Introduction
Sometimes a major vessel is interposed between the target lesion and the echoendoscope.
Lesions of this kind are classically considered to be beyond the reach of the endosonographer.
Historically, the transvascular approach has been avoided because of concerns about
bleeding, but the previous experience of radiologists has shown that traversing major
vascular structures adjacent to the target biopsy site (i. e., aorta, cava, porta)
does not increase the risk of adverse events (AEs) and should be considered when the
result of the biopsy will affect the clinical strategy of patient care [1 ]
[2 ]
[3 ].
In recent years, a slow proliferation of studies regarding endoscopic ultrasound (EUS)
and endobronchial ultrasound bronchoscopy (EBUS-guided transvascular biopsies, especially
of intrathoracic lesions, has emerged.
EUS-guided transvascular fine-needle aspiration (EUS-TV-FNA) has been described as
a feasible and generally safe alternative approach in selected patients if other proven
methods entail greater potential morbidity and no other target is available. This
statement is based on small case series and retrospectives studies; to date, little
is known about when EUS-TV-FNA can be recommended [4 ].
The primary aim of this multicenter study was to analyze the diagnostic yield and
safety of EUS-TV-FNA in thoracic and abdominal lesions. Secondary aims were to assess
the clinical impact and technical aspects of the procedure.
Patients and methods
A retrospective multicenter study was designed, consisting of examination of a nationwide
database involving all Spanish hospitals experienced in EUS-TV-FNA. All members of
the Spanish Group of Endoscopic Ultrasound were invited by mail to participate (89
endoscopists). Six centers participated. The inclusion period ran from July 2007 to
January 2020. Inclusion criteria were all EUS-TV-NA performed during the inclusion
period. Exclusion criteria were coagulopathy, portal hypertension, and lack of follow-up
information. The following variables were reviewed: demographic details, clinical
data, staging imaging, procedure and technical details, cytological data, medication
with potential risk of bleeding, follow-up data, incidents, and AEs. All imaging parameters
were reviewed and taken from the original written reports.
Technique
All patients provided written informed consent before the procedure. All EUS-TV-FNA
were performed by five experienced endosonographers (JCS, JRA, CDS, EVS, and JBG),
each of whom had more than 15 years of experience in interventional EUS). Deep sedation
was provided by a non-anesthesiologist or an anesthesiologist, depending on each center’s
protocol. For patients with antiplatelet or anticoagulant therapy, the recommendations
of the international guidelines were followed [5 ]. Antibiotic prophylaxis was considered depending on each center’s protocol.
Based on available imaging information, including the same-day EUS study, transvascular
access was regarded as the only option to diagnose or stage these cases. The transvascular
approach was considered only when the pathological information to be obtained would
have an impact on the clinical plan, and it was subject to approval by a multidisciplinary
committee.
A linear array echoendoscope (GF-UCT140-AL5, GF-UC160P-OL5 or GF-UCT180, Olympus;
EG3870UTK, Pentax; or EG-580UT, Fujifilm) was used to identify and puncture the target
lesion. Prior to transvascular puncture, technical attempts were made to avoid an
intravascular route (e. g., deflecting the tip or changing scope position). In the
transaortic cases, a special effort was made to avoid intraluminal aortic plaques.
Color Doppler imaging was used to avoid interposal vessels and to identify major vascular
structures. The target was identified, and the needle was advanced, traversing the
vessel until the tip was seen inside the lesion, and then the stylet was removed.
The suction technique applied, if any (stylet slow-pull vs. standard suction), was
applied, and needle type and size were selected at the discretion of the endosonographer
(25 or 22G; EchoTip Ultra-HD, Cook or Expect Slimline, Boston Scientific). Fanning
technique was avoided. The number of passes was determined by the quantity of material
or the presence of the cytopathology team.
Examples of different EUS-guided transvascular approaches are presented in [Fig. 1 ] and [Fig. 2 ]
, and Fig. S1 ).
Fig. 1 a , b A suspicious mediastinal lymph node located behind the left pulmonary artery, close
to the aorto-pulmonary window. c A 25-G needle crossing the major vessel; the tip of the needle is seen in the target.
d Doppler flow is detected in the pulmonary artery during the puncture.
Fig. 2 a Abdominal lymph node suggestive of lymphoma with the inferior cava vein interposed. b Doppler effect in the cava vein. c, d A transcaval endoscopic-guided puncture with a 22-G needle is performed.
