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# 12. Malignant Pleural Effusion with near total opacification of the hemithorax

# 12. Malignant Pleural Effusion with near total opacification of the hemithorax. Objectives: Describe the clinical relevance of malignant pleural effusion Describe the role of bronchoscopy in patients with malignant pleural effusions.

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# 12. Malignant Pleural Effusion with near total opacification of the hemithorax

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  1. # 12. Malignant Pleural Effusion with near total opacification of the hemithorax • Objectives: • Describe the clinical relevance of malignant pleural effusion • Describe the role of bronchoscopy in patients with malignant pleural effusions. • Describe an appropriate choice of palliative treatments available for a patient with malignant pleural effusion. Bronch Intern; Practical Approach #12

  2. Case Description(practical approach # 12) • 43 woman with a history of breast cancer metastatic to the lungs presents with shortness of breath and right sided pleuritic chest pain. • She underwent a right sided mastectomy and chemotherapy 3 years earlier. • Several thoracenteses were performed, but results of the pleural fluid analysis are not available • The family reports a rapidly declining functional status. • She lives abroad, but is visiting her son in the United States. Bronch Intern; Practical Approach #12

  3. Initial Evaluation Procedural Strategies Techniques and Results Long term Management The Practical Approach • Examination and, functional status • Significant comorbidities • Support system • Patient preferences and expectations • Indications, contraindications, and results • Team experience • Risk-benefits analysis and therapeutic alternatives • Informed Consent • Anesthesia and peri-operative care • Techniques and instrumentation • Anatomic dangers and other risks • Results and procedure-related complications • Outcome assessment • Follow-up tests and procedures • Referrals • Quality improvement Bronch Intern; Practical Approach #12 BI #. Practical Approach Title

  4. Initial Evaluation (practical approach #12) • Physical examination reveals: • Normal vital signs • Spanish-speaking female, appears older than stated age • Mild bi-temporal wasting • Decreased right-sided breath sounds, with dullness to percussion over entire right lung field • Normal cardiac exam • Chest wall demonstrates evidence of right breast mastectomy • Benign abdominal exam • No extremity edema Bronch Intern; Practical Approach #12

  5. Initial Evaluation (practical approach # 12) • Admission chest radiograph: near complete opacification of the right hemi-thorax Bronch Intern; Practical Approach #12

  6. Initial Evaluation (practical approach # 12 ) • Chest CT: Massive right pleural effusion filling the right hemi-thorax, with leftward mediastinal shift and a rim of soft tissue thickening in the pleura Bronch Intern; Practical Approach #12

  7. Initial Evaluation (practical approach # 12) Diagnostic and therapeutic thoracentesis reveals an exudative effusion Cytology demonstrates malignant cells consistent with primary breast cancer Bronch Intern; Practical Approach #12 BI #. Practical Approach Title

  8. Initial Evaluation Our patient’s goal: To leave the hospital, return to her home country, and spend time with her family. Bronch Intern; Practical Approach #12 8

  9. The Practical Approach Initial Evaluation Procedural Strategies Techniques and Results Long term Management • Examination and, functional status • Significant comorbidities • Support system • Patient preferences and expectations • Indications, contraindications, and results • Team experience • Risk-benefits analysis and therapeutic alternatives • Informed Consent • Anesthesia and peri-operative care • Techniques and instrumentation • Anatomic dangers and other risks • Results and procedure-related complications • Outcome assessment • Follow-up tests and procedures • Referrals • Quality improvement Bronch Intern; Practical Approach #12 BI #. Practical Approach Title 9

  10. Procedural Strategies • Possible treatment strategies for malignant pleural effusion: • Serial therapeutic thoracenteses • Pleurodesis • Pleuroperitoneal shunting • Indwelling pleural drain • Pleurectomy • Anti-tumor therapies • End-of-life care Bronch Intern; Practical Approach #12

  11. Procedural Strategies: Thoracentesis • Thoracentesis is minimally invasive and can be performed on an outpatient basis • Can provide immediate relief of dyspnea • The maximum amount of fluid that can be safely removed is unknown; caution should be taken to avoid re-expansion pulmonary edema • Fluid can be safely removed until the pleural pressure falls below -20 cm H2O Light, et al. Am Rev RespirDis 1980;121:799-804 • Chest pressure is associated with an unsafe drop in pleural pressures and can be used as a marker for volume that can be safely removed. Feller-Kopman, et al. Chest 2006;129:1556-1560 Bronch Intern; Practical Approach #12

