because the fluid compresses on the lung,
restricting its expansion.
Why are patients breathless?
Effects on Diaphragm: Weight of the effusion profoundly affects the diaphragm Dyspnea related to effect on the diaphragm:
- No dyspnea if diaphragm domed and moves normally- Severe dyspnea if diaphragm inverted and not move
with respiration
Lee YCG & Light RW. in Encyclopedia of Respiratory Disease 2006
Effects on Lung Function: For 1 L fluid drained: FEV1 or FVC 0.2 L; TLC 0.4 LLung Compression not the key factor
Why are patients breathless? The pleural cavity expands to accommodate the fluid.
Altered respiratory mechanics contribute to breathlessness
Why are patients breathless? Drainage of effusion remove weight from
hemidiaphragm and restore respiratory mechanics
Courtesy: Dr Naj Rahman
Small effusion Diaphragm normal
Large effusion Diaphragm inverted
2.93kg
Sofia Lee born Sept 09
3kg
3L effusion
Myth:
Drainage of effusion in patients with a trapped
lung is not useful.
Drainage of effusion in patients with a trapped lung can still improve symptoms
70/M Metastatic Thyroid Cancer
Myth:
The more fluid sent for cytology, the more likely
you can make a malignant diagnosis.
Pleural fluid for Cytology Analyses
‘More likely to make a malignant diagnosis on cytology if you send more fluid?’ True or False
No significant increase in sensitivity of cytology when >50mL of fluid is sent:
Swiderek J et al Chest 2010 Abouzgheib W et al Chest 2009Sallach SM et al Chest 2002Anderson CB et al Cancer 1974
Cytology diagnostic sensitivity 20-60% depends on: type of tumor (adeno >> mesothelioma)
experience of cytologiststumor load
Benign MPM TTF-1
Light RW & Lee YCG. Textbook of Pleural Disease, 2nd ed. 2008
Indication: Diagnosis of Pleural Malignancy
Myth:
Pleuroscopy or Thoracoscopy biopsy can safely
exclude malignant pleural disease.
Pleuroscopy / Medical Thoracoscopy
Jacobaeus performing thoracoscopy
Felice Cova
Tassi GF. International Pleural Newsletter 2004
• Thoracoscopy is not gold standard
• 142 Medical Thoracoscopy / Pleuroscopy
• Negative Predictive Value 90%
• False negative occurs – all mesothelioma
• Similar rate to previous papers - despite advances in immunohist/thoracoscopy
Mesothelioma: nodular lesions
Mesothelioma: diffuse thickeningbiopsy often fibrous tissue onlyfalse negative possible
Myth:
FDG PET is not useful in management of
malignant pleural diseases.
PETLimited diagnostic value:
• Malignancy vs benign pleural diseases• Mesothelioma vs metastatic carcinoma
West SD & Lee YCG. Clin Pulm Med 2006
Percutaneous biopsy guided by PET/CTEvolving option. In selected patients can be useful.
Response – 1 cycle chemo
Francis et al J Nucl Med 2007;48:1449-1458
Prognosis
Nowak et al. Clin Cancer Res; 2010, 16(8); 2409–17.
Semiquantitative FDG PET using volume-based parameter of TGV
Novel Tracers in mesothelioma
FLT – FluorothymidineThymidine is a pyrimidine analogue incorporated into DNA CELL PROLIFERATION tracerNot influenced by pleural inflammation, infection or pleurodesis
Courtesy Prof Ros Francis (Australia)
baseline
post chemo
FLT PET response assessment
Courtesy Prof Ros Francis (Australia)
Hypoxia imaging in mesothelioma
FMISO PET-CT
FDG PET-CT
18F-Annexin Phase I: apoptosis markerScan before vs after chemotherapy to assess response
Myth:
Pleurodesis is the standard first choice for
management of malignant pleural effusions.
• This approach is now strongly challenged
i) Pleurodesis (talc) is less efficacious as often reported and can induce significant complications
ii) Aim for management is relief of Dyspnea and QoL: Drainage is the key
Pleural Effusion: Management
Light RW & Lee YCG. Textbook of Pleural Diseases 2nd ed 2008
Cou
rtes
y D
r R
odri
guez
Pan
ader
o
Courtesy Dr Carla Lamb
Controversy: Is talc better delivered via • thoracoscopy (poudrage) or chest tube (slurry)
‘Talc poudrage is superior: Distribute talc over entire pleural surface’Fact or Myth?
