Introduction
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become an essential
tool for the diagnosis of solid pancreatic and nonpancreatic lesions, with 85 % sensitivity
and 98 % specificity [1]. Several factors have been previously evaluated to optimize outcomes of EUS-FNA
[1], such as use of rapid on-site evaluation (ROSE) for immediate cytopathological assessment
[2]
[3], use of needles of different calibers and types [4], number of needle passes [5], and different sampling techniques [6].
In the past decade, new EUS needles for the acquisition of histological specimens
(fine-needle biopsy [EUS-FNB]) have been developed to overcome the limitations of
cytology, facilitating the differential diagnosis of rare conditions through performance
of specific immunohistochemical staining [7], and obviating the need for ROSE [8]. Two end-cutting needles (i. e. fork-tip SharkCore needle, Covidien/Medtronic, Boston,
Massachusetts, USA; and the Franseen-type needle, Acquire, Boston Scientific, Marlborough,
Massachusetts, USA) have shown excellent histological yields [9]
[10], with comparable diagnostic performance in two randomized controlled trials (RCTs)
and two metanalyses [11]
[12]
[13]
[14]. Importantly, EUS-FNB samples have been demonstrated to be suitable for next-generation
sequencing [15] when containing a tumor fraction of ≥ 20 %, either for pancreatic ductal adenocarcinoma
(PDAC) [16] or pancreatic neuroendocrine tumors (pNETs) [17]. Consequently, current practice has almost completely shifted from EUS-FNA to EUS-FNB
[18].
Different sampling techniques have been introduced and compared with the standard
suction technique, including the slow-pull and wet-suction techniques. With standard
suction, the stylet is removed and an air-filled pre-vacuum 10 mL or 20 mL syringe
is attached to the proximal end of the needle and opened once inside in the lesion
to apply negative pressure suction [19]. In the slow-pull technique, negative pressure is created by slowly withdrawing
the stylet from the needle [20]. In the wet-suction technique, the needle is flushed with saline to replace the
column of air, and a pre-vacuum 10 mL or 20 mL syringe is utilized to apply suction
[21]. The standard suction and slow-pull techniques have been widely studied for EUS-FNA.
A recent meta-analysis, including seven RCTs comparing them for sampling of solid
pancreatic lesions, demonstrated similar adequacy and accuracy, with less blood contamination
for the slow-pull method [22]. The wet-suction technique has been introduced more recently and two RCTs comparing
standard and wet suction for EUS-FNA reported significant higher specimen cellularity,
adequacy, and accuracy with wet suction, both for solid pancreatic and nonpancreatic
lesions [21]
[23].
To date, a single-center pilot RCT has evaluated different sampling techniques on
EUS-FNB of solid pancreatic lesions, comparing standard, slow-pull, and wet-suction
methods, using both the fork-tip and Franseen-type needles. No difference in cellularity
scores or blood contamination were found, regardless of the technique or needle type
used [24]. However, the small sample size, inclusion of only solid pancreatic lesions, and
the single-center design did not allow definitive conclusions to be drawn, leaving
these issues still open for further evaluation.
We performed a multicenter RCT with the primary aim of comparing the histological
yield of EUS-FNB using the slow-pull and wet-suction techniques in patients with pancreatic
and nonpancreatic solid lesions. Secondary aims included evaluation of sample quality,
tumor fraction, and diagnostic accuracy.
Methods
Study design
This study was an international, single-blinded, crossover, randomized study involving
nine centers. It was first approved by the ethics committee of the provinces of Verona
and Rovigo on 29 March 2021 (protocol number 18440), and subsequently by ethics committees
and institutional review boards of all participating centers. All patients signed
informed consent before inclusion into the study.
Patient population
Consecutive adult patients with a solid lesion of ≥ 1 cm who were referred for EUS
evaluation and were able to provide informed consent were assessed for study eligibility.
Patients with bleeding disorders (uncorrectable with coagulation factors or fresh
frozen plasma), concomitant anticoagulants use (not to be discontinued), an international
normalized ratio of > 1.5, platelet count of < 50 000, pregnant or breastfeeding,
lesions with cystic component (> 50 % of the volume), or included in another study,
were excluded.
