Technological review on endoscopic submucosal dissection: available
equipment, recent developments and emerging techniques
, Juergen Hochberger
, Pierre Deprez
, Morteza Shafazand
, Dimitri Coumaros
Department of Endoscopy, Mediterraneo Hospital, Glyfada, Athens, Greece;
Department of Gastroenterology, Vivantes-Friedrichshain
Hospital, Berlin, Germany;
Department of Hepatogastroenterology, Cliniques Universitaires Saint-Luc, Universit!
e Catholique de Louvain,
Department of Endoscopy, Internal Medicin Clinic, Sahlgrenska University Hospital/East Hospital, Gothenburg, Sweden;
Department of Gastroenterology, Clinique Saint Barbe, Strasbourg, France;
Department of Gastroenterology, Japan Community Healthcare
Organization Osaka Hospital, Fukushima, Osaka, Japan
Endoscopic submucosal dissection (ESD) is widely practiced in Japan and the Eastern World and is rap-
idly expanding in western countries for the management of early malignancies of the upper and lower
gastrointestinal tube. In addition, novel therapeutic applications deriving from ESD have emerged
including the treatment of achalasia, of submucosal tumors, of diverticula, of strictures and of reflux
disease. An ESD procedure necessitates not only skills and specific training, but also familiarization
with a vast spectrum of devices (endoscopes, high-frequency generators and their settings, endoknives,
hoods, irrigation devices) and techniques (such as countertraction, artificial ulcer closure), that render
the procedure faster, more efficient and safer. This technological article gives an overview on current
and novel equipment for an ESD and associated techniques.
Received 30 September 2016
Revised 5 December 2016
Accepted 7 December 2016
Endoscopic submucosal dissection (ESD) is widely practiced
in Japan and some Asian countries as a minimal invasive
modality for ‘en bloc’resection of superficial malignancies of
the GI tract. Indications are early cancers exceeding 10 mm
and widespread premalignant lesions in order to achieve a
complete histo-pathologic analysis and reduce local recur-
rence to a minimum. The choice of suggesting an ESD treat-
ment depends on several parameters such as the
macroscopic aspect, the ‘lifting’of the lesion, after submuco-
sal injection, and the evaluation by means of high-resolution
ultrasound. However, the value of this later modality in local
staging had been overestimated in the past. Only the exact
analysis of the resected specimen gives accurate information
of the depth of infiltration, as well as of the lymphatic and
vessel involvement. Additional treatments such as surgical
resection or chemo-radiation have to be considered in a glo-
bal setting and discussed in an oncology meeting. In an
effort to further define which lesions are suitable for ESD, the
European Society of Gastrointestinal Endoscopy (ESGE)
recently published guidelines . Consequently, partial or
complete reimbursement of ESD procedures has been
achieved in several European countries such as Germany,
Belgium and Italy. However, the learning curve for ESD is
long, making systematic training necessary . In addition,
ESD-derived techniques including endoscopic esophageal
myotomy (POEM), submucosal tunneling endoscopic resec-
tion (STER) and laparoscopic endoscopic cooperative surgery
(LECS) have broken the boundaries between medicine and
surgery and are rapidly evolving into areas beyond the GI
lumen. This paper gives an overview of recent procedural
and technological developments in the field.
Various liquids have been used for lifting. Hyaluronic acid
solution (MucoUP, Johnson and Johnson, Tokyo, Japan) cre-
ates a long-lasting submucosal cushion. However, due to its
high cost, it is not widely used. Another commonly used
agent in Japan is Glyceol (Chugai Pharmaceutical, Tokyo,
Japan), which consists of 10% glycerol and 5% fructose in
normal saline, combined with a small amount of sodium hya-
luronate. Hydroxypropyl methylcellulose (‘artificial eye
drops’), hydroxyethyl starch (Voluven
) and modified gelatin
plasma substitutes (Geloplasma
) are relatively
inexpensive solutions, mostly used in non-Asian studies.
Normal saline is inexpensive, and universally available, but
the lifting is of short duration in the range of only 5 min,
compared to, e.g., hydroxyethylic starch, with about 30 min
CONTACT Georgios Mavrogenis email@example.com Kavetsou 10, 81132, Mytilene, Lesvos, Greece
!2016 Informa UK Limited, trading as Taylor & Francis Group
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2016
mean elevation time . NaCl 0.9% is commonly used with
the Hybrid Knive (ERBE Elektromedizin, Tuebingen, Germany)
due to the possibility of fast and repeated injections, as
necessary. A small amount of Indigocarmine 0.2% (0.5 ml in
500 ml of solution) should be added to the injection solution,
in order to better delineate the submucosal plane. For lesions
close to the dentate line, lidocaine (1%) or ropivacaine
(75 mg)  is added to the solution for local anesthesia.
Irrigation of the dissection plane
A water pump is an indispensable accessory since irrigation
of the bleeding permits faster and accurate coagulation. The
waterjet pump is connected either to the jet channel of the
endoscope, to a modified valve at the biopsy channel or to a
modified irrigation hood (Type KUME, Create Medic, Japan).
Lately, newly developed endoknives provide a multi-
purpose jet function designed for irrigation of the tip of the
knife, of the operation field and for submucosal injection.
In this case a second water pump can be connected to the
accessory channel of the knife. However, if a second pump is
not available, then a single pump may be used for both
functions, by adding a three-way port.
