Digestive Endoscopy 2022; 34(Suppl. 2): 40–45
14166
Editorial
Endoscopic treatment of esophagogastric varices
Katsutoshi Obara
Endoscopy Center, Fukushima Preservative Service Association of Health, Fukushima, Japan
Necessary keys to success for the safe and effective
treatment of esophagogastric varices include deep under-
standing of the mechanism of treatment drugs, selection of
the optimal treatment method considering patient condition
and portal hemodynamics, practice of treatment procedures,
prevention of complications, careful monitoring and peri-
odic follow-up of a patient, and building a good medical
team. The following describes an historical overview of
endoscopic treatment for esophagogastric varices in Japan.
Endoscopic injection sclerotherapy (EIS) and endoscopic
variceal ligation (EVL) are popular endoscopic treatment
procedures for esophageal varices (EV). EIS by intravariceal
injection of 5% monoethanolamine oleate (EO) was devel-
oped in the UK by Hunt and Johnstone and introduced in
Japan in 1978 by Takase et al.1 They employed the
embolization method or the EO method in which EO mixed
with a contrast agent was injected to embolize feeding veins
as well as EV under fluoroscopy, and it became a cornerstone
of EIS in Japan. On the other hand, extravariceal injection of
1% polidocanol (Aethoxysklerol [AS]; Ferndale Phamaceu-
ticals Ltd., Wetherby, UK) introduced by Raschke and Kapp
in West Germany was developed by Paquet (1978), and
employed in Japan by Suzuki and Nagao in 1981 to become
very popular as intra/extravariceal injection of AS (AS
method).2 Furthermore, Futagawa et al.3 reported extravar-
iceal injection of sodium morrhuate followed by that of
Phenol (Paoscle; Torii Phamaceutical Co. Ltd., Tokyo, Japan)
by Kumagaya and Makuuchi in 1981.4 In 1987, Kitano and
Sugimachi developed a new technique using a transparent
over-tube (K-S tube, ST-E1; Olympus, Tokyo, Japan) to
secure a field of vision for the precise injection of EO without
X-ray fluoroscopy,5 and Obara et al.6 reported the EO-AS
combination method,6 which is a procedure based on
metachronous combination of the Takase method (EO
method) and the Suzuki method (AS method). Obara et al.7
also introduced the AS consolidation method in 1989
followed by the laser consolidation method in 1994 for
prevention of variceal recurrence.8 Now, argon plasma
coagulation (APC) is widely used instead of laser owing to
its ease of operation (Fig. 1). EIS rapidly became very
popular in Japan owing to widespread dissemination of
endoscope and development of treatment procedures.
40
doi: 10.1111/den.
Endoscopic injection sclerotherapy was performed
nationwide in the 1980s; however, the drugs used were
not approved by the Ministry of Health and Welfare
(MHW). Therefore, according to the discussion at the 1st
Research Conference on Endoscopic Injection Sclerotherapy
for Esophageal Varices, a subcommittee was established
within the Japan Gastroenterological Endoscopy Society
(JGES) in 1986 to promote MHW approval of sclerosing
agents. Clinical studies on 5% EO and 1% AS were
conducted from January to July in 1988 and they were
approved in October in 1991. For about 20 years since the
endoscopic treatment for EV was introduced in Japan in
1978, procedures were developed and revised aggressively
to further seek safe and effective procedures. In the 2000s,
EIS using the EO-AS combination method followed by
APC consolidation method, and EVL were performed
nationwide, and a number of excellent studies were reported
on long-term outcome and prognosis after EIS or EVL in
Digestive Endoscopy and Gastroenterological Endoscopy,
the official journals of the JGES.
Endoscopic variceal ligation reported by Stiegmann in
19869 was introduced in Japan by Yamamoto et al. in
1990.10 As EVL is easy to perform without the complica-
tions of sclerosing agents, a good indication for EVL is a
case where EIS is contraindicated. EVL can be combined
with EIS (AS method) in order to reduce the high rate of
variceal recurrence after EVL. Moreover, as feeding veins
still remain after this EVL-AS combination method, APC
consolidation can be additionally performed to further
reduce recurrence rates which are still higher than those of
the cases treated using the EO-AS combination method
(Fig. 1). EVL spread rapidly and is selected as the first-line
treatment for EV in many institutions; however, indications
for EVL in elective/prophylactic cases should be discussed
again taking into consideration long-term prognosis and
patient quality of life (QOL).
Treatment options for isolated gastric varices (GV)
include endoscopic treatment, interventional radiology
such as balloon-occluded retrograde transvenous obliter-
ation, and Hassab’s operation, among which endoscopic
treatment made a rapid progress by adoption of
cyanoacrylate adhesives (CA). Suzuki et al. in 198811
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Digestive Endoscopy 2022; 34(Suppl. 2): 40–45 Esophagogastric varices 41

