Introduction
Endoscopic ultrasound (EUS)-guided sampling is an established method for pathological
diagnosis of pancreatic masses. The diagnostic performance of EUS-guided sampling
for pancreatic masses is good, with sensitivity rates of about 90 % reported [1]. However, the amount of tissue obtained by EUS-guided sampling is very small because
only 19- to 25-gauge needles can be used, and the diagnostic yield still depends on
endoscopic and pathological skills. Therefore, further improvement of needles was
expected and needed. The ideal needle is maneuverable and easy to puncture with, and
can obtain sufficient material in almost one pass.
The Franseen needle, which has three symmetric heels at the tip [2], was recently developed to improve the quantity and quality of the samples obtained,
and subsequently diagnostic yields, by preserving the structural integrity of the
tissues. An experimental study in an animal model [3] showed that the Franseen needle has better tissue acquisition abilities of than
conventional needles, and clinical studies on 22-gauge needles have also shown good
results [2]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]. However, it is sometimes relatively difficult to obtain a puncture with the Franseen
needle because of the unique design of the tips. Generally, a 25-gauge needle can
penetrate the mass more easily, but obtains inferior amounts of the specimen compared
to 19- to 22-gauge needles [1]. We hypothesized that the 25-gauge Franseen needle can strike a good balance between
technical maneuverability and obtaining sufficient tissue, resulting in improved diagnostic
ability. The present study aimed to evaluate the diagnostic ability of 25-gauge Franseen
needles for EUS-guided sampling of solid pancreatic masses.
Patients and methods
Study design and patients
This was a prospective single-center observational study conducted at Aichi Medical
University Hospital between July 2017 and December 2018. Consecutive patients who
were 20 years or older and had a solid pancreatic mass requiring EUS-guided sampling
were enrolled. Exclusion criteria were (1) severe comorbidity in any other organ;
(2) a performance status of 4; (3) inability to undergo an endoscopic approach; (4)
coagulopathy; (5) pregnancy; and (6) inability to provide informed consent. Whether
the mass was solid, was judged by EUS with/without magnetic resonance cholangiopancreatography.
Our hospital’s institutional review board approved this study in accordance with the
principles of the Declaration of Helsinki (approval number: 2017-H147). The study
protocol was registered in the University Hospital Medical Information Network Clinical
Trial Registry database (identifier: UMIN000028273).
Procedural technique
A linear-array echoendoscope (GF-UCT260; Olympus Medical Systems Corp., Tokyo, Japan)
was used with an EU-ME2 processor (Olympus Medical Systems Corp.). Contrast-enhanced
EUS was used if required. The target lesion was punctured under EUS guidance using
25-gauge Franseen needles (Acquire; Boston Scientific Corporation, Marlborough, MA).
After puncturing the target lesion, the stylet was removed and suction was applied
using a 10-mL syringe. Subsequently, about 10 to 20 strokes were performed within
each lesion. All procedures were performed by experienced endoscopists who were skilled
at performing EUS-guided sampling.
Pathological assessment
After the needle was removed from the lesion and the endoscope, the stylet was inserted
into the needle again and the sample was expelled onto a tray. Aspirated specimens
were smeared using slides and air-dried. Then, air-dried smears were subjected to
May-Giemsa staining and rapid onsite cytological evaluation (ROSE) was performed to
assess sample adequacy. Punctures were repeated until ROSE determined that the tissue
obtained was satisfactory; however, the maximum number of passes was set at 5. If
the residual sample after ROSE seemed inadequate for histological examination, one
more puncture was performed. The specimen was fixed in formalin, embedded in paraffin,
and sectioned for histopathological analysis. Tissues were processed by experienced
cytotechnologists, and all samples were assessed by experienced cytopathologists.
Outcomes and definitions
The primary outcomes were sensitivity for malignancy, number of needle passes required
to reach a plateau of sensitivity, and rate of obtaining adequate specimens for histological
assessment. Furthermore, the predictive factors that affected adequate specimen acquisition
were evaluated, including sex, age, lesion location and size, puncture route, number
of passes, and type of lesion.
