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Current Status of Bronchoscopic Ultrasound

Imaging and Staging

Kazuhiro Yasufuku MD, PhD


Director, Interventional Thoracic Surgery Program
Associate Professor, University of Toronto
Division of Thoracic Surgery, Toronto General Hospital

AATS Focus on Thoracic Surgery, Novel Technologies in Lung Cancer

Nov 21-22nd, 2014

Disclosure
Industry-sponsored

grants

Educational and research grants from Olympus Medical Systems Corp.

Consultant

Olympus America Inc.


Intuitive Surgical Inc.
Covidien
Johnson and Johnson

Research

Collaboration

Siemens
Novadaq Corp.
Veran Medical Technologies

Endobronchial Ultrasound
Radial

probe endobronchial ultrasound

Central Airway
Peripheral Nodules

Convex-probe
EBUS-TBNA

endobronchial ultrasound

Endobronchial Ultrasound
Radial

probe endobronchial ultrasound

Central Airway
Peripheral Nodules

Convex-probe
EBUS-TBNA

endobronchial ultrasound

Radial probe EBUS Central airway

Determination of depth of tracheobronchial tumor invasion

Evaluation of peritracheal and peribronchial lymph nodes

Probe
BS20-26R

Balloon sheath
MAJ-643R
O.D.= 2.6mm

FBS
BF-ST30

EBUS Image and Anatomy of Bronchial Wall Structures


Extracartilaginous

Intracartilaginous

Layers 1~2 : Mucosa, submucosa, muscle


3~4 : Cartilage 5~6 : Adventitia

Conventional vs EBUS-guided TBNA


A

randomized trial to compare the yield of EBUS


guided TBNA and conventional TBNA

Subcarinal LN:
86% (EBUS) vs 74% (TBNA)
Other stations:
84% (EBUS) vs 58% (TBNA)

Herth FJ et al. Chest 2004

Radial Type EBUS Peripheral


UM-3R (O.D. = 2.5mm)

UM-S20-20R (O.D. = 1.7mm)

Diagnosis of peripheral pulmonary lesions

EBUS-GS for TBBx

Radial probe EBUS - results

Meta-analysis of 7 studies using radial probe EBUS for


peripheral lesions

Pooled sensitivity for lesions < 25 mm was 71%

One randomized prospective trial has compared radial EBUS


with CT guided biopsy
Similar diagnostic accuracy
Complication rates 3% vs. 27%

Eur Respir J. 2011; 37: 902-10


Respir Med. 2011; 105: 1704-11

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Endobronchial Ultrasound
Radial

probe endobronchial ultrasound

Central Airway
Peripheral Nodules

Convex-probe
EBUS-TBNA
Olympus
Pentax
Fujifilm

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endobronchial ultrasound

Convex Probe EBUS (Olympus)

Outer Diameter: 6.9 mm


Scanning Range 50 degrees
Instrument Channel 2.2 mm
Optics 35 degrees forward oblique

Division of Thoracic Surgery


Toronto General Hospital

Convex Probe EBUS (Olympus)

Division of Thoracic Surgery


Toronto General Hospital

EBUS-TBNA Equipment (Olympus)

EU-ME1
EU-ME2
EU-C60

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EBUS - EB1970UK (Pentax Medical)


New Small Hitachi Linear Array Ultrasound Transducers

19 French
6.3mm Insertion Tube
2mm working channel
Color CCD video images
45 Forward Oblique

Hitachi 5500 scanner


75 Forward Oblique
5,6.5,7.5,9, 10 MHz
options

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EBUS scope EB-530US (FUJIFILM)


Fujifilm Ultra Small Super CCD
Chip installed
10forward oblique view
Wide Field of View: 120
6.7mm

6.3mm
2.0mm

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NA-201SX-4022, 4021 (Olympus)

21G and 22G needles

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SonoTip EBUS Pro Flex (Medi-Globe)

Dimensionally stable 22G Nitinol needle


Eliminates needle deformation

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EchoTip ProCore EBUS Needles (Cook Medical)

Core trap design to obtain tissue


22G and 25G

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Cell blocks often contain a


mini-core of tumour.
Can be used for multiple
immunohistochemical stains.
Can provide prognostic
information (cell-cycle
proteins, EGFR mutation).

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EBUS-TBNA

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Access to all LN stations accessible by Med as well as


part of N1 nodes
A minimally invasive modality
Sensitivity 85-96%
Real time procedure
Doppler mode enables differentiation of LN from vessels
The test of first choice to confirm mediastinal disease in
accessible LN stations

Clinical Applications of EBUS-TBNA


Lymph

node staging of lung cancer

Pre-operative staging
Post-operative evaluation
Restaging

Dx

of centrally located intrapulmonary tumors

Mediastinal

and hilar adenopathy NYD

Sarcoidosis (Overall yield of 90-96% )


Lymphoma (Sensitivity 57-91%)

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Lung ca mediastinal staging


Invasive

Mediastinal Staging of Lung Cancer

ACCP Evidence-Based Clinical Practical Guideline (3rd Edition)


Overall sensitivity 89% (46-97%), NPV 91% (n=2756)

Minimally invasive needle techniques to stage the


mediastinum have become increasingly accepted and
are the tests of first choice to confirm mediastinal
disease in accessible LN stations
If negative, these needle techniques should be
followed by surgical biopsy
All abnormal scans should be confirmed by tissue
biopsy (by whatever method is available) to ensure
accurate staging

