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, 2 nd ed. 2008 Slide 2 Malignant
Pleural Effusions 95% MPM pts suffer from a pleural effusion 95%
MPM pts suffer from a pleural effusion Dyspnea most common
presenting symptom Dyspnea most common presenting symptom Fear of
drowning to death Fear of drowning to death Slide 3 Malignant
Effusion: significant burden Western Australia (population 2
million): ~8,000 inpatient bed days per year US$10 million
inpatient cost per year Slide 4 Myths in Malignant Effusions
Although 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 Slide 5 Myth: Patients with malignant
effusions are breathless because the fluid compresses on the lung,
restricting its expansion. Slide 6 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: FEV 1 or FVC 0.2 L; TLC 0.4 L Lung
Compression not the key factor Slide 7 Why are patients breathless?
The pleural cavity expands to accommodate the fluid. Altered
respiratory mechanics contribute to breathlessness Slide 8 Why are
patients breathless? Drainage of effusion remove weight from
hemidiaphragm and restore respiratory mechanics Slide 9 Courtesy:
Dr Naj Rahman Small effusion Diaphragm normal Large effusion
Diaphragm inverted Slide 10 2.93kg Sofia Lee born Sept 09 3kg 3L
effusion Slide 11 Myth: Drainage of effusion in patients with a
trapped lung is not useful. Slide 12 Drainage of effusion in
patients with a trapped lung can still improve symptoms 70/M
Metastatic Thyroid Cancer Slide 13 Myth: The more fluid sent for
cytology, the more likely you can make a malignant diagnosis. Slide
14 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 2009 Sallach SM et al Chest 2002 Anderson CB et al
Cancer 1974 Slide 15 Cytology diagnostic sensitivity 20-60% depends
on: type of tumor (adeno >> mesothelioma) experience of
cytologists tumor load Benign MPM TTF-1 Light RW & Lee YCG.
Textbook of Pleural Disease, 2 nd ed. 2008 Indication: Diagnosis of
Pleural Malignancy Slide 16 Myth: Pleuroscopy or Thoracoscopy
biopsy can safely exclude malignant pleural disease. Slide 17
Pleuroscopy / Medical Thoracoscopy Jacobaeus performing
thoracoscopy Felice Cova Tassi GF. International Pleural Newsletter
2004 Slide 18 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 Slide 19 Mesothelioma:
nodular lesions Slide 20 Mesothelioma: diffuse thickening biopsy
often fibrous tissue only false negative possible Slide 21 Myth:
FDG PET is not useful in management of malignant pleural diseases.
Slide 22 PET Limited diagnostic value: Malignancy vs benign pleural
diseases Malignancy vs benign pleural diseases Mesothelioma vs
metastatic carcinoma Mesothelioma vs metastatic carcinoma West SD
& Lee YCG. Clin Pulm Med 2006 Slide 23 Percutaneous biopsy
guided by PET/CT Evolving option. In selected patients can be
useful. Slide 24 Response 1 cycle chemo Francis et al J Nucl Med
2007;48:1449-1458 Prognosis Nowak et al. Clin Cancer Res; 2010,
16(8); 240917. Semiquantitative FDG PET using volume-based
parameter of TGV Slide 25 Novel Tracers in mesothelioma FLT
Fluorothymidine Thymidine is a pyrimidine analogue incorporated
into DNA CELL PROLIFERATION tracer Not influenced by pleural
inflammation, infection or pleurodesis Courtesy Prof Ros Francis
(Australia) Slide 26 baseline post chemo FLT PET response
assessment Courtesy Prof Ros Francis (Australia) Slide 27 Hypoxia
imaging in mesothelioma FMISO PET-CT FDG PET-CT Slide 28
18F-Annexin Phase I: apoptosis marker Scan before vs after
chemotherapy to assess response Slide 29 Myth: Pleurodesis is the
standard first choice for management of malignant pleural
effusions. Slide 30 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 2
nd ed 2008 Slide 31 Courtesy Dr Rodriguez Panadero Slide 32
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?
