A Case of Mesothelioma

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A Case of Mesothelioma

  1. 1. Dr. Prasanth Sankar Prof. Dr. E. Dhandapani’s Unit
  2. 2. <ul><li>Ramu </li></ul><ul><li>38/m </li></ul><ul><li>Thiruvannamalai </li></ul><ul><ul><li>C/o </li></ul></ul><ul><ul><ul><li>Left sided chest pain </li></ul></ul></ul><ul><ul><ul><li>6 mo </li></ul></ul></ul><ul><ul><ul><li>Breathlessness </li></ul></ul></ul>
  3. 3. <ul><li>H/o breathlessness – 6 mo </li></ul><ul><ul><li>Progressively increasing </li></ul></ul><ul><ul><li>Initially on exertion, later on at rest </li></ul></ul><ul><ul><li>More on lying on right side </li></ul></ul><ul><ul><li>No PND, orthopnea </li></ul></ul><ul><ul><li>Severe for the last 6 days </li></ul></ul>
  4. 4. <ul><ul><li>Left sided Chest Pain </li></ul></ul><ul><ul><li>Pleuritic type initially </li></ul></ul><ul><ul><li>Later on persistant, aching and pricking type </li></ul></ul><ul><ul><li>More on the lateral aspect of L chest </li></ul></ul><ul><ul><li>Not assoc with palpitation, sweating </li></ul></ul><ul><ul><li> with coughing and lying on left side </li></ul></ul><ul><li>Cough </li></ul><ul><ul><li>Mostly non productive </li></ul></ul><ul><ul><li>Occasional expectoration of mucoid sputum </li></ul></ul><ul><ul><li>Non purulent; No hemoptysis </li></ul></ul>
  5. 5. <ul><li>Gradual restriction of movements of L chest </li></ul><ul><li>Painful Swelling -Lateral side of L chest-3 wks </li></ul><ul><li>H/o loss of weight -6-8 kg/6mo </li></ul><ul><li>H/o Loss of Appetite + </li></ul><ul><li>No h/o </li></ul><ul><ul><li>Cyanosis </li></ul></ul><ul><ul><li>Leg swelling, Abdominal distension </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Oliguria </li></ul></ul><ul><ul><li>Giddiness, LOC </li></ul></ul><ul><ul><li>Chest Trauma </li></ul></ul>
  6. 6. <ul><li>Evaluated for symptoms at local hospital </li></ul><ul><li>Based on X ray findings – empirical ATT </li></ul><ul><li>Symptoms continued to progress </li></ul><ul><li>Discontinued ATT after 3 mo </li></ul><ul><li>Attended CT OP at GSH- adv CT chest </li></ul><ul><li>Severe dyspnea at rest -6 days </li></ul><ul><li>Referred from local hospital to GSH </li></ul>
  7. 7. <ul><li>No history S/o </li></ul><ul><ul><li>Bronchial Asthma, COPD, TB, </li></ul></ul><ul><ul><li>Radiation Exposure </li></ul></ul><ul><ul><li>Heart disease/ HTN/DM/CKD </li></ul></ul><ul><ul><li>Trauma/interventions </li></ul></ul><ul><ul><li>Connective tissue disorders </li></ul></ul><ul><ul><li>Smoker – beedis – 25 pack yrs </li></ul></ul><ul><ul><li>Consumes alcohol once/twice per week </li></ul></ul><ul><ul><li>No high risk behaviour </li></ul></ul><ul><ul><li>Manual labourer – rice godown </li></ul></ul>Personal History
  8. 8. <ul><li>G/E- </li></ul><ul><ul><li>Conscious , Oriented </li></ul></ul><ul><ul><li>Moderate built & poorly nourished </li></ul></ul><ul><ul><li>Severely Dyspneic, Tachypneic, restless </li></ul></ul><ul><ul><li>Difficult to speak in sentences </li></ul></ul><ul><ul><li>No pallor, icterus, cyanosis, clubbing, edema </li></ul></ul><ul><ul><li>No significant lymph nodes </li></ul></ul><ul><ul><li>BP – 110/70 </li></ul></ul><ul><ul><li>Pulse – 108/min, regular </li></ul></ul><ul><ul><li>RR – 34/min SpO2 – 88% (room air) </li></ul></ul><ul><ul><li>JVP – not raised </li></ul></ul>
