Introduction
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was first reported in
1992 [1] and is now used for a wide range of lesions. This widely used non-surgical biopsy
procedure provides safe, consistent results under ultrasound guidance [2]
[3]
[4].
A recent meta-analysis of pancreatic lesions showed that EUS-FNA was a modality producing
excellent diagnostic accuracy, and EUS-FNA has now been established as an important
modality for histopathologic diagnosis of pancreatic lesions [5]. This modality is not, however, without unresolved issues, including the need for
by-lesion needle selection, availability of rapid onsite evaluation (ROSE), and skilled
endoscopists [6]
[7].
New clinical applications for biopsies are on the horizon, such as genetic diagnostics
and anticancer drug-sensitivity assays in addition to conventional diagnostics. Such
applications will inevitably require collection of an adequate tissue volume to achieve
better diagnostic accuracy [8]. In EUS-FNA, 19-G needles are useful for histologic diagnostics, providing sufficient
sample for immunostaining, but the greater puncture resistance encountered at this
size increases the difficulty of the procedure [9]
[10]. This has left users wanting smaller-gauge needles that could collect comparable
volumes of tissue. Needle options for fine-needle biopsy (FNB) have increased with
recent development of needles including a core-trap construction [11]
[12] and fork-tip needles [13].
Marketing of an FNB needle with a reversed bevel design in 2011 (ProCore; Cook Medical,
Tokyo, Japan) was well received. A meta-analysis, however, showed no significant difference
in diagnostic accuracy between the ProCore (85 %) and conventional FNA needles (86 %)
[14]. No consensus has yet been reached regarding which needles are best. In 2016, the
Franseen needle emerged as an FNB device [15] with the potential to provide better histologic diagnostic accuracy than conventional
FNA needles [8]. This device, however, remains under-researched. The Franseen needle, with three
tips, is designed to collect biopsy samples by cutting and holding tissue from three
cut surfaces [15]. The tip structure of the needle may allow acquisition of a large volume of tissue,
but may show poor puncture performance.
We recently evaluated diagnostic accuracy and utility of EUS-FNB performed with a
22-G Franseen needle for solid pancreatic lesions, comparing the results to those
obtained through EUS-FNA with conventional needles.
Patients and methods
This study was approved by the ethics review board at Saitama Medical University International
Medical Center and complied with the Declaration of Helsinki, as revised in Brazil
2013. All patients provided written informed consent for EUS-FNA and FNB.
We carried out a retrospective review of all patients who underwent EUS-FNA or EUS-FNB
to evaluate solid pancreatic lesions at our center between July 2013 and November
2018. During the study period, we enrolled 132 patients who had undergone EUS-FNA
using a 22-G conventional needle from July 2013 to January 2017. A total of 95 patients
who had undergone EUS-FNB using a 22-G Franseen needle from February 2017 to November
2018 were enrolled in another group. We checked electronic medical records of patients,
and recorded age, sex, tumor size, tumor site, puncture site, experience of the clinician
who performed examination, and final diagnosis. After propensity score-matching, data
on 190 patients were analyzed ([Fig. 1]).
Fig. 1 Diagram of the study design.
The primary endpoint of this study was to compare diagnostic accuracy between a 22-G
conventional needle group and a 22-G Franseen needle group. The secondary endpoint
was to compare the number of punctures required.
Procedures
EUS-FNA and FNB procedures were performed using a convex linear-array echoendoscope
(GF-UCT260; Olympus Optical, Tokyo, Japan) paired with an ultrasound system (EU-ME2
Premier Plus; Olympus Optical). EUS was performed with the patient under conscious
sedation using intravenous midazolam and pethidine hydrochloride. After excluding
regional and collateral vasculature, the target lesion was punctured. The stylet was
removed, and continuous suction was applied with a 20-ml syringe.
Next, 20 to 30 rapid strokes were made within the lesion, suction was released, and
the needle was removed. Aspirated samples were smeared onto glass slides by inserting
the stylet and applying air pressure. Samples were examined visually for white color
and then fixed in formalin for histologic examination.
Because on-site cytologic examination was not performed, the procedure was repeated
whenever possible under our supervision with a cytology technician until visual confirmation
was obtained of an adequate sample for histopathology and immunostaining.