  12. Procedural Strategies: Thoracentesis • Other potential complications: • Pneumothorax • Bleeding • Pain • Empyema • Skin infection • Infection Bronch Intern; Practical Approach #12

  13. Procedural Strategies: Thoracentesis • Ultrasound guidance: • Significantly reduces the risk of pneumothorax Grogan et al, Arch Int Med 1990;150:873-877 Raptopoulos et al, Am J Roentgenol 1991;156:917-920 Barnes et al, J Clin Ultrasound 2005;33:442-446 • No risk reduction if ultrasound localization of fluid is performed prior to the procedure (likely due to changes in patient and fluid positioning) Barnes et al, J Clin Ultrasound 2005;33:442-446 An ultrasound technician localizes a pocket of pleural fluid in the procedure room at the start of the thoracentesis Bronch Intern; Practical Approach #12

  14. Procedural Strategies: Thoracentesis • Serial thoracenteses are usually reserved for patients who fulfill one of the following: • Re-accumulate fluid slowly after each thoracentesis • Have cancers that commonly respond to therapy with resolution of associated effusion • Appear unlikely to survive past 1 to 3 months • Are unable to tolerate more invasive procedures Heffner JE, Klein JS. Mayo Clin Proc 2008;83:235-250 Bronch Intern; Practical Approach #12

  15. Procedural Strategies: Pleurodesis • Pleurodesis involves permanent apposition of the visceral and parietal pleura through sclerosis of the pleural surfaces • Can be performed using various agents: • Chemical (doxycycline, tetracycline, bleomycin) • Mineral (talc) • Mechanical • Can be performed through a chest tube or thoracoscopically Bronch Intern; Practical Approach #12

  16. Procedural Strategies: Pleurodesis • Indications: • Malignant effusion that is rapidly recurrent and unresponsive to systemic therapy • Symptomatic improvement after thoracentesis and recurrence of symptoms after fluid re-accumulation • Karnofsky score 40 or above • Estimated survival greater than 3 months Colt HG, Mathur PN. Manual of Pleural Procedures, Philadelphia: Lippencott Williams and Williams;199:155 Bronch Intern; Practical Approach #12

  17. Procedural Strategies: Pleurodesis • Contraindications: • Expected survival less than 3 months • Symptoms not attributable to the effusion • Selected patients which may still benefit from systemic therapy • Patients who refuse hospitalization or refuse tube thoracostomy • Incomplete lung re-expansion following complete removal of pleural fluid (i.e. trapped lung) Colt HG, Mathur PN. Manual of Pleural Procedures, Philadelphia: Lippencott Williams and Williams;199:155 Bronch Intern; Practical Approach #12

  18. Procedural Strategies: Pleurodesis • Pleurodesis via chest tube: • Chest tube should be placed in a posterior and inferior position • After the pleural fluid is completely drained, confirm lung re-expansion with a chest x-ray • With the chest tube off suction, the sclerosing agent (mixed with saline) is instilled through the tubing into the pleural space • The chest tube is then clamped for two hours Bronch Intern; Practical Approach #12

  19. Procedural Strategies: Pleurodesis • Pleurodesis via chest tube (con’t): • Patient positioning and rotation are not likely to improve sclerosing agent distribution or pleurodesis success Lorch, et al. Chest 1988;93:527-529 Dryzer, et al. Chest 1993;104:1763-1766 • Clamps are then removed and the system placed to suction • Chest tube may be removed when the daily drainage is less than 100 ml Bronch Intern; Practical Approach #12

  20. Techniques and Results: Rapid Pleurodesis • Technique described by Spiegler et al: • Using local anesthesia and systemic analgesia, a small bore (14F) chest tube is placed in the posterior axillary line directed towards the posterior pleural gutter • The pleural space is drained without suction into a water-seal system • After 15 minutes, suction at -20 cm H2O added unless drainage exceeds an arbitrary volume of one liter • A portable chest x-ray is obtained after two hours • If the pleural fluid is not completely evacuated on the 2 hour x-ray, suction is continued for a another 2 hours and the x-ray is repeated • Pleurodesis not attempted if the chest radiograph is consistent with trapped lung Spiegler et al, Chest 2006;123:1895-1898 Bronch Intern; Practical Approach #12 20

  21. Rapid pleurodesis • Rapid pleurodesis technique (con’t): • When fluid is completely evacuated, pleurodesis is performed by injecting sclerosing agent into the chest tube • Spiegler et al utilized either 60 units of bleomycin or 4g of talc slurry diluted in a 50 mL saline solution • All patients received 10 mL of 2% lidocaine solution instilled into the pleural space prior to the sclerosing agent. Systemic analgesia given if needed. • The chest tube is clamped for 90 minutes with the patient lying in bed (no special positioning), then unclamped and returned to suction. • Chest tube removed after two hours. • Minimal incidence of pain, fever, or iatrogenic pneumothorax Spiegler et al, Chest 2006;123:1895-1898 Bronch Intern; Practical Approach #12 21