Insufflation with CO
has become a prerequisite for most
ESDs, allowing the use of fewer sedative medications and
reducing the risk of compartment syndrome following perfor-
is strictly obligatory for POEM and STER
A transparent hood facilitates visualization during dissection
by keeping the field ‘open’during dissection. In addition,
transient compression of a bleeding vessel can help during
hemostasis. The choice of the hood depends on the diameter
of the endoscope, the location of the lesion and endo-
scopist’s preference. Attention should be paid to ensure that
the cap is fixed tightly at the tip of the endoscope and if
necessary stabilized with a sterile tape.
Tables 1 and 2present different endoscopes often used for
ESD. The morphology of the lesion, its location, the type
of endoknife, and the bleeding risk, influence the choice
of instrument. The ideal endoscope should possess a high-
definition image with close focus and magnification for easier
determination of lateral margins and better characterization
of the microvascular pattern. A large biopsy channel
(>2.8 mm) is preferred by some endoscopists, since aspir-
ation of blood or water becomes easier. A potential disad-
vantage of a large channel is the loss of precise control of
instruments (e.g., endoknives, forceps) with small caliber due
to inadvertent movement. Finally, a water jet channel is
undoubtedly desirable for cleaning of oozing and debris
Table 1. Technical characteristics of gastroscopes suitable for ESD procedures.
Manufacturer Olympus Olympus Olympus Olympus Pentax Pentax Pentax Fujifilm Fujifilm Fujifilm
Model name GIF-HQ290 GIF-HQ190 GIF-1TH190 GIF-2TH180 EG27-i10 EG29-i10 EG-3890TK EZ-600ZW EG-580RD EG-530D
Field of view (degrees) 140 140 140 140 140 140 140 140 140 140
Depth of field (mm) 3–100 2–100 2–100 2–100 2 –100 2–100 4–100 1.5–100 3–100 3–100
Biopsy channel(s) (mm) 2.8 2.8 3.7 2.8/3.7 2.8 3.2 2.8 and 3.8 2.8 3.2 2.8/3.8
Angulation range (degrees)
Up 210 210 210 210 210 210 180 210 210 210
Down 90 90 90 90 120 120 120 90 120 90
Right-Left 100 100 100 100 120 120 120 100 100 100
Distal end diameter (mm) 10.2 9.9 10 12.2 9.2 9.9 12.8 9.9 9.8 11.5
Water-jet Yes Yes Yes Yes No Yes Yes Yes Yes Yes
Close focus Yes Yes Yes Yes Yes Yes No Yes Yes No
Manual Zoom Optical Optical No No No No No Optical Digital No
Chromoendoscopy NBI NBI NBI NBI i-scan i-scan no FICE FICE No
Compatible processor CV-290/CLV-190 CV-190/CVL-190 CV-190/CLV-190 CV-180/CLV180 EPK-i5000/i7000 EPK-i5000/i7000 EPK-100p EPX-4450HD/3500HD EPX-4450HD/3500HD EPX-4450HD/3500HD
Featured endoscopes possess at least one major characteristic: latest image sensor, large biopsy channel or two channels. Disclaimer: this is not an extensive list. Some endoscopes are not available in all countries.
2 G. MAVROGENIS ET AL.
during dissection. Endoscopes like the Olympus GIF-1TH190
(Japan), the Pentax EG29-i10 (Japan) and the Fuji EG580RD
(Japan) combine high-definition imaging, closed focus, water
jet capabilities and a large channel (3.7 and 3.8, respectively).
The latest Fujifilm 600 series and Olympus HQ series provide
a manual zoom option capable of impressive microvascular
pattern analysis. However, not all endoscopic suites have the
luxury to afford the price tag of a high-end endoscope and
compromises are usually made. For standard endoscopes
with a 2.8 channel but without water jet channel, the add-
ition of a valve with a lateral water pump connection may
overcome this default. Double-channel endoscopes provide
the advantage of easier suction and may accelerate the pro-
cedure since the second channel can be used for insertion of
an additional instrument (needle, clip or coagulation forceps).
However, double-channel endoscopes often lack the image
quality of latest series and have a wider distal end, which is
not desirable when moving into tight spaces. A multibending
double-channel endoscope by Olympus, also known as R
Scope, offers additional flexure in front of the normal flexure
. However, its use in routine endoscopy has not been
ESD requires a high-frequency generator with an automatic-
ally controlled system. Most published ESD cases have been
performed with the ERBE ICC200, ERBE VIO 200/300 series
or Olympus ESG-100. These units have a sensor that can
control the power automatically and adjust to the circum-
stance achieving smoother and safer dissection. Table 3
illustrates suggested settings for ESD based on the authors’
ERBE VIO200S and VIO200D
VIO200 devices offer the following modules: The ENDO CUT
mode fractionates the cutting process into controlled cut-
ting and coagulation intervals and is used for both incision
and dissection. The operator can adapt the desired intensity
of coagulation based on the thickness of the intestinal wall
and the risk of bleeding (Effect 1: no coagulation, Effect 2:
soft coagulation, Effect 3: fast coagulation, Effect 4: maxi-
mized coagulation; commonly set at 2–3) and the duration
of the intervals. SOFT COAG is applied for marking and
selective hemostasis with a hot biopsy forceps (80W).
FORCED COAG is suitable for marking (20W) and hemostasis
of smaller vessels with the cutting electrode of the endo-
knife (30–60 W). VIO200D has two additional modules not
available to VIO200S: DRY CUT and SWIFT COAG. DRY CUT
provides more cutting and coagulation effect than ENDO
CUT and is used for both incision and dissection (Effect 2,
30 W). SWIFT COAG has a smaller cutting effect than DRY
CUT, while its coagulation power is situated between that
of FORCED COAG and DRY CUT. It can be used for dissec-
tion (effects 3–4, 50 W). VIO200D is supplied with a foot
pedal that has an additional button for changing among
the pre-saved settings.