EUS procedure and specimen processing
EUS procedures were performed by expert endosonographers without involvement of trainees.
Once the target lesion was visualized on EUS, interposed vessels were excluded using
color Doppler. A 22 G end-cutting needle, fork-tip or Franseen-type, was used in all
cases, with the choice of needle type left to the endosonographer’s discretion or
according to availability at each center. Four passes were performed using the same
needle, alternating the sampling techniques according to the randomization list (see
below). During each pass, regardless of the sampling procedure, approximately 10 to-and-fro
movements of the needle were performed inside the lesion, utilizing the fanning technique
whenever possible [25]. For wet suction, the stylet was removed and the needle pre-flushed with 1–2 mL
of saline. The lesion was then punctured, and suction applied using a 10 mL pre-vacuum
syringe [23]. For the slow-pull method, after puncturing the lesion, the stylet was slowly and
gradually withdrawn for at least 40 cm. The samples collected were finally pushed
into two formalin vials. The samples retrieved with the same sampling technique (i. e.
1st/3 rd passes and 2nd/4th passes) were placed in the same container. Specimens were
processed as standard biopsies (e. g. after being embedded in paraffin, sections of
5 μm thickness were cut from paraffin blocks and stained with hematoxylin and eosin).
ROSE was not used in any case. Patients were excluded if the lesion was impossible
to puncture and dropped out if at least one needle pass with each technique was not
performed.
Randomization and blinding
Once the eligibility for inclusion into the trial was verified, patients were randomized
in a 1:1 ratio in a crossover design into Group A and Group B, based on a computer-generated
randomized block sequence (block size of 10). For Group A, the pass sequence was wet
suction, slow pull, wet suction, slow pull. For Group B, the pass sequence was slow
pull, wet suction, slow pull, wet suction. The randomization list was stratified by
the type of lesion (pancreatic vs. nonpancreatic).
A data manager not involved in the data analysis or patient enrollment generated the
randomization list. At each center, sealed envelopes containing the group assignment
were prepared and opened after obtaining study consent and EUS baseline assessment,
just prior to EUS-FNB.
The pathologists designated for sample evaluation were blinded to patients’ randomization
and type of EUS-FNB technique performed during the entire study.
Definition of study end points
Primary end point
The primary end point was the tissue core procurement rate. A tissue “core” was defined
as at least one intact piece of tissue of 550 μm or more in length [26]
[27]. The length of histological fragments was measured using dedicated software at each
participating center.
Secondary end points
Sample quality was evaluated in terms of tissue integrity and blood contamination,
applying a previously utilized, simplified, score [28]
[29]
[30]
[31]. Briefly, a score ranging from 0 to 3 was assigned to the specimens by a blinded
pathologist. For both tissue integrity and blood contamination, the higher the score
the better the sample quality ([Table 1]).
Table 1
Sample quality scores (tissue integrity and blood contamination).
|
Score
|
Tissue integrity
|
|
0
|
No cells/tissue
|
|
1
|
Cytological specimen (disaggregated cells representative of the target lesion not
allowing for tissue architectural assessment)
|
|
2
|
Histological microfragments (sample adequate for histological evaluation, namely an
architecturally intact piece of tissue but without a “core”)
|
|
3
|
Histological “core” (defined as an architecturally intact piece of tissue measuring
at least 550 μm)
|
|
Score
|
Blood contamination
|
|
0
|
Only blood
|
|
1
|
High blood contamination (> 50 % of the surface of the slide)
|
|
2
|
Moderate blood contamination (25 %–50 % of the surface of the slide)
|
|
3
|
Low blood contamination (< 25 % of the surface of the slide)
|
The rate of samples containing an adequate tumor fraction was assessed for PDAC and
pNET cases. Tumor fraction was considered adequate if the ratio of tumor cells in
a background of benign nucleated cells exceeded 20 % [16]
[17].
