Introduction
Visceral artery pseudoaneurysm is a common complication of pancreatitis seen in 10 %
of patients with chronic pancreatitis and with a risk of rupture as high as 50 % and
with a rate of mortality after rupture of 15–40 % [1]
[2]. Therefore, visceral artery pseudoaneurysm should be promptly diagnosed and treated.
Digital subtraction angiography with subsequent coil embolization is the standard
treatment to occlude the pseudoaneurysm [3].
Indication for endoscopic ultrasound (EUS)-guided thrombin injection
Occasionally, coil embolization is not possible for various reasons such as short
neck of the pseudoaneurysm, inaccessible vascular territory, or angiographically occult
pseudoaneurysm, which can be seen on ultrasound and computed tomography (CT) of the
abdomen. In these cases, ultrasound or CT-guided percutaneous thrombin injection can
be performed [4]
[5]. EUS-guided thrombin injection is another option in these patients, especially when
pseudoaneurysm localization is difficult on transabdominal ultrasound, thus we can
avoid surgery and morbidity. This procedure is simple, minimally invasive, effective,
and cheaper than angioembolization.
Methods
Endoscopic ultrasound with a curved linear array transducer in conjunction with a
light source was used for this procedure. An intravenous antibiotic was administered
30 minutes before the procedure. The pseudoaneurysm was identified, and the shortest
path without any intervening vessel was chosen. Sterile lyophilized human thrombin
was used, reconstituted with 1 mL of calcium chloride and 4 mL of distilled water
to a total of 5 mL. An EchoTip Ultra 22-gauge EUS needle (Cook Medical, Bloomington,
Indiana, United States) was used to puncture the pseudoaneurysm, under EUS guidance.
After puncture, the reconstituted thrombin was injected in aliquots of 1 mL until
the pseudoaneurysm became echogenic. Further details of the procedure are given later
in Materials and methods [3]
[6].
Outcome
There is limited data on EUS-guided thrombin injection in visceral artery pseudoaneurysms.
Initial case reports revealed successful use of EUS-guided thrombin injection in the
management of visceral artery pseudoaneurysms [7]
[8]
[9]
[10]
[11]
[12]. A case series on three patients with visceral artery pseudoaneurysms due to pancreatitis
revealed complete thrombosis of the pseudoaneurysm and on short follow-up of 1 month,
none of the patients had recurrence of symptoms [3]. Another small case series with short follow-up showed similar results [6]. EUS-guided thrombin injection has also been used successfully along with coil in
a bleeding gastroduodenal artery pseudoaneurysm [13]. A recently published case report showed that EUS-guided thrombin can also be used
in cystic artery pseudoaneurysm [11]. So the limited available literature favors the use of EUS-guided thrombin injection
in the management of visceral artery pseudoaneurysms without significant side effects,
although long-term follow-up data are not available. Various vascular pathologies
and the proximity of the vascular structure to the gastrointestinal tract wall have
prompted EUS experts to perform various EUS-guided vascular procedures. High resolution,
proximity of vascular pathology to the gastrointestinal tract wall, and real-time
guidance offer precise delivery of the intervention. To date, various EUS-guided vascular
therapies have been identified such as EUS-guided management of nonvariceal gastrointestinal
bleeding, variceal bleeding, pseudoaneurysm, embolization of the portal venous system,
and creation of portosystemic shunts [14].
Visceral artery pseudoaneurysms include aneurysms of the celiac, superior, or inferior
mesenteric arteries and their branches. Pseudoaneurysms have a high risk of rupture
with life threatening consequences [15]. With reported incidences of 0.1–0.2 %, visceral artery aneurysms and pseudoaneurysms
are relatively rare, but the true incidence is not known since many are asymptomatic
[16]. Pseudoaneurysms usually occur after vascular injuries or erosions such as in trauma
or inflammation. The increasing use of instrumentation and advanced imaging technologies
has led to the increased incidental detection of asymptomatic pseudoaneurysms [17]
[18]. The established procedure to manage pseudoaneurysms is angiography with coil embolization
but, due to non-visualization with angiography or inaccessibility (small caliber vessels
or short neck of pseudoaneurysm), this technique is not possible in some cases.