Elective/prophylactic cases

EO-AS combination method Consolidation method

EO method APC Consolidation

AS method
consolidation completed
Bleeding cases

Endoscopic
injection
EVL sclerotherapy

Absent

(e) (f) (g) (h)

Severe hepatic disorder (d)
(Child-Pugh C,
TBIL 4 mg/dl)

EVL-AS combination method Consolidation method

Present Intensive EVL

AS method APC consolidation Consolidation completed
procedure
(a) (c)

Endoscopic variceal
ligation (EVL)

(i) (j) (k) (l)

(b)

Figure 1 Treatment procedures for esophageal varices (EV). (a) Confirm the bleeding point with emergency endoscopy under
general physical condition management. (b) Balloon tamponade using a scope-attached balloon. (c) When the bleeding has
subsided, ligate the bleeding point with a rubber O-ring for hemostasis. (d) Puncture on the anal side of the ligated area and
inject monoethanolamine oleate (EO). (e) Inject 5% EO into the EV and the blood supply routes to produce occlusive thrombosis.
(f) Inject 1% Aethoxysklerol (AS) into the thrombosed EV after the EO method to occlude the remaining small blood vessels. (g)
Apply argon plasma coagulation (APC) circumferentially on the lower esophagus to form a circumferential ulcer. (h) When the
ulcer is cured, the esophageal wall is replaced by thick fibrous tissues (sclerosis). (i) A dense array of rubber O-rings are hooked
onto the EV from the esophagogastric junction to the lower esophagus. (j) 1w after EVL, AS is injected into the mucosa between
ulcers formed by EVL. (k) 1w after the AS method, the remaining mucosa in the lower esophagus (except for the ulcers formed
by the AS method) is cauterized circumferentially with APC. (l) As the circumferential ulcers are cured, the esophageal wall is
replaced with thick fibrous tissue, but the blood supply route remains (arrow).

introduced N-butyl-2-cyanoacrylate (Histoacryl; B. Braun
Surgical SA, Rubi, Spain) and Obara et al.12 in 1989
introduced a-cyanoacrylate monomer (Arona-A; Toago-
sei Co., Ltd., Toyama, Japan) which made possible safe
and effective GV treatment. The general consensus is
that intravariceal injection of CA (CA method) should be
the first choice in GV bleeding cases, while in elective/
prophylactic cases, each institution adopts its own
treatment approach. In addition, endoscopic treatment
using the CA-EO combination method is widely per-
formed, which consists of obliteration of GV using the
CA method and occlusion of the blood supply routes
using the EO method (Fig. 2).
The Guidelines for Gastrointestinal Endoscopy (1st
edition) were published by the JGES in 1999, and revised
as the 2nd edition in 2002 and the 3rd edition in 2006, where
“Guidelines for treatment of esophagogastric varices”
showed updated treatment strategies.13 In 2010, Evidence-
based Guidelines for Liver Cirrhosis 2010 were published
by the Japanese Society of Gastroenterology, and revised in
2015 and 2020.14 At the beginning of the 2000s, one of the
big challenges was how to standardize EV treatment
strategy, and it was discussed in the JGES-attached study
groups, the Study Group for Portal Hemodynamics from
2003 to 2005 and the Varix Standardization Study Group
from 2006 to 2008. It was strongly desirable to conduct

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42 K. Obara Digestive Endoscopy 2022; 34(Suppl. 2): 40–45