TALC IS NOT GLUE !!!
Even spread over pleura not essential
Dresler CM. Chest 2005: Multicenter phase III study talc poudrage (n=242) vs slurry (n=240)
at 6 months < 50%
Thoracoscopic poudrage v Bedside pleurodesisDresler et al.Chest 2005
Poudrage n=242
Slurryn=240
Successful Pleurodesis (30 d) 78% 71% p=NS
Yim AP et al. Ann Thorac Surg 1996
Poudragen=28
Slurryn=29
No recurrence 27 26 p=NS
Terra RM et al. Chest 2009
Poudragen=30
Slurryn=30
No symptomatic recurrence 25 26 p=NS
Mohsen et al. Eur J Cardiothorac Surg 2010
Poudragen=22
Iodinen=20
No further intervention 20 17 p=NS
Failed VATS Pleurodesis
Dresler CM. Chest 2005: CALGB phase III study
More side effects from thoracoscopic (VATS) poudrage
2.3% patients died from ARDS
Complications of Talc Pleurodesis
Thoracoscopic Poudrage
(n=223)
Chest Tube Slurry (n=196)
Pneumonia (antibiotics) 21 (9%) 7 (4%) p=0.03
Respiratory Failure 18 (8%) 8 (4%) p=0.007
Fatal Resp Failure 5 (2%) 6 (3%) p=NS
Significant shortcomings: • Success rate low (70%) even in selected patients
• Unsuitable in trapped lung
Overall <50% pts benefit
• Side effects common: can be lethal
Talc Pleurodesis
Do we really need to create pleurodesis?
Relieve symptoms without pleurodesis using
Ambulatory Small Bore Catheter Drainage
Tunnelled Indwelling Pleural Catheter
• Ambulatory drainage outside hospital • Patient controlled drainage whenever breathless
Tunnelled Indwelling Pleural Catheter
• 39,000 units sold in USA alone each year• 1st choice for malignant effusion in many centers
Malignant Pleural Effusion
Talc Pleurodesis
Indwelling Pleural Catheter
Cost Economics: Bed days; Inpatient costs
IPC significantly reduce hospital days for patients with malignant effusions over talc pleurodesis
p<0.001
Effusion-Related Bed Days
IPC Pleurodesis
Day
s
0
10
20
30
40
50
60
p<0.001
N: 34 31Median: 3.0 10.0 IQR: 1.75-8.25 6.0-18.0
Fysh E et al. Chest 2012
JAMA 2012 in press
Randomized Trial on Management of Malignant Effusion using Indwelling Pleural Catheters
(British Lung Foundation)
Malignant Pleural Effusionsn=110
Visual Analog Score for breathlessness (daily)QoL: Wks 1, 2, 4, 6, 10, 14, 18, 22, 26, 39, 52
Ambulatory indwelling catheter drainage
Standard care & in-patient talc pleurodesis
randomize
From: Effect of an Indwelling Pleural Catheter vs Chest Tube and Talc Pleurodesis for Relieving Dyspnea in Patients With Malignant Pleural Effusion: The TIME2 Randomized Controlled Trial JAMA. 2012;307:2383-9
Indwelling Pleural Catheters offer the same improvement in QoL as talc pleurodesis
Puri V et al. Ann Thorac Surg.2012 Treatment of Malignant Pleural Effusion: A Cost-Effectiveness Analysis
The most cost-effective treatment for a malignant pleural effusion (in USA setting):
• Indwelling Pleural Catheter if survival short (3 mths) • Bedside Pleurodesis if survival > 12 mths
Cost-Effectiveness
• Define place of IPC in management algorithm of MPE
• Define optimal management and aftercare
• Significant potential to grow in its use in both malignant and non-malignant effusions
Fysh E and Lee YCG. J Thorac Oncol 2011
Myth:
Indwelling pleural catheters are associated with
significant and serious complications
eg infection, protein loss.
