bronch intern; practical approach #12 # 12. malignant pleural effusion with near total opacification...

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 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 #12BI #. Practical Approach Title 3

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


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

4


Initial Evaluation (practical approach # 12)

► Admission chest radiograph: near complete opacification of the right hemi-thorax

5


Initial Evaluation (practical approach # 12 )

6

► 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


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 7


Initial Evaluation

►Our patient’s goal: To leave the hospital, return to her home country, and spend time with her family.

8









expectations











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

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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;121:799-804

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

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► Other potential complications: Pneumothorax Bleeding Pain Empyema Skin infection Infection

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► Ultrasound guidance: Significantly reduces the

risk of pneumothorax Grogan et al, Arch Int Med 1990;150:873-877Raptopoulos et al, Am J Roentgenol 1991;156:917-920Barnes 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

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An ultrasound technician localizes a pocket of pleural fluid in the procedure room at the start of the 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

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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

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►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

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►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

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►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

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►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

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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

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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

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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

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Colt HG, Mathur PN. Manual of Pleural Procedures, Lippincott Press.


Preparing for video-assisted thoracoscopy using flex-rigid pleuroscope.


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

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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 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)


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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%)


Note: The issue of thorascopic talc insufflation vs. medical talc slurry pleurodesis is still controversial…!

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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

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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

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Reported Adverse Effects:Shaw P, Agarwal R. Cochrane Database of Systematic Reviews 2004, Issue 1

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• 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


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;119:1901-1905

► 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

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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;75:801-805Genc et al, Eur J Cardiothorac Surg 2000;18:143-146

31


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

32


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

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But some complications are noted

► Tremblay and Michaud study (con’t)- Complications:

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Tremblay A, Michaud G, Chest 2006;129:362-368


Procedural Strategies: Indwelling Pleural Drain

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►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;85:1049-1055



36

► 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;85:1049-1055



► Warren et al study (con’t): The recurrence rate was lowest when the primary

site was breast or gynecologic Complication rates were low

37

Warren et al, Ann Thorac Surg 2008;1049-1055


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, Surg Clin N Am 2002;82:867-883

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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

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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

40


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

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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 necessarySeto et al, Br J Cancer 2006;95:717-721

42


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 inconclusiveAntony et al, Am J Respir Crit 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 needed43


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 44









expectations











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.

46


Q 1: Describe the clinical relevance of a malignant pleural

effusion


Frequency

48

►The annual incidence of malignant pleural effusion is estimated to be > 150 000 cases

►Malignancies cause 42% to 77% of exudative effusions

Antony et al, Am J Respir Care Med 2000;162:1987-2001


Chest radiography

49

►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;105:458-460

Malignancy causes 55% of large or massive pleural effusions Porcel JM, Vives M, Chest 2003;124:978-983

Absence of contralateral mediastinal shift implies:

►Fixation of the mediastinum►Mainstem bronchus occlusion►Extensive pleural involvement



Yield of diagnostic procedures

50

► Reported yield of various diagnostic approaches: Pleural fluid cytology: Sensitivity 62-90%


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, Clin Radiol 2006;61:700-705

Thoracoscopy: Sensitivity 80-100% Harris et al, Chest 1995;108-828-841


Etiologies

► Lung 48% 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%

51

Cell type or Origin of Malignant Effusions:

Sanchez-Armengol A and Rodriguez-Panadero F, Chest 1993;104:1482-1485


Parietal pleural metastases. This photograph was taken during a thoracoscopic procedure. A serous effusion is also visualized adjacent to the lung parenchyma (arrows)


Q2: Describe the role for bronchoscopy in a patient with

malignant pleural effusion


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;105:1663-1667

►Bronchoscopy yield is low in evaluating undiagnosed pleural effusions in absence of other indications

Feinsilver et al, Chest 1986;90:516-519

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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;27:309-319

55

Bronchoscopy can thus reveal causes for atelectasis and trapped lung.


Q 3. Describe an appropriate choice of palliative treatment modalities for patients with malignant pleural effusions


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?

A. PleurectomyB. Thoracoscopic talc pleurodesisC. Chest tube talc pleurodesisD. Serial thoracentesesE. Indwelling pleural drain

57


Answer to interactive questionD. 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. 58


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Prepared by Steven C. Wong MD (USA)

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bronch intern; practical approach #12 # 12. malignant pleural effusion with near total opacification...

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