Diagnostic accuracy was measured as conventional “malignancy” analysis using strict
criteria (i. e. samples reported as suspicious for malignancy were categorized as
negative). Definitive diagnosis was assessed on surgical specimens whenever available,
while in nonresected patients it was based on the diagnostic work-up (combined outcomes
of imaging studies and any additional biopsy sample result) and clinical course of
the disease of at least 6 months [32]. Follow-up was performed by the study investigators at each center by outpatient
visits, electronic chart review, and telephone contacts, and was terminated in case
of surgical resection or death. The Papanicolaou classification [33] was used to classify both EUS-FNB samples and surgical specimens of pancreatic masses.
Low grade tumors (e. g. neuroendocrine tumor, solid pseudopapillary tumor) were considered
malignant. Lymph nodes were simply classified as benign or malignant. Specimens that
contained inadequate material were considered as negative for malignancy.
Sample size
The sample size was calculated in the context of the primary binary outcome and considering
the crossover study design with each lesion sampled using the two techniques. Assuming
an expected pooled histological yield of 95 % with wet suction [23] and 85 % with slow pull [34]
[35], with α = 0.05, power = 0.9, and calculating the proportion of discordant pairs
(equal to 0.18) with the approximation of Machin D et al. [36] due to the lack of data in the current literature, the total required sample size
was established to be of 185 patients. Assuming an approximate 8 % drop-out rate,
a sample size of 200 patients was initially calculated. After the study was initiated,
some concerns about a potential higher drop-out rate were raised. Therefore, an amendment
to the protocol was made and the drop-out rate was increased to 20 %, resulting in
a final sample size of 220 patients.
Statistical analysis
The characteristics of the samples were summarized by descriptive statistics (mean
with SD for continuous variables and frequency distributions for categorical variables).
The follow-up time in nonresected patients was reported as median with 95 %CI.
Rate of tissue cores, samples containing an adequate tumor fraction, and diagnostic
accuracy (defined as true positive + true negative divided by total number of patients)
were compared using McNemar test, whereas tissue quality scores were compared by means
of Wilcoxon signed-rank test. All the analyses were performed in the overall cohort
and in the subgroups of pancreatic and nonpancreatic lesions. A Bonferroni correction
for multiple comparisons was applied in the subgroup analyses. A further sub-analysis
concerning the primary outcome was performed according to the different needles utilized.
Both intention-to-treat (i. e. including all patients who underwent at least one needle
pass with each technique) and per-protocol (i. e. two passes with each technique were
performed) analyses were scheduled.
In order to account for eventual center effects in the analysis, a random-effects
analysis fitting a logistic regression model was performed according to the formula
log it (πij) = α + βtreatXij + uj,
where πij
is the probability of an event for the ith patient in the jth center, βtreat
indicates the log odds ratio for treatment, Xij
indicates whether the patient received the treatment or control, and uj
is the effect of the jth center [37].
All analyses were performed using R Statistical Software 3.0.2 (Foundation for Statistical
Computing, Vienna, Austria) with a statistical level of significance of 5 % and respective
95 %CIs. Sample size calculation was performed with R Statistical Software 3.0.2 (pwr package). A two-tailed distribution was used and statistical significance was considered
for P < 0.05.
Results
Between April 2021 and October 2021, 244 patients were assessed for eligibility. A
total of 24 patients were excluded and 220 underwent EUS-FNB. Two and eight patients
in groups A and B, respectively, dropped out due to the inability to perform the second
needle pass as a result of the onset of anesthesiological complications in three patients
(desaturation in two cases and bradycardia in one) and perilesional self-limiting
hematoma in seven cases. Consequently, a strict intention-to-treat analysis was not
possible due to the lack of comparative samples in these cases, and therefore only
a per-protocol analysis was performed. No protocol deviation occurred in the analyzed
patients.
A total of 210 patients (mean age 65.9 [SD 11.3] years; 55.5 % male) were analyzed:
108 in Group A and 102 in Group B. The flow chart of the study is presented in [Fig. 1]. No differences in patient demographics and lesion characteristics were observed
([Table 2]). Overall, there were 146 pancreatic and 64 nonpancreatic lesions, with a mean size
of 35.1 (SD 17.5) mm.
