Lorriana Leard, M.D. Tri-Hospital Chest Conference February 25, 2003

1. 75 y.o. Man with NSCLCa and a pleural effusion Lorriana Leard, M.D. Tri-Hospital Chest Conference Feb. 25, 2003 Lorriana Leard, M.D. Tri-Hospital Chest Conference February 25, 2003

2. History 75 y.o. WM with h/o NSCLCa who presents with SOB & increasing DOE over the past 3 months

3. Pertinent Pulmonary History In 9/01: • Presented with 80 lb wt. loss, cough, SOB

4. Pertinent Pulmonary History In 9/01: • Presented with 80 lb wt. loss, cough, SOB • Chest CT scan: • large subcarinal mass with RLL collapse

5. Pertinent Pulmonary History In 9/01: • Presented with 80 lb wt. loss, cough, SOB • Chest CT scan: • large subcarinal mass with RLL collapse • Bronchoscopy 9/7/01: • Near complete compression of bronchus intermedius • Wang needle biopsies from R side of carina  poorly differentiated AdenoCa  NSCLCa

6. Pertinent Pulmonary History • Staged as IIIB

7. Pertinent Pulmonary History • Staged as IIIB • Treated with Chemotherapy / XRT 9/01-12/01

8. Pertinent Pulmonary History • Staged as IIIB • Treated with Chemotherapy / XRT 9/01-12/01 • Repeat Chest CT 2/21/02: • Resolution of 5 x 6 x 6 cm subcarinal mass • New bilateral pleural effusions R>L

9. Pertinent Pulmonary History • Thoracentesis 4/02: 1400 mL serous fluid • Chemistries: GLUCOSE 125 mg/dl PROTEIN, TOTAL 5.2 g/dl (Serum 7.1) LDH 95 U/L (Serum 116) TRIGLYCERIDE 26 mg/dl • Cell Count RBC 990 #/cmm WBC 600 #/cmm (PMNs 2%, Lymphs 75%, Other 21%, Eos 1%) • Cultures: Fungal, AFB, Bacterial Cx negative • Cytology: Few atypical cells, probably reactive

10. Current Presentation • Now presents w/ increased DOE over 3 mo.

11. Current Presentation • Now presents w/ increased DOE over 3 mo. • R chest pain (intermittently) for past year • No CP with deep inspiration

12. Current Presentation • Now presents w/ increased DOE over 3 mo. • R chest pain (intermittently) for past year • No CP with deep inspiration • No hemoptysis • Cough productive of clear to white phlegm

13. Current Presentation • Now presents w/ increased DOE over 3 mo. • R chest pain (intermittently) for past year • No CP with deep inspiration • No hemoptysis • Cough productive of clear to white phlegm • Gaining weight since discontinuation of chemotherapy --113 --> 181

14. Past Medical History • NSCLCa per HPI • COPD: FVC 3.30 (80%) TLC 6.29 (94%), FEV1 1.98 (70%) DLCO 21.17 (88%) FEV1/FVC 60% • Atrial fibrillation • HTN • DM2 • CVA

15. Albuterol MDI Atrovent MDI Azmacort MDI Metoprolol Lasix Lisinopril Prazosin Aspirin Metformin Medications

16. Social History • Lives with his wife of 52 years in Cloverdale • Employment: • Air Force  in saw mills  rancher handyman • Retired since 1994 • Tobacco - 45 pack yr hx, quit 10 yrs ago • EtOH- prior socially, but none x 20 yrs • Drugs - never

17. Physical Examination VS: T 97, HR 56, BP 176/84, RR 24, O2S 95% on RA , Wt 182 lbs.   Gen: alert WM, ambulatory in NAD Neck: supple, no JVD Lungs: decreased BS with DTP and decreased fremitus at R base CV: s1 s2 with RRR Abd: NABS, soft, NT, ND, Extrem: no edema, + clubbing

18. Labs 9.6 7.6 >-----< 218 29 Coags normal Creat 0.9 LFTs normal LDH 117

19. CXR 2/7/03

20. Comparison CXRs 4/24/2002 10/23/2002 2/7/2003

22. Differential Diagnosis for Pleural effusion?

23. Differential Diagnosis for Pleural effusion? • Next diagnostic step? Management?

25. Differential Diagnosis of Exudative Pleural Effusion • Infectious: Bacterial, TB, Fungal • Iatrogenic: drug induced, central line misplacement • Malignant Pleural Effusion • Inflammatory disorders: PE, BAPE, XRT, • Connective Tissue Disease • Lymphatic abnormalities: Chylothorax, malignancy • Traumatic: Esophageal rupture, Hemothorax

26. Thoracentesis GLUCOSE 113 mg/dl ALBUMIN 2.0 gm/dL PROTEIN, TOTAL 3.7 g/dl (Serum 7.2) LDH 108 U/L (Serum 117)

27. Thoracentesis GLUCOSE 113 mg/dl ALBUMIN 2.0 gm/dL PROTEIN, TOTAL 3.7 g/dl (Serum 7.2) LDH 108 U/L (Serum 117) RBC 3300 #/cmm WBC 1370 #/cmm NEUTROPHILS 1 % LYMPHOCYTES 80 % OTHER 19 % (Others = monocytes, macrophages, histiocytes)

28. Thoracentesis Gram Stain • Occasional WBCs • No Organisms Seen Culture Negative Fungal Smear Negative AFB Smear Negative Cytology Negative