Table 2. Technical characteristics of latest coloscopes suitable for ESD procedures.
Manufacturer Olympus Olympus Olympus Pentax Pentax Fujifilm Fujifilm Fujifilm
Model name CF-HQ290 CF-HQ190 PCF-H190 EC38-i10 EC34-i10 EC-600WL EC-600LS EC-600ZW/L
Field of view (degrees) 170 170 170 140 140 140 170 140
Depth of field (mm) 4–100 2–100 2–100 4–100 2–100 2–100 2–100 1.5–100
Biopsy channel(s) (mm) 3.7 3.7 3.2 3.8 3.8 3.8 3.8 3.8
Angulation range (degrees)
Up 180 180 180 180 180 180 180 180
Down 180 180 180 180 180 180 180 180
Right-Left 160 160 160 160 160 160 160 160
Distal end diameter (mm) 13.2 13.2 11.7 13.2 11.5 12 11.5 12.8
Water-jet Yes Yes Yes Yes Yes Yes Yes Yes
Manual Zoom Optical Optical No Optical Optical No No Optical
Chromoendoscopy NBI NBI NBI i-scan i-scan FICE FICE FICE
Length (mm) L:2005, I:1655 L:1680, I:1330 L:2005, I:1.655 L:2016, F:1816, M:1616 L:2016, F:1816, M:1616 L:1990, I:1820, M:1630 1630 L:1990, M:1630,
Compatible processor CV-290/CLV-190SL/CLV-190 CV-190/CLV-190 CV-190/CLV-190 EPK-i5000 EPK-i5000 EPX-4450HD/3500HD EPX-4450HD/3500HD EPX-4450HD/3500HD
Disclaimer: this is not an extensive list. Some endoscopes are not available in all countries.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 3
This is an upgrade of the VIO200D series that offers the add-
itional module of SPRAY COAG. This effect applies a non-
contact coagulation effect (stronger than FORCED COAG)
with low-penetration depth. It can be used for both sub-
mucosal dissection and hemostasis of diffuse bleeding.
This unit has been replaced by the VIO series. Available mod-
ules for ESD are that of ENDOCUT, SOFT COAG and FORCED
ESG-100 has two settings for incision and/or dissection (Pulse
Cut Fast and Slow). These modes alternate a cutting phase of
15 ms (Fast mode) or 800 ms (Slow mode). Coagulation
modes include: ForcedCoag1, ForcedCoag2 and Soft Coag.
ForcedCoag1 is a fast superficial pinpoint coagulation used
for coagulation of small vessels with the tip of the knife.
ForcedCoag2 is a cutting current used for dissection. An
interesting feature is the presence of a third button at the
footswitch that triggers the water jet.
Several ESD knives are available based on the location of
lesion (esophagus, stomach, colon, rectum), the aspect of the
lesion (sessile, flat, submucosal), the level of fibrosis and the
axis of the knife in relation to the dissection plan (parallel or
vertical to the lesion). Endoknives may be divided in three
basic categories. Tip cutting knives have a needle-knife
extremity that can be used for marking, cutting, dissection
and hemostasis (Figure 1). Blunt-tip knifes consist of an insu-
lated tip that prevents coagulation of the muscle layer
(Figure 2). Although not suitable for marking, submucosal
dissection may be faster. Most recently, scissor-type knives
have emerged (Figure 3) and have been used for all steps of
ESD at various locations. However, their use is not yet wide
Tip cutting knifes
DualKnife (Olympus, Japan) was developed by Yahagi. It fea-
tures a tiny non-insulated dome-shaped electrode at the tip
of the knife of 1.5 mm (for the esophagus and colon) or
2 mm (for stomach), with two different working lengths of
1.6 or 2.3 m. The knife length can be fixed in two positions:
retracted or extended. In the retracted position, the length of
Figure 1. Tip cutting endoknives. (A) DualKnifeJ (B) B-Knife (C) Flush Knife BT (D) ESD AqaNife (E) FlexKnife (F) Splash M-Knife (G) HookKnifeJ (H) Triangle Tip Knife
(I) Ksnare (J) Endo FK (K) Hybrid Knife I-type (L) Hybrid knife T-Type (M) Optimos.
Table 3. Electrocautery settings for tip-cutting endoknives (e.g., DualKnife).
Incision Dissection Hemostasis with forceps Marking
Olympus ESG-100 Pulse Cut Slow, 25–40W
Forced Coag2, 30W
Pulse Cut Fast, 30W
Forced Coag1, 40W
Forced Coag2, 50W
Soft Coag, 80W Forced Coag1, 20–30W
Soft Coag, 50W
ERBE VIO200/300 ENDOCUT I or Q E1, D3, I3
DRY CUT, E2, 30W
ENDOCUT I or Q E2-3, D2, I 2-3
DRY CUT, E2, 30W
FORCED COAG E2, 40W
SWIFT COAG, E2, 40–50W
SOFT COAG, E5, 80W
SWIFT COAG, E2-4, 50W
SOFT COAG, E5, 50-80W,
FORCED COAG, E2, 20W
SWIFT COAG, E2, 50W
ERBE ICC200 ENDOCUT E2-3, 120W ENDOCUT E2-3, 120W SOFT COAG, 80W FORCED COAG, 20W
Disclaimer: these settings represent the authors’suggestion and should be individualized according to the site of dissection, the type of lesion and available
equipment. It is strongly advised to check the coagulation effect on healthy tissue and adapt the settings accordingly prior to use.