Pseudoaneurysms are reported in 10–21 % of patients with chronic pancreatitis, and
the splenic artery is most commonly affected [19]. EUS-guided thrombin injection is another possible approach, especially in patients
where the established management procedure is not possible. High resolution and real-time
guidance by EUS offer an attractive access route and precise delivery of the intervention
[14]. Thrombin is the principal enzyme of hemostasis. It catalyzes the conversion of
fibrinogen to fibrin and activates procoagulant factors V, VIII, XI, and XIII. It
also activates platelets and forms a solid clot. Thrombin activated with calcium chloride
causes the immediate formation of a clot which leads to obliteration of the pseudoaneurysm
[20]. There are limited data on EUS-guided thrombin injection for treatment of pseudoaneurysms.
The aim of this study is to assess the efficacy and safety of EUS-guided thrombin
injection in pseudoaneurysms.
Materials and methods
At SMS Hospital, Jaipur, India between January and December 2018, prospective data
were collected from consecutive patients in all age groups with symptomatic visceral
artery pseudoaneurysms, and who were unable to undergo coil embolization. The diagnosis
of pseudoaneurysm was made on the basis of clinical features, radiological evidence,
and endosonographic findings. Each patient underwent detailed clinical evaluation
and laboratory investigations including hemogram, prothrombin time, and liver and
kidney function tests. A computed tomography (CT) scan along with angiography of the
abdomen were performed to look for pseudoaneurysms and any intraabdominal shunts.
All patients were admitted and started on standard treatment including intravenous
fluid, blood products, and antibiotics. The upper gastrointestinal endoscopy was carried
out using a forward viewing endoscope (Olympus GIF-1TQ 160, Tokyo, Japan). After initial
stabilization, patients underwent detailed EUS examination and thrombin was injected
in the pseudoaneurysm. The required amount of thrombin, procedure time, and any complications
were observed. Follow-up EUS was performed after 72 hours, 1 month, and 3 months to
look for recanalization. Follow-up CT scan of the abdomen was also performed after
1 month to identify any side effects distant to the target. The study protocol was
approved by the institutional ethics committee. Informed written consent was obtained
from each patient before the procedure and the research was carried out in accordance
with the Helsinki Declaration.
Technique of endoscopic ultrasound-guided thrombin injection
Endoscopic ultrasound was performed using a curved linear array transducer (Olympus-GFUCT-180)
in conjunction with an EVIS EXERA CLV‑180 light source (Olympus Medical System Corp.,
Tokyo, Japan). An intravenous antibiotic (2 g of ceftriaxone) was administered 30
minutes before the procedure. The procedures were performed under conscious sedation
(3 mg intravenous midazolam). The pseudoaneurysm was identified, and the shortest
path without any intervening vessel was chosen. Characteristics of the pseudoaneurysm
such as vessel involved, size, neck size, and relationship to adjacent structures
were assessed. To-and-fro flow of blood in the pseudoaneurysm suggestive of the yin-yang
sign was confirmed with color Doppler ([Fig. 1b, d, f]). Sterile lyophilized human thrombin was used, made from pooled human blood plasma.
Just before the procedure, thrombin was reconstituted with 1 mL of calcium chloride
and 4 mL of distilled water to a total of 5 mL. Thus, each 1 mL of reconstituted solution
contained 100 IU of thrombin. An EchoTip Ultra 22-gauge EUS needle (Cook Medical,
Bloomington, Indiana, United States) was used to puncture the pseudoaneurysm, under
EUS guidance ([Fig. 2a]). After puncture, the reconstituted thrombin was injected in aliquots of 1 mL until
the pseudoaneurysm became echogenic. The thrombin was injected into the sac but away
from the neck to reduce the risk of distant thromboembolism. The technical success
of the procedure was confirmed with loss of Doppler signal inside the pseudoaneurysm
sac ([Fig. 2b]) and the needle was removed. A gastroenterologist, who had sufficient experience
(> 100 EUS-guided therapeutic procedures), performed these procedures.
Fig. 1 a Computed tomography angiography of a patient showing a left hepatic artery pseudoaneurysm
(*). b EUS-Doppler of the same patient showing the left hepatic artery pseudoaneurysm. c Computed tomography angiography of a patient showing a splenic artery pseudoaneurysm
(*) within pancreatic walled off necrosis. d EUS-Doppler of the same patient showing the splenic artery pseudoaneurysm. e Computed tomography angiography of a patient showing a splenic artery pseudoaneurysm
(*) within pancreatic walled off necrosis. f EUS-Doppler of the same patient showing the splenic artery pseudoaneurysm.