The puncture needles used were a 22-G conventional needle (Group C) and a 22-G Franseen
needle (Group F). The Expect conventional needle (Boston Scientific Japan, Tokyo,
Japan) used in Group C was primarily used in patients between July 2013 and January
2017, while the Acquire Franseen needle (Boston Scientific Japan) used in Group F
was primarily used in patients thereafter ([Fig. 2]). Procedures were performed by six endoscopists (three trainee endoscopists and
three experienced in performing EUS-FNA). The three trainee endoscopists had sufficient
experience, having conducted more than 1,000 regular esophagogastroduodenoscopies
(EGDs), 500 colonoscopies, and 20 EUS procedures. They had also attended 20 EUS-FNA
procedures performed by EUS-FNA experts as assistants. The three expert endoscopists
had performed regular EGD, colonoscopy, and EUS procedures, and had performed more
than 50 EUS-FNA procedures before the beginning of this study. Technical success was
defined as a successful puncture to the target.
Fig. 2 A 22-gauge Franseen needle with three tips for puncture.
Histologic evaluation
EUS-FNA and EUS-FNB specimens were smeared onto glass slides, and we checked if an
adequate sample had been obtained. The sample was then preserved in 10 % formalin
and embedded in paraffin. Sections were stained with hematoxylin and eosin (ΗΕ) for
histologic examination, and immunostaining was performed if needed. These sections
were examined by two pathology technicians and two pathologists. Only histologic diagnoses
were analyzed in this study.
Study definitions
Final diagnosis was classified as the histologic diagnosis from surgery for those
patients who underwent surgery, and as the clinical outcome after ≥ 6 months for those
patients who did not undergo surgery. Pancreatic adenocarcinoma, pancreatic neuroendocrine
tumor (NET), metastatic tumor from an extra-pancreatic malignancy, pancreatic carcinoma
other than adenocarcinoma, and solid pseudopapillary neoplasms (SPN) were considered
as malignant lesions. Lesions such as focal pancreatitis and other non-neoplastic
lesions were considered benign, absent malignant findings on histologic examinations
and a lack of progression for ≥ 6 months of follow-up. NET, metastases from extra-pancreatic
malignancies, pancreatic carcinomas other than adenocarcinoma, and SPN requiring immunostaining
were classified as “special pancreatic tumors.”
Statistical analysis
Categorical variables are expressed as absolute (n) and relative (%) frequencies,
and were compared using Fisher’s exact test. For comparisons of continuous data, the
two-sample t-test was used if a normal distribution was likely, and the Mann-Whitney
test was used if normality could not be demonstrated. A propensity score-matched cohort
was created by attempting to match each patient who had undergone EUS-FNA with a patient
who had undergone EUS-FNB. In this regard, we used an optimal matching technique to
reduce selection bias and potential confounding. A total of seven variables that could
possibly influence outcome were used to generate, by logistic regression, a propensity
score ranging from zero to one. P < 0.05 was considered significant. Statistical calculations were performed using
SAS JMP version 14.1.0 and SAS version 9.4 software (SAS Institute, Cary, North Carolina,
United States).
Results
We used the propensity-matched analysis and performed confounder adjustment. Clinical
features of each propensity-matched patient group are shown in [Table 1]. As a result, Groups C and F showed no significant differences in sex, age, lesion
diameter, or tumor type. In Group F, the ratio of pancreatic head lesions and trans-duodenal
punctures were higher compared to Group C (P < 0.001 each). The most common final diagnosis from surgery or clinical outcome was
adenocarcinoma (141 patients) ([Table 2]). No procedural complications were encountered in this study.
Table 1
Clinical features of patients.
|
All patients
|
Propensity-matched patients
|
|
Group C
|
Group F
|
P
|
Group C
|
Group F
|
P
|
|
Sex, male/female
|
72/60
|
52/43
|
> 0.99
|
50/45
|
52/43
|
0.89
|
|
Age (years), median (IQR)
|
66.5 (60.0 – 73.0)
|
68.0 (58.0 – 74.0)
|
0.54
|
67.0 (60.0 – 74.0)
|
68.0 (58.0 – 74.0)
|
0.89
|
|
Tumor size (mm), median (IQR)
|
27.4 (19.8 – 34.2)
|
28.3 (21.4 – 37.1)
|
0.35
|
27.5 (20.0 – 34.4)
|
28.3 (21.4 – 37.1)
|
0.59
|
|
Pancreatic head/body or tail
|
34/98
|
49/46
|
< 0.001
|
24/71
|
49/46
|
< 0.001
|
|
Transgastric/transduodenal
|
107/25
|
48/47
|
< 0.001
|
72/23
|
48/47
|
< 0.001
|
|
Trainee/expert
|
92/40
|
88/7
|
< 0.001
|
88/7
|
88/7
|
> 0.99
|
|
Lesions requiring/not requiring immunostaining
|
15/117
|
17/78
|
0.18
|
10/85
|
17/78
|
0.21
|
IQR, interquartile range; n, number of lesions
Table 2
Final diagnosis of propensity-matched patients.