SPRAY COAG is only available in ERBE VIO 300D series. E: Effect; D: duration; I: interval.
4 G. MAVROGENIS ET AL.
the exposed tip measures 0.3 mm. A new version with water
jet function is currently available (DualKnifeJ).
FlexKnife (Olympus) was developed by Yahagi. This knife
features a braided 0.8 mm cutting knife with a looped tip
adjusted to different lengths, suitable for marking, incision
and dissection. The distal end of the sheath, which functions
as a stopper, was designed to prevent perforation by allow-
ing better control of the cutting depth.
Flush Knife (Fujifilm, Japan) was developed by
Toyonaga. There are 13 variations of this knife according
to the length of the needle knife (1, 1.5, 2, 2.5 or 3 mm),
with the presence or absence of a ball tip and the length
of the catheter (1.8 and 2.3 m). The main advantage of
this knife is the water-jet capability (thus the name
‘flush’), which is designed to clean the operation field, the
tip of the knife and most importantly reestablish the sub-
mucosal fluid cushion in the submucosa. It is often used
in combination with viscous substances such as hydrox-
yethyl starch 6%.
HookKnife (Olympus) was developed by Oyama and
Kikuchi. This knife has an L-shaped cutting wire, designed to
hook tissue and pull it away, to minimize the risk of damage
of the muscle layer. The orientation of the hook is changed
by rotating the handle. It is particularly useful for fibrotic
areas, and when the endoscope is positioned in front of and
against the lesion . A new version with a jet function will
be soon available (HookKnifeJ).
Triangle Tip Knife (Olympus) was developed by Inoue and
Kudo. This knife features a conductive triangle tip. Its design
is suitable for marking, incision and dissection. It became
popular with the introduction of POEM since it facilitates
grasping and dissection of muscular fibers. However, it is less
commonly used for ESD procedures due to the larger size of
Figure 3. Scissor Type knives and coagulation forceps (A) SB Knife (B) Clutch Cutter (C) Maryland (D) Coagrasper (E) HemoStat-Y.
Figure 2. Blunt tip knives. (A) IT2 Knife (B) IT nano (C) Mucosectom (D) Swanblade (E) Hybrid Knife O-Type (F) Safe Knife V.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 5
Hybrid Knife (ERBE). This is a multifunction knife that can
be used for marking, incision, dissection and most import-
antly submucosal injection. This later feature is provided by a
central capillary within the knife that can serve as an ultrafine
120-lm water jet when coupled with a foot pedal-activated,
computerized jet lavage unit (ERBEJET 2 System, ERBE).
Three versions are commercialized: The I-Type (needle type
with adjustable length), the T-Type (with a disc-shaped non
insulated tip) and the O-Type (presenting an insulated hemi-
spherical, dome-like tip similar to the IT2 Knife). Attention
should be paid when used with spray coagulation, since car-
bonized tissue may obstruct the water-jet canal.
B-Knife (Xemex, Zeon Medical, Japan). This is a ball-tip
bipolar knife with a water-jet function that does not require a
counter-electrode plate. Burning of the muscularis propria
layer is considered to be less with this knife than with other
monopolar knives .
ESD AqaNife (Ovesco, Germany). This is a needle-type knife
with a straight needle and a ceramic sheath. The needle
length is available in 1.5, 2, 2.5 and 3 mm. It incorporates a
flushing channel for irrigation and submucosal injection.
Splash M-Knife (Pentax). This is tip-cutting knife with jet
function. The blade contains a metal disk that is used to
hook tissue and provide clear marking.
Optimos (Taewoong, South Korea). The Optimos knife has
a 1.9 mm wide and 2.5 mm long anchor-shaped tip which
can be rotated with the help of a dedicated button. It has a
water-jet function and it can be used for all steps of ESD .
Endo FK (Kachu Technology, South Korea). EndoFK is a
multifunction knife that can be used for all steps of an ESD pro-
cedure . It consists of two interchangeable knives, a fixed
flexible snare similar to the FlexKnife and a forked knife, which
form a single working unit, and has an inlet for material injec-
tion or saline irrigation during the procedure. The knives can
be changed during a procedure by using two switches.
Ksnare (Pentax, Japan). This knife consists of a snare with
a modified tip designed for circumferential incision-trimming
and then snare-resection of the retracted lesion (Hybrid-ESD).
This concept is of particular use for lateral spreading adeno-
mas of the colon.
Blunt tip knives
IT Knife 2 (Olympus) was developed by Hosokawa and
Yoshida. This knife has a ceramic tip at the distal end of
the device, which is insulated, to help prevent damage of
the muscle layer. Dissection is performed in vertical or hori-
zontal direction with the help of an electrode situated at
the proximal side of the ceramic tip. Dissection using this
knife is fast due to the large amount of tissue dissected at
once by the long blade and attention should be made for
inadvertent perforation . Since visualization of the dissec-
tion plan is less optimal than with needle knifes, its use is
preferred for gastric lesions and especially when a drooping
flap has been created.
IT Knife nano (Olympus). This knife is similar to the IT2 but
with a smaller ceramic tip and electrode. These modifications
make it attractive for organs with thinner submucosal layer
such as the esophagus and colon.
Mucosectom (Pentax) was developed by Kawahara. It com-
prises a rotatable, (rotating) non-conducting plastic shaft, and
a 5-mm cutting wire, located at the side of the plastic shaft.
It can be used for incision, dissection and hemostasis.
Swanblade (Pentax). This novel knife has a round, snare-
like rotating tip on one side of the sheath. It can be used for
marking and dissection.
Hybrid Knife-O type (ERBE), see above.
