EBUS-TBNA, EUS-FNA or their combination have finally gained acceptance as the tests of first choice in mediastinal staging. In suspected non-small cell lung cancer, endobronchial ultrasound may be preferred in the histologic sampling of paratracheal and subcarinal mediastinal adenopathy because the diagnostic yield can surpass mediastinoscopy

1. Endobronchial Ultrasound Guidance of TBNA
Current Approach To Lung Cancer Staging
- How EBUS Became a Game Changer Bassel Ericsoussi, MD
Pulmonary and Critical Care Consultant
Franciscan Medical Specialists

2. Types of EBUS

3. Spatial Difficulties with Transbronchial Biopsy
Using Monoplanar Fluoroscopy Only

4. Radial EBUS for Peripheral Pulmonary
Lesions
• Utilizes radial
ultrasound probe
• 1.7mm probe
inserted through the
working channel of a
therapeutic
bronchoscope
• Frequency is 20Mhz

5. Radial EBUS

6. Radial EBUS

7. Washington University Experience
with Radial EBUS
• 446 of 467 (96%) nodules located using radial
EBUS only
• Overall diagnostic yield 69%
• Diagnostic yield 84% when a concentric view
was obtained vs 31% when an eccentric view
was obtained

8. Radial EBUS
Things to Look For

9. Combining Radial EBUS with ENB will
Increase the Diagnostic Yield
Am J Respir Crit Care Med 2007; 176:36-41

10. Radial EBUS
Summary
• Radial probe EBUS can be used to target
peripheral nodules
• Provides real-time feedback about location
relative to peripheral nodules
• Radial probe EBUS can complement existing
methods of sampling peripheral nodules

11. Convex Probe EBUS Bronchoscope

13. Real-time Guidance of Transbronchial
Needle Aspiration (EBUS-TBNA)

14. Understand the Orientation

15. Understand the Orientation

17. How EBUS Became a Game Changer
• Minimally invasive
• Ability to access nearly all nodal stations
• Ability to combine diagnosis and staging in a
single procedure
• Equivalent (if not better) yield when c/w
mediastinoscopy
• Ability to provide adequate tissue for
molecular analysis
Ernst et al, J Thorac Oncol 2008; 3:577
Annema et al, JAMA 2010; 304: 2245

18. Conventional vs EBUS-TBNA
• Randomized trial 200 patients
• Level 7 nodes : no significant difference in
diagnostic yield
• Other mediastinal nodal stations: 58% vs 84%
diagnostic yield ( conventional vs ebus )
Chest 2004; 125: 322-325

19. Conventional vs EBUS-TBNA
Herth,Ernst. Chest 2004; 125:322-325

20. EBUS Vs. Standard TBNA In Patients
With Suspected Sarcoidosis
Tremblay et al, Chest 2009; 136:340-346

22. ABILITY TO ACCESS NEARLY ALL
NODAL STATIONS

23. Lymph Node Map
Update
The International
Association for the Study
of Lung Cancer (IASLC)
Lymph Node Map 2009
Accurate assessment of
lymph node involvement is
essential for staging and
treatment of lung cancer.

24. Naruke Lymph Node Map
Mountain-Dressler
Japan Lung Cancer Society
Modification of ATS Map

27. Conventional Mediastinoscopy
Does not access :
1R and 1L: supraclavicular nodes
3A: prevascular nodes
5-6: Subaortic (AP window), para-aortic nodes
7 posterior
8: paraesophageal nodes
9: pulmonary ligaments nodes
• 2R and 2L: right and left
upper paratracheal
nodes
• 4R and 4 L: right and
left lower paratracheal
nodes
• Station 7: subcarinal
nodes (but not 7
posterior)
Morbidity 2%
Mortality 0.08%

28. Extended Mediastinoscopy
Left Anterior Mediastinoscopy
Chamberlain Procedure
• Station 5: subaortic (AP
window) LN
• Station 6: paraaortic
nodes
• Contraindications:
Far less easy and therefore less routinely
performed than conventional mediastinoscopy
- Mobidity 8%
- Mortality < 1%
– Calcified aorta
– Post operative aorta

29. Endoscopic Ultrasound with Fine Needle Aspiration
EUS-FNA
Lower mediastinum LN
• Station 7: subcarinal,
including posterior
subcarinal
• Station 8: paraesophageal
• Station 9: Pulmonary
ligament
• 3P: prevertebral
• Left adrenal gland
• Left liver lobe

30. Endobronchial Ultrasound Transbronchial Needle Aspiration
EBUS-TBNA
UIC Bassel Ericsoussi, MD
30

32. EQUIVALENT (IF NOT BETTER) YIELD
WHEN C/W MEDIASTINOSCOPY

33. EBUS-TBNA VS. Mediastinoscopy
• Prospective, crossover trial 66 patients
• Biopsy results of paratracheal and subcarinal
lymph nodes were compared
• The prevalence of malignancy was 89% (59/66
cases)
Ernst et al JTO 2008

34. EBUS-TBNA VS. Mediastinoscopy
• Diagnostic yield:
– EBUS 91%
– Mediastinoscopy 78%
– p = 0.007
• EBUS the sensitivity, specificity, and negative
predictive value were 87, 100, and 78%,
respectively
• Mediastinoscopy the sensitivity, specificity, and
negative predictive value were 68, 100, and 59%,
respectively
Ernst et al JTO 2008