  9. 9. <ul><li>RS </li></ul><ul><ul><li>Trachea – marked left shift </li></ul></ul><ul><ul><li>Marked scoliosis of thoracic spine- concavity to Left </li></ul></ul><ul><ul><li>Severe crowding of ribs left side, Dilated veins + </li></ul></ul><ul><ul><li>Chest movements markedly restricted on L side </li></ul></ul><ul><ul><li>5X3X2cm tender firm swelling over Left 7,8,9 interspaces </li></ul></ul><ul><ul><ul><li>Immobile </li></ul></ul></ul><ul><ul><ul><li>Tendernss of surrounding areas of chest wall </li></ul></ul></ul><ul><ul><ul><li>No sinuses, </li></ul></ul></ul><ul><ul><ul><li>non pulsatile </li></ul></ul></ul>
  10. 10. <ul><ul><li>Dull/ stony dull percussion note - Left </li></ul></ul><ul><ul><li>Hyper-resonance - Right </li></ul></ul><ul><ul><li>VF/VR  - Left </li></ul></ul><ul><ul><li>BS markedly dimnished L hemithorax </li></ul></ul><ul><ul><li>No adventituous sounds </li></ul></ul><ul><li>CVS </li></ul><ul><ul><li>Apex not localised </li></ul></ul><ul><ul><li>S1, S2 + </li></ul></ul><ul><li>Abdomen, CNS - WNL </li></ul>
  11. 14. <ul><li>PT sequelae </li></ul><ul><li>Left pleural fibrosis </li></ul><ul><li>Malignancy </li></ul>
  12. 15. <ul><li>Shifted to IMCW </li></ul><ul><ul><li>O2 inhalation/Propped up positioning </li></ul></ul><ul><ul><li>Bronchodilators </li></ul></ul><ul><ul><li>Antibiotics </li></ul></ul><ul><ul><li>Analgesics </li></ul></ul><ul><ul><li>IV Fluids </li></ul></ul><ul><ul><li>Supportives </li></ul></ul><ul><li>With Treatment </li></ul><ul><ul><li>Mild improvement of symptoms </li></ul></ul><ul><ul><li>SpO2 – 95-96% </li></ul></ul>
  13. 16. <ul><li>Hb -10.5 </li></ul><ul><li>PCV - 35 </li></ul><ul><li>TC -9800 </li></ul><ul><li>DC – P44/L53/E3 </li></ul><ul><li>PLT – 2.1L </li></ul><ul><li>ESR-10/22 </li></ul><ul><li>RBS – 121 Urea -24 Creat – 0.8 </li></ul><ul><li>Na – 135 K – 3.4 </li></ul>
  14. 17. <ul><li>LFT – WNL </li></ul><ul><li>BT/CT/INR – WNL </li></ul><ul><li>RUE – WNL </li></ul><ul><li>HIV/VDRL - negative </li></ul><ul><li>ECG – Sinus tachycardia, P pulmonale </li></ul><ul><li>Sputum </li></ul><ul><ul><li>GS & AFB – negative </li></ul></ul><ul><ul><li>Culture – no growth </li></ul></ul><ul><ul><li>Cytology – no malignant cells. </li></ul></ul><ul><li>CXR- </li></ul><ul><li>CT chest- </li></ul>
  15. 24. <ul><li>CTS opinion </li></ul><ul><li>imp: Pleural Mesothelioma </li></ul><ul><li>Adv: CT guided biopsy </li></ul><ul><li>Medical oncology: </li></ul><ul><li>imp: Mesothelioma Stage IV </li></ul><ul><li>Adv: CT guided/open Biopsy </li></ul><ul><li>Review with results </li></ul>
  16. 25. <ul><li>CT guided biopsy was fixed in GH </li></ul><ul><li>Patients dyspnea and chest pain persisted </li></ul><ul><li>SpO2 – 92-94% with O2 </li></ul><ul><li>On 4 th day of admission..patient went into sudden cardiac arrest </li></ul><ul><li>Resuscitated and recovered. </li></ul><ul><li>Intubation-Mechanical Ventilation given </li></ul><ul><li>Again went into cardiac arrest & expired.. </li></ul>
  17. 26. <ul><li>Malignant Mesothelioma - Stage IV </li></ul>