  22. Thoracoscopic pleurodesis Colt HG, Mathur PN. Manual of Pleural Procedures, Lippincott Press. • A rigid telescope and working instruments are inserted through small incisions in the lateral chest wall • Allows for direct visualization of the pleura and lung • Fluid drainage and pleural biopsies can be performed under visual guidance • Pleurodesis can be performed by utilizing a pneumatic atomizer for talc insufflation through a trocar Bronch Intern; Practical Approach #12

  23. Preparing for video-assisted thoracoscopy using flex-rigid pleuroscope. Bronch Intern; Practical Approach #12

  24. Pleurodesis: expected outcomes dependent on agent used • Cochrane Review comparing techniques in pleurodesis for malignant pleural effusion: • Talc is the most efficacious agent • Relative risk of non-recurrence was 1.34 (95% CI 1.16 to 1.55) compared to bleomycin, tetracycline, mustine, and tube drainage alone • Not associated with increased risk of death Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1 Bronch Intern; Practical Approach #12

  25. Outcomes dependent on procedure and agent used • Cochrane Database review (con’t): • Thoracoscopicpleurodesis with talc is more effective than tube thoracostomypleurodesis • RR of non-recurrence is 1.19 (95% CI 1.04-1.36) in comparison to tube thoracostomy using talc • RR of non-recurrence is 1.68 (95% CI 1.35-2.10) in comparison to tube thoracostomy using various agents (tetracycline, bleomycin, talc, or mustine) Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1 Bronch Intern; Practical Approach #12

  26. Talc vs other • Cochrane Database review (con’t): • Comparison of successful pleurodesis • Talc (74%) more successful than tetracyclines (57%) • Talc (79%) more successful than bleomycin (64%) • Tetracyclines (63%) and bleomycin (62%) have similar success rates • Thoracoscopic talc (96%) more successful than medical talc (81%) Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1 Note: The issue of thorascopic talc insufflation vs. medical talc slurry pleurodesis is still controversial…! Bronch Intern; Practical Approach #12

  27. Outcomes dependent on techniques used • Still debated: Thoracoscopic talc insufflation (TTI) vs. talc slurry (TS) • Dresler et al performed a prospective randomized trial of treatment with either TTI or TS • No difference in success at 30 days in TTI (78%) vs. TS (71%) • Subgroup analysis of primary lung and breast cancer patients reveals an advantage of TTI (82%) vs. TS (67%) Dresler et al, Chest 2005;127:909-915 Bronch Intern; Practical Approach #12

  28. Thoracoscopy vs talc slurry • Thoracoscopic talc insufflation vs. talc slurry (con’t): • The authors suggest that thoracoscopic talc insufflation: • Allows for direct pleural visualization and intervention for adhesions and loculations • May be indicated in patients with prior ipsilateral surgery, prior attempted pleurodesis, or trapped lung • Is equal in efficacy to talc slurry, but may be more advantageous in primary lung or breast cancer Dresler et al, Chest 2005;127:909-915 Bronch Intern; Practical Approach #12

  29. Procedural Strategies: Pleurodesis • Respiratory failure • Fever • Pain • Rigors • GI side-effects • Wound infections • Cardiac arrest under general anesthesia • Hemorrhage • Percutaneous fistula • Pulmonary emboli • Air leaks • Pulmonary edema • Leukopenia • Hypotension • subcutaneous emphysema Reported Adverse Effects: Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1 Bronch Intern; Practical Approach #12

  30. Does talc pleurodesis cause ARDS Case studies are contradictory. Occurrence in some series and absence in others appears independent of underlying disease, quantity of talc used, or instillation method. Data on particle size is absent in most reports. Smaller particles may be able cause pneumonitis by entering the systemic circulation through the lymphatic stomaFerrer et al, Chest 2001;119:1901-1905 No cases of ARDS occurred in 558 patients who underwent pleurodesis with 4g of large particle talc (11% of particles <5μm) Janssen et al, Lancet 2007;369:1535-1539 Bronch Intern; Practical Approach #12