Fig. 1 CONSORT flow chart of the study [38]. EUS, endoscopic ultrasound.
Table 2
Patient demographic details, lesion characteristics, procedures performed, and outcomes
in 210 patients who underwent endoscopic ultrasound-guided fine-needle biopsy performed
using the wet-suction and the slow-pull sampling techniques.
|
Variable
|
Overall (n = 210)
|
Group A (wet suction first) (n = 108)
|
Group B (slow pull first) (n = 102)
|
P value
|
|
Age, mean (SD), years
|
65.9 (11.3)
|
65.4 (12.0)
|
66.4 (10.5)
|
0.51
|
|
Sex, n (%)
|
0.70
|
|
|
114 (54.3)
|
60 (55.6)
|
54 (52.9)
|
|
|
|
96 (45.7)
|
48 (44.4)
|
48 (47.1)
|
|
|
Lesion site, n (%)
|
0.17
|
|
Submucosal
|
18 (8.6)
|
7 (6.5)
|
11 (10.8)
|
|
|
|
1
|
0
|
1
|
|
|
|
13
|
6
|
7
|
|
|
|
3
|
0
|
3
|
|
|
|
1
|
1
|
0
|
|
|
Pancreatic
|
146 (69.5)
|
72 (66.7)
|
74 (72.5)
|
|
|
|
80
|
35
|
45
|
|
|
|
46
|
27
|
19
|
|
|
|
20
|
10
|
10
|
|
|
Lymph node
|
20 (9.5)
|
13 (12.0)
|
7 (6.9)
|
|
|
Other
|
26 (12.4)
|
16 (14.8)
|
10 (9.8)
|
|
|
|
8
|
5
|
3
|
|
|
|
8
|
4
|
4
|
|
|
|
4
|
4
|
0
|
|
|
|
1
|
1
|
0
|
|
|
|
2
|
1
|
1
|
|
|
|
1
|
0
|
1
|
|
|
|
1
|
0
|
1
|
|
|
|
1
|
1
|
0
|
|
|
Lesion size, mean (SD), mm
|
35.1 (17.5)
|
33.5 (17.6)
|
36.7 (17.3)
|
0.18
|
|
Needle type, n (%)
|
0.25
|
|
|
124 (59.0)
|
63 (58.3)
|
61 (59.8)
|
|
|
|
86 (41.0)
|
45 (41.7)
|
41 (40.2)
|
|
|
Use of fanning technique, n (%)
|
183 (87.1)
|
93 (86.1)
|
90 (88.2)
|
0.31
|
|
Follow-up
|
0.20
|
|
|
42 (20.0)
|
18 (16.7)
|
24 (23.5)
|
|
|
|
168 (80.0)
|
90 (83.3)
|
78 (76.5)
|
|
|
|
187 (141–225)
|
191 (142–228)
|
183 (140–222)
|
|
|
Final diagnosis, n (%)
|
0.77
|
|
|
113 (53.8)
|
53 (49.1)
|
60 (58.8)
|
|
|
|
19 (9.0)
|
10 (9.3)
|
9 (8.8)
|
|
|
|
9 (4.3)
|
6 (5.6)
|
3 (2.9)
|
|
|
|
13 (6.2)
|
6 (5.6)
|
7 (6.9)
|
|
|
|
6 (2.9)
|
3 (2.8)
|
3 (2.9)
|
|
|
|
6 (2.9)
|
3 (2.8)
|
3 (2.9)
|
|
|
|
18 (8.6)
|
12 (11.1)
|
6 (5.9)
|
|
|
|
26 (12.4)
|
15 (13.9)
|
11 (10.8)
|
|
IQR, interquartile range; GIST, gastrointestinal stromal tumor.
* Other includes: pancreatic metastasis (3), intrahepatic cholangiocarcinoma (2), leiomyoma
(2), lipoma (2), benign lymph node (2), lung cancer (2), benign adrenal nodule (2),
adrenal metastasis (2), gallbladder cancer (1), spleen lymphoma (1), cervical cancer
(1), retroperitoneal schwannoma (1), retroperitoneal lymphoepithelial cyst (1), pancreatic
solid pseudopapillary neoplasm (1), pancreatic serous cystadenoma (1), duodenal neuroendocrine
tumor (1), perianastomotic rectal granuloma (1).