35. EBUS-TBNA VS. Mediastinoscopy
In suspected non-small cell lung cancer,
endobronchial ultrasound may be preferred in
the histologic sampling of paratracheal and
subcarinal mediastinal adenopathy because the
diagnostic yield can surpass mediastinoscopy
Ernst et al JTO 2008

36. ABILITY TO PROVIDE ADEQUATE
TISSUE FOR MOLECULAR ANALYSIS

37. Adequacy Of Sample For Molecular
Studies
• EBUS-TBNA samples of enlarged mediastinal
and hilar nodes obtained are Adequate in
quantity and quality for genetic and molecular
subtyping in upwards of 90% and 77% of
samples respectively.
• Samples collected with this technique were
found to be just as good as other sampling
meth-ods such as mediastinscopy.
Nivani N et al:Am J Respir Crit Care Med. 2012;185 (12):1316-132
Nakajima T et al. Ann Thorac Surg. 2012; 94:2097-2101

38. EBUS for Mutation Analysis
• Retrospective analysis of 209 cytology
specimens from patients with lung cancer at
MD Anderson
– 99 EBUS samples
– 67 TTNA samples
– 27 body fluid samples
– 10 ultrasound-guided FNA of superficial sites
• DNA sequencing for EGFR and KRAS
performed on all specimens
Billah S, et al. Cancer Cytopathol. 2011;119(2):111-117

39. EBUS for Mutation Analysis
• EGFR found in 19% (29% of adeno)
• kRAS in 24%
• Overall specimen insufficiency rate was low:
6.2%
– Body fluid: 3.7%
– EBUS: 4%
– TTNA: 7.5%
– US-guided superficial FNA: 10%
Billah S, et al. Cancer Cytopathol. 2011;119(2):111-117

40. EBUS for Multi-Gene Mutational Analysis
• Review of 156 EBUS cases
– 22ga needle
– formalin fixed core split for cytopath analysis &
Alloprotect Tissue Reagent
– needle flushed with NS for cytology / cell block
– EGFR: PCR
– kRAS & p53: direct sequencing
Nakajima T, et al. Chest 2011; 140: 1319

41. EBUS for Multi-Gene Mutational Analysis
• EGFR analysis was possible in 98.7%
– + in 26.9% (46% of female, non-smokers w/adeno)
– gefitinib  PR of 54%, disease control (PR +
stable disease 86%)
• kRAS: + in 3.5% (all male, smokers)
• p53: + in 41.6% (70% had adenoCA)
– associated w/significant chemoresistance
Nakajima T, et al. Chest 2011; 140: 1319

42. Does Needle Size Matter
• Nakajima: 33 patients
– no difference in yield
– better histologic preservation w/21ga
– more blood contamination
• Saji: 56 patients
– 21 is better
• Yarmus / Aquire: 1299 patients
– no difference in adequacy or yield
• Above are for Dx, no data on markers (yet)
Saji et al, J Bronchol & Intervent Pulmol 2011; 18:239
Nakajima et al, Respirology 2011; 16:90
Yarmus et al, CHEST 2013; 143:1036

43. EBUS Strategy
• Sample from more than one nodal station
• Choose most advanced nodal station ( N3 vs
N2 vs N1)
• Lymphnodesize > 1cm
• Non-necrotic appearing
• Number of passes : range of 3 - 5

44. EBUS-TBNA: How Many Aspirates Per
Lymph Node?
• A study of EBUS-TBNA in 163 Mediastinal LN
stations in 102 NSCLC patients
• Sample adequacy was:
– 90.1% for one aspiration
– 100% for three aspirations
– The sensitivity for differentiating malignant from
benign LN stations was 69.8%, 83.7%, 95.3%, and
95.3% for one, two, three, and four aspirations,
respectively.
– Maximum diagnostic values were achieved in three
aspirations
Lee. H.S. CHEST 2008; 134:368–374

45. # of Passes
• For diagnosis: 3 needle passes
• For markers:
– 90 patients diagnosed with adenoCA via EBUS
– 94% adequacy for mollecular analysis with 5
needle passes
Seok Lee et al, Chest 2008; 134:368
Yarmus etl al, Ann Am Thorac Soc [in press]

46. EBUS Number of Passes
• Plateau in yield at 7 passes
Am J Respir Crit Care Med 2002,166: 377-381
• ** 3 transbronchial needle passes established
a tissue diagnosis
• ** 4 – 5 passes for lung cancer staging
Eur Respir J 2007; 29: 112-116

47. Conclusions
• Histologic subtyping and mutation analysis are
critical steps in the evaluation of patients with
NSCLC
• Communication between oncologist, pathologist,
and pulmonologist is a key to effective use of
molecular analysis.
• As the majority of patients with NSCLC are not
surgical candidates, EBUS FNA is a less invasive
means of tissue acquisition for molecular
analysis.

48. The American College of Chest
Physicians Lung Cancer Guidelines
(3rd Ed) Editorial
• EBUS-TBNA, EUS-FNA or their combination
have finally gained acceptance as the tests of
first choice in mediastinal staging.
• More complete staging improves outcomes.
• Safer and cheaper than mediastinoscopy
without compromising accuracy (pooled
sensitivities of 89%, 89%, and 91% (for EUS,
EBUS, and combined EUS/EBUS respectively).

49. Talk to Your Patient
• Discuss the risks and benefits of alternative
management strategies and elicit patient
preferences