At the end of the procedure, the needle was retracted, and the para-vascular area
was observed for 2 minutes to assess potential immediate procedure-related AEs.
Samples were prepared with rapid on-site evaluation (ROSE) or without, depending on
each center’s protocol. All patients were monitored in the recovery room of the endoscopy
unit for at least 6 hours, and at the discretion of each center were discharged or
admitted for 24-hour clinical observation. No routine chest or abdominal imaging was
done after the procedure.
AEs were defined and graded according to the ASGE lexicon severity grading system
[6 ].
Statistical analysis
Categorical variables were described by the number of cases, percentages, and missing
data. Continuous variables were described by the number of cases, mean and standard
deviation, or the median and the interquartile range (IQR). Categorical variables
were compared using the chi-squared test. Quantitative variables were compared using
the student’s t test. Univariate analysis was performed to identify variables associated with incidents,
cytopathological diagnoses and clinical impact. Multivariate analysis using multiple
logistic regression was performed on predictor variables with a P < 0.05.
Sensitivity, specificity, diagnostic accuracy, negative predictive value (NPV), and
positive predictive value (PPV) were calculated. Positive biopsies were treated as
true positive. Cases with non-representative material were considered as false negatives.
Diagnostic performance was considered as total amount of conclusive cytopathology
results (malignancy plus benignity) excluding inconclusive results (atypical, suspected,
or insufficient samples).
The level of statistical significance was set at < 0.05. The statistical package used
was SPSS version 22.0.
Results
Demographics
A total of 49 cases and 50 EUS-TV-FNA were collected, with a mean age of 64 years
(SD 10.6); more than half were men (54 %). Demographic and clinical characteristics
are shown in [Table 1 ].
Table 1
Clinical and demographic characteristics.
Variables
Data
n = 49 patients/50 procedures
Age, mean (SD)
64.4 (10.6)
Sex, n (%) male/female
27 (54), 23 (46.9)
CCI, mean (SD)
5.16 (2.64)
No comorbidities, n (%)
9 (18)
Cardiovascular risk factors, n (%)
32 (64)
Chronic pulmonary disease, n (%)
9 (18)
Cardiovascular diseases, n (%)
12 (24)
Chronic kidney disease, n (%)
4 (8)
Coagulopathy, n (%)
1 (2)
Active neoplasia, n (%)
7 (14)
Antithrombotic drugs, n (%)
12 (24.4)
0 (0)
ASA classification, n (%)
5 (10)
22 (44)
23 (46)
0 (0)
Sedative agents, n (%)
39 (78)
11 (22)
Sedation carried out by:
16 (32)
34 (68)
Inpatient treatment, n (%)
29 (58)
16 (32)
5 (10.2)
19 (38)
ASA, American Society of Anesthesiologists; CCI, Charlson Comorbidity Index; SD, standard
deviation.
Intrabdominal lesions were the most common targets (n = 28), and the aorta (n = 19)
and portal system (n = 17) the vessels most frequently punctured. Information related
to types of vessels, target lesions, and their respective anatomical regions are summarized
in [Table 2 ].
Table 2
Vessels, target lesions, and respective anatomical regions.
Vessels
Target Locations
THORAX[1 ]
ABDOMINAL[2 ]
Mediastinum
Lung
Pancreas
Non-pancreatic
Adrenal
Total
Aorta
14
3
1[3 ]
18
Pulmonary artery
4
4
Superior mesenteric artery
2
2
Hepatic artery
1
1
Splenic artery
2
1
3
Gastroduodenal artery
1
1
Porta
9
3
12
Superior mesenteric vein
1
4
5
Inferior vena cava
1
1
2
Azygos
1
1
Splenic vein
1
1
Total
19
3
17
10
1
50
1 Thorax lesions included mediastinal masses, lymph nodes, and lung masses.
2 Abdominal lesions: pancreatic tumors, non-pancreatic tumors, pancreatic cyst, lymph
nodes,
2 and right adrenal lesion.
3 Peripancreatic lymph node
Interventional procedures
In all 50 procedures, real-time visualization of the needle traversing the vessel
and into the target was technically feasible and aspiration was applied in all. Most
instances of deep sedation were controlled by anaesthesiologists (68 %), and the majority
of patients were discharged after a period of observation of at least 6 hours (58 %).
