Bronch Intern; Practical Approach #12

Bronch Intern; Practical Approach #12
# 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

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

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

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

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

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

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

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

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 BI #. Practical Approach Title Bronch Intern; Practical Approach #12 9

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

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 Respir Dis 1980;121: 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: Bronch Intern; Practical Approach #12

Other potential complications: Pneumothorax Bleeding Pain Empyema Skin infection Infection Bronch Intern; Practical Approach #12

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

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: Bronch Intern; Practical Approach #12

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

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

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

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

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: Dryzer, et al. Chest 1993;104: 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

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: Bronch Intern; Practical Approach #12 20

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: Bronch Intern; Practical Approach #12 21

Thoracoscopic pleurodesis
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 Colt HG, Mathur PN. Manual of Pleural Procedures, Lippincott Press. Bronch Intern; Practical Approach #12

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

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

Outcomes dependent on procedure and agent used
Cochrane Database review (con’t): Thoracoscopic pleurodesis with talc is more effective than tube thoracostomy pleurodesis RR of non-recurrence is 1.19 (95% CI ) in comparison to tube thoracostomy using talc RR of non-recurrence is 1.68 (95% CI ) 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

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

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: Bronch Intern; Practical Approach #12

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: Bronch Intern; Practical Approach #12

Reported Adverse Effects: Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1 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 Bronch Intern; Practical Approach #12

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 stoma Ferrer et al, Chest 2001;119: 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: Bronch Intern; Practical Approach #12

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: Genc et al, Eur J Cardiothorac Surg 2000;18: Bronch Intern; Practical Approach #12

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: Effective as a treatment option for Trapped Lung Syndrome Pien et al, Chest 2001;119: Bronch Intern; Practical Approach #12

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: Bronch Intern; Practical Approach #12

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

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 Thorac Surg 2008;85: Bronch Intern; Practical Approach #12

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 Warren et al, Ann Thorac Surg 2008;85: Bronch Intern; Practical Approach #12

Warren et al study (con’t): The recurrence rate was lowest when the primary site was breast or gynecologic Complication rates were low Warren et al, Ann Thorac Surg 2008; Bronch Intern; Practical Approach #12

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: Not generally recommended because of high mortality Putnam JB, Surg Clin N Am 2002;82: Bronch Intern; Practical Approach #12

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 Respir Crit Care Med 2000;162:1987 Bronch Intern; Practical Approach #12

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: 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

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: Bronch Intern; Practical Approach #12

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: Bronch Intern; Practical Approach #12

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 Respir Crit Care Med 2000;162: Combining intrapleural chemotherapy and intrapleural immunotherapy may be more effective than either regimen alone Nio et al, Br J Cancer 1999;80: More studies are needed Bronch Intern; Practical Approach #12

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

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

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

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

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

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

Yield of diagnostic procedures
Reported yield of various diagnostic approaches: Pleural fluid cytology: Sensitivity 62-90% Antony et al, Am J Respir Care Med 2000;162: Closed pleural biopsy: Sensitivity 40-75% Blind percutaneous pleural biopsy (Abrams): Sensitivity 43-51% Chakrabarti et al, Chest 2006;129: Image-guided pleural biopsy (CT and ultrasound): Sensitivity 76% Benamore et al, Clin Radiol 2006;61: Thoracoscopy: Sensitivity % Harris et al, Chest 1995; Bronch Intern; Practical Approach #12 50

Etiologies Lung 48% Cell type or Origin of Malignant Effusions:
Epidermoid carcinoma 9% Adenocarcinoma 19% Large cell carcinoma 2% Giant cell carcinoma 2% Small cell carcinoma 24% Breast 24% Gastrointestinal 9% Ovary 6% Kidney 5% Uterus 2% Thyroid 1% Unknown 14% Sanchez-Armengol A and Rodriguez-Panadero F, Chest 1993;104: Bronch Intern; Practical Approach #12 51

Parietal pleural metastases. This photograph was taken during a thoracoscopic procedure. A serous effusion is also visualized adjacent to the lung parenchyma (arrows) Bronch Intern; Practical Approach #12 52

Q2: Describe the role for bronchoscopy in a patient with malignant pleural effusion Bronch Intern; Practical Approach #12

Role of bronchoscopy Routine use of bronchoscopy may not be warranted in patients with pleural effusion of unknown etiology Not useful in small to moderate size pleural effusions (filling less than 75% of the hemithorax) without other findings Poe et al, Chest 1994;105: Bronchoscopy yield is low in evaluating undiagnosed pleural effusions in absence of other indications Feinsilver et al, Chest 1986;90: Bronch Intern; Practical Approach #12 54

Bronchoscopy is useful in case
Pulmonary infiltrate present on chest x-ray or CT Hemoptysis, which increases the likelihood that a malignancy is present Massive pleural effusion, of which malignancy is the most common cause (helps exclude airway obstruction by exophytic tumor, mucosal infiltration, or extrinsic compression). Mediastinum is shifted toward the side of the effusion, suggestive of an obstructing endobronchial lesion. Light RW, Clin Chest Med 2006;27: Bronchoscopy can thus reveal causes for atelectasis and trapped lung. Bronch Intern; Practical Approach #12 55

Q 3. Describe an appropriate choice of palliative treatment modalities for patients with malignant pleural effusions Bronch Intern; Practical Approach #12

Interactive question A frail, cachetic 72 year old man lives alone and is without family. He has a symptomatic recurrent left-sided pleural effusion secondary to metastatic small cell lung cancer. Thoracentesis 3 months ago relieved his symptoms. There was full re-expansion of the lung afterwards. His functional status is poor (Karnofsky score of 30), and the oncologist feels that he has less than 3 months to live. Which of the following might be the most appropriate palliative treatment strategy? Pleurectomy Thoracoscopic talc pleurodesis Chest tube talc pleurodesis Serial thoracenteses Indwelling pleural drain Bronch Intern; Practical Approach #12

Answer to interactive question
Some would say serial thoracenteses, others might say indwelling pleural catheter (but he is unlikely to be able to be able to maintain the catheter on his own and as he becomes weaker), and still others might suggest rapid pleurodesis (to avoid pleurodesis-related hospitalization). Pleurectomy has a high mortality and is generally not recommended. Thoracoscopic pleurodesis is often not recommended for patients with an expected survival less than 3 months or a Karnofsky score less than 40. In addition to serial thoracenteses to relieve symptoms, his physicians should discuss end-of-life care, including advanced directives, pain control, and hospice care. Bronch Intern; Practical Approach #12

All efforts are made by Bronchoscopy International to maintain currency of online information. All published multimedia slide shows, streaming videos, and essays can be cited for reference as: Bronchoscopy International: Practical Approach, an Electronic On-Line Multimedia Slide Presentation. Published 2009 (Please add “Date Accessed”). Thank you Bronch Intern; Practical Approach #12

Prepared by Steven C. Wong MD (USA)
Bronch Intern; Practical Approach #12

Bronch Intern; Practical Approach #12

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