  18. 27. <ul><li>Uncommon but no longer be considered rare. </li></ul><ul><li>3000 cases/year diagnosed in the US alone. </li></ul><ul><li>In countries where control of asbestos was delayed by several decades, the “epidemic” of mesothelioma will also be delayed by several decades </li></ul><ul><li>Asbestos continues to be mined, and its use is actually increasing in many developing countries </li></ul>
  19. 28. <ul><li>Asbestos industry </li></ul><ul><li>Insulators </li></ul><ul><li>Pipefitters </li></ul><ul><li>Shipyard workers </li></ul><ul><li>Brake mechanics </li></ul><ul><li>Railroad workers </li></ul><ul><li>Construction trades </li></ul><ul><li>Carpenters </li></ul><ul><li>Plumbers </li></ul><ul><li>Electricians </li></ul><ul><li>Painters </li></ul><ul><li>Non-asbestos miners </li></ul><ul><li>Welders </li></ul><ul><li>Machinists </li></ul><ul><li>Manufacturers of mineral products </li></ul><ul><li>Maintenance and repair in buildings with asbestos insulation. </li></ul>
  20. 29. <ul><li>Women with asbestos-induced mesothelioma -only clear asbestos exposure was from exposure to their spouses' contaminated clothing. </li></ul><ul><li>Children incidentally exposed -develop mesothelioma in early adult life. </li></ul><ul><li>Incidence may rise - dust that settled after the collapse of the World Trade Center </li></ul><ul><li>Of nanoparticles and nanotubes raises concerns </li></ul>
  21. 30. <ul><li>Simian virus (SV40) – animal studies </li></ul><ul><li>Oil refinery workers-petroleum oil and its products ? </li></ul><ul><li>Cigarette smoking and Silica- - not associated with increased incidence of mesotheliomas </li></ul><ul><li>Radioactive contrast medium thorotrast </li></ul><ul><li>Therapeutic radiation for of lymphoma or breast Ca. </li></ul><ul><li>In turkey, -exposure to erionite dust, a non-asbestos crystalline fibrous form of the mineral zeolite. </li></ul><ul><li>Chronic inflammation of the pleura as in familial mediterranean fever </li></ul>
  22. 31. <ul><li>Although millions exposed, only a few develop mesothelioma </li></ul><ul><li>High degree of aneuploidy, but no single oncogene or tumor suppressor gene found culprit </li></ul><ul><li>p16 INK4A -p14 ARF (9p21), (NF2) gene (22q12) </li></ul><ul><li>P53 & Kras – not mutated </li></ul><ul><li>1p, 3p, 6q, 9p, 15q, and 22q </li></ul><ul><li>Growth-promoting genes – PDGF, EGFR </li></ul><ul><li>long latency period-multiple genetic abnormalities </li></ul>
  23. 35. <ul><li>Constitutional symptoms </li></ul><ul><ul><li>Weight loss (30%), cough (10%) and fatigue are not common in the early presentation. </li></ul></ul><ul><ul><li>HPOA and intermittent hypoglycemia are unusual </li></ul></ul><ul><li>Serous effusions </li></ul><ul><ul><li>Most common presentation - 95% </li></ul></ul><ul><ul><li>Dyspnoea (40–70%) </li></ul></ul><ul><ul><li>Non-pleuritic chest pain (60%) </li></ul></ul>
  24. 36. <ul><li>Local invasion </li></ul><ul><ul><li>Direct invasion of adjacent structures is characteristic of malignant mesothelioma. </li></ul></ul><ul><ul><ul><li>SVC obstruction, Spinal cord compression, </li></ul></ul></ul><ul><ul><ul><li>Horner’s syndrome, oesophageal compression, </li></ul></ul></ul><ul><ul><ul><li>Chest wall masses, Malignant pericardial disease. </li></ul></ul></ul><ul><ul><li>Metastasis along tracks of previous invasive procedures (2 – 51 %) </li></ul></ul><ul><ul><li>Chest wall, rib or intercostal nerve- pain. </li></ul></ul><ul><ul><li>Pericardial invasion- pericardial effusion, cardiac tamponade and/or arrhythmias, </li></ul></ul><ul><ul><li>Invasion into c/l hemithorax or peritoneal cavity </li></ul></ul>
