Digestive Endoscopy 2022; 34(Suppl. 2): 61–63 doi: 10.1111/den.

14165

Editorial

Endoscopic hemostasis for nonvariceal upper

gastrointestinal bleeding
Satoshi Tanabe
Department of Research and Development Center for New Medical Frontiers, Kitasato University School of
Medicine, Kanagawa, Japan
Nonvariceal upper gastrointestinal bleeding (NVUGIB) is
one of the most common and important gastrointestinal
conditions encountered in daily practice. The main cause of
NVUGIB is bleeding gastroduodenal ulcers.1 The number of
deaths due to bleeding gastroduodenal ulcers in Japan was
nearly 20,000 in the 1950s, but has decreased to approx-
imately 3000 in recent years.2 This decrease is attributed to
the eradication of Helicobacter pylori (H. pylori), develop-
ment of gastric acid secretory inhibitors, such as proton
pump inhibitors, and advances in endoscopic hemostasis. In
particular, advances in endoscopic techniques have been
remarkable, and endoscopic hemostasis has been positioned
as the first choice of treatment for NVUGIB.3 In this article,
I review the history and future prospects of endoscopic
hemostasis for NVUGIB.
While emergency endoscopic examination is now com-
mon for upper gastrointestinal bleeding, the endoscopic
approach to upper gastrointestinal bleeding began with
Palmer’s4 vigorous diagnostic approach in 1952 (Table 1).
Palmer’s suggestion was groundbreaking because, at that
time, endoscopy was contraindicated for gastrointestinal
bleeding. He reported 1400 cases of upper gastrointestinal
bleeding in a prospective manner over the next 23 years,5
and although the availability of endoscopic equipment and
laboratories was presumably difficult at that time, he
conducted a detailed study on the cause of bleeding in the
upper gastrointestinal tract. It is interesting to note that a
prospective study was planned 50 years ago, and was
conducted over 23 years.
On the other hand, in Japan, Kawai presented an article
titled “Observations on bleeding stomach” in the journal
Gastroenterological Endoscopy in 1964.6 He contributed to
the popularization of emergency endoscopy by explaining
its necessity in determining the need for emergency surgery.
In 1971, Hiratsuka successfully attempted to cauterize the
exposed vessel at the bottom of an ulcer by inserting a
cautery terminal into the forceps hole using a small high-
frequency electric current, which was used during cys-
toscopy at that time.7 In 1975, Hayashi et al.8 reported the
development of a prototype clip in collaboration with
Machida Endoscope (Chiba, Japan) and Olympus (Tokyo,
Japan), and applied it in clinical practice. Subsequently,
improvements were made to the clip, which became the
mainstay of endoscopic hemostasis.

Table 1 History of endoscopic hemostasis for NVUGIB

Year Name Emergency endoscopy/endoscopic hemostasis Pharmacotherapy

1952 Palmer Vigorous diagnostic approach

1964 Kawai Emergency endoscopy in Japan
1971 Hiratsuka High-frequency coagulation
1975 Hayashi Clip hemostasis
1976 €hmorgen
Fru Laser hemostasis
1978 Protell Heater probe
1980 Hirao Local injection of hypertonic sodium-epinephrine
solution
1981 Asaki Local injection of 99.5% ethanol 1982 H2 receptor antagonist
1994 Grund Argon plasm coagulation 1990 Proton pump inhibitor
2004 Enomoto High-frequency hemostatic forceps 2000 H. pylori eradication covered by insurance in
Japan
2015 P-CAB (Vonoprazan)
H. pylori, Helicobacter pylori; NVUGIB, nonvariceal upper gastrointestinal bleeding.