Slide 33 TALC IS NOT GLUE !!! Even spread over pleura not essential
Slide 34 Dresler CM. Chest 2005: Multicenter phase III study talc
poudrage (n=242) vs slurry (n=240) at 6 months < 50% Slide 35
Thoracoscopic poudrage v Bedside pleurodesis Dresler et al. Chest
2005 Poudrage n=242 Slurry n=240 Successful Pleurodesis (30 d)
78%71% p=NS Yim AP et al. Ann Thorac Surg 1996 Poudrage n=28 Slurry
n=29 No recurrence 2726 p=NS Terra RM et al. Chest 2009 Poudrage
n=30 Slurry n=30 No symptomatic recurrence 2526 p=NS Mohsen et al.
Eur J Cardiothorac Surg 2010 Poudrage n=22 Iodine n=20 No further
intervention 2017 p=NS Slide 36 Failed VATS Pleurodesis Slide 37
Dresler CM. Chest 2005: CALGB phase III study l More side effects
from thoracoscopic (VATS) poudrage l 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 Failure18 (8%)8 (4%)p=0.007 Fatal Resp
Failure5 (2%)6 (3%)p=NS Slide 38 Significant shortcomings: Success
rate low ( 70%) even in selected patients Unsuitable in trapped
lung Overall 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
Slide 48 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 Slide 49 Myth: Indwelling pleural
catheters are associated with significant and serious complications
eg infection, protein loss. Slide 50 n=Incidence Mild Pain after
insertion20/5635.7% Symptomatic loculation44/6217.0% Pain during
drainage8/1475.4% Catheter Occlusion29/6244.6%
Pneumothorax15/4383.4% Tumour Seeding20/5963.4% Empyema29/10912.7%
Skin infection/ Cellulitis22/8322.6% Complications of Indwelling
Catheters Wrightson J, Fysh E, Maskell N, Lee YCG. Curr Opin Pulm
Med 2010 Slide 51 Catheter Tract Metastases Incidence 0-6% Response
to radiotherapy IPCs withstand irradiation Janes SM, Lee YCG et al.
Chest 2007 Slide 52 Slide 53 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 Slide 54 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 Slide 55 IPC Fracture Safe to leave
fractured IPC in situ Safe to leave fractured IPC in situ No
increased infection risk No increased infection risk No need to
retreive No need to retreive Fysh et al. Chest 2012 Slide 56 Myth:
Pleural effusion is always the cause of the breathlessness in
patients with a malignant pleural effusion. Myth: Malignant pleural
mesothelioma seldom metastasize. Slide 57 Breathlessness Always
consider other concomitant causes of dyspnea - Lung parenchymal
causes Consolidation, Trapped lung, Asbestosis - Lung vascular and
lymphatic causes Emboli, Lymphangitis - Cardiac causes Myocardial
and Pericardial diseases; Arrhythmia - Deconditioning Slide 58
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% Slide 59 Known (L) MPM with
loculated effusion Presented acute dyspnea Slide 60 Results:
Mesothelioma metastasizes Intra-thoracic Sites Ipsilateral
parenchyma56.8% Pericardium44.7% Diaphragm39.5% Contralateral
parenchyma35.7% Contralatateral pleura31.8% Chest wall
invasion29.6% Myocardium12.5% Slide 61 Results: Mesothelioma
metastasizes Extra-thoracic Sites Liver29.1% Peritonium24.2%
Bone15.0% Adrenals11.7% Spleen11.3% Kidneys9.5% G I tract8.0%
Thyroid7.3% Brain2.9% Slide 62 Known (R) MPM with loculated
effusion Presented acute dyspnea Pulmonary emboli 6%; Cause of
death in 4% of MPM Slide 63 Median age of MPM (UK) 75 yrs old
Co-morbidity common Slide 64 70% of asbestos workers were heavy
smokers COPD common Slide 65 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. Slide 66 The incidences of
mesothelioma and malignant pleural effusion are likely to continue
to rise Slide 67 Respirology 2011 Slide 68 Courtesy Prof Bai
(Shanghai) Slide 69 Slide 70 Slide 71 Pleural Effusions and Vienna
Percussion (stony) dullness Percussion (stony) dullness described
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 Slide 72 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