Primary outcome
Results of the primary outcome are shown in [Table 3]. Overall, a tissue core was obtained in 71.4 % and 61.4 % of patients using the
wet-suction and slow-pull techniques, respectively (P = 0.03). According to the random-effects model adjusted for center effects, the odds
ratio (OR) for tissue core acquisition was 1.58 (95 %CI 1.05–2.38; P = 0.03). No difference for the primary outcome in the subgroup analysis of solid
pancreatic lesions (73.3 % vs. 67.1 %, respectively; P = 0.25) and in the subgroup of nonpancreatic lesions (67.2 % vs. 48.4 %, respectively;
P = 0.03 with a significance threshold set at 0.025 based on Bonferroni adjustment
for multiple comparisons) was observed between the wet-suction and slow-pull techniques,
respectively.
Table 3
Results of the primary and secondary aims in the overall cohort and in the subgroups
of patients with solid pancreatic and nonpancreatic lesions who underwent endoscopic
ultrasound-guided fine-needle biopsy performed using the wet-suction and slow-pull
sampling techniques.
|
Wet suction
|
Slow pull
|
P value
|
|
Presence of tissue core[1], n (%)
|
|
|
150 (71.4)
|
129 (61.4)
|
0.03
|
|
|
107 (73.3)
|
98 (67.1)
|
0.25[2]
|
|
|
43 (67.2)
|
31 (48.4)
|
0.03[2]
|
|
Tissue integrity score, mean (SD)
|
|
|
2.63 (0.62)
|
2.48 (0.74)
|
0.02
|
|
|
2.66 (0.61)
|
2.55 (0.71)
|
0.16[2]
|
|
|
2.57 (0.66)
|
2.30 (0.79)
|
0.04[2]
|
|
Blood contamination score, mean (SD)
|
|
|
2.09 (0.81)
|
2.44 (0.74)
|
< 0.001
|
|
|
2.15 (0.77)
|
2.45 (0.74)
|
< 0.001[2]
|
|
|
1.95 (0.88)
|
2.42 (0.75)
|
< 0.001[2]
|
|
Adequate tumor fraction rate[3], n/N (%)
|
112/132 (84.8)
|
106/132 (80.3)
|
0.41
|
|
Diagnostic accuracy, n (%)
|
|
|
192 (91.4)
|
183 (87.1)
|
0.16
|
|
|
132 (90.4)
|
126 (86.3)
|
0.28[2]
|
|
|
60 (93.7)
|
57 (89.1)
|
0.64[2]
|
1 Intact piece of tissue of at least 550 µm.
2 Based on Bonferroni correction for multiple comparisons, significance threshold was
set at 0.025 in subgroup analysis.
3 Tumor fraction rate was evaluated including only cases of pancreatic ductal adenocarcinomas
and neuroendocrine tumors.
The study population was further stratified according to the needle type. The two
needles showed similar performance in obtaining a tissue core based on sampling technique
for both solid pancreatic lesions (fork-tip needle: 54/82 (65.9 %) for wet suction
vs. 54/82 (65.9 %) for slow pull, P > 0.99; Franseen-type needle: 53/64 (82.8 %) for wet suction vs. 44/64 (68.8 %) for
slow pull, P = 0.09) and nonpancreatic lesions (fork-tip needle: 26/42 (61.9 %) for wet suction
vs. 18/42 (42.9 %) for slow pull, P = 0.12; Franseen-type needle: 17/22 (77.3 %) for wet suction vs. 13/22 (59.1 %) for
slow pull, P = 0.33).
