Introduction
Endoscopic submucosal dissection (ESD) is an established treatment for early gastrointestinal
cancer in Japan. However, this procedure is associated with postoperative bleeding
rates of approximately 5 % to 38 % [1]
[2]. Coagulation of nonbleeding visible vessels (NBVVs) has been identified as a useful
and safe method for decreasing the rate of early rebleeding [3]
[4]
[5]. However, 7 % of patients bleed despite coagulation of NBVVs [6]. Invisible vessels (IVs) are related to early rebleeding, and usefulness, such as
mapping method and observation of post-ESD ulcer using magnification function scope,
has been reported [6]
[7]. In addition, in our experience, early rebleeding may occur from IVs that could
not be detected immediately after ESD ([Fig. 1a], [Fig. 1b], [Fig. 1c]). Consequently, it is important to detect IVs.
Fig. 1 A representative case of early rebleeding from a post-endoscopic submucosal dissection
(ESD) ulcer. a Immediately after ESD, no obvious sites of bleeding stigmata are visible via endoscopy.
b Rebleeding from the post-ESD ulcer occurred 12 hours after ESD. Emergency endoscopy
revealed spurting bleeding from the center of the ulcer. c Additional coagulation was performed and no signs of bleeding were observed immediately
after ESD, suggesting presence of an invisible artery.
Doppler probe ultrasonography (DOP) was recently introduced to the field of endoscopy
[8]. Briefly, DOP is used to evaluate blood flow and can thus detect IVs in the gastrointestinal
tract that could potentially cause bleeding [9]. One previous report described the effectiveness of DOP in terms of decreasing the
gastric ulcer rebleeding rate [10]. However, that report did not sufficiently demonstrate the efficacy of DOP for detection
of IVs in post-ESD ulcers. Furthermore, the limitations of prior DOP devices with
respect to the fixed depth of signal detection have prevented identification of blood
flow below a depth of 1.5 mm [11]. Moreover, some Doppler models produce an audible output but do not have a visual
display [12]. To address these limitations, we conducted this preliminary study to explore the
impact and safety of DOP with a new system, which includes a high-quality audio and
visual monitor display, for detection of IVs at the post-ESD ulcers of the stomach.
Patients and methods
Patients
From June 2019 to August 2019, 12 patients underwent ESD for early gastric cancer
at St. Luke’s International Hospital in Tokyo, Japan. DOP was performed to evaluate
post-ESD ulcers in these patients. The study protocol was approved by the ethics committee
at our hospital (19-R151). We received approval from the clinical ethics committee
regarding use of DOP for post ESD ulcers and received informed consent directly from
the patients prior to hemostatic treatment.
Doppler probe ultrasonography methods
The Doppler Box DOP system (Compumedics, DWL, Germany; [Fig. 2]) and probe are marketed for use in vascular surgery departments [13]. The 16-MHz Doppler probe has a length and diameter of 2 m and 1 mm, respectively,
and is reusable after gas sterilization or high-level liquid disinfection. The monitor
includes a center screen that displays pulse waves and eight screens that display
different scan depths. This system has a high-definition-compatible screen and produces
a high-quality audible signal.
Fig. 2 The Doppler-BOX 16-MHz pulse-wave system with a reusable doppler probe and monitor.
The Doppler probe ultrasonography (DOP) output signal is both visual and audible.
Reproduced with permission from Compumedics, Inc.
We evaluated post-ESD ulcers using the following procedure. A water-jet scope (GIF-Q260 J
or GIF-2TQ260M; Olympus Corp., Tokyo, Japan) attached to a transparent hood was used;
the specific scope was selected according to the endoscopist’s preference. After routine
coagulation of the NBVVs, the Doppler probe was pushed to the post-ESD ulcer at an
angle of 60º and maneuvered mainly around the pigmented spots and NBVV to detect the
whole ulcer. The Doppler pulse wave was observed to shift depending on the speed and
direction of the blood flow relative to the probe. Blood flow sites were observed
at depths of 0.5 to 5 mm. Once IVs were detected, additional coagulation was performed
(HDB2418 W, Pentax Co, Japan) to a maximum depth of 3 mm. The subsequent disappearance
of the corresponding Doppler pulse wave was then confirmed ([Fig. 3a], [Fig. 3b], [Fig. 3c], [Fig. 3d] and [Video 1]). IVs with a depth of > 3 mm were considered subserosal blood flow and were not
coagulated [12].