|
Final diagnosis
|
n (%)
|
|
Adenocarcinoma
|
141 (74.2 %)
|
|
NET
|
10 (5.3 %)
|
|
SPN
|
10 (5.3 %)
|
|
Metastatic pancreatic tumor
|
4 (2.1 %)
|
|
Acinar cell carcinoma
|
3 (1.6 %)
|
|
Benign lesions
|
22 (11.6 %)
|
|
Overall
|
190 (100 %)
|
n, number of lesions; NET, neuroendocrine tumor; SPN, solid pseudopapillary neoplasm
Groups C and F showed no significant differences in in technical success rate. Group
F displayed a significantly lower number of punctures and slightly longer procedure
time than Group C ([Table 3]).
Table 3
Comparison of procedure outcomes between Franseen needle and conventional needle groups.
|
Propensity-matched patients
|
|
Group C
|
Group F
|
P
|
|
Number of punctures, median (IQR)
|
3 (2 – 3)
|
2 (2 – 3)
|
0.028
|
|
Procedure time (min), median (IQR)
|
28.0
(21.0 – 39.0)
|
33.0
(28.0 – 42.0)
|
0.003
|
|
Technical success, n (%)
|
95/95 (100 %)
|
94/95 (98.9 %)
|
> 0.99
|
IQR, interquartile range; n, number of lesions; n, number of lesions
Diagnostic accuracy was higher in Group F (91.6 %, 87/95) than in Group C (86.3 %,
82/95; P = 0.36), but no significant difference was evident. In Group F, diagnostic accuracy
for pancreatic head lesions and lesions sampled by transduodenal puncture was 98.0 %
(48/49) and 97.9 % (46/47) respectively. These values were significantly higher than
in Group C (P = 0.013, 0.01) ([Table 4]).
Table 4
Comparison of diagnostic accuracy between Franseen needle and conventional needle
groups.
|
Propensity-matched patients
|
|
Diagnostic accuracy, n (%)
|
Group C
|
Group F
|
P
|
|
Location
|
|
|
19/24 (79.2 %)
|
48/49 (98.0 %)
|
0.013
|
|
|
63/71 (88.7 %)
|
39/46 (84.8 %)
|
0.58
|
|
Puncture route
|
|
|
64/72 (88.9 %)
|
41/48 (85.4 %)
|
0.59
|
|
|
18/23 (78.3 %)
|
46/47 (97.9 %)
|
0.01
|
|
Tumor type
|
|
|
64/77 (83.1 %)
|
57/64 (89.1 %)
|
0.34
|
|
|
10/10 (100 %)
|
16/17 (94.1 %)
|
> 0.99
|
|
|
8/8 (100 %)
|
14/14 (100 %)
|
> 0.99
|
|
Tumor size
|
|
|
62/72 (86.1 %)
|
71/76 (93.4 %)
|
0.18
|
|
|
20/23 (87.0 %)
|
16/19 (84.2 %)
|
> 0.99
|
|
|
82/95 (86.3 %)
|
87/95 (91.6 %)
|
0.36
|
n, number of lesions
In differentiation of benign from malignant lesions, Group C showed 85.1 % sensitivity
(74/87), 100 % specificity (8/8), 100 % positive predictive value (74/74), and 38.1 %
negative predictive value (8/21), compared to values of 90.1 % (73/81), 100 % (14/14),
100 % (73/73), and 63.6 % (14/22), respectively, in Group F. Sensitivity and negative
predictive value were better in Group F ([Table 5]).