The plateau of number of needle passes was defined as the point at which increasing
needle passes cease to improve sensitivity. Histological adequacy was determined,
by experienced cytopathologists, based on whether samples allowed adequate histological
interpretation. Lesion size was defined as the length of the lesion on the ultrasonographic
images within the field of view of the puncture site, that is, the maximum length
of the needle’s penetration rather than the maximum diameter of the lesion.
The final pathological diagnoses were based on the surgical specimens obtained from
those patients who underwent surgery. For patients who did not undergo surgery, final
diagnoses were based on disease clinical course, which was evaluated for at least
6 months and included repeated imaging assessments.
Definitions and severity of adverse events (AEs) were classified according to the
lexicon of the American Society for Gastrointestinal Endoscopy [12].
Statistical analyses
The target sample size was set to 100, based on the number of patients we could enroll
within a 1.5-year period. The differences in categorical variables were evaluated
using Fisher’s exact tests. Continuous variables were compared using the Mann-Whitney
U-test. To evaluate the factors that affected adequate specimen acquisition, multivariate
analyses were carried out using logistic regression analyses of the variables with
values of P < 0.2 in the univariate analyses. P < .05 was considered to indicate statistical significance. All statistical analyses
were performed using R version 3.4.1 (The R Foundation for Statistical Computing,
Vienna, Austria).
Results
Patient characteristics
During the study period, 116 patients met the eligibility criteria for study inclusion.
[Table 1] presents the patients’ characteristics, including sex, age, lesion location and
size, puncture route, number of passes, and final diagnosis. The final diagnosis was
benign disease in nine patients and malignancy in 107, 98 of which had pancreatic
adenocarcinoma.
Table1
Baseline patient characteristics (n = 116).
|
Characteristics
|
|
Sex, (male/female), n
|
62/ 54
|
|
Median age (range), years
|
72 (42–92)
|
|
Location of lesion, n (%)
|
|
|
51 (44)
|
|
|
46 (40)
|
|
|
19 (16)
|
|
Median lesion size (range), mm
|
15 (5–31)
|
|
Puncture route, n (%)
|
|
|
67 (58)
|
|
|
49 (42)
|
|
Median number of passes (range), n
|
2 (1–5)
|
|
Final diagnosis, n (%)
|
|
|
98 (85)
|
|
|
4 (3)
|
|
|
2 (2)
|
|
|
2 (2)
|
|
|
1 (1)
|
|
|
4 (3)
|
|
|
4 (3)
|
|
|
1 (1)
|
Diagnostic performance
[Table 2] presents the outcomes. The technical success rate was 100 % (116/116), and diagnostic
adequacy on ROSE was 98 % (114/116). The sensitivity, specificity, positive predictive
value (PPV), negative predictive value (NPV), and accuracy for malignancy were 98 %
(105/107), 100 % (9/9), 100 % (105/105), 82 % (9/11), and 98 % (114/116), respectively.
Cumulative sensitivity for malignancy was 87 % (93/107) on pass 1, 97 % (104/107)
on pass 2, and 98 % (105/107) on pass 3, within no increase in sensitivity after four
or more passes. Subgroup analyses based on lesion location and size are shown in [Table 3], where patients were divided into four groups according to location in the head
or body/tail, and size above or below the median. The number of passes required to
reach a plateau of sensitivity were two, two, two, and three in the head lesion < 15 mm,
head lesion ≥ 15 mm, body/tail lesion < 15 mm, and body/tail lesion ≥ 15 mm subgroups,
respectively.