Fig. 3 a Detection of a Doppler probe ultrasonography (DOP)-positive vessel at the post-ESD
ulcer. The Doppler probe was maneuvered while observing the blood flow. b Visual graphic display of the three positive Doppler waves corresponding to the vessel.
The blood flow velocity (cm/s) and time (s) are plotted on the Y axis and X axis,
respectively. The blood flow depth (2.0 mm) is indicated at the upper left of the
plot. c Performance of additional coagulation for the vessel. d The Doppler wave disappeared after additional coagulation of the vessel.
Video 1 We report a case using DOP for post-ESD ulcer.
Follow-up after ESD
On the first day after the procedure, a second look was performed to evaluate post-ESD
ulcers without reference to the DOP findings. Additional coagulation was performed
at the sites of exposed vessels.
Endpoints and statistical analysis
The primary study endpoint was the post-ESD rebleeding rate. IV detection rate, procedure
time, and adverse events (AEs) were measured as the secondary endpoints. The definition
of early rebleeding was a lesion requiring hemostasis within 7 days after ESD. The
IVs were divided two groups according to a depth of ≤ 3 or > 3 mm. Procedural duration
was defined as total time required for the DOP examination and subsequent coagulation.
AEs were evaluated according to the National Cancer Institute Common Terminology Criteria
for Adverse Events, version 5.0 [14].
Statistical analyses were performed using JMP, version 14 (SAS Institute, Inc., Cary,
North Carolina, United States). The patient age and procedural duration are reported
as means ± standard deviations.
Results
Characteristics and study findings of the 12 patients who underwent DOP are presented
in [Table 1]. Mean age was 65.5 ± 12 years old. Mean post-ESD ulcer size was 36 mm × 30 mm (range:
345–1802 mm2). Two patients (No. 11 and 12) had used antithrombotic agents (low-dose aspirin in
both cases). A total of 30 NBVVs were initially detected and coagulated in the 12
patients.
Table 1
Summary of the study results.
|
No.
|
Age
|
Sex
|
Location
|
Type
|
Size
|
NBVV
|
IV ( ≤ 3 mm)
|
IV ( > 3 mm)
|
Procedure time (min)
|
Additional coagulation in second look
|
Antithrombotic agents
|
Early rebleeding
|
|
1
|
70
|
F
|
U, LC
|
IIc
|
32 × 21
|
3
|
2
|
2
|
18
|
–
|
–
|
–
|
|
2
|
61
|
M
|
U, LC
|
IIc
|
52 × 32
|
4
|
2
|
1
|
15
|
–
|
–
|
–
|
|
3
|
68
|
F
|
M, LC
|
IIc
|
34 × 30
|
2
|
0
|
2
|
12
|
–
|
–
|
–
|
|
4
|
66
|
M
|
A, GC
|
IIc
|
23 × 15
|
3
|
0
|
0
|
8
|
–
|
–
|
–
|
|
5
|
63
|
M
|
M, PW
|
IIc
|
38 × 34
|
2
|
2
|
0
|
8
|
–
|
–
|
–
|
|
6
|
49
|
M
|
M, LC
|
IIc
|
38 × 30
|
3
|
2
|
0
|
8
|
–
|
–
|
–
|
|
7
|
69
|
M
|
L, GC
|
IIc
|
36 × 30
|
3
|
1
|
0
|
10
|
–
|
–
|
–
|
|
8
|
54
|
M
|
U, GC
|
IIc
|
35 × 30
|
1
|
0
|
0
|
10
|
–
|
–
|
–
|
|
9
|
72
|
M
|
M, AW
|
IIc
|
34 × 20
|
2
|
1
|
1
|
14
|
–
|
–
|
–
|
|
10
|
45
|
M
|
A, GC
|
IIc
|
26 × 20
|
1
|
1
|
0
|
10
|
–
|
–
|
–
|
|
11
|
80
|
M
|
L, LC
|
IIc
|
33 × 26
|
3
|
2
|
0
|
11
|
–
|
+
|
–
|
|
12
|
90
|
F
|
A, AW
|
IIa
|
42 × x32
|
3
|
0
|
1
|
10
|
+
|
+
|
–
|
NBVV, non-bleeding visible vessels: IV, invisible vessel; U, upper third; L, lower
third; LC, lesser curvature; M, middle third; A, anterior; PW, posterior wall; GC,
greater curvature; AW, anterior wall
Early rebleeding did not occur in any cases (0 %). Although there was no bleeding,
prophylactic coagulation was performed in a very small vessel in one patient (No. 12).
