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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, 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