Safe Knife V (Fujifilm) was developed by Yamamoto. The
Safe Knife V has a sandwich-like structure with a central elec-
trode-plate placed between insulated plates. It enables dis-
section of the submucosal layer with a vertical approach.
Scissor type knives
Clutch Cutter (Fujifilm) was developed by Akahoshi. This is a
scissor-like electrosurgical knife with the ability to grasp, pull,
coagulate and incise the targeted tissue using electrosurgical
current. It has a 0.4 mm-wide and 3.5 mm or 5 mm long ser-
rated cutting edge to facilitate grasping tissue. The outer
side of the forceps is insulated to avoid unintentional dam-
age of the muscle layer.
SB Knife (itomo Bakelite, Japan). This knife incorporates a
centrally positioned 1.2 mm electrode, surrounded by an
electrically insulating coating. Three versions are available:
one with a 7 mm blade for the stomach (standard type), a
6 mm blade for the esophagus (short type) and an even
smaller version for colorectal applications (Jr Type) .
Endo-Maryland Dissector (Ovesco). The tip design is ins-
pired by laparoscopic surgical instruments. Dissection with
Maryland can be performed in several ways including dissec-
tion by opening the jaws or by grapsing and pulling the sub-
mucosal tissue with or without electrocautery. It requires a
biopsy channel of at least 3.2 mm .
Basic steps of ESD
Demarcation of the borders
The lateral extension of the lesion is evaluated by means of
high-definition endoscopy, zoom endoscopy, virtual chro-
moendoscopy and spray chromoendoscopy. Squamous cell
carcinomas and dysplasias are easily demarcated with virtual
chromoendoscopy such as Narrow Band Imaging or 0.75%-1%
iodine dye spray (Lugol’s iodine). Barrett’s esophagus and flat
gastric lesions are studied with acetic acid, methylene blue or
indigo carmine (Figure 4). Colorectal lesions are usually stained
with indigocarmine and/or crystal violet for analysis of the
microvascular pattern under magnification. Improved digital
chromoendoscopy capabilities of modern endoscopes often
allows the endoscopist to delineate the lesion without the
need of dye spraying, as lugol and blue solutions often impair
vision when they are mixed with blood.
Marking is performed with a 5 mm safe margin with intermit-
tent and short application of coagulation. For circumferential
6 G. MAVROGENIS ET AL.
lesions circular dots reveal the anal and oral margins.
Instruments used for marking include tip cutting knives
(FORCED COAG, effect 2, 20W or SOFT COAG, effect 4,
50–80W or SWIFT COAG effect 2, 40w), the tip of a snare,
needle knife used for sphincterotomy or argon plasma
coagulation. In order to avoid excessive coagulation of the
mucosa, we usually test coagulation settings at a distant nor-
mal area of the mucosa. Marking is performed in gastric
lesions and esophageal lesions, but it is rarely used in colo-
rectal lesions because of a clearer margin.
A solution is injected to the submucosal layer prior to the
mucosal incision. Optimal elevation of the submucosal layer
is crucial for safe submucosal dissection. The above-men-
tioned injection agents are used for submucosal injection.
Often a 23–25G needle with a transparent stopper is used
(e.g., Interject, Boston Scientific, Natick, MA, USA). In order to
avoid ‘seeding’of potentially malignant cells injection
through the lesion is avoided.
Incision of the periphery and trimming
Marking of the periphery is followed by circumferential inci-
sion outside the marked area. Sometimes only the proximal
and distal side are incised, in order to avoid excessive loss of
submucosal solution. Incision of the mucosa is followed by
incision of the muscularis mucosa (trimming), which results
in retraction of the lesion. This step prepares the access to
the submucosal layer underneath the lesion. Incision is per-
formed with a tip cutting knife or a blunt tip knife. However,
this later option usually precludes the creation of at least
two mucosal entrance holes at the oral and anal side of the
lesion. Then, the blunt tip knife is inserted into the distant
hole and the endoscope progressively retracted or moved
laterally. This method achieves fast incision and is particularly
useful when the axis of the knife is vertical to the lesion.
However, visibility is less optimal. Usual settings for mucosal
incision are ENDOCUT Q/I, Effect 2, cutting duration 3, cut-
ting interval 3 or DRY CUT Effect 2–3, 80W.
Two elements are crucial for successful and easier submuco-
sal dissection: the direction of gravity and the detection of
the easiest point of access. If appropriate, countertraction
measures are taken for better exposure of the dissection
plane. Cutting of the submucosal fibers is performed with
precision under good visualization and abundant submucosal
lifting. Deciding ‘where to cut’maybe confusing and is the
riskiest part of the procedure. The axis of the tip of the cut-
ting knife should be parallel or oblique to the muscularis
area; The pedal is usually pressed intermittently, particularly
when visualization is suboptimal; the submucosal fibers
should be hooked and retracted before cutting and visible
vessels coagulated before dissection; repeated back and for-
ward movements are undertaken as long as the submucosal
plane is exposed conveniently, before changing the access
point. For circumferential lesions of the esophagus or rectum,
the tunneling technique maybe useful .
Small vessels comparable to the thickness of the knife can be
directly coagulated before cutting (FORCED COAG, 20–30W).