Table 2
Outcomes of endoscopic ultrasound-guided sampling using 25-gauge Franseen needles.
|
Technical success, % (n)
|
100 (116/116)
|
|
Diagnostic adequacy on ROSE, % (n)
|
98 (114/116)
|
|
Adequate specimen for histological assessment, % (n)
|
79 (92/116)
|
|
Adverse events, % (n)
|
1 (1/116)
|
|
|
1
|
|
Sensitivity, % (n)
|
98 (105/107)
|
|
Specificity, % (n)
|
100 (9/9)
|
|
Positive predictive value, % (n)
|
100 (105/105)
|
|
Negative predictive value, % (n)
|
82 (9/11)
|
|
Accuracy, % (n)
|
98 (114/116)
|
ROSE, rapid onsite cytological evaluation
Table 3
Cumulative sensitivities for malignancy.
|
Cumulative sensitivity, % (n)
|
|
Pass 1
|
Pass 2
|
Pass 3
|
|
Location of lesion
|
Lesion size
|
|
|
|
|
Head
|
< 15 mm
|
90 % (18/20)
|
95 % (19/20)[1]
|
|
|
Head
|
≥ 15 mm
|
81 % (22/27)
|
100 % (27/27)[1]
|
|
|
Body/tail
|
< 15 mm
|
90 % (18/20)
|
100 % (20/20)[1]
|
|
|
Body/tail
|
≥ 15 mm
|
88 % (35/40)
|
95 % (38/40)
|
98 % (39/40)[1]
|
|
Total
|
87 % (93/107)
|
97 % (104/107)
|
98 % (105/107)[1]
|
1 Diagnostic sensitivity did not increase with additional needle passes
An adequate specimen for histological assessment was obtained in 79 % of patients
(92/116). With regard to AEs, mild pancreatitis was observed in one patient, which
improved with conservative management.
Factors affecting adequate specimen acquisition
Sex, age, lesion location and size, puncture route, number of passes, and type of
lesion were assessed as predictive factors for obtaining adequate specimens for histological
assessment ([Table 4]). Univariate analyses determined that the median lesion size was significantly smaller
in the failed cases (10 mm) than in successful cases (15 mm) (P = 0.035). The receiver operating characteristic curve analysis of lesion size revealed
an area under the curve of 0.638. The optimal cutoff for prediction of successful
adequate histological specimen acquisition was calculated to be 13 mm, with a sensitivity
of 67 % and specificity of 63 %. Multivariate logistic regression analyses determined
that lesion size smaller than 13 mm was a predictive factor that was significantly
associated with failure of obtaining adequate specimen for histological assessment
(odds ratio, 0.282; 95 % confidence interval, 0.107–0.738; P = 0.010) ([Table 5]).
Table 4
Univariate analysis of the factors associated with acquisition of adequate histological
samples.
|
Successful acquisition of adequate histological sample (n = 92)
|
Failure to obtain adequate histological sample (n = 24)
|
P value
|
|
Sex, n (%)
|
|
|
0.068
|
|
|
45 (49)
|
17 (71)
|
|
|
|
47 (51)
|
7 (29)
|
|
|
Median age (range), years
|
73 (42–92)
|
70 (48–85)
|
0.611
|
|
Location of lesion, n (%)
|
|
|
0.645
|
|
|
39 (42)
|
12 (50)
|
|
|
|
53 (58)
|
12 (50)
|
|
|
Median lesion size (range), mm
|
15 (5–31)
|
10 (5–28)
|
0.035
|
|
Puncture route, n (%)
|
|
|
0.817
|
|
|
54 (59)
|
13 (54)
|
|
|
|
38 (41)
|
11 (46)
|
|
|
Median number of passes (range)
|
2 (1–4)
|
2 (1–5)
|
0.164
|
|
Type of lesion, n (%)
|
|
|
0.390
|
|
|
86 (93)
|
21 (88)
|
|
|
|
6 (7)
|
3 (13)
|
|
Table 5
Multivariate analysis of the factors associated with acquisition of adequate histological
samples.
|
Odds ratio
|
95 % CI
|
P value
|
|
Sex (male)
|
0.368
|
0.135–1.01
|
0.052
|
|
Lesion size (< 13 mm)
|
0.282
|
0.107–0.738
|
0.010
|
|
Number of passes
|
1.520
|
0.818–2.840
|
0.184
|
CI, confidence interval
Discussion
The current study showed that the sensitivity of the 25-gauge Franseen needle for
solid pancreatic masses was very high at 98 %, in which plateaued at three passes.