Silvestri et al. Chest. 2013; 143: e211s-250s

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Cost Effectiveness
A

decision-tree analysis to compare downstream


costs of EBUS-TBNA, conventional TBNA and
mediastinoscopy.
EBUS-TBNA (-ve results surgically confirmed) most cost-beneficial
approach (AU$2961)
EBUS-TBNA (-ve results not surgically confirmed) ($3344)
Conventional TBNA ($3754)
Mediastinoscopy ($8859)

Steinfort et al. J Thorac Oncol. 2010;5: 15641570

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EBUS Morphology

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Standard EBUS Image Classification

(g) homogeneous

(h) heterogeneous

Fujiwara T, Yasufuku K et al. Chest. 2010 138(3):641-7

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Vascular Pattern Classification of EBUS Images


Negative finding

Grade 0

Positive finding

Grade 1
Positive finding

Grade 2

Grade 3

BA inflow

Grade 0: no blood flow or small amounts of flow


Grade 1: a few main vessels toward center of lymph node from hilum
Grade 2: a few punctiforms or rod-shapes of flow signal, a few small vessels could be found as a long strip of a curve
Grade 3: rich flow, more than four vessels can be found with different diameters and twist or helical flow signal
BA inflow sign: a color blood flow from bronchial artery (BA) toward to lymph node
Nakajima T, Yasufuku K et al. J Thorac Oncol. 2012; 7(6):1009-14

EBUS vascular pattern and Survival


Survival rate

p=0.033

Low blood flow signal


High blood flow signal

Survival perioddays
Nakajima T, Yasufuku K et al. J Thorac Oncol. 2012; 7(6):1009-14

Ultrasound imaging modes


B-mode

Harmonic Imaging

Based on non-linear echoes

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M-mode

Color-doppler

Elastgraphic Imaging

Contrast-agent Imaging

Evaluation of stiffness

Microbubbles are used for


evaluation of tumor lesion

EU-ME2

H-FLOW

Soft

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Pulse wave Doppler

Elastography

Hard

Assessment of Mediastinal LNs


Benign LN

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Malignant LN

Assessment of Mediastinal LNs


Benign LN

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Malignant LN

EBUS and Molecular Analysis

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Molecular Testing using EBUS-TBNA Samples

IHC

Direct sequence

Flow cytometry

RT-PCR

FISH

Real time RT-PCR

Nakajima T, Yasufuku K. J Thorac Oncol. 2011;6: 203206


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Beyond Tissue Dx: Personalized Medicine for NSCLC

The tissue is the issue remains an important principle for further


progress in personalized medicine.
EBUS-TBNA samples can be used for biomarker assessments
EGFR mutation
cell-cycle proteins
Aberrant methylation
EML4-ALK Fusion Gene

Nakajima et al. Chest. 2007; 32: 597-602


Mohamed et al. Thorax. 2008; 63: 642-7
Nakajima et al. JOB 2009; 16: 10-14
Sakairi et al. Clin Cancer Res. 2010 ; 16:4938-45

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Suitability of EBUS-TBNA Specimens for Subtyping


and Genotyping of NSCLC: A Multi-Centre Study of 774 Patients

5 centres in the UK (2009 and 2011) , N=774

Subtype classified in 77% (95% CI 73% - 80%)

The rate of NSCLC-NOS significantly reduced with IHC

EGFR mutation analysis possible in 107/119 (90%)

Sensitivity 88% (95% CI 86%-91%) , NPV 72% (95% CI 66% - 77%),


Dx accuracy 91% (95% CI 89% - 93%)
Navani N et al. Am J Respir Crit Care Med. 2012 Apr

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Microarray Analysis of EBUS-TBNA samples


1) whole transcript array (WT array) mRNA expression
2) miRNA array miRNA expression

Metastatic lymph node samples

mRNA
Nakajima, Yasufuku et al Ann Thorac Surg. 2012; 94(6): 2097-101

miRNA

Surgery for Early Lung Cancer

Lobectomy

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Limited Resection

CALGB 140503

Phase III Randomized Trial of Lobectomy vs Sublobar


Resection for Small (<2cm) Peripheral NSCLC

Surgery
Confirmation of NSCLC on Path
N0 status on frozen section
(4R, 7, 10R on right)
(5or6, 7, 10L on left)

Randomization
Lobectomy

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Limited Resection

LN assessable by EBUS
2, 3p, 4, 7, 10, 11, (12, 8, 9)

LN not assessable
by EBUS

LN not assessable
by EBUS
N1 LNs
part of 12, 13, 14

Thin EBUS-TBNA scope


outer diameter 5.9mm

outer diameter 6.9mm


Wada et al, JOBIP 2014 in press
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Endoscopic visibility range & Maximum reach


LUL bronchus

Tracheobronchus

(mm)

(mm)

100

30

RUL bronchus
(mm)
170

150
80

20

60

10

110

40

90

130

(n=3)
Maximum reach
Endoscopic visibility range

Wada et al, JOBIP 2014 in press

Summary

Radial probe EBUS improves the yield of TBBx

EBUS-TBNA is less invasive, more safer and as accurate


as surgical staging in NSCLC patients with discrete
mediastinal lymph node enlargement

In direct comparison with surgical staging, EBUS-TBNA and


other needle techniques have emerged as the best first
diagnostic tools to obtain tissue

Molecular analysis of cytological specimens obtained by


EBUS-TBNA from metastatic lymph node is possible

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Division of Thoracic Surgery


Toronto General Hospital
University Health Network
Kazuhiro Yasufuku, MD, PhD, FCCP
kazuhiro.yasufuku@uhn.ca

Thank you
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