Fig. 2 a EUS-guided insertion of a 22 gauge needle into pseudoaneurysm. b Loss of Doppler flow signals in pseudoaneurysm after injection of thrombin. c Thrombosed pseudoaneurysm with loss of Doppler flow signals on EUS 72 hours after
the procedure. d Thrombosed pseudoaneurysm with loss of Doppler flow signals on EUS 4 weeks after
the procedure.
Statistical analysis
Statistical analysis was performed using IBM SPSS Statistics for Windows, trial version
23.0 (IBM Corp, Armonk, NY, United States). Data were expressed as absolute numbers
with percentages for categorical variables. Continuous data were expressed as median
with interquartile range as appropriate. Data related to demography, laboratory parameters,
radiological imaging, pseudoaneurysm, and endotherapy were analyzed.
Results
In total, eight patients underwent EUS-guided thrombin injection for pseudoaneurysms
during the study period. Baseline demographic, clinical, and laboratory parameters
are shown in [Table 1]. Six patients (75 %) had chronic pancreatitis. The etiology of chronic pancreatitis
was alcohol abuse in all six patients. None of the patients had a history of trauma,
surgery or any vascular intervention in the past. Two patients (25 %) with left hepatic
artery pseudoaneurysms had evidence of hemobilia on side view endoscopy. CT of the
abdomen revealed that 5 patients (62.5 %) had pseudoaneurysm of the splenic artery,
2 (25 %) had pseudoaneurysm of the left hepatic artery, and 1 patient (12.5 %) had
gastroduodenal artery pseudoaneurysm ([Fig. 1a, c, e]). None of the patients had intraabdominal shunts. Procedural and outcome details
of individual patients are shown in [Table 2]. One patient with left hepatic artery pseudoaneurysm also had acute cholangitis
and required endoscopic retrograde cholangiopancreatography (ERCP) with stenting of
the common bile duct (CBD) after thrombin injection and was treated with intravenous
antibiotics (Ceftriaxone). In three of our study patients, coil embolization was refused
by the cardiologist and radiologist because of non-visualization or inaccessibility
of the feeding vessel, and five could not afford to undergo coil angioembolization,
as this procedure is very expensive compared to EUS-guided thrombin injection.
Table 1
Demographics and clinical characteristics of the study patients (n = 8).
|
Parameter
|
Value
|
|
Age, median (range), years
|
34 (27–58)
|
|
Sex, male/female, n
|
8:0
|
|
Smoker, n (%)
|
8 8 (100 %)
|
|
Chronic alcohol consumption, n (%)
|
6/8 (75 %)
|
|
Presenting symptoms, n (%)
|
|
|
8/8 (100 %)
|
|
|
8/8 (100 %)
|
|
|
6/8 (75 %)
|
|
|
2/8 (25 %)
|
|
|
2/8 (25 %)
|
|
Biochemical parameters
|
|
|
5.8 (4.1–8.8)
|
|
|
8.6 (6.35–15.12)
|
|
|
1.85 (1.54–6.95)
|
|
|
1.2 (0.9–1.52)
|
|
Blood transfusion requirement, median (range), units
|
3 (2–5)
|
|
Follow-up, median (range), months
|
3 (1–6)
|
|
Thrombin required, median (range), IU
|
400 (200–500)
|
PT-INR, prothrombin time expressed as international normalized ratio; TLC, total lymphocyte
count.
Table 2
Clinical features, procedural details, and outcomes of the study patients.
|
Serial number
|
Age, years
|
Etiology
|
Vessel involved
|
Pseudoaneurysm size, cm
|
Pseudoaneurysm neck length, mm
|
Thrombin required, IU
|
Procedure time, minutes
|
Outcome (after 6 months)
|
|
1
|
35
|
Chronic pancreatitis
|
Splenic artery
|
4 × 5
|
3.3
|
500
|
12
|
Obliterated
|
|
2
|
27
|
Chronic pancreatitis
|
Splenic artery
|
4 × 4
|
2.8
|
400
|
11
|
Obliterated
|
|
3
|
43
|
Chronic pancreatitis
|
Splenic artery
|
2.9 × 2.6
|
3.1
|
300
|
11
|
Obliterated
|
|
4
|
55
|
Chronic pancreatitis
|
Splenic artery
|
1.8 × 1.9
|
3.1
|
200
|
8
|
Obliterated
|
|
5
|
30
|
Idiopathic
|
Left hepatic artery
|
2 × 2
|
3.1
|
400
|
10
|
Obliterated
|
|
6
|
31
|
Idiopathic
|
Left hepatic artery
|
2.3 × 2.2
|
2.8
|
400
|
15
|
Obliterated
|
|
7
|
58
|
Chronic pancreatitis
|
Gastroduodenal artery
|
4 × 5
|
2.9
|
500
|
13
|
Recanalized. Repeat procedure required after 6 weeks
|
|
8
|
33
|
Chronic pancreatitis
|
Splenic artery
|
2.9 × 2.6
|
3.5
|
400
|
10
|
Obliterated
|
Description of lesion
The median pseudoaneurysm sac size was 2.9 cm × 2.6 cm (1.8 × 1.9–4 × 5 cm). The median
neck length of the pseudoaneurysm from the vessel of origin was 3.1 mm (2.8–3.5 mm)
and it was narrower than a point source at its origin. Two patients had pancreatic
pseudocysts and three had walled off necrosis.