  25. 37. <ul><li>Distant spread </li></ul><ul><ul><li>Extrathoracic spread- 54–82% PM </li></ul></ul><ul><ul><li>Often clinically silent and rarely cause of death </li></ul></ul><ul><ul><li>Hilar or mediastinal lymph node metastasis -44% </li></ul></ul><ul><ul><li>Intracranial metastases-3% </li></ul></ul><ul><ul><li>‘ Miliary mesothelioma’- rare. </li></ul></ul>
  26. 38. <ul><li>Pleural effusion or pleural mass </li></ul><ul><li>Large effusions or tumour masses-m ediastinal displacement. </li></ul><ul><li>Tumour may erode through chest wall and cause localised tenderness and/or palpable masses </li></ul><ul><li>Spread within the pleural cavity - ‘ fixed’ hemithorax , with reduced chest expansion. </li></ul><ul><li>Signs of compression or invasion of mediastinal structures. </li></ul><ul><li>Signs of extrathoracic involvement are uncommon </li></ul><ul><li>Clubbing of fingers -not a feature </li></ul>
  27. 41. <ul><ul><li>Unilateral pleural effusion with or without evidence of pleural thickening </li></ul></ul><ul><ul><li>Occasionally-large visible mass at presentation </li></ul></ul><ul><ul><li>Pleural thickening and encasement of the underlying lung </li></ul></ul><ul><ul><ul><li>may neutralise the mediastinal shift </li></ul></ul></ul><ul><ul><ul><li>contracture of the affected hemithorax. </li></ul></ul></ul><ul><ul><li>Pleural plaques and asbestosis - (20%) </li></ul></ul>
  28. 43. <ul><li>Rind-like tumor extension on pleural surfaces - 70% </li></ul><ul><li>Circumferential encasement by multiple nodules -28% </li></ul><ul><li>Pleural thickening with an irregular margin between the lung and the pleura - 26% </li></ul><ul><li>Pleural thickening;pleural-based nodules - 20% </li></ul><ul><li>Invasion of soft tissues & chest wall with rib erosion </li></ul><ul><li>Lung encased with tumor, volume loss with a shift of mediastinum toward side of primary tumor </li></ul><ul><li>Signs of lymphatic metastasis – late </li></ul><ul><li>Mediastinal adenopathy – very rare </li></ul>
  29. 44. <ul><li>CT features that favor diagnosis of malignant mesothelioma over metastatic pleural disease </li></ul><ul><ul><li>Rind like pleural involvement, </li></ul></ul><ul><ul><li>Mediastinal pleural involvement, and </li></ul></ul><ul><ul><li>Pleural thickness more than 1 cm </li></ul></ul><ul><li>MRI may demonstrate extent of disease and in particular chest wall and diaphragmatic invasion better than CT </li></ul><ul><li>FDG-PET and particularly PET/CT -differentiate benign from malignant disease and as adjunctive tools for staging </li></ul>
  30. 46. <ul><li>No specific haematological or biochemical test </li></ul><ul><li>Anemia, thrombocytosis, high ESR, hypergammaglobulinaemia. </li></ul><ul><li>Only serum biomarker clinically useful is serum mesothelin </li></ul><ul><ul><li>High specificity (>90%). </li></ul></ul><ul><ul><li>But only a 50% sensitivity for the diagnosis. </li></ul></ul>
