CHEST DISEASE CENTER AT of Harvard Medical School ...

CHEST DISEASE CENTER AT A Teaching Hospital of Harvard Medical School

CHEST DISEASE CENTER AT A Teaching Hospital of Harvard Medical School

Management of Malignant Pleural Effusion

Jefferson University Hospital

5/1/13

Erik Folch MD, MSc

Division of Thoracic Surgery and Interventional Pulmonary

CHEST DISEASE CENTER

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Objectives

Case in point

Epidemiology

Prognosis

Evaluation

Therapeutic Options


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Recurrent Pleural Effusion

73 yo man with recurrent symptomatic pleural effusion

Exudative, lymphocytic (>90%), with negative cytology.

Removal of 4.6 L

Widespread grape-like appearance in visceral and parietal pleura

Pathology: small cell lung cancer!


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Causes of Pleural Effusion

Congestive heart failure 500,000

Pneumonia 300,000

Malignancy 200,000

Pulmonary embolism 150,000

Viral 100,000

Cirrhosis with ascites 50,000

GI disease 25,000

Collagen-vascular disease 6,000

Tuberculosis 2,500

Asbestos 2,000

Mesothelioma 1,500

Light,RW: Pleural Diseases (3rd) edition, Philadelphia: Lea & Febiger,

1995, p 76


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All Malignant Effusions

50% of patients with lung CA will develop an effusion during their illness

If malignant, translates into stage IV (7th TNM classification)

Sivestri, et a. CHEST 2002;122:1028-36

ATS, AJRCCM 2000; 162: 1987

Sahn, Clin Chest Med 1998; 19:351

Light, Pleural Disease, 4th ed

Antunes et al, Thorax 2003; 58(sII): ii29

Naruke et al, J Thorac Cardiovasc Surg 1988; 96: 440

Sugiura et al, Clin Cancer Res 1997; 3: 47

Ruffini et al, Eur J Cardiothorac Surg 2002; 21: 508

Lung

Breast

Lymphoma

Ovary

Stomach

Unknown

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25

10

52

7

Lung Cancer-associated MPE


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Clinical Manifestations of Pleural Metastasis

Dyspnea 57

Cough 43

Weight loss 32

Chest pain 26

Malaise 22

Fever 8

Chills 5

Asymptomatic 23

Symptom Patients with

symptom (%)

Chernow, B., Sahn, SA., Carcinomatous involvement of the pleura. Am J Med,

1977;63:695-702


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Dyspnea in Pleural Effusion

Dyspnea: up to 96% Multifactorial

• Decreased compliance of chest wall • Contralateral mediastinal shift • Decreased ipsilateral lung volume

– Neurogenic reflexes from lungs and chest wall Sahn SA. Semin Respir Crit Care Med 2001;22(6)

Large effusion alteration in chest wall P-V

curve Estenne M, Yernault JC, Troyer A. Mechanism of relief of dyspnea after thoracentesis in patients with large pleural effusions. Am J Med 1983;74:813-19


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Mechanism of malignancy-associated pleural effusion Direct metastasis Lymphatic obstruction Bronchial obstruction with atelectasis Post obstructive pneumonia Thoracic duct involvement Pericardial disease Hypoproteinemia Pulmonary embolism Radiation therapy Chemotherapy (methotrexate, procarbazine,

cyclophophamide, mitomycin, bleomycin)

Sahn, SA, Clin Chest Med, 1998

Light, RW, Pleural Disease, 6th edition


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Diagnosing Malignant Pleural Effusion Pleural fluid cytology

Pleural fluid tumor markers

Pleural fluid flow cytometry

Needle biopsy of the pleura

Abrams

Cope

Thoracoscopy

Open pleural biopsy


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Pleural Effusion in Malignancy Malignant

Malignant Pleural Mesothelioma

Lung Cancer

Breast Cancer

Ovarian Cancer

Lymphoma

Melanoma

Uterine & Cervical

Stomach cancer

Colon Cancer

Pancreatic Cancer

Paramalignant

Endobronchial obstruction causing atelectasis

Post-obstructive pneumonia causing parapneumonic effusion

PE associated to cancer

Hypoalbuminemia

Post-radiation

Secondary to chemotherapy

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Malignant vs. Paramalignant

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Pyng Lee, et al. Medical Thoracoscopy/Pleuroscopy: Manual and Atlas 2011


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Characteristics of Malignant Pleural Effusion

Usually exudative (5% transudates)

