Jpn J Clin Oncol 2014;44(9)841– 845
doi:10.1093/jjco/hyu095
Advance Access Publication 23 July 2014
Comparison of Two 22 G Aspiration Needles for Histologic Sampling
During Endobronchial Ultrasound-guided Transbronchial Needle
Aspiration (EBUS-TBNA)
Takehiro Izumo*, Shinji Sasada, Junko Watanabe, Christine Chavez, Yuji Matsumoto and Takaaki Tsuchida
Department of Endoscopy, Respiratory Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
*For reprints and all correspondence: Department of Endoscopy, Respiratory Endoscopy Division, National Cancer
Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan. E-mail: [email protected]
Received April 30, 2014; accepted July 3, 2014
Objective: Endobronchial ultrasound-guided transbronchial needle aspiration is widely used
for mediastinal and hilar lesions. Histologic specimens from this procedure are important for
specific diagnosis and targeted therapy. Studies on the traditional endobronchial ultrasoundguided transbronchial needle aspiration needles reported yields of only 50 – 60% for diagnostic
histologic specimens. Recently, a new needle has become available in Europe, USA and Asia.
The investigators aimed to evaluate the histologic specimen retrieval yields of the two needles.
Methods: Patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the new 22 G needle (M group, n ¼ 94) were compared with a historical control
group who underwent endobronchial ultrasound-guided transbronchial needle aspiration with
the traditional 22 G needle (O group, n ¼ 82). The quality of needle aspirates from both groups
was evaluated.
Results: There were no significant differences between the two groups in terms of demographics, lesion characteristics, primary disease and examiner experience. The M group had a significantly shorter procedure time than the O group (P ¼ 0.049). Of the 214 punctures by the
M group, 159 (74.3%) were diagnostic, 28 (13.1%) were non-diagnostic and 27 (12.6%) had no
histologic specimen. The 235 punctures by the O group were diagnostic in 144 (61.3%), nondiagnostic in 60 (25.5%) and had no histologic specimen in 31 (13.2%). The yield for diagnostic
histologic specimens of the M group was significantly higher than the O group (P ¼ 0.0035).
There were no major complications observed.
Conclusions: The yield for diagnostic histologic specimens by the new 22 G endobronchial
ultrasound-guided transbronchial needle aspiration needle was high. Further technical improvements of histologic sampling yields are very important when selecting targeted therapy.
Key words: bronchoscopy – EBUS-TBNA – endobronchial ultrasound – histology/cytology –
transbronchial needle aspiration needle
INTRODUCTION
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for sampling mediastinal
and hilar lesions, providing not only cytology but also histology samples (1 – 3). A previous report has indicated the
diagnostic utility of histologic samples, with success rates
ranging from 50 – 60% (4). Recently, histologic samples have
become very important because of the emergence of therapeutic targets based specific molecular alterations (3, 5, 6). Further
development of new chemotherapy regimens and gene targeted
therapy is expected in the near future and correspondingly,
improvement of the histologic sampling rate is essential.
# The Author 2014. Published by Oxford University Press. All rights reserved.
For Permissions, please email: [email protected]
842
EBUS-TBNA needles for histologic sampling
For many years in Japan, the 21 G needle (NA201SX-4021) or 22 G needle (NA-201SX-4022, O needle,
Fig. 1A and C), the ‘ViziShot w ’ by Olympus Ltd has been
the only available sampling device used to perform
EBUS-TBNA. Some studies have reported similar histologic
sampling rates between these two needle sizes (4, 7, 8).
Recently, a new 22 G EBUS-TBNA needle, the ‘SonoTip
EBUS Pro with stainless steelw’ (GUS-45-18-022, Fig. 1B) by
Medi-Globe Ltd (M needle) has become available. The tip of
the M needle is very sharp (Fig. 1D) and has an easy handling
design. The aim of this study was to evaluate and compare the
histologic specimen retrieval yields of the two currently available 22 G needles during EBUS-TBNA.
PATIENTS AND METHODS
PATIENTS
The EBUS-TBNA database of the Department of Endoscopy,
National Cancer Center, Japan from November 2012 to
December 2013 was retrospectively reviewed. Consecutive
patients who had hilar and/or mediastinal tumors and lymphadenopathy were included. Lymphadenopathy was defined
as an enlargement ( 10 mm in short-axis diameter) on
chest computed tomography (CT), or an increased 18
[F]-fluorodeoxyglucose (FDG) uptake (standardized uptake
value (SUV) max . 2.5) on positron emission tomography-CT.
The patients were divided into two groups. The M group
consisted of patients who underwent EBUS-TBNA between
June 2013 and December 2013 with the use of M needle. The
O group served as historical control and included those who
underwent EBUS-TBNA with O needle from November 2012
to May 2013. Institutional review board approval was granted
for this retrospective review.
To compare the diagnostic yield and utility of each needle,
the EBUS-TBNA aspirates and histologic core level from
each needle were analyzed.