Bleeding cases 75% CA

method

Emergency
hemostasis using
the CA method

(a)
Isolated fundal varices Isolated cardio-fundal varices

CA method EO method CA method EO method

Blood supply routes Blood supply routes

Left gastric vein

Short gastric vein
(SGV) or (LGV), SGV, PGV
SGV Posterior gastric vein LGV
(PGV)
Elective/Prophylactic
cases Gastrorenal PGV SGV
shunt

Obliteration of GV and (PGV)

the blood supply routs
using the CA/EO
combination method

EO (PGV)
EO (SGV)

(b) (c)

Figure 2 Treatment procedures for isolated gastric varices (GV). (a) 1.4 mL of 75% a-cyanoacrylate monomer mixed with lipiodol
was injected into the bleeding GV under fluoroscopy. Abdominal X-ray image showed the blood inside the GV was completely
polymerized. Bleeding stopped immediately. (b) Preprocedural endoscopic findings were markedly enlarged nodular GV in the
fundus. As GV diameter was 10 mm in 20 MHz ultrasound miniprobe (UMP) image, 75% a-cyanoacrylate monomer was injected at
two points to block the blood flow of GV, and 5% monoethanolamine oleate (EO) was injected in the blood supply rout (PGV). (c)
Preprocedural endoscopic findings were moderately enlarged beady GV located from the cardiac orifice to the fundus. As GV
diameter was 8.5 mm in UMP image, 62.5% a-cyanoacrylate monomer was injected at five points to block the blood flow of GV,
and 5% EO was injected into the blood supply routes (PGV and SGV).

multidisciplinary treatment by selecting or combining withstand endoscopy or if no endoscopist is available for an

therapeutic procedures that were safe and free from
rebleeding, and that take the patient’s QOL into consider-
ation. Therefore, the Study Group for Multidisciplinary
Varix Treatment was set up, where multicenter research was
conducted to establish current treatment strategies.
Treatment strategies based on the patient conditions are as
follows (Fig. 3). In bleeding cases, check the whole-body
condition of the patient and perform emergency endoscopy
to confirm the bleeding source. With or without hepatocel-
lular carcinoma (HCC) or severe hepatic disorder (Child-
Pugh C, TBIL ≥4 mg/dL), temporary hemostasis should be
achieved using EVL for EV bleeding and the CA method for
GV bleeding. If the whole-body condition is too poor to
emergency patient, perform astriction by means of balloon
tamponade and conduct elective treatment within 12 h or
transfer the patient to the facilities where endoscopic
treatment can be performed. In cases with severe hepatic
disorder, avoid EIS whenever possible because it aggravates
bilirubin value leading to hepatic failure, and select EVL for
EV and the CA method for GV. In cases without severe
hepatic disorder, select EIS for EV and the CA-EO
combination method or B-RTO for GV. HCC complicated
cases should be treated according to the degree of portal
vascular invasion (Vp).15 In cases without Vp (Vp0) and
those with Vp into the third-order branch (Vp1) or the
second-order branch (Vp2), the treatment policy can be

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Digestive Endoscopy 2022; 34(Suppl. 2): 40–45 Esophagogastric varices 43

Gastric varices (GV)

Esophageal varices

Bleeding cases Elective/prophylactic cases

Bleeding cases Elective/prophylactic cases
Presence of severe hepatic disorders
General physical condition (Child-Pugh C, TBIL 4 mg/dl)
General physical management
Presence of severe hepatic disorders
condition management
(Child-Pugh C, TBIL 4 mg/dl)
Absent Present
Emergency endoscopy Emergency endoscopy
HCC
for confirmation of for confirmation of
Vp3,4)
bleeding source bleeding source
Absent Present GV diam. 12 mm

Balloon tamponade
using an SB tube Balloon tamponade With or without GR shunt With GR shunt
using a gastric balloon

Temporary hemostasis EIS EVL

Endoscopic treatment B-RTO
with EVL
Temporary hemostasis (CA-EO combination
using the CA method method)
EVL Follow-up

APC consolidation Hassab’s operation GR shunt-occluded

Elective treatment CA method

Elective treatment

Transfer to the
professional facilities Transfer to the
professional facilities CA method