Larger vessels should be coagulated with a small biopsy for-
ceps such as the Coagrasper (Olympus) or the HemoStat-Y
(Pentax), either with the tip of the closed forceps (for small
vessels) or after grasping and retraction (SOFT COAG, 70-80
watt). Excessive coagulation may traumatize the muscular layer
and carbonize adjacent tissue. For this reason larger vessels
Figure 4. Basic steps of an ESD procedure (A) Flat intramucosal adenocarcinoma of the gastric body. (B) Spray chromoendoscopy with indigo carmine reveals the
lateral borders. (C) Marking is followed by incision and trimming of the periphery (D) Submucosal dissection with a 2 mm DualKnife. (E) Small vessels are coagulated
with the tip of the knife. (F) Larger vessels are grasped and coagulated with the Coagrasper. (G) Inspection of the artificial ulcer for residual vessels and injuries of
the muscle layer. (H) Clipping of the defect in a zipper fashion.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 7
are isolated before coagulation by dissecting the surrounding
tissue and/or by creating a sufficient submucosal cushion.
Finally, spray coagulation can be applied for diffuse capillary
oozing with the tip of the cutting knife.
The key element for a successful, easier and faster ESD pro-
cedure is the convenient exposure of the dissection plane.
Gravity should be taken into consideration and the patient’s
position changed accordingly. In addition, a variety of trac-
tion techniques have been published in an effort to
improve visualization and access of the submucosa. Each
technique has advantages and disadvantages. However, the
clip with line method is probably the easiest and most cost
Conventional devices and techniques for traction
Clip with line. This is a simple traction technique using a
hemoclip and a silk suture or dental floss [12,13]. A hemoclip
is inserted into the endoscope and then the dental floss or
suture line is tied at the base of one arm of the clip.
Subsequently, the clip is withdrawn inside the cap and the
endoscope is advanced to the target lesion. Then the clip is
anchored to a mucosal flap for traction. The anchoring site
depends on the location of the lesion. In gastric lesions
approached in a retro position, the clip is anchored at the
anal side of the lesion. For lesions that are dissected in a
straight position, the clip is anchored at the oral side.
Creation of a mucosal flap is strongly suggested before
deployment of the clip, in order to avoid grasping part of
the active submucosal plane, which will complicate further
dissection. The efficacy of this technique on reducing the
overall time of a gastric ESD was studied in 43 matched
cases and showed a mean gain of at least 30 minutes per
Clip and snare. A clip is deployed on the mucosal flap
which is subsequently grasped with an external polypectomy
snare that changes the axis of countertraction by pulling or
pushing the snare [4,14,15]
Clip-Flap. This is a simple technique that helps the cre-
ation of a mucosal flap (Figure 5). After incision, one or more
clips are placed at the edge of the lesion. The effectiveness
of this technique was recently demonstrated in a large study
with colorectal lesions .
Use of external forceps. A grasping forceps is advanced
through the secondary channel of a dual channel endoscope,
which is used to grasp an auxiliary external bendable forceps.
This is later used for traction .
Thin endoscope-assisted ESD. In this technique a second
thin endoscope (<7 mm) is inserted and the edge of the
lesion is slightly elevated using a biopsy forceps or a snare
according to the size of the flap [18,19].
Double-channel scope method. Grasping forceps is inserted
into the second channel of a double-channel endoscope in
order to create traction. Even though the concept is good,
the forceps moves synchronously with the scope, thus
changing the direction of traction during dissection.
Furthermore, double-channel endoscopes have a bigger size,
making them inconvenient for tight spaces .
Endolifter (Olympus). This device consists of a modified
cap, available in two different diameters of 13.85 and
14.95 mm that possesses an accessory channel at 12 o’clock
which enables manipulation of an external bending biopsy
forceps used for tissue traction .
Figure 5. Clip-flap technique. (A) Lateral spreading tumor non-granular type of the transverse colon. Before performing ESD, the lesion is moved upward against
gravity. (B) After partial peripheral incision from the anal side, (C) a clip is positioned at the edge of the exfoliated mucosa. The tail end of the clip falls towards the
colonic lumen due to gravity. (D) The distal attachment is inserted under the clip, and then the exfoliated mucosa is lifted and the submucosal layer is clearly visual-
ized. At the moment, the clip applies counter-traction to the submucosal layer and facilitates the creation of the mucosal flap. In addition it serves as a grip for the
cap. (E, F) Complete resection of the lesion.
8 G. MAVROGENIS ET AL.
Suture pulley method. In this technique, countertraction is
applied by suturing the mucosal flap on the opposite gastric
wall proximally or distally to the lesion . By pulling the
tail of the suture, the tension of the traction can be modified.
Although attractive, the main limitation of this method is the
need of a double-channel endoscope and its higher cost.
Percutaneous traction. A small snare is introduced into the
gastric lumen through a percutaneous gastric port (2-mm
diameter), to grasp and pull the lesion away from the muscu-
laris propria, thus facilitating resection .
Experimental techniques/devices for traction
Overtube with built in side channel. This device is designed to
improve traction for esophageal ESD. An overtube with a
side channel is advanced over the scope, thus creating an
accessory channel that can be rotated independently of the
axis of the endoscope .
Magnetic countertraction. A small magnet is fixed with two
clips at the mucosal flap. Traction is applied with an external
larger marker, which is moved according to the desired direc-
tion of traction .