n= Incidence
Mild Pain after insertion 20/56 35.7%
Symptomatic loculation 44/621 7.0%
Pain during drainage 8/147 5.4%
Catheter Occlusion 29/624 4.6%
Pneumothorax 15/438 3.4%
Tumour Seeding 20/596 3.4%
Empyema 29/1091 2.7%
Skin infection/ Cellulitis 22/832 2.6%
Complications of Indwelling Catheters
Wrightson J, Fysh E, Maskell N, Lee YCG. Curr Opin Pulm Med 2010
Catheter Tract Metastases
• Incidence 0-6% • Response to radiotherapy• IPCs withstand irradiation
Janes SM, Lee YCG et al. Chest 2007
IPC Removal
Auto-pleurodese: No drainage 4-6 wk. No fluid on CXR
Pleural infection: Only if uncontrolled sepsis
No symptom improvement with drainage
• Removal as outpatient
• Careful dissection around the cuff. PULL HARD!
• Fracture of IPC during removal a risk
IPC Fracture• Pro-fibrotic cuff to secure
IPC in place
• Dense subcut adhesions develop over time
• Can be difficult/impossible to free adhesions to remove
• Fracture can occur, often at cuff level
• Pro-fibrotic cuff to secure IPC in place
• Dense subcut adhesions develop over time
• Can be difficult/impossible to free adhesions to remove
• Fracture can occur, often at cuff level
IPC Fracture
• Safe to leave fractured IPC in situ • No increased infection risk• No need to retreive
Fysh et al. Chest 2012
Myth:
Pleural effusion is always the cause of the
breathlessness in patients with a malignant
pleural effusion.
Myth:
Malignant pleural mesothelioma seldom
metastasize.
Breathlessness Always consider other concomitant causes of dyspnea
- Lung parenchymal causesConsolidation, Trapped lung, Asbestosis
- Lung vascular and lymphatic causes Emboli, Lymphangitis
- Cardiac causes Myocardial and Pericardial diseases; Arrhythmia
- Deconditioning
Mesothelioma in Western Australia & Bristol:A two-centre post-mortem study
• Largest post-mortem series in MPM (n=318)• Mesothelioma not a local disease: Metastatic spread common
• Extra-pleural metastases 85.2%• Nodal metastases 57.1% • Extra-thoracic metastases 59.7%
Known (L) MPM with loculated effusionPresented acute dyspnea
Results: Mesothelioma metastasizes
Intra-thoracic Sites
Ipsilateral parenchyma 56.8%
Pericardium 44.7%
Diaphragm 39.5%
Contralateral parenchyma 35.7%
Contralatateral pleura 31.8%
Chest wall invasion 29.6%
Myocardium 12.5%
Results: Mesothelioma metastasizes
Extra-thoracic SitesLiver 29.1%Peritonium 24.2%Bone 15.0%Adrenals 11.7%Spleen 11.3%Kidneys 9.5%G I tract 8.0%Thyroid 7.3%Brain 2.9%
Known (R) MPM with loculated effusionPresented acute dyspnea
Pulmonary emboli 6%; Cause of death in 4% of MPM
Median age of MPM (UK) 75 yrs oldCo-morbidity common
70% of asbestos workers were heavy smokersCOPD common
Summary• Weight of malignant effusion contributes
significantly to dyspnea.
• Pleural fluid cytology is useful but large volume beyond 60mL adds little diagnostic sensitivity.
• Pleuroscopy biopsy can be false negative (~10%). Imaging guided biopsy useful alternatives.
• Indwelling pleural catheter and talc pleurodesis offer different advantages.
• Talc poudrage has no advantages over slurry.
The incidences of mesothelioma and malignant pleural effusion are likely to continue to rise…
Respirology 2011
Courtesy Prof Bai (Shanghai)
Courtesy Prof Bai (Shanghai)
Pleural Effusions and Vienna
Percussion (stony) dullnessdescribed 1808 by a Prof of Medicine at Vienna University
Prof Josef Leopold Auenbrugger
Son of innkeeper; used to watch his father tapping on wine barrels for level of wine left
If only we are elephants…
Elephant are auto-pleurodesed and live happily without a pleural cavity, and never have to worry about effusions!
West J. International Pleural Newsletter 2004