After coagulating the NBVVs, DOP detected 20 IV sites in the 12 post-ESD ulcers. Of
these, 13 IVs with depths ≤ 3 mm were detected in eight patients, while seven IVs
with depths > 3 mm were detected in five patients. We performed coagulation of the
13 IV sites at depths ≤ 3 mm, with a mean procedural duration of 11.6 ± 4.6 minutes
(range: 8–18 minutes). No adverse events related to the DOP were observed.
Discussion
Our study findings revealed that DOP is a feasible method for detecting IVs in post-ESD
ulcers and preventing early rebleeding from these lesions.
Post-ESD ulcers may rebleed, leading to serious complications such as hemorrhagic
shock. Increasing use of antithrombotic drugs may further increase risk of rebleeding.
As noted above, we experienced rebleeding after NBVV coagulation, which we attributed
to presence of IVs. Therefore, we performed a preliminary study to demonstrate the
feasibility of a novel DOP system for preventing early rebleeding and detecting IVs
in post-ESD ulcers. Notably, we detected 13 IVs with depths ≤ 3 mm in two-thirds of
our patient sample. After coagulation, none of these cases experienced rebleeding,
and only one required additional coagulation after a second look. Although the procedural
duration was influenced by the size of the post-ESD ulcer and the requirement for
additional coagulation, this variable was gradually reduced as the clinicians became
more familiar with the procedure.
Compared to previous DOP systems, the DOP system used in this study is novel, as it
assesses blood flow at multiple depths and provides high-quality audio and video outputs.
In contrast, the Doppler US unit used by Uedo (VTI Endoscopic Doppler System, Vascular
Technology Inc., Nashua, New Hampshire, United States) had three fixed preset depths:
from the surface to 1.5, 4, and 7 mm and lacked a video display [11]. Similarly, the VTI Endoscopic Doppler System (Vascular Technology, Inc., Lowell,
Massachusetts, United States) described by Richard produced only an audible signal
and was not accompanied by a visual monitor display [12]. The observation range of the above system is limited due to fixed depths. In addition,
becaues blood flow is sensed by sound, the depth is not known, and blood flow outside
the stomach wall (> 3 mm) may be sensed.
In this study, the DOP system used in the vascular surgery department was considered
to have a high ability to detect blood flow. However, one visible vessel was considered
DOP-negative. The Doppler wave was easier to detect near 60 ° and may be related to
the angle between the Doppler probe and vessels. This issue should be investigated
in future studies. An earlier study reported a reduction in frequency of post-hemostatic
rebleeding from 26 % to 11 % by performing a hemostasis procedure on the DOP-positive
in advance among patients with severe non-variceal upper gastrointestinal bleeding
[10]
[15]. Other reports suggested that it is less costly and more useful (14 % lower rebleeding
rate) than traditional endoscopic visual assessment for the management of severe non-variceal
upper gastrointestinal bleeding [16]. DOP is considered to be useful not only for post-ESD ulcers, but also gastrointestinal
bleeding in general.
Conclusion
This preliminary study revealed the safety and feasibility of a novel DOP system for
detection of IVs in post-ESD ulcers. In the future, to describe the effectiveness
of DOP, a controlled study with a sufficient number of patients will be needed.
In conclusion, this novel DOP system provides a safe and feasible method for detecting
IVs in post-ESD ulcers. A further investigation of the clinical relevance is warranted.