Secondary outcomes
Results of secondary outcomes are summarized in [Table 3]. Overall, tissue integrity score was higher with the wet-suction compared with the
slow-pull technique (P = 0.02). Center effects-adjusted OR for tissue integrity score was 1.66 (95 %CI 1.12–2.41;
P = 0.02). However, in the two subgroup analyses, the tissue integrity score was not
significantly different between the two techniques (P = 0.16 and P = 0.04 for solid pancreatic lesions and nonpancreatic lesions, respectively, with
a significance threshold set at 0.025 based on Bonferroni adjustment for multiple
comparisons). The blood contamination score was higher among slow-pull specimens,
both in the overall population, and in the pancreatic and nonpancreatic subgroups,
respectively (P < 0.001). Center effects-adjusted OR for blood contamination score was 0.56 (95 %CI
0.12–0.81; P < 0.001).
The rate of samples with adequate tumor fraction was evaluated among the 132 cases
of PDAC and pNETs, and was similar with wet-suction and slow-pull techniques (84.8 %
vs. 80.3 %, respectively; P = 0.41). Based on random-effects model adjusted for center effects, the OR for adequacy
of tumor fraction was 1.35 (95 %CI 0.70–2.55; P = 0.39).
Six and eight specimens were deemed not diagnostically adequate using the wet-suction
and slow-pull techniques, respectively. Overall, among specimens collected using the
wet-suction technique, there were 173 true positives, 19 true negatives, 0 false positives,
and 18 false negatives, corresponding to a diagnostic accuracy of 91.4 % (95 %CI 86.8–94.8).
Specimens collected using the slow-pull technique were assessed as 163 true positives,
20 true negatives, 0 false positives, and 27 false negatives, corresponding to a diagnostic
accuracy of 87.1 % (95 %CI 81.5–91.4), with no significant difference between the
two techniques (P = 0.16). Based on random-effects model adjusted for center effects, the OR for diagnostic
accuracy was 1.58 (95 %CI 0.81–2.93; P = 0.16). Similarly, diagnostic accuracy was also comparable when evaluating the subgroup
of solid pancreatic lesions (P = 0.28) and nonpancreatic lesions (P = 0.64).
Discussion
Possible differences in tissue core procurement between available sampling techniques
using fork-tip and Franseen-type needles have not been fully investigated. In 2021,
Bang et al. published an RCT comparing standard suction vs. slow-pull technique vs.
no suction with various types of needles [39]. This study showed that, in contrast to side-fenestrated reverse-bevel, and Menghini-tip
needles, for Franseen-type and fork-tip needles there was no difference between the
standard suction and slow-pull techniques, and neither technique significantly improved
the rate of diagnostic adequacy and accuracy when compared with no suction [39]. However, the wet-suction method was not evaluated, and the potential advantage
of this technique remains unknown. To better clarify this issue, we performed a randomized,
crossover trial with the primary aim of comparing wet-suction and slow-pull techniques
in their capability to acquire proper tissue “core” samples for histological evaluation.
In the overall study population evaluated in the present study, wet suction showed
a higher rate of tissue core acquisition. However, this statistical difference was
mainly related to the higher rate of tissue core retrieved in the subgroup of nonpancreatic
lesions (67.2 % vs. 48.4 %). In this subgroup of patients, we also found that wet
suction provided a higher tissue integrity score. For both outcomes, in this subgroup
of patients, statistical significance was not reached but a trend toward significance
was observed (P = 0.03 and P = 0.04 for tissue core rate and tissue integrity score, respectively, with a significance
threshold set at 0.025 based on Bonferroni adjustment for multiple comparisons) and
it is likely that, with a larger population, significance would have been achieved.
In contrast, for solid pancreatic lesions, tissue core procurement rate and tissue
integrity score were similar between the two techniques. The present study seems to
support the findings of a previous pilot study comparing wet suction with slow pull
and standard suction for sampling of solid pancreatic lesions using end-cutting needles,
where all three techniques resulted in similar histological yields [24].
As previously described for EUS-FNA [22], slow-pull specimens resulted in lower blood contamination compared with wet-suction
samples. This finding differs from the pilot study mentioned above, in which blood
contamination was similar regardless of the sampling technique used [24]. However, the blood contamination score used was extremely simplified (score 0 =
blood present and 1 = blood clots present), thus limiting the possibility of accurately
differentiating and stratifying the results. On the other hand, the significance of
blood contamination in the assessment of histological samples could be questioned.