Table 5
Diagnostic performance in differentiating malignant and benign lesions.
|
Propensity-matched patients
|
|
Diagnostic accuracy, n (%)
|
Group C
|
Group F
|
P
|
|
Sensitivity
|
85.1 % (74/87)
|
90.1 % (73/81)
|
0.36
|
|
Specificity
|
100 % (8/8)
|
100 % (14/14)
|
> 0.99
|
|
Positive predictive value
|
100 % (74/74)
|
100 % (73/73)
|
|
|
Negative predictive value
|
38.1 % (8/21)
|
63.6 % (14/22)
|
|
n, number of lesions
Discussion
The Franseen needle, with three tips, is designed to collect biopsy samples by cutting
and holding tissue from three cut surfaces. Tissue acquisition with Franseen needles
is therefore adequate [11]. We have previously reported on the usefulness of Franseen needles [16]. Although the unique tip design of the Franseen needle may not allow puncture as
easily as conventional FNA needles, we found no significant difference in technical
success rates in evaluations at our hospital and encountered only one unsuccessful
puncture, which was in a patient scheduled to undergo puncture from within the stomach.
In that case, we performed puncture from the body of the stomach, but failed to penetrate
the stomach wall and the procedure was unsuccessful. Although transduodenal puncture
may involve greater needle-related variability than transgastric puncture because
of poorer scope operability, Group F actually showed significantly higher diagnostic
accuracy in terms of transduodenal puncture biopsies in the current study. We attribute
this finding to the larger number of patients with pancreatic head lesions than lesions
of the body and tail in Group F and the effectiveness of the specific procedure applied
due to the up angle of the puncture that allows the lesion to be fixed firmly and
the puncture to be completed quickly [16]. The current study showed that trainee operators are capable of properly performing
the procedure with a Franseen needle, provided they have been correctly trained under
the guidance of an expert. Although procedure time was slightly longer in Group F,
which had a larger proportion of procedures performed very carefully by trainees,
no complications were encountered and all times were within an acceptable range. From
the above findings, puncture performance with a Franseen needle can be concluded to
be relatively good.
Franseen needles have been shown to collect larger volumes of tissue than conventional
FNA needles [8]
[11]. Following puncture, tissue is collected from the target by stroking while moving
the needle within the target. At our institution, we stroke the tissue using the “door-knocking
method,” which involves rapidly moving the needle back and forth within the target.
A multicenter study showed no differences in diagnostic accuracy between door-knocking
and conventional methods, but revealed that more tissue was acquired under the door-knocking
method [17]. This finding of greater tissue acquisition suggests that using the door-knocking
method with a Franseen needle should prove useful. Use of the Franseen needle increases
the sample volume. As a result, visual confirmation becomes easier and the number
of punctures is significantly reduced.
ROSE has been shown to improve diagnostic accuracy [6], and pairing ROSE with use of a Franseen needle offers diagnostic accuracy in excess
of 95 % [11]
[14]. Implementing ROSE, however, is not feasible in certain medical institutions, even
in high-volume sites such as ours. Iwashita et al. reported achieving diagnostic results
comparable to ROSE when evaluating macroscopically identifiable white samples [18]. Larger amounts of tissue can be acquired with a Franseen needle, which could simplify
macroscopic identification of white tissue samples. Acquiring larger amounts of sample
could improve diagnostic precision by pathologists and fewer punctures. In the present
study, Group F showed a diagnostic accuracy exceeding 90 % and required fewer punctures
than Group C. Larger sample volumes would facilitate not only sample-based histologic
diagnosis, but also genetic diagnosis and anticancer drug-sensitivity assays performed
with samples collected by FNB, as well as other clinical applications [19]
[20]
[21]
[22].
In recent years, occasional reports about the Franseen needle have been published
[23]
[24]. To the best of our knowledge, this is the largest study to compare Franseen FNB
and conventional FNA in the diagnosis of solid pancreatic lesions. Although ROSE is
unavailable at our hospital, we achieved high diagnostic accuracy, with particularly
excellent results for transduodenal puncture and pancreatic head lesions.
Conclusion
We conclude that Franseen needles have similar puncture performance at different lesion
sites, provide high diagnostic accuracy even at facilities where ROSE is unavailable,
and require fewer punctures than conventional needles. However, because this study
was retrospective, some limitations must be considered when interpreting the results.
The potential influence of use of different needles during different periods cannot
be excluded. In addition, all data were retrospectively collected from a single center.
The procedures were performed by six endosonographers, and thus carried a risk of
heterogeneity between operators. A prospective study with a larger number of cases
will be necessary.