Mononuclear cell predominant (lymphocytes, macrophages, and mesothelial cells)

1/3 will have low pH (less than 7.3)

Sahn, SA, Clin Chest Med, 1998

Good, TJ, et al: American Review of Respiratory Disease, 1985


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Pleural Fluid Cytology

Very useful test

1st specimen positive in 50-60%

Very effective with adenocarcinoma

Less effective

lymphoma,

squamous cell carcinoma, mesothelioma or

Hodgkin’s disease

Pleural fluid, ThinPrep, 4x objective

Pleural fluid, ThinPrep, 40x objective


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Pleural Fluid Cytology vs. Thoracoscopy in Different Types of Tumors

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Anthony 2001


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Sensitivity of Different Diagnostic Methods for Malignant Pleural Effusion

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Loddenkemper 1983


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ERS & ESTS Guidelines

Conclusive dx only if

Representative material

Sufficient material for IH

Presence of clinical, radiological and/or surgical findings

Biopsy normal and abnormal pleura (1c)

No Dx should be made on frozen section

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Boutin and Rey 1983

Scherpereel A,Astolul P, Baas, P, et al. Guidelines of the ERS and the ESTS

for managmetn of MPM. Eur Respir J 2010;35:479-95

Sensitivity of Different Diagnostic Methods for Mesothelioma


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Diagnostic Techniques: Tumor Markers

Tumor markers

CEA,

CA 15-3

CA 19-9

enolase

All have been disappointing if used to establish diagnosis

May use to select patients for more invasive procedure if unclear exudate or need for more tissue


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Chest X-ray Moderate large

(500 – 2,000 cc) 75% 70% of pts with

massive effusion have underlying CA

If > 1,500 cc and no contralateral shift think: ipsilateral main stem

occlusion

fixed mediastinum (LN)

mimic of effusion due to extensive tumor involvement

Chernow, Sahn, Am J Med 1977; 63: 695

Rabin, J Mt Sinai Hosp 1957; 24: 45

Sahn, Clin Chest Med 1998; 19: 351

ATS, AJRCCM 2000; 162: 1987


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Survival with Malignant Pleural Effusion

Primary Total Low pH Normal pH

Breast 14 3.5 16.6

Lymphoma 7 1.7 8.8

Lung 5.3 2.4 6.8

GI 3.8 1.2 5.2

Other 6.3 1.8 17.5

Total 7.3 2.1 9.8

Sahn SA, Good JT. Pleural fluid pH in malignant effusions. Ann Intern Med

1988;108:345-9

*time in months


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Prognosis 417 patients: median survival 4.0 months

most important predictor = primary tumor • 2.3 months for GI primary • 3 months for lung CA • 5.0 months for breast CA / unknown primary • 6.0 months for mesothelioma

Karnofsky score related to prognosis

KPS < 30: median 34d KPS > 70: 395 days No relationship to:

• age • extent of pleural carcinomatosis • pH • glucose

Heffner et.al., Chest 2000; 117: 79

Burrows CM, Mathews WC, Colt HG. Predicting Survival in Pts with Recurrent Syptomatic

Malignant Pleural Effusions. Chest 2000; 117: 73-8


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During Initial Thoracentesis

During thoracentesis • Complete drainage better than 60mL

Pain during thoracentesis?

Normal manometry?

After Thoracentesis:

Subjective discomfort or pain?

Lung reexpansion?

How fast does fluid come back? • Fluid accumulation when production rate is >30x the normal

rate and accompanying reduced transit

Light R. Pleural effusion. N Engl J Med 2002;346:1971-7

Sahn S. The pathophysiology of pleural effusions. Annu Rev Med 1990;41:7-13

Feller-Kopman et al, Chest 2006; 129: 1556

Feller-Kopman et al, Ann Thorac Surg 2007


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Pleural Pressure Predicts lung entrapment

pleurodesis vs. PleurX

OP < -5 cmH20 only seen with malignant effusions or trapped lung

Non-expandable lung is predicted by:

opening Ppl -10 cm H20

closing Ppl -20 cm H20

Eps0.5 19 cm H20 Lan et al, Ann Intern Med 1997; 126: 768

Light et al, ARRD 1980; 121: 799

Villena et al, AJRCCM 2000; 162: 1534


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Pleural Pressure

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Anechoic

Hyperechoic

Hypoechoic

Isoechoic

Echogenicity


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AT Tsai et al. Curr Opin Pulm Med 2003, 9:282-290


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Feller-Kopman, in Ultrasound Guided Procedures and Investigations