29. Thoracentesis • Appearance: LIPEMIC • TRIGLYCERIDE 1040 mg/dl

30. Diagnosis

31. Diagnosis Chylothorax

32. Diagnosis and Management of a Chylothorax • Chylothorax vs. Pseudochylothorax • Etiology of a Chylothorax • Management of a Chylothorax

34. Diagnosis of Chylothorax • Pleural fluid triglyceride level >110 mg/dL • Ratio of pleural to serum triglyceride > 1.0 • Ratio of pleural to serum cholesterol < 1.0 • Lipoprotein analysis of pleural fluid: chylomicrons

35. Chyle Chyle: • High triglyceride content (Chylomicrons) • produces milky, opalescent appearance • BUT milky appearance may clear during a fast and rapidly returns after ingestion of fat • Not irritating (does not evoke thickening of pleura) • Bacteriostatic • Cellular component of chyle: T-lymphocytes • Prolonged loss of chyle  nutritional depletion, water and electrolyte loss, hypolipemia, lymphopenia

36. Chyle Chylomicrons formed in gut  enter intestinal lacteal vessels  travel to cisterna chyli  thoracic duct leaves cisterna chyli, travels up through mediastinum, and terminates in region of L jugular and subclavian veins

37. Etiology of Chylothorax Disruption of Thoracic duct • anatomy determines location of effusion • thoracic duct crosses the mediastinum at 5-6th vertebral body therefore • Lymphatic injury below = R pleural effusion • Lymphatic injury above = L pleural effusion • Wide anatomic variation • Flow through duct 1.5-2.5 L/day

39. Etiology of Chylothorax • Tumors: > 50% (lymphoma 75%) • Trauma: • CV or thoracic surgical procedure • 0.5%CV surgery • 4% of esophageal resections • Nonsurgical trauma • Penetrating injuries involving neck or thorax • Nonpenetrating: spine hyperextended or vertebral fx • Minor “traumas:” weight lifting, straining, coughing or vomiting, childbirth, vigorous stretching while vigorous stretching while yawning

40. Etiology of Chylothorax Other reported etiologies: • Pulmonary lymphangiomyomatosis • SVC or subclavian vein thrombosis • Filariasis • Lymph node enlargement • Mediastinal tuberculosis • Lymphangitis of the thoracic duct • Aneurysms of thoracic aorta that erode duct • Tuberous sclerosis • Amyloidosis

41. Etiology of Chylothorax From UpToDate.com

42. Etiology of Chylothorax From Light RW: Pleural Diseases 3rd Ed.

43. Etiology of Chylothorax Post-thoracic-XRT described in few case reports • Etiology unclear: • ? lymphatic obstruction due to mediastinal fibrosis • spontaneous rupture of duct which has been 'damaged' by prior XRT and, therefore, more susceptible to minimal trauma • Must rule out recurrent malignancy

44. Etiology of Chylothorax • McWilliams and Gabbay describe 52 y.o. man with R chylothorax 23 yrs after mantle XRT for Hodgkin’s lymphoma • thoracentesis, pleural biopsies, thoracoabdominal imaging and thoracoscopy performed to r/o recurrent lymphoma • Treated with talc pleurodesis • Van Renterghem reported chylothorax 6 years after mantle XRT for Stage IA Hodgkin's disease

45. Clinical Manifestations • Incidence: 2.3-4.4% of nontraumatic effusions • Onset of symptoms usually gradual • fatigue • dyspnea on exertion • heaviness and discomfort in affected side • Rarely pleuritic chest pain / fever because chyle is not irritating to pleural surface

46. Treatment Traumatic Chylothorax: • Spontaneous closure • Pleuroperitoneal shunt: chyle shunted to peritoneal cavity, where absorbed w/o sig. ascites • Tube thoracostomy: w/ minimization of chyle flow • Minimization of Chyle flow: • Keep stomach empty with NG suction and use TPN • Feed pt. low-fat diet with most fats in form of medium-chain triglycerides

47. Treatment If Persists: • Pleurodesis (talc) • Repair or ligation of thoracic duct (Thoracotomy or VATS) with attempt to find actual site of leakage from duct • Preop: lymphangiogram to identify site of leak • Case report: Thoracoscopic high-frequency ultrasonic coagulation of the thoracic duct without clipping • Parietal pleurectomy to obliterate pleural space

48. Treatment Non-Traumatic Chylothorax: If known diagnosis or lymphoma / malignancy: • Mediastinal radiation • Pleuroperitoneal shunt, if not controlled by XRT • Reports of Pleurodesis If unknown etiology: • Treat as Traumatic • Aggressively pursue diagnosis (CT / lymphangiogram)

49. Treatment Future Potential Treatments: • Percutaneous catheterization and embolization of thoracic duct • Somatostatin / octreotide reported to decrease chyle production in postop chylothorax and in dog models

50. Summary • Chylothorax results from disruption of thoracic duct • Must be distinguished from Pseudochylothorax • Most common cause tumor, then surgical trauma. IF undiagnosed etiology, must evaluate for malignancy • Management depends upon etiology, but may include: • Treatment of underlying malignancy (Chemo / XRT) • Dietary restriction and Chest tube drainage • Thoracotomy / VATS with Thoracic Duct Ligation • Pleurodesis • Avoid prolonged drainage which can lead to immunosuppression / malnutrition