Figure 3 Treatment strategies for esophagogastric varices. APC, argon plasma coagulation; B-RTO, balloon-occluded
retrograde transvenous obliteration; CA, cyanoacrylate adhesives; EIS, endoscopic injection sclerotherapy; EO, ethanolamine
oleate; EVL, endoscopic variceal ligation; GR, gastrorenal; HCC, hepatocellular carcinoma. Modified from Obara et al.13

identical to that for the hepatic cirrhosis cases not compli-
cated by HCC, which is based on severity of hepatic
disorder. In cases with Vp into the first-order branch (Vp3)
or the main trunk/contralateral branch (Vp4), patients should
be followed closely without endoscopic treatment taking
into consideration the life prognosis of patients. However,
EVL is indicated for EV and the CA method is for GV when
bleeding occurred during follow-up in prophylactic cases
and when the risk of bleeding is high in elective cases.
Treatment strategies based on portal hemodynamics are as
follows. Endoscopic ultrasonography (EUS) and three-
dimensional computed tomography (3D-CT) are indispens-
able in the evaluation of portal hemodynamics before and
after treatment (Fig. 4). EUS is a useful means of performing
non-invasive identification of blood routes inside and
outside the esophagogastric walls. With observation using
a 20 MHz ultrasonic miniprobe (UMP), EV are imaged as a
non- or low-echoic lumen in the submucosa. EV often
communicate with the peri-esophageal veins (Peri-v) and
para-esophageal veins (Para-v) through a perforating vein
(Pv). Peri-v are the small vessels located adjacent to the
esophageal adventitia and partially in the muscle layer.
Para-v are the large vessels located at a distance from the
esophageal adventitia. Irisawa et al. reported that the
recurrence frequency is high when the remaining Peri-v or
large Pv is observed during UMP examination after
treatment.16 Therefore, it is important to obliterate Peri-v
and a Pv during the initial EIS. If Peri-v and/or a Pv remain
after treatment, the APC consolidation method should be
additionally employed to prevent recurrence. Furthermore,
in cases with a large Pv which acts as a shunt to the outside
of the EV during EIS, appropriate measures need to be taken
to prevent the sclerosant from leaking into the general
circulation. 3D-CT is useful for evaluating the portal venous
system such as the development of blood supply/drainage
routs and the presence of a gastrorenal shunt leading to
greater circulatory system. This examination method can
replace and is less invasive than abdominal angiography or
percutaneous transhepatic angiography.
For these 41 years since endoscopic treatment of esoph-
agogastric varices was first employed, a number of studies
have demonstrated the safest and the most effective
treatment procedures in Japan. As a result, it is now
possible to provide the optimal treatment that best matches
the pathologic condition and portal hemodynamics of each
patient. Taking into consideration patient QOL, endoscopic
treatment is the first choice. In order to achieve the utmost
safety and effectiveness, it is essential that endoscopists

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44 K. Obara Digestive Endoscopy 2022; 34(Suppl. 2): 40–45

Esophageal varices UMP 3D-CT

peri-esophageal veins (Peri-v)

Esophageall varices

perforating vein (Pv)

para-v

pv
para-esophageal veins (Para-v) peri-v

(a) (b) (c)

Gastric varices

para-gastric veins
peri-gastric veins (Para-v) Pv Gastric varices
Left gastric vein
(Peri-v)
Short gastric vein

Gastrorenal
shunt
Gastric varices

perforating vein (Pv)

Maximum Intensity Projection method

(d) (e) (f)

Figure 4 Evaluation of portal hemodynamics with endoscopic ultrasonography (EUS) using a 20 MHz ultrasonic miniprobe
(UMP) and three-dimensional computed tomography (3D-CT). (a) Schema of UMP image inside and outside the esophageal wall.
Modified from Irisawa et al.16 (b) Blood supply routes inside and outside the esophageal wall. (c) A risky extraesophageal shunt
(arrow). (d) Schema of UMP image inside and outside the gastric wall. Modified from Irisawa et al.16 (e) Measurement of gastric
varices diameter and evaluation of the supply routes inside and outside the gastric wall. (f) Blood supply routes and the drainage
veins.

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3 Futagawa S, Hiraide Y, Saito M et al. Endoscopic injection
sclerotherapy for esophageal varices. Dig Surg 1983; 6: 329–
CONFLICT OF INTEREST
36. Japanese.

A UTHOR DECLARES NO conflict of interest for this

article.
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