Pleural Anatomy by US


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Treatment of Malignant and Paramalignent Pleural Effusions

Serial thoracentesis

Chest tube with pleurodesis

Thoracoscopy with talc poudrage

Pleuroperitoneal shunt

Pleurectomy


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Rationale of Treatment

Consider life expectancy and KPS

Palliate dyspnea Engage the patient in the

decision Two primary treatment

options Indwelling pleural catheter

(Pleurx) particularly in trapped lung

Thoracoscopy with pleurodesis


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Treatment Options

Palliation

02 / MSO4

Observation

for asymptomatic patients, most will progress

Repeat thoracentesis

relief of dyspnea, 100% recurrence at 1 month

reserved for the sick ones

Antunes et al, Thorax 2003; 58(suppl II): ii29

ATS, AJRCCM 2000; 162: 1987



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Treatment Options Chemotherapy

small cell, lymphoma, breast, ovarian, prostate, thyroid and germ-cell

Thoracentesis first: accumulation of drugs can increase toxicity

Intrapleural chemotherapy

XRT

for lymphoma

Pleurodesis

Antunes et al, Thorax 2003; 58(suppl II): ii29


Shoji et.al., Chest 2002; 121: 821


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The PleurX Catheter

15.5 F

66 cm long

side ports along distal 24 cm

valve at hub end

600 cc

matching dilator to connect to

hub on tubing


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Insertion of Tunneled Pleural Catheter

Inserted in a procedure room or OR

Local anesthesia Outpatient Ultrasound or fluoroscopic guidance

optional (suggested) Seldinger technique Catheter tunneled under skin to a counter

incision 5-8 cm away Insertion can be done by pulmonologist,

interventional radiologist or surgeon


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Large Series Retrospective analysis of 250 tunneled pleural catheter insertions in

223 patients (Calgary)

4.4% failed insertion

Symptom control complete in 39%, partial in another 50%

No further procedure necessary in 90.1% with successful insertions

Spontaneous pleurodesis 43% at 59 d

Tremblay, A et al. Chest 2006; 129:368

Retrospective analysis 418 TPC (355 patients) over 2 years (MSKC)

4.8% complications (infection and PTX)

Symptom control 89%

No further procedure necessary in 380 of 418 (91%)

Spontaneous pleurodesis achieved in 26% at median of 44 d

Suzuki, K et al. Journal of Thoracic Oncology 2011;6:762


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Problems with the PleurX

Chronic foreign body

Need support

Symptom control

39% complete

50% partial

4% none

Malignant seeding of the tract in up to 7%

Empyema 3.2%

Tremblay et al, Chest 2006; 129: 362

Janes et al, Chest 2007; 131: 1232

http://www.chestjournal.org/content/vol131/issue4/images/large/zcb0020706820003.jpeg


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Incidence Of Spontaneous Pleurodesis With Indwelling Catheter

Study N % SP Time (days)

Putnam 1 91 46% 29

Putnam 2 100 21%

Pollak 31 42%

Musani 24 58% 39

Tremblay 250 43% 59


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Complications of Pleurx

Don’t underestimate delirium

Don’t underestimate the creativity of individuals under stress

Most complications resolve without removal

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Nassim F. Folch E., Majid E. Tunneled Pleural Catheter Dysfunction.

J Bronchology and Interventional Pulmonology 2012;19(2)


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Diagnostic Yield of Thoracoscopy

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Janssen JP. Why you do or do not need thoracoscopy.

Eur Respir Rev 2010;19:117:213-6


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Medical Thoracoscopy

Underutilized in the USA • Growing interest

• Window into the pleura

• Development of semi-rigid thoracoscope was expected to impact its use.

Integral part of Interventional Pulmonary • “art and science of medicine related to the

performance of invasive diagnostic and therapeutic procedures that require additional training and expertise beyond the required within a standard training program in respiratory medicine”

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Beamis and Mathur 1999


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Procedural Interest - Time

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Thoracoscopy

Percutaneous

needle biopsies

Mediastinoscopies

Open Lung Biopsies

Bronchoscopy

Number of Thoracoscopies compared to other procedures at

Lungerklinik 1948-1981. Brandt et al, 1985.