Indeed, no data demonstrated that blood contamination impairs diagnostic accuracy
or the capability to retrieve histological tissue. Indeed, in the present study, samples
collected using wet suction were highly contaminated with blood. Nevertheless, the
other outcomes were similar to or even better than those obtained with the slow-pull
technique.
In particular, diagnostic accuracy was slightly higher with wet suction for both solid
pancreatic (90.4 % vs. 86.3 %) and nonpancreatic (93.7 % vs. 89.1 %) lesions, despite
a significant difference not being observed. A similar result was observed for tumor
fraction adequacy. Based on these results, in patients with solid pancreatic lesions,
the choice of technique between slow pull and wet suction strongly depends on agreement
with and preference of the pathologist, considering the lower blood contamination
using the slow-pull method. In patients with nonpancreatic lesions, our study seems
to favor the use of wet suction over slow pull due to the higher rates of tissue core
acquisition, with higher tissue integrity score. However, our findings should be interpreted
with caution for different reasons. First, the number of patients included may be
insufficient to detect a significant difference in clinically important outcomes such
as diagnostic accuracy. Second, we included all nonpancreatic lesions, and further
confirmation in specifically designed and adequately powered studies focused on these
types of lesions are needed. Nonetheless, to the best of our knowledge, this is the
first study to compare wet-suction and slow-pull techniques for EUS-FNB of nonpancreatic
lesions.
The difference we observed between solid pancreatic lesions and nonpancreatic lesions
can be easily explained by the nature of the lesion biopsied. In fact, most solid
pancreatic lesions were PDAC, which are characterized by a large amount of fibrous
stroma increasing mass stiffness. Therefore, it is plausible that the end-cutting
design of the needles used in this study allowed the coring of hard lesions such as
PDACs regardless of the sampling technique. In contrast, nonpancreatic lesions are
usually softer, and, therefore, the application of suction might have impacted the
quantity of aspirated tissue into the needle. No differences in the primary outcome
between the two needles used in this study were detected. This result is consistent
with previous literature reporting the same performance of the fork-tip and Franseen-type
needles [11]
[12]
[13]
[14].
Our study has some limitations. First, all involved centers were highly experienced,
and results might not be reproducible in other settings. Second, we excluded very
small lesions because performing four needle passes on lesions of < 1 cm is often
difficult and in the case of solid pancreatic lesions may increase the risk of acute
pancreatitis. Therefore, we cannot be sure that our results would be similar in small
lesions, especially considering the reported impact of lesion size on the outcome
of EUS sampling [40]. Third, we used a single needle caliber, and our findings could be different with
both larger and smaller needles. Fourth, both fork-tip and Franseen-type needles were
used without randomization. Further studies, adequately powered, should investigate
and compare the performance of these two needle types using different sampling techniques.
Fifth, we included both pancreatic and nonpancreatic lesions, and subgroup analyses
were performed. Because the performance of EUS-FNB can be different in pancreatic
and nonpancreatic lesions, and this trial was not powered to compare the two techniques
based on the lesion type, further studies are needed to properly evaluate this matter.
Sixth, despite the quite large number of patients included, our study may not have
been adequately powered, as the definitions of histological yield and tissue core
are not standardized, and the sample size calculation was based on previous literature
that reported a very high histological yield, which was different from the tissue
core rate we observed in the present study. Finally, we did not evaluate the standard
suction technique. However, a recent meta-analysis of EUS-FNA RCTs comparing the slow-pull
technique with standard suction demonstrated similar adequacy, but lower blood contamination
and slightly higher accuracy using the slow-pull technique, making this technique
preferred over standard suction in modern practice [22].
In conclusion, our study demonstrated that EUS-FNB performed with wet suction provided
a higher tissue core procurement rate than a slow-pull technique. Diagnostic accuracy
and rate of samples with adequate tumor fraction were slightly higher using wet suction,
but no statistically significant difference between the two techniques was observed.
Further large, specifically powered, multicenter studies are needed to definitively
recommend one of these two techniques.