All centers except two contributed more than five cases. The median number of cases
per center was 8.3 (range 1–18).
Endoscopist suspicion of malignancy, based on the EUS image, was the most common finding
(70 %), and the most frequent final diagnoses were malignant mediastinal lymph nodes
(n = 13), pancreatic tumours (n = 11) and lung cancer (n = 8). Mean (SD) of target
diameter and distance to the target were 24 mm (14) and 21.3 mm (SD9.7) respectively.
More data related to the EUS findings and final diagnoses are presented in [Table 3 ].
Table 3
Endoscopic ultrasound findings and diagnosis.
Characteristics
Total, n-50
EUS findings:
24.4 (14.0)
6 (12.2)
21.2 (9.4)
10 (20.4)
Echo pattern n (%)
20 (40.8)
29 (59.2)
Endoscopist suspicion, n (%)
6 (12.2)
34 (69.4)
9 (18.4)
Final diagnosis, n (%):
13 (26.5)
11 (22.4)
8 (16.3)
4 (8.2)
3 (6.1)
2 (4.1)
5 (10.2)
3 (6.1)
EUS, endoscopic ultrasound; SD, standard deviation; LN, lymph nodes.
1 Cholangiocarcinoma (1), lung adenocarcinoma (1), serous pancreatic cyst (1), pancreatic
pseudocyst (1), neuroendocrine tumour (1), granuloma (1).
Technical aspects of FNA: needle size, 22 and 25G (52 % and 48 % respectively); aspiration
technique, suction-syringe and slow-pull (44 % and 58 % respectively); median number
of passes was two (interquartile range: 1.0 to 8.0). Other technical aspects of EUS-TV-FNA,
including pathological and safety results, are summarized in [Table 4 ] and Table S1 . The diagnostic yield of EUS-TV-FNA was 86 %, representing malignant plus benign
final results. Non-diagnostic samples were found in seven cases; these included dysplasia
(n = 2), suspicious but not conclusive matter (n = 2), and insufficient matter (n = 3).
Table 4
Univariate analysis of potential factors related to cytopathological diagnosis.
Variables
Data
P value[1 ]
Age, mean (SD)
64.4 (10.6)
0.05
Procedure time, median (IQR)
30 (24–75)
0.08
FNA passes, median (IQR)
2 (1–8)
0.51
Needle size, n (%)
0.04
26 (52)
25 (51.0)
ROSE[2 ], n (%)
0.02
33 (66)
17 (34.7)
FNA technique, n (%)
0.64
27 (54)
21 (42.9)
2 (4.1)
EUS suspicious, n (%)
0.17
6 (12.2)
35 (70)
9 (18.4)
FNA, fine needle aspiration; IQR, interquartile range; ROSE, rapid-on site evaluation;
SD, standard deviation.
1
P obtained with student’s t -test and chi-squared test. Statistical significance at P < 0.05
2 Half of centers (n-3) had ROSE available.
Intraluminal aorta plaques were found in three cases and changing the position of
the scope was undertaken to avoid the plaques.
Diagnostic performance
A positive cytological diagnosis of malignancy was confirmed in 36 cases. Two suspected
cytological diagnoses were confirmed as true positive with progression on follow-up
imaging. Benign cytological results (n = 7) were confirmed by surgical biopsy (n = 1)
and regression/stability on follow-up imaging procedures. Three insufficient samples
were considered as false negative. The number of total false negatives rose to five,
including two cases of pancreatic cystic tumors (dysplasia by cytological diagnosis).
Only one considered false negative was confirmed as malignancy despite an insufficient
sample with EUS (abdominal mass, diagnosed as lymphoma by percutaneous-guided biopsy
in another more accessible point). The rest of false negatives were confirmed due
to progression or suspicious behaviour in follow-up imaging tests The overall sensitivity,
specificity, positive and negative predictive value, and accuracy were 88 % (95 %CI,
74–96), 100 % (95 %CI, 59–100), 100 % (95 %CI, 88–100), 58 % (95 %CI, 38–76) and 90 %
(95 %CI, 78–96) respectively (Table S2 ).
Safety
No AEs occurred, either during procedures or in the post-procedural period. Only three
incidents were encountered. Two minor mural hematomas (aorta and pulmonary artery)
were detected on EUS images immediately after a transvascular FNA. Self-limited bleeding
after the EUS-guided puncture of a gastroduodenal artery was observed in a patient
with antiplatelet therapy. None of these patients were symptomatic.