Overtube with manipulatory arms. This device consists of
an 18 mm in diameter overtube with 2 arms at the tip of the
device which are independently manipulated. Such a device
enables bimanual tasks to be performed with one instrument
used to hold the tissue and a second instrument used for
Closure of artificial ulcers-perforations
Closure of the post-ESD ulcer is a matter of debate and no
guidelines exists on best practice. However, in high risk
patients with large lesions, under antiaggregation/anticoagu-
lation treatment and/or injuries of the muscle layer, several
techniques have been described to reduce the risk of late
perforation, bleeding and decrease the hospital stay. Clipping
of large defects in a sequential zipper fashion can be cum-
bersome or even impossible. Alternative options include the
use of a double-channel endoscope with an endoloop and
clips, a figure of 8-shaped stainless clip in combination
with clips, a nylon string loop attached to a clip, over-the
scope-clips, the overstitch endoscopic suturing device, tissue
shielding with polyglycolic acid sheets and fibrin glue and
Two simple and cost-effective ways of closure of wide
mucosal defect are (a) the technique of lateral incision and
clips illustrated in Figure 6 [28,29] and that of double-layer
suturing . This later is carried out in two steps. First an
initial set of 3–4 hemoclips are applied at the center of
Figure 6. Closure of an artificial ulcer with lateral incisions and clips (A) Early gastric cancer of the angulus (Paris IIb þIIc, Tis) (B) Post-ESD mucosal defect. Small
incisions (holes) are made using a DualKnife around the lateral borders (asterisks). C The extremity of the first clip is ‘anchored’into the hole (arrow) and the muco-
sal border is dragged towards the opposite mucosal border (D) The other arm of the clip is inserted into the opposite hole and then it is deployed (E, F) After place-
ment of two clips using the aforementioned method, the remaining gap is clipped in a conventional zipper fashion. Used with permission from reference .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 9
the ulcer. Now that the ulcer has been shrunk and the
edges of the mucosal defect are closer to each other, a
second set of clips is deployed in the spaces between the
previous clips. In practice, closure of a 4-cm defect needs
"10 conventional clips.
Most recently, a promising suturing method was intro-
duced for the closure of large artificial ulcers, with the help
of a single channel endoscope, a slip knot string and stand-
ard clips . A slip knot loop is anchored onto the mucosal
defect’s proximal margin with a clip. Additional clip anchored
the slip knot loop and is placed at the opposite side of the
margin. The slip knot loop is tightened by pulling the string.
Additional clips are placed to achieve complete closure.
Moreover, a modified clip and snare technique has been
described for the closure of large defects. A pre-looped snare
over the endoscope is tightened over a deployed clip at the
margin of the defect and provides appropriate countertrac-
tion for further closure in a zip fashion .
Indications for ESD in Japan and Europe
Early squamous cell carcinoma of the esophagus
ESGE recommends ESD for superficial esophageal squamous
cell cancers without signs of submucosal involvement, if en
bloc resection is probable . According to the Japan
Esophageal Society, the absolute indication for endoscopic
resection is defined as flat lesions (Paris 0 –II) and circumfer-
ential extent of #2/3 and is considered curative in case of
m1–m2 invasion, therefore with a depth infiltration not
exceeding the lamina propria layer . Endoscopic resection
alone is acceptable in surgical high risk cases when infiltra-
tion involves m3–sm1 esophageal squamous cell cancer even
exceeding an extent $3
4of the circumference but without
lymphatic or vessel infiltration [1,33].
The role of ESD in the management of Barrett’s esophagus is
debated due to the satisfactory results obtained by standard
endoscopic mucosal resection techniques for the resection of
visible lesions <1 cm in combination with other ablative
methods for the destruction of residual flat Barrett mucosa.
ESGE guidelines currently favor ESD only for selected cases,
such as lesions larger than 15 mm, poorly lifting tumors, and
lesions at risk for submucosal invasion .
Early gastric cancer
ESGE  and Japan Gastroenterological Endoscopy Society
(JGES)  recommend ESD for gastric lesions that accom-
plish the following criteria:
Macroscopically intramucosal (cT1a) differentiated carcin-
oma measuring less than 2 cm in diameter. The macroscopic
type does not matter, but there must be no finding of ulcer-
ation (scar); i.e., UL(–).
1. UL(–) cT1a differentiated carcinomas greater than 2 cm
2. UL(þ) cT1a differentiated carcinomas less than 3 cm in
3. UL(–) cT1a undifferentiated carcinomas less than 2 cm
4. Differentiated-type adenocarcinoma with superficial
submucosal invasion (sm1, #500 lm), and size #3 cm.
Figure 7. (A, B) Residual nodular mixed type granular lateral spreading adenoma with signs of grade F2 severe fibrosis (arrows), secondary to several previous piece
meal snare resections (C, D) Initial incision with a DualKnife was performed at the normal mucosal away form the fibrotic area. (E, F) Dissection was copious due to
the adherence of the submucosal layer to the muscular layer. At the end of the procedure, a clip was deployed to close a tiny wall defect.
10 G. MAVROGENIS ETAL.
When vascular infiltration is absent together with the
above-mentioned criteria, the risk of lymph node metastasis
is extremely low, and it may be reasonable to expand the
indications. If a lesion falls within the indication criteria at
the initial ESD or endoscopic mucosal resection, subsequent
locally recurrent intramucosal cancers may be dealt with
under expanded indications.
ESGE suggests ESD for the removal of colonic and rectal
lesions with high suspicion of limited submucosal invasion
that is based on two main criteria of depressed morphology
and irregular or nongranular surface pattern, particularly if the
lesions are larger than 20 mm ; ESD can be considered for
colorectal lesions that otherwise cannot be optimally and rad-
ically removed by snare-based techniques, such as in cases of
extensive fibrosis or lesions larger than 3 cm (Figure 7). JGES
recommends ESD for the following indications :
1. Lesions for which en bloc resection with snare mucosal
resection is difficult to apply such as:
%Lateral spreading tumors –non granular type
%Lesions showing a V
–type pit pattern
%Carcinoma with shallow T1 submucosal invasion
%Large depressed-type tumors
%Large protruded-type lesions suspected to be
2. Mucosal tumors with submucosal fibrosis
3. Sporadic localized tumors in conditions of chronic
inflammation, such as ulcerative colitis
4. Local residual or recurrent early carcinomas after endo-
Current indications for endoscopic mucosal
resection (EMR) according to ESGE 
%EMR may be considered for superficial esophageal squa-
mous cell cancers without obvious submucosal involve-
ment that are smaller than 10 mm. However, even for
these cases ESD remains the first option.