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Definition and Controversy

“Pleuroscopy”

“Medical Thoracoscopy”

“Thoracoscopy” • Used interchangeably

through time

• Some experts suggest pleuroscopy while others just thoracoscopy

• Not a debate in Europe

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Medical vs. Surgical Thoracoscopy

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Pleural Biopsies and Pleurx Placement

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Pleurodesis and Chest Tube Placement

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Distribution of tumor implants in:

The Pleura The Lung

Horeweg N, Van del Aalst CM, Thunnissen E, et al. Characteristics of

lung cancers detected by CT screening in the randomized NELSON

trial. AJRCCM 2013;187(8):848-54.


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Pleural biopsy, H&E, 10x objective Pleural biopsy, TTF-1 IHC


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Common Indications for Thoracoscopy

Diagnostic • Recurrent Pleural Effusions

• Staging of Lung Cancer

• Suspected Tuberculosis

• Suspected Lung Cancer

Therapeutic • Pleurodesis by poudrage

• Early empyema

• Spontaneous Pneumothorax

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Adenocarcinoma or Mesothelioma?


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Complications of Thoracoscopy

Prolonged air leak

Hemorrhage

SQ emphysema

Postoperative fever

Empyema

Wound infection

Cardiac arrhythmias

Hypotension

Seeding of chest wall

(eg. Mesothelioma)

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Ideal Agent

Antineoplastic agents

Tetracyclines

Talc

Silver nitrate

Corynebacterium parvum

Iodopovidone

VEGF

INF-2b

TGF- 2

• Effective

• Inexpensive

• Available

• Easy to administer

• Low Morbidity

Available Agents:


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Talc & ARDS Risk is likely overestimated

0% in 558 pts w/French talc

temp & oxygen x 48hrs

Talc contents

Particle size

Impurity No risk of asbestos contamination Evaluated by difraction x-rays Infrared specrophotometry

DO NOT USE TALC IN RABBITS OR RATS

Ferrer et al, Chest 2001; 119: 1901 Montes et al, AJRCCM 2003; 168: 348 Fraticelli et al, Chest 2002; 122: 1737 Montes et al, AJRCCM 2003; 18: 348 Maskell et al, Am J Respir Crit Care Med 2004; 170: 377

U.S.

10-20 m

French

33 m

Sahn, AJRCCM 2000; 162: 2023

Janssen et al, Lancet 2007; 369: 1535

http://www.chestjournal.org/content/vol119/issue6/images/large/cb0613797001.jpeg


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Dresler, C. M. et al. Chest 2005;127:909-915

Time to recurrence of MPE


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Talc slurry vs. Poudrage

53 Dresler, C. M. et al. Chest 2005;127:909-915


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Rapid Pleurodesis

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Our Experience Reddy, et al

No. patients 8 30

Most common primary

site

Lung (5) Lung (9)

Length of hospitalization median (mean)

1 (1.5) 1.79 days (3.19)

Length of time with TPC

Median (mean)

16 (21)

**time to office visit

7.54 (16.65)

Need for thoracostomy

tube

No Yes

Violation of visceral

pleura

No No

Technique used to

determine likelihood of

pleurodesis

Post-thoracentesis

radiograph

Pleural manometry

Immediate postoperative

drainage technique

TPC to continuous suction

at -20 cmH20

24F chest tube to

continuous suction at -20

cmH20

Anesthesia General anesthesia Moderate sedation

Procedure related complications

0 Fever (2), Empyema (1)

Procedure related deaths 0 0

Patients who died with

TPC in place: N (%)

1 (12.5%) 4 (13%)

Clogging of TPC 0 0

Folch E, Santacruz JF. Rapid Pleurodesis: an outpatient alternative. CHEST 2011;140(6)

Reddy C, Ernst A, Lamb C, Feller-Kopman D; Rapid pleurodesis for malignant pleural

effusions: a pilot study, Chest 2011 1396 1419-1423


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Thorough investigation of exudative pleural effusions is warranted.

Palliation is very important!

Aggressive treatment of MPE should be considered and ALL options discussed with the patient

Thoracoscopy is safe and effective technique under moderate sedation or GA

TPC are an excellent option for patients with low KPS, trapped lung physiology or who decline thoracoscopy

Training and proctored cases are of paramount importance

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Take Home Message


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Erik Folch MD, MSc Associate Director, Interventional Pulmonology Fellowship

Division of Thoracic Surgery and Interventional Pulmonary

Beth Israel Deaconess Medical Center

One Deaconess Rd., Suite 201

Boston, MA 02215

617-632-8060

[email protected]

BETH ISRAEL DEACONESS

MEDICAL CENTER HARVARD

MEDICAL

SCHOOL

CHEST DISEASE CENTER AT of Harvard Medical School ...

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