EBUS-TBNA PROCEDURES
EBUS-TBNA was performed under conscious sedation
with intravenous midazolam by pulmonary residents or pulmonary staff physicians (supervisors). As briefly, local anesthesia was achieved by spraying 4% lidocaine solution
(10 ml) to the pharynx. The convex probe EBUS (CP-EBUS;
BF-UC260FW, Olympus, Tokyo, Japan) was inserted through
the oral route, in the same way as usual bronchoscopy.
Intermittent 2 ml aliquot doses of 2% lidocaine were used
during the procedure.
CP-EBUS, which consists of a convex probe transducer that
is incorporated with the tip of a bronchoscope, scans parallel
to the insertion direction of the bronchoscope. The ultrasound
images were generated using a dedicated ultrasound processor
(Olympus, EU-ME1). When the target lesions were visualized
by CP-EBUS, the TBNA needle was inserted through the
working channel of the CP-EBUS and advanced through the
tracheobronchial wall into the target lesion under real-time
EBUS guidance. Aspiration was done by moving the needle
Figure 1. The endobronchial ultrasound-guided transbronchial needle aspiration needle. (A) NA-201SX-4022 needle (Olympus Ltd). (B) GUS-45-18-022 needle
(Medi-Globe Ltd). (C) The tip of NA-201SX-4022. (D) The tip of GUS-45-18-022.
Jpn J Clin Oncol 2014;44(9)
843
Figure 2. Characterization of histologic specimen. (A) Histologic specimen of adenocarcinoma categorized as diagnostic. (B) Histologic specimen containing
clot, categorized as non-diagnostic. (hematoxylin and eosin stain, original magnification 100).
back and forth inside the target lesion for 10 – 20 times, under
negative pressure. After sampling, suction was released and
the needle was retracted from the scope. EBUS-TBNA was
performed repeatedly until a historical core was macroscopically available (maximum of three punctures per lesion).
Procedure time was recorded from insertion to removal of the
CP-EBUS through the vocal cords.
The specimen collected in the needle lumen was pushed out
with a stylet onto a glass slide. The tissue aspirate on the glass
slide was then collected and transferred into containers filled
with formalin for histopathologic evaluation. The remaining
fluid aspirate inside the needle was then flushed with air on to
the glass slide and smeared for cytology evaluation. Rapid
on-site cytology evaluation was performed for every case. The
final diagnosis was confirmed by pathological diagnosis of
EBUS-TBNA or surgical samples.
Table 1. Baseline characteristics of patients
Characteristics
Sonotip EBUS Pro
22 G with stainless steel
Vizishot
22 G
P valuea
Patients, no
94
82
–
Male/female
65/29
56/26
1.00
Age, years,
(median, range)
68 (37–85)
68
(40– 84)
0.92
86/8
69/13
0.164
13/81
9/73
0.651
Primary disease
Malignant/benign
Examiner
Supervisor/resident
Data are presented as number or median (range). aFisher’s exact test or
Mann–Whitney U test.
PATHOLOGIC EVALUATION
RESULTS
The quality of the needle aspirate and histologic core tissue
was evaluated by a pathologist and described according to a
previously reported classification (4). Briefly, the histologic
specimens were classified as follows: A, diagnostic (Fig. 2A);
B, non-diagnostic (e.g. clot, cartilage: Fig. 2B); C, no specimen. Samples that were classified as A were designated as
adequate.
There were a total of 176 EBUS-TBNA cases during the study
period. Table 1 shows the baseline characteristics of the
patients. There were 94 patients in the M group, while the
O group had 82 patients. There were no significant differences
between the two groups in terms of sex, age, prevalence of
malignancy in primary disease or examiner experience (supervisor or resident). The baseline characteristics of the punctured lesions are shown in Table 2. There were 214 punctures in
the M group, while the O group had 235 punctures. There
were no significant differences between the two groups
in terms of lesion size, FDG-PET uptake or location of the
punctured lesion. Procedure time of the M group was significantly shorter than that of the O group (P ¼ 0.049). The diagnostic yields of EBUS-TBNA in the M and O groups were
93.6% (88/94 cases) and 87.7% (71/81 cases), respectively
(P ¼ 0.197).
The quality and classification of histologic specimens from
EBUS-TBNA punctures with each needle group are shown in
Table 3. Of the 214 punctures by the M group, 74.3% provided
adequate histologic specimens, 13.1% was non-diagnostic and
12.6% did not provide tissue samples. In the O group, histologic specimens were adequate in 61.3% and non-diagnostic
STATISTICAL ANALYSIS
The diagnostic yield was calculated per patient. The yield for
diagnostic histology samples was analyzed per puncture.
Descriptive statistics was presented as frequency, percentage
and median (range). The differences between two groups were
calculated with Fisher’s exact test or Student’s t-test. All
P values were two sided and a level ,0.05 was considered
statistically significant. Statistical analyses were performed
with EZR (Saitama Medical Center, Jichi Medical University;
http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html;
Kanda), a graphical user interface for R (The R Foundation for
Statistical Computing, Vienna, Austria, Ver. 2. 13.0) and a
modified version of R commander (Ver. 1.8-4).