Technical success
With EUS-guided direct and precise thrombin injection, we were able to achieve 100 %
technical success. The median amount of injected thrombin was 400 IU (200–500 IU)
which depended upon the size of the pseudoaneurysm sac. The median procedure time
was 11 minutes (8–15 minutes). After the procedure, patients were monitored closely
for hemodynamic stability. Two patients developed post-procedural pain in the abdomen,
which required intravenous analgesics. None of the patients had a rupture of the pseudoaneurysm,
bleeding or distal arterial thromboembolism. After 72 hours and 4 weeks, repeat EUS
showed obliterated pseudoaneurysm in all patients ([Fig. 2c, d]).
Clinical success
Clinical success of the procedure was observed in 7 patients (87.5 %) after a median
sustained follow-up of 6 months (1–9 months), and 1 patient (12.5 %) had recanalization
after 6 weeks, as he presented with hematemesis which required repeat thrombin injection.
Follow-up CT scans of the abdomen, performed after 1 month to look for any side effect
distant to the target, were normal in all patients. These data indicate that the procedure
was very successful in all patients.
Discussion
Our study presents a novel management approach using EUS-guided thrombin injection
in visceral artery pseudoaneurysms. This treatment was successful in all eight patients
in the study. Injection of coil and glue has also been described in the literature
for management of visceral artery pseudoaneurysms. A small case series showed the
efficacy of EUS-guided transgastric injection of coil and glue in patients with splenic
artery pseudoaneurysms. In that study, six patients with splenic artery pseudoaneurysm,
who failed angiographic embolization, underwent EUS-guided cyanoacrylate glue and
coil injection in pseudoaneurysms. All patients had complete occlusion of the pseudoaneurysms
at week 4 and 12 without any complications [21]. Another study proved the efficacy of ultrasound-guided tissue glue injection for
the treatment of femoral artery pseudoaneurysms [22]. Initial studies on percutaneous ultrasound-guided thrombin injection concluded
that it is a quick, effective, and safe treatment for pseudoaneurysms [18]
[19]. A few initial case reports showed the successful use of EUS-guided thrombin injection
in the management of visceral artery pseudoaneurysms [7]
[8]
[9]
[10]
[11]
[12]. Another small case series described the successful use of EUS-guided human thrombin
with no recurrence on short follow-up [6].
To date, no large study has been published on EUS-guided thrombin injection in pseudoaneurysms.
EUS-guided interventions are minimally invasive, can be performed under conscious
sedation, and decrease procedure time and hospital stay. They are also simple, effective,
and cheaper than angioembolization. Human thrombin does not have the risk of immunological
reaction and contamination with prions which was observed in a few cases with bovine
thrombin [23]. Thrombin injection can cause complications in the form of downstream embolization
into the arterial system and, although rare, this has been well documented [24]. This risk is high if the neck is less than 3 mm in length or wider than a point
source at its origin. In our study, the median neck length was 3.1 mm (2.8–3.5 mm)
and we injected thrombin into the aneurysmal sac, away from the neck. None of our
patients developed distal arterial embolization.
A limitation of this study was that it was a small case series with short duration
follow-up. Larger studies with long-term follow-up are needed to further prove the
efficacy and safety of the procedure.
In conclusion, EUS-guided thrombin injection provides an alternative for management
of visceral artery pseudoaneurysms. It is most useful in patients where endovascular
coil embolization is not possible or in patients having a high surgical risk but can
be used in all patients as it is simple, minimally invasive, effective and cheaper
than angioembolization.