  31. Pleuroperitoneal Shunting Involves a drain from the pleural space into the peritoneal cavity Useful in providing symptomatic relief in the setting of trapped lung Requires the patient to provide digital pressure over a valve multiple times a day to pump the pleural fluid into the abdomen Has the potential risk of peritoneal seeding of malignant cells . Other complications are frequent (15%): shunt occlusion, infection, skin erosion. Petrou et al, Cancer 1995;75:801-805 Genc et al, Eur J Cardiothorac Surg 2000;18:143-146 Bronch Intern; Practical Approach #12

  32. Indwelling Pleural catheter to external evacuation system Allows the patient to intermittently drain the effusion at home. Results in rapid improvement in symptoms General anesthesia not required for placement Can be placed as an outpatient safely and cost-effectively Putnam et al, Ann Thoracic Surg 2000;69:369-375 Effective as a treatment option for Trapped Lung Syndrome Pien et al, Chest 2001;119:1641-1646 Bronch Intern; Practical Approach #12

  33. Indwelling Pleural Drain • Tremblay and Michaud studied 250 tunneled pleural catheter insertions in 223 patients: • Complete symptom control achieved at two weeks in 38.8%, partial in 50%, and absent in 3.6% • Spontaneous pleurodesis occurred in 42.9% • No further ipsilateral pleural procedures (i.e. thoracentesis, repeat catheter placement, chest tube) required in 90.1% of successful catheter placements Tremblay A, Michaud G, Chest 2006;129:362-368 Bronch Intern; Practical Approach #12

  34. But some complications are noted Tremblay A, Michaud G, Chest 2006;129:362-368 Tremblay and Michaud study (con’t)- Complications: Bronch Intern; Practical Approach #12

  35. Procedural Strategies: Indwelling Pleural Drain • Warren et al. inserted 231 pleural catheters into 202 patients: • Generally utilized a Seldinger technique rather than tunneling for insertion • No intraoperative complications • All but 14 patients were able to care for the catheter without nursing help • 97% of patients were compliant with the drainage schedule (every day during the first week, then every other day) • The patient’s symptoms were palliated in all cases Warren et al, Ann ThoracSurg 2008;85:1049-1055 Bronch Intern; Practical Approach #12

  36. Procedural Strategies: Indwelling Pleural Drain Warren et al, Ann Thorac Surg 2008;85:1049-1055 • Warren et al study (con’t): • Spontaneous pleurodesis occurred in 58% of all patients • Higher spontaneous pleurodesis rates occurred when the primary site was breast or gynecologic Bronch Intern; Practical Approach #12

  37. Procedural Strategies: Indwelling Pleural Drain Warren et al, Ann Thorac Surg 2008;1049-1055 • Warren et al study (con’t): • The recurrence rate was lowest when the primary site was breast or gynecologic • Complication rates were low Bronch Intern; Practical Approach #12

  38. Procedural Strategies: Pleurectomy Pleurectomy involves surgical stripping of the pleura and pericardium Decortication may be required if tumor hinders lung re-expansion Highly effective (100%), but also carries high mortality (12.5%) Fry WA, Khandekar JD, Annals of Surgical Oncology1995;2:160-164 Not generally recommended because of high mortality Putnam JB, SurgClin N Am 2002;82:867-883 Bronch Intern; Practical Approach #12

  39. Procedural Strategies: Systemic Chemotherapy Recommended in symptomatic malignant pleural effusion from chemotherapy-responsive tumors (such as breast, small cell lung, and lymphoma) Can be used in combination with pleurodesis or thoracentesis When contraindicated or ineffective, then local therapy (such as pleurodesis) should be applied Antony et al, Am J RespirCrit Care Med 2000;162:1987 Bronch Intern; Practical Approach #12

  40. Procedural Strategies: Intrapleural Chemotherapy • Aims to locally treat pleural tumor without systemic toxicities • Trials using etoposide, fluorouracil, mitomycin-c, doxorubicin, and cisplatin-based regimen have not shown sufficient efficacy for use Seto et al, Br J Cancer 2006;96:717-721 • Intrapleural chemotherapy has also been studied in combination with intravenous chemotherapy; more study necessary Su et al, Oncology 2003;64:18-24 Bronch Intern; Practical Approach #12

  41. Procedural Strategies: Intrapleural Chemotherapy • A multi-institution phase II study of hypotonic cisplatin treatment by Seto et al shows promise • Instilled a mixture of cisplatin 25 mg in 500 ml of distilled water through a chest tube • The chest tube was clamped for one hour, then allowed to drain and removed when the drainage was < 200 ml per day • Of 80 patients with malignant pleural effusion from NSCLC, the 4 week overall response rate was 83% • Complete response (no effusion) noted in 34% • Partial response (effusion < 25% of the hemithorax) noted in 49% Seto et al, Br J Cancer 2006;95:717-721 Bronch Intern; Practical Approach #12