  31. 47. <ul><li>Thoracocentesis - difficult to distinguish between reactive mesothelial cells and malignant ones. </li></ul><ul><li>Aspirate cytology of effusions - 33% to 54% </li></ul><ul><li>Pleural fluid Mesothelin – useful biomarker. </li></ul><ul><li>Closed pleural biopsy – sensitivity of 55% </li></ul><ul><li>CT-guided biopsy – sensitivity of 88% </li></ul><ul><li>Accuracy - morphologic appearance and results of tumour marker staining using light microscopy </li></ul>
  32. 48. <ul><li>Preferred technique -surgical biopsy via pleuroscopy </li></ul><ul><ul><li>Large samples </li></ul></ul><ul><ul><li>Drainage of effusions </li></ul></ul><ul><ul><li>Freeing up of a trapped lung </li></ul></ul><ul><ul><li>Talc pleurodesis if lung not trapped </li></ul></ul><ul><li>Bronchoscopy, BAL and Ga scan-no useful role </li></ul>
  33. 49. <ul><li>Median survival- 4 -12 mo from the time of diagnosis </li></ul><ul><li>Epithelial cell type do best and those with the sarcomatous cell type the worst </li></ul><ul><li>Poor Prognosis </li></ul><ul><ul><li>Age, </li></ul></ul><ul><ul><li>male gender, </li></ul></ul><ul><ul><li>performance status, </li></ul></ul><ul><ul><li>leukocytosis, and </li></ul></ul><ul><ul><li>chest pain </li></ul></ul><ul><ul><li>microvessel density </li></ul></ul><ul><ul><li>tumor necrosis </li></ul></ul>
  34. 51. <ul><li>Surgical Therapy - Debulking </li></ul><ul><ul><li>Pleurectomy with Decortication (P/D) </li></ul></ul><ul><ul><li>Extrapleural Pneumonectomy (EPP) </li></ul></ul><ul><ul><li>Epithelial cell type, clean margins after resection, and negative lymph nodes </li></ul></ul><ul><ul><li>Tumor debulking using EPP followed by chemotherapy and high-dose radiation therapy </li></ul></ul><ul><li>Chemotherapy </li></ul><ul><ul><li>Pemetrexed – Cisplatinum </li></ul></ul><ul><ul><li>Gemcitabine with a platinum agent </li></ul></ul><ul><li>Radiation Therapy </li></ul><ul><ul><li>Limited to adjunctive therapy </li></ul></ul>
  35. 52. <ul><li>Drugs </li></ul><ul><ul><li>Gefitinib and Imatinib </li></ul></ul><ul><ul><li>Thalidomide </li></ul></ul><ul><ul><li>Superoylanilide hydroxamic acid (SAHA)- histone deacetylase inhibitor </li></ul></ul><ul><ul><li>Proteasome inhibitors </li></ul></ul><ul><ul><li>Bevacizumab </li></ul></ul><ul><li>Immunotherapy </li></ul><ul><ul><li>Intrapleural interferon- γ </li></ul></ul><ul><ul><li>Infusion of interleukin-2 </li></ul></ul><ul><li>Gene Therapy </li></ul>
  36. 53. <ul><li>Palliative Therapy </li></ul><ul><ul><li>Pain management </li></ul></ul><ul><ul><li>Pleurodesis </li></ul></ul><ul><ul><li>Placement of a tunneled pleural catheter </li></ul></ul><ul><li>Chemoprevention and Screening </li></ul><ul><ul><li>Screening of high-risk populations </li></ul></ul><ul><ul><li>Sensitivity of serum mesothelin is not sufficient for use as a marker </li></ul></ul><ul><ul><li>Daily vitamin A (retinol) or β-carotene - trial </li></ul></ul><ul><ul><li>Routine low-dose CT scanning - trials </li></ul></ul>
  37. 54. <ul><li>2010 – Murray and Nadel's Textbook of Respiratory Medicine, 5th ed </li></ul><ul><li>2010 – Pleural Disease- Second Edition </li></ul><ul><li>2008 – Fishman’s Pulmonary Diseases and Disorders-Fourth Edition </li></ul><ul><li>2002 – Mesothelioma </li></ul><ul><li>2002 – Crofton And Douglas’s Respiratory Diseases – Fifth Edition </li></ul>

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