%EMR is the treatment of choice for the excision of muco-
sal cancer in Barrett’s esophagus. ESD should be preferred
for lesions larger than 15 mm, with poor lifting and
lesions at risk for submucosal invasion.
%EMR is restricted for gastric lesions smaller than 10–15 mm
with very low probability of advanced histology.
%The majority of colonic and rectal superficials lesions can
be effectively removed with standard polypectomy and/or
EMR. ESD can be considered for lesions with high suspi-
cion of limited submucosal invasion or for those that can-
not be optimally removed by snare-based techniques
Hiki described first in 2008 an innovative procedure called
LECS that combined the strongest points of interventional
endoscopy and laparoscopic surgery for the removal of gas-
tric wall lesions. Following that, a series of other innovative
techniques such as inverted LECS, laparoscopic-endoscopic
full-thickness resection, clean non-exposure technique and
non-exposed wall-inversion surgery have emerged. When
performed by expert teams, they show a lot of promise and
achieve solid oncologic results. The reader is referred to a
recent detailed review describing the aforementioned techni-
POEM is the application of esophageal myotomy by utilizing
a submucosal tunneling method. Since the first case of POEM
was performed for treating achalasia in Japan in 2008 by
Inoue, this procedure is being expanding in western coun-
tries. Furthermore, the indications for POEM progress to
include long-standing, sigmoid shaped esophagus in achala-
sia, even previously failed endoscopic treatment or surgical
myotomy, and other spastic esophageal motility disorders
. A recent meta-analysis demonstrated comparable results
in terms of safety and short term efficacy between POEM
and surgical Heller’s myotomy . However, long-term
results are lacking. Several ongoing randomized trials com-
paring POEM to pneumatic dilatation and surgery will further
elucidate the role of POEM in achalasia.
Inspired by POEM procedures, Xu et al.  used working
space for endoscopic resections called STER. This technique
is applied for tumors up to 3.5 cm in size, since larger tumors
cannot be easily extracted from the submucosal tunnel. An
entrance hole is created 5 cm proximally to the lesion, and a
submucosal tunnel is extended beyond the lesion. For lesions
involving the muscularis propria, full thickness resection
maybe necessary. After removal of the lesion, the entrance is
closed with conventional clips.
Emerging applications inspired from POEM and ESD
Submucosal tunneling combined with myotomy has been
reported in the management of a variety of ‘functional’disor-
ders such as gastroparesis  and most recently Hirschprung
disease of the rectum . Furthermore, submucosal tunnel-
ing methods have been utilized for the recanalization of com-
plete post-radiation esophageal obstruction , for the
inversion of esophageal diverticulum and peritoneal sampling
. Other innovative applications include the management
of esophageal fistula  and reflux disease .
Training opportunities in Europe
The learning curve of ESD is long and includes multiple steps.
In addition, it should be restricted only for endoscopists with
appropriate skills such as patience, accurate orientation in the
operation field, precision and familiarization with the oncologic
principles of staging and postoperative management. The
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 11
training is initiated with ex-vivo and then in-vivo animal pro-
cedures in combination with the observation of many ESD
procedures. After familiarization with the available endo-
scopic tools, electrosurgical settings and management of
bleeding and perforation, the trainee is invited to perform
basic steps of the procedure in human cases under close sur-
veillance. Marking, peripheral incision and trimming are the
first steps followed by dissection and understanding the
orientation of the dissection plane. Only after acquaintance
of these ESD steps, the endoscopist should handle individual
cases under surveillance until obtaining full autonomy.
Usually, organs with thicker walls such as the stomach and
lower rectum are selected for the first cases.
Lately, several hands-on animal courses endorsed by the
ESGE have been organized in several countries including
Greece, Austria, Spain, Holland and Germany that are
addressed to beginners and more experienced ESD practi-
tioners. These workshops are of the utmost importance in
order to better perceive how to use different endoknives and
how to handle complications such as bleeding and perfor-
ation. Hopefully, national endoscopic societies will promote
official ESD training programs in the corresponding high vol-
ume centers of each country.
What to expect in the future?
Great efforts are made to improve actual equipment. Besides
Olympus, who developed the first ESD knives in 1998, several
new designs flooded the market in the past years and many
others are under evaluation in an effort to create the ‘swiss
army knife’of ESD, which will be accessible, easy to use, safe
and suitable for various applications. In addition, we expect
slimmer therapeutic endoscopes with the image quality of
diagnostic zoom endoscopes, and advanced flexibility proper-
ties permitting the endoscopist to access difficult points such
as the angulus and the gastric cardia. Other hot topics in the
ESD-related research field include new substances for long-
standing submucosal lifting, novel hemostatic and ‘ulcer-
healing’powders, easy to use suturing devices, novel counter-
traction techniques, augmented reality and robotic flexible
ESD incorporates a fascinating world of procedures and devi-
ces that constantly evolve. Besides sufficient training, familiar-
ization with available equipment and techniques is a
prerequisite for successful, safe and cost effective interven-
tion. Hopefully, additional training opportunities through ani-
mal and live workshops and also establishment of
reimbursement of the dedicated-material by national health
systems will make ESD more accessible in the West.
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SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 13