844
EBUS-TBNA needles for histologic sampling
Table 2. Baseline characteristics of the punctured lesions
Characteristics
Sonotip EBUS Pro
22 G with stainless
steel
Vizishot 22 G
Punctured lesions, no
214
235
Table 3. Classification of histologic specimens obtained by EBUS-TBNA
P valuea
Category of
Sonotip EBUS Pro
Vizishot 22 G
histological specimens 22 G with stainless steel
A. Diagnostic
Size, short axis
Median, mm (range)
16.8 (3.8–57.6)
8.59 (2.2–22.9)
8.3 (2.4–28.5) 0.289
Location
Upper paratracheal
(2R, 2L)
Retrotracheal (3p)
6
4
5
2
101
95
56
70
5
2
Interlobar and lobar
(11s, 11i, 11L, 12L)
32
49
Central parenchymal
9
13
Lower paratracheal
(4R, 4L)
Subcarinal (7)
Hilar (10R, 10L)
61.3% (144/235) 0.0035
B. Non-diagnostic
13.1% (28/214)
25.5% (60/235)
C. No specimen
12.6% (27/214)
13.2% (31/235)
16.0 (6.3–70.4) 0.567
FDG-PET SUVmax
Median, mm (range)
74.3% (159/214)
P valuea
0.235
Data are presented as number or median (range).
a
Fisher’s exact test or Mann–Whitney U test.
in 25.5% of the 235 punctures; there were 31 punctures
(13.2%) by the O group that did not yield tissue samples. The
sampling yield for diagnostic histologic specimens by the M
group was significantly higher than that of the O group
(74.3% vs. 61.3%, P ¼ 0.0035). There were no significant
complications observed in the procedures of both groups.
DISCUSSION
To our knowledge, this is the first report to evaluate the differences between two different 22 G EBUS-TBNA needles.
EBUS is a very important procedure to determine and collect
samples from target sites in mediastinal, hilar and peripheral
locations under real-time ultrasound (9 – 14). Although the
diagnostic yield was the same between the two groups, the
sampling yield for diagnostic histologic specimens was different. Then why such a difference between two groups was
observed? M needle has some advantages that could be particularly important for EBUS-TBNA. First is that, the tip of
the needle is very sharp, facilitating an easy and smooth puncture through the bronchial mucosa. This allows safe performance of EBUS-TBNA and procurement of better samples by
preventing cartilage from being mixed with mucosal wall
during puncture. Another noticeable feature of this new
needle is the soft sheath that allows more flexion of the
CP-EBUS fiber even when the needle is inside the working
channel.
Data are presented as percentage and number.
EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle
aspiration.
a
Using Fisher’s exact test, P ¼ 0.0035 across the sampling yield of diagnostic
histological specimens (A vs. B and C) in each needle group.
Nowadays, adequate sampling of histologic specimens is
necessary for development of new treatment options for
cancer, especially chemotherapy and gene targeted therapy, so
further improvements of the histologic sampling yield is
essential (5, 6).
For this reason, it was necessary to do repeated punctures
per patient until core tissue was obtained. Although the baseline characteristics of the two groups were similar (Table 1
and Table 2), transbronchial needle puncture and macroscopic
specimen collection were technically easier in the M group
than in the O group. This may explain the smaller average
number of punctures in the M group (214/94 or 2.27 per
patient) compared with that of the O group (235/82 or 2.86 per
patient). Our data also suggest that the preserved histologic
samples obtained by the new M needle may be useful not only
for diagnosis but also for molecular analysis.
Theoretically, a larger-bore needle would seem to be effective in acquiring core tissue samples (15, 16) but previous
studies indicated that there was no significant difference
between 21 and 22 G Olympus needles (4, 7, 8). Additionally,
we have observed that when a larger diameter needle is inside
the working channel of a bronchoscope, maximal flexion is
limited.
In our study, procedure time of the M group was significantly shorter than that of the O group. This can be explained by
the fewer number of punctures per patient in the M group. In
addition, given that there was no significant difference
between the two groups in terms of examiner experience,
these results may imply that use of the M needle has easily
become familiar for residents, making it faster to perform
EBUS-TBNA.
Although the M needle for EBUS-TBNA is capable of providing adequate histologic core tissue, there are some points
that should be improved. First, the tip of the M needle is a
little hard to see under the endobronchial ultrasound image in
comparison with the O needle. Second, the needle lock adjuster can be easily dislocated, so careful attention is necessary
during aspiration.
There are several limitations in this study. First, this is a
retrospective, non-randomized study. Second, this was performed at a single institution and multi-center trial is ideal.
Jpn J Clin Oncol 2014;44(9)
Third, prospective, randomized trials that take into account
these confounding variables are needed in the future.
CONCLUSIONS
This study demonstrates that the new M needle is superior in
providing adequate histologic specimens from hilar and mediastinal lesions. With the discovery of specific molecular alterations in cancer and the development of targeted therapy, further
investigations on the technical ability of an EBUS-TBNA
needle to provide adequate histologic core materials are
warranted.
Acknowledgements
We thank Koji Tsuta for supporting the pathologic examinations.
Funding
This work was supported by The National Cancer Center
Research and Development Fund (25-A-12).
Conflict of interest statement
None declared.
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