© 2021 Japan Gastroenterological Endoscopy Society 61


62 S. Tanabe
In 1976, Fr€uhmorgen et al. reported a laser hemostasis
method,9 while in 1978, Protell et al.10 developed the heater
probe method, one of the thermal coagulation methods. This
method involves the application of a probe with a heat-
emitting diode to the bleeding site to stop the bleeding. It is
also possible to achieve hemostasis by lateral application of
the probe, which is useful for tangential lesions. A water jet
is ejected from the tip of the probe to remove clots. In Japan,
Okada et al.11 reported hemostatic results in 1986 and we
also reported basic studies in dogs, including clinical
results.12 In the basic study of this method on the canine
gastric wall, both the depth and width of tissue degeneration
increased with increasing heat. However, the heat applied to
the same site was limited to submucosa or proper muscle at
60 J, and the degeneration range was approximately 6 mm,
which is considered to be a safe heat level for clinical
application. Regarding the hemostatic mechanism, the
spasm of small blood vessels in the gastric wall was
considered to cause narrowing of the lumen of the vessels
and further degeneration of vascular smooth muscle and
endothelial cells, resulting in the formation of a thrombus
that exerted a hemostatic effect.
In 1979, Akasaka et al.13 performed endoscopic hemosta-
sis by electrocoagulation in 29 cases of upper gastrointesti-
nal bleeding and reported a 100% rate of hemostasis. In
1980, Hirao et al.14 reported the usefulness of hypertonic
sodium-epinephrine (HS-E) solution for hemostasis. The
vasoconstrictive effect of epinephrine and tissue swelling
caused by hypertonic saline aid in hemostasis, and this
approach is characterized by its simplicity and high hemo-
static effect. In 1981, Asaki et al.15 developed a 99.5%
ethanol local injection method and reported high hemostatic
results. The dehydration and fixation of tissues by pure
ethanol constricts blood vessels and damages vascular
endothelial cells to form a thrombus for hemostasis. In the
1980s, various hemostatic methods such as HS-E injection,
pure ethanol injection, clip hemostasis, and the heater probe
method were developed and applied in clinical practice.
In the 1990s, Grund et al.16 introduced an ablation
method with argon plasma coagulation to the field of
endoscopy, which had been previously used in the surgical
field. It is a noncontact electrocoagulation method that
allows cauterization of a large area at a constant, shallow
depth, and has been reported to be useful for the manage-
ment of gastric antral vascular ectasia and diffuse bleeding
from tumors. In addition to the development of various
hemostatic methods, the development of attachment hoods
has enabled reliable hemostatic treatment, even for tangen-
tial lesions and cases with large respiratory variability.
In the 2000s, endoscopic submucosal dissection (ESD) was
developed for the treatment of early-stage gastric cancer, and
© 2021 Japan Gastroenterological Endoscopy Society
14431661, 2022, S2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.14165 by Nat Prov Indonesia, Wiley Online Library on [31/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Digestive Endoscopy 2022; 34(Suppl. 2): 61–63
its use has rapidly spread. Intraoperative hemostasis is
essential for ESD, necessitating a reliable hemostatic tech-
nique. This is where hemostasis with high-frequency hemo-
static forceps comes into play. It is a method of cauterizing and
stopping bleeding by accurately grasping the bleeding point or
exposed vessel, and has become an essential method for the
treatment with ESD due to its simplicity and reliability.
Enomoto et al.17 focused on the usefulness of high-frequency
hemostatic forceps for bleeding during ESD, and reported the
usefulness and safety of this method when applied to bleeding
gastric ulcers. In cases of active bleeding, such as Forrest Ia
and Ib, HS-E was first used to reduce the momentum of
bleeding; subsequently, cauterization of the blood vessel with
high-frequency hemostatic forceps was established as a
reliable method of hemostasis.
In 2016, the Japan Gastroenterological Endoscopy Soci-
ety, led by Fujishiro et al., prepared treatment guidelines for
NVUGIB in Japan, and reported detailed information on the
prevention of rebleeding, including epidemiology, indica-
tions for hemostasis, and the use of various treatment tools.3
With the recent advances in endoscopic treatment, new
devices have emerged and are now used for hemostasis.
Over the scope clip (OTSC) (Ovesco Endoscopy, T€ ubingen,
Germany) has been used for hemostasis.18 OTSC has
traditionally been used to close perforations and fistulas in
the gastrointestinal tract; however, its hemostatic application
has been reported in European countries and Japan.
Furthermore, the application of a hemostatic spray has been
reported in a prospective multicenter study conducted
mainly in Europe and the United States.19 It was found to
have a high initial hemostatic rate and contributed to a
decrease in mortality within 30 days.
As described above, various hemostatic methods have
been developed and are being used in clinical practice.
Although there are differences in the reports, the initial
hemostatic rate of any of these methods, alone or in
combination, is approximately 90%. It is important to
understand the characteristics and hemostatic mechanisms
of each hemostatic method and select a hemostatic method
based on the condition and location of bleeding.
However, there are a small number of cases in which
hemostasis is not possible, despite the use of various
hemostatic methods. Predictors of difficulty in endoscopic
hemostasis include Forrest Ia classification of bleeding,
ulcers larger than 2 cm in diameter, and shock.20 Further
investigation of factors associated with difficulty in endo-
scopic hemostasis may be necessary. When encountering
such cases, it is important to primarily consider the patient’s
survival and decide on interventional radiology or surgical
treatment rather than continuing to pursue endoscopic
treatment.

Digestive Endoscopy 2022; 34(Suppl. 2): 61–63
In this article I reviewed the history of endoscopic
hemostasis for NVUGIB and discussed its current status and
future prospects. Approximately 70 years have passed since
the introduction of emergency endoscopy to clinical prac-
tice, and endoscopic hemostasis has become an essential
therapeutic technique in daily clinical practice. Further
advances in technology and the development of new tools
are expected to lead to the establishment of a safer and more
reliable method for endoscopic hemostasis.
ACKNOWLEDGMENTS
T HE AUTHOR WOULD like to thank Dr Yo Kubota, Dr
Kenji Ishido, and Dr Akinori Watanabe at Kitasato
University School of Medicine for editing a draft of the
manuscript.
CONFLICT OF INTEREST
A UTHOR DECLARES NO conflict of interest for this
article.
FUNDING INFORMATION
N ONE.
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© 2021 Japan Gastroenterological Endoscopy Society