  42. Procedural Strategies:Intrapleural chemotherapy • Hypotonic cisplatin study (con’t): • Median response time was 206 days and median survival time was 239 days • No hematologic toxicities or grade 4 non-hematologic toxicities were noted • Grade 3 adverse toxicities included nausea (4%), vomiting (1%), pyothorax (1%) and dyspnea (1%) • Mechanism of action is believed to involve a combination of cytotoxic effects and increased cellular cisplatin levels due to hypotonicity • A phase III trial is necessary Seto et al, Br J Cancer 2006;95:717-721 Bronch Intern; Practical Approach #12

  43. Procedural Strategies:Intrapleural Immunotherapy • Variable success noted with instillation of active cytokines (such as IL-2, IFN-α, IFN-β, and IFN-γ) • The mechanism of observed responses is unclear (sclerosing activity vs. immunologic effect) • Results of phase II trials have been inconclusive Antony et al, Am J RespirCrit Care Med 2000;162:1987-2001 • Combining intrapleural chemotherapy and intrapleural immunotherapy may be more effective than either regimen alone Nio et al, Br J Cancer 1999;80:775-785 • More studies are needed Bronch Intern; Practical Approach #12

  44. Procedural Strategies: End-of-Life Care • ACCP recommendations for end-of-life care • Communication between the physicians, patients, and family is central to the overall care • Need for advanced directive, and the clinician should assume responsibility for placing it in the chart • The hospital ethics committee is underutilized and may be effective in clarifying issues surrounding end-of-life decisions • Palliative care should be an integral part of treatment of all patients, including those still pursuing life-prolonging therapies. • The goal of palliative care should be to achieve the best quality of life for the patients and their families. • Terminal illness defined as expected survival less than 6 months. Griffin et al, Chest 2003;123:312S-331S Bronch Intern; Practical Approach #12

  45. Initial Evaluation Procedural Strategies Techniques and Results Long term Management The Practical Approach • Examination and, functional status • Significant comorbidities • Support system • Patient preferences and expectations • Indications, contraindications, and results • Team experience • Risk-benefits analysis and therapeutic alternatives • Informed Consent • Anesthesia and peri-operative care • Techniques and instrumentation • Anatomic dangers and other risks • Results and procedure-related complications • Outcome assessment • Follow-up tests and procedures • Referrals • Quality improvement Bronch Intern; Practical Approach #12 BI #. Practical Approach Title

  46. Results and Long-Term Management Rapid pleurodesis performed with success. The palliative care services consulted Patient discharged within two days. Patient returned safely to her home abroad. Patient expired eight months later without evidence of recurrent effusion. Bronch Intern; Practical Approach #12

  47. Q 1: Describe the clinical relevance of a malignant pleural effusion Bronch Intern; Practical Approach #12

  48. Frequency Antony et al, Am J Respir Care Med 2000;162:1987-2001 Bronch Intern; Practical Approach #12 The annual incidence of malignant pleural effusion is estimated to be > 150 000 cases Malignancies cause 42% to 77% of exudative effusions 48

  49. Chest radiography Bronch Intern; Practical Approach #12 • Chest radiography: • Only 10% of malignant effusions will present as a massive effusion (filling the entire hemithorax) Maher GG, Berger HW, Am Rev RespirDis 1972;105:458-460 • Malignancy causes 55% of large or massive pleural effusions Porcel JM, Vives M, Chest 2003;124:978-983 • Absence of contralateralmediastinal shift implies: • Fixation of the mediastinum • Mainstem bronchus occlusion • Extensive pleural involvement Antony et al, Am J Respir Care Med 2000;162:1987-2001 49

  50. Yield of diagnostic procedures Bronch Intern; Practical Approach #12 • Reported yield of various diagnostic approaches: • Pleural fluid cytology: Sensitivity 62-90% Antony et al, Am J Respir Care Med 2000;162:1987-2001 • Closed pleural biopsy: Sensitivity 40-75% Antony et al, Am J Respir Care Med 2000;162:1987-2001 • Blind percutaneous pleural biopsy (Abrams): Sensitivity 43-51% Chakrabarti et al, Chest 2006;129:1549-55 • Image-guided pleural biopsy (CT and ultrasound): Sensitivity 76% Benamore et al, ClinRadiol 2006;61:700-705 • Thoracoscopy: Sensitivity 80-100% Harris et al, Chest 1995;108-828-841 50

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