However, the rate of obtaining adequate specimen for histological assessment was 79 %,
and was particularly low for small lesions.
The Franseen needle’s tips are uniquely structured with three-symmetric heels to improve
the quantity and quality of the samples obtained, and subsequently the diagnostic
yields, by preserving the structural integrity of the tissue. Some studies have already
investigated the utility of 22-gauge Franseen needles, showing very good results with
a pooled diagnostic yield rate of 92.7 % [11].
Higher sample quality and presence of histology are associated with enhanced diagnostic
performance and agreement among pathologists of varying expertise [13]. Although thick needles are generally superior for obtaining histologic cores, a
25-guage may be sufficient to collect samples of adequate quality if the Franseen
needle is used. If the diagnostic yields among different sized needles are equal,
a thinner needle would be preferable in terms of operation and reducing tissue injures.
The 25-gauge Franseen needle may achieve a good balance between maneuverability and
amount of sample obtained.
However, to our knowledge, only one study [14] on the 25-gauge Franseen needle has been reported. The study comprised 100 varying
lesions including the pancreas, lymph nodes, and subepithelial tumors, and showed
that the sensitivity, specificity, and accuracy was 87 %, 100 %, and 88 %, respectively,
at only one pass. Our study is the first to focus on the effectiveness of the 25-gauge
Franseen needle for pancreatic masses only. We were able to report sensitivity, specificity,
and accuracy rates of 98 %, 100 %, and 98 %, respectively, using multiple passes and
with ROSE available. Both our own and the aforementioned report showed very good diagnostic
results, with technical success rates of 100 % in both. Conversely, technical failure
has been reported when using the 22-gauge Franseen needle [2]. Although the unique structure of the tip leads to a lower penetrative ability than
conventional needles, this may not be an issue when a 25-gauge needle is used.
The rate of adequate specimen acquisition for histological assessment using the 25-gauge
Franseen needle was 82 % in the aforementioned report [14]. The present study showed a rate of 79 %. Both studies reported results superior
to recent large-scale studies of conventional 25-gauge needles, which reported rates
of 44–67 % [15]
[16]. However, the rates were lower than those of 22-gauge Franseen needle, which were
reported as 94–100 % [2]
[4]
[6]
[9]
[10]. If a disease that requires an adequate histologic specimen for immunohistological
evaluation, such as neuroendocrine tumors, is suspected before EUS-guided sampling,
use of a 22-gauge or thicker needle may be preferable.
Regarding the number of passes, a previous study of EUS-guided sampling for pancreatic
lesions using conventional needle reported that the number of needle passes to reach
a plateau for head lesions < 15 mm, head lesions > 15 mm, body/tail lesions < 15 mm,
and body/tail lesions > 15 mm was four, four, three, and four, respectively [17]. In the current study, the number of passes required was two, two, two, and three,
respectively. Since the sensitivity did not increase with the use of four or more
passes, it may be better to limit the number of passes when using a Franseen needle
to a maximum of three.
An increase in AEs associated with use of the Franseen needle is a matter of concern
because the structure of the tip may cause tissue injuries. In previous studies, bleeding
[2]
[7], pancreatitis [10], and pancreatic fistula [14] were reported as AEs. In the present study, pancreatitis occurred in one patient.
Because evidence regarding AEs associated with the Franseen needle is lacking, more
careful monitoring after procedures involving Franseen needles is desirable.
The results of the current study should be considered in the context of its limitations,
which include its nonrandomized design and single-center setting. Furthermore, only
experienced endoscopists, cytotechnologists, and cytopathologists were involved in
EUS-guided sampling. Therefore, multicenter, randomized, controlled trials are warranted
before drawing definitive conclusions.
Conclusion
In conclusion, the 25-gauge Franseen needle showed excellent technical success rates
and diagnostic sensitivity for solid pancreatic masses. Although the ability to obtain
adequate histological samples was also good compared to conventional needles, it may
still be insufficient, especially when dealing with small lesions.