Twelve patients were treated with antiplatelet therapy without any additional cases
of bleeding or hematomas. Antibiotic prophylaxis was administered in 38 % of patients,
and no cases of fever or infection related to the procedure were reported.
Clinical impact
Only in six cases did EUS-TV-FNA not cause a change in the global management of the
patients. In most cases (88 %), the interventional procedure directly impacted the
clinical management of the patient.
Univariate and multivariate analysis
An arterial vessel and ASA III had a significant trend with incidents related to transvascular
puncture. No significant factors were found to be related in clinical impact. Univariate
analysis of incidents and final diagnoses is summarized in [Table 4 ] and Table S3 . On multivariate analysis, ROSE (OR6.2; 95 %CI, 1.063–36.737, P < 0.043) was found to be an independent predictor of obtaining a conclusive sample
for a final diagnosis.
Discussion
Since Vincent et al and Wallace et al (2006 and 2007, respectively) published papers
on the first transvascular (pulmonary artery and aorta) puncture guided by EBUS and
EUS, respectively, only a few case reports and small case series have been published
[7 ]
[8 ]. Much of the current literature on EUS-TV-FNA has paid special attention to intrathoracic
lesions, and most of the knowledge about this technique comes from the EBUS field
[9 ]
[10 ]
[11 ]
[12 ]. Many of the reports related to EUS-guided FNA involve the transaortic approach
and focus on the study of lung cancer [4 ]
[8 ]
[13 ]
[14 ]
[15 ]. Other vascular interventions have included EUS-guided portal access for diagnostic
or therapeutic purposes in sampling for hepatocellular carcinoma and portal embolization
[16 ]
[17 ]
[18 ]
[19 ].
To our knowledge, this is the first study of EUS-TV-FNA combining experience with
intrathoracic and intrabdominal lesions and traversing different types of vessels
with a considerable range of sample sizes. In the present study, a total of 50 transvasculars
biopsies were taken, guided by EUS, and using 22-G and 25-G needles with an average
of two passes. Intrabdominal lesions were more frequent targets than thoracic lesions,
with the thoracic aorta and porta the most frequently traversed vessels.
An updated literature review is included ([Table 5 ]), and three retrospective case series stand out for comparison to our results [4 ]
[8 ]
[9 ]
[11 ]
[12 ]
[13 ]
[14 ]
[15 ]
[16 ]
[20 ]
[21 ].
Table 5
Transaortic, transcarotid, transportal, and transcaval endoscopic ultrasound-guided
fine-needle aspiration. A literature review.
Author, y
Journal
n
Target
Vessel
Needle
Passes
Diagnostic
AE or incidents
Wallace MB
2007
Ann Thor Surg
1
LN
Thor. aorta
22-G
1
1
1 small hematoma
Bartheld MB
Gastrointest Endosc
14
Lung (9)
Thor. aorta
22-G
1
71 %
2 small hematomas
Bang JY
2012
Am Surg
1
LN
Thor. aorta
25-G
1
1
Noe
Lococo F
Endoscopy
1
LN
Carotid
25-G
3
1
No
Lococo F
Endoscopy
1
Right adrenal
Cava
22-G
2
1
No
Galasso
Endoscopy
1
LN
Abd. aorta
25-G
3
1
No
Lee NK
Gastrointest Endosc
1
LN
Abd. aorta
25-G
2
1
No
Kazakov J
Ann Thor Surg
19
LN
Thor Aorta
22-G
–
73 %
No
Ravaglia C
Eur Clin Respir J
11
LN
Thor aorta
21-G, 22-G
1
45 %
No
Wang M
Ann Transl Med
26
Pancreas
Porta, SMV
22G, Cook
4
92 %
No
MolinaJC
J Thorac Cardiovasc Surg
65
LN, Lung
Thor aorta
22-G
2
74 %
1 pseudoaneurysm
Present study
–
50
Thorax & abdominal
Multiples
22-G,25-G
2
86 %
3 hematomas, 1 minor bleeding
Abd, abdominal; LN, lymph node; Thor, thoracic; SMV superior mesenteric vein.
Bartheld et al. performed 14 transaortic EUS-FNA in the diagnosis of mediastinal LN
and lung tumors, using 25-G needles and a single pass. They reported a diagnostic
yield of 71 % and two hematomas (14 %) at the site of aortic puncture, without clinical
consequences [4 ].
Wang et al. reported 26 transportal system EUS-guided transgastric procedures in diagnosing
pancreatic tumours, using a 22-G needle, with an average of four passes, and a sensitivity
and accuracy of 91 % and 92 %, respectively, without any AEs. The authors argued that
the lower portal pressure compared with aortic pressure could explain why no hematomas
were detected [16 ].
Recently, Molina et al. reported 65 cases of EUS-FNA, plus 35 EBUS cases of transvascular-guided
biopsies of intrathoracic lesions, with the aorta the most common vessel traversed.
The authors used a 22-G needle, with an average of two passes per target, and obtained
an overall sensitivity and accuracy of 71.5 % and 74.5 %, respectively. No immediate
AEs were reported, and only one delayed aortic pseudoaneurysm. One possible explanation
for this lower diagnostic performance is that the number of passes made in a transvascular
approach is less than with standard EUS-FNA, and this might affect sample adequacy
[12 ].
The diagnostic yield of our study was higher than in other studies. This may be because
an average of two attempts (range: 1–8) at transvascular FNA was made and ROSE was
possible in most cases. Concretely, all transaortic cases, and all transportal cases
except one, yielded a final diagnosis. On univariate analysis we found that a 25-G
needle and ROSE were significantly related to obtaining a final diagnosis, but only
ROSE was significant on the multivariate analysis. The fact that our endoscopists
had extensive experience in the EUS-guided FNA technique surely contributed to these
results.
In terms of safety, to date the reported AE rate in transvascular biopsies taken with
EUS or EBUS guidance seems to be low and without fatal events. In the radiological
literature, a rate of 0.05 % major AEs related to translumbar aortography is reported,
but asymptomatic mural hematomas are not uncommon [1 ]
[2 ]
[3 ]. To our knowledge, three immediate hematomas have been described after transaortic
punctures guided by EUS, without the need for interventional therapy. One case of
pseudo-aneurysm was detected 3 weeks after a transaortic EUS-FNA that was managed
conservatively [4 ]
[8 ]
[12 ].
In our study, no AEs were detected, and three incidents were reported: two hematomas
after transaortic EUS-FNA using a 25-G needle (2 passes), and one self-limited bleed
after a gastroduodenal puncture using a 22-G needle (2 passes). No interventional
procedures were required to manage these incidents. An arterial vessel and ASA III
were almost significantly related to incidents, and no other factors were found to
be related. Curiously, none of the transaortic cases with more than two passes was
associated with incidents or AEs. Given these data, and their congruence with previously
reported hematomas with transaortic approaches, we should offer a word of caution,
and suggest that FNA should only be performed in the absence of alternative means
to obtain a tissue diagnosis for para-aortic lesions.
Therefore, from a technical point of view, it seems reasonable to recommend, whenever
possible, the use of 25-G needles and ROSE in these types of interventional procedures,
especially in arteries, without limit to a single pass.
However, some questions remain: Does the use of thinner needle (25-G) really reduce
the risk of bleeding? And does increasing the number of passes carry a greater risk
of tumor seeding? To address these questions and their concerns, prospective studies
are needed.
Finally, in addition to broad knowledge of echo-anatomy in the EUS field, a transvascular
approach requires skills and expertise in the FNA technique. In our opinion, the degree
of challenge depends on the vessel size. Crossing a splenic vessel and crossing the
aorta with a needle are not the same. A transaortic or trans-pulmonary artery scenario
must be recognized as being of greater complexity. The distance between the lesion
and the tip of scope may be greater than 5 cm and predicting needle trajectory requires
experience. The procedure should be performed by endoscopists with proven experience
and with a favourable balance of benefits/risks.
Limitations
This study has some limitations, mainly owing to its retrospective design. First,
variation between centers with a potential population bias cannot be excluded. Second,
the variability of target lesions and different anatomical location of the vessels
included in this study may have imposed a selection bias on the study population.
Third, the lack of a standardized protocol with no specific follow-up implies a lack
of information missing on follow-up, associated with a possible failure to catch some
AEs.
Conclusions
This interventional technique is feasible and seems to be safe. The balance between
diagnostic benefit and safety must be weighed. It is likely that a 25-G needle and
ROSE may be recommended, especially in arteries; an endoscopic transvascular approach
should be considered when no other locations are possible for taking samples in selected
patients.
