Advancements in endoscopic closure: Embracing a new era of managing complications and postprocedural defects after endoscopic submucosal dissection

Table 1 The characteristics of the most common endoscopic submucosal dissection complications[15,19,29-32,59,87,151-153]

Characteristic	The prevalence of ESD complication, %
	Gastric ESD	Colorectal ESD
Major immediate bleeding	10[19]	0.75[153]
Immediate perforation	2.3-3.7[29,30,87]	4.2-20.4[15,153]
Delayezd bleeding	4.1-8.5[29-32]	2.1-8.0[59,153]
Delayed perforation	0.1-0.45[87,151]	0.22[152]

ESD: Endoscopic submucosal dissection.

Table 2 Complication rates and risk factors in esophageal endoscopic submucosal dissection

Ref.	Country of origin	Intraoperative perforation rate	Delayed bleeding rate	Stricture rate
Tsujii et al[23]	Japan	5.2%	0%	7.1%
		Risk factors: Early treatment periods, low volume institutions		Risk factor: Circumferencial lesion
Yang et al[24]	United States	2.2%	6.5%	-
Iizuka et al[25]	Japan	1.2 vs 1.8%	0 vs 0.8%	20.8 vs 11%
				Risk factor: Age
Huang et al[26]	China	-	12.02%	-
			Risk factors: Hypertension, lesion diameter, submucosal fibrosis, C-reactive protein serum level, albumin serum level
Ishihara et al[27]	Japan	1.8%	0.6%	Risk factors: Tumor location, circumferencial lesion
		Risk factors: Tumor location, low volume institution
Shi et al[154]	China	-	-	11.6%
				Risk factors: Depth of invasion above m2, circumferential extension > 75%

Table 3 Complication rates and risk factors in gastric endoscopic submucosal dissection

Ref.	Country of origin	Intraoperative perforation	Delayed bleeding	Stricture risk
Hatta et al[38]	Japan	-	4.7%-5.0%	-
			RFs: Chronic kidney disease with hemodialysis, antithrombotic agents (aspirin, P2Y12RA, cilostazol, warfin, DOAC), multiple tumors, tumor size > 30 mm, tumor location in lower third
Suzuki et al[87]	Japan	2.3%	4.4%	-
Zullo et al[86]	Western countries	3.1%	5.8%	-
Yano et al[32]	Japan	-	8.5% (7.3% in the first 5 days)	-
			RFs in first 5 days: Tumor location in the distal stomach, expanded indications or non-indicated lesions, a specimen diameter of ≥ 40 mm, and antithrombotic therapy
			Risk factors after 5 days: Tumor location in the proximal stomach, hemodialysis, and antithrombotic therapy
Okada et al[37]	Japan	-	4.81%	-
			RFs in first 4 days: Size of the specimen, tumor location in the lower third of the stomach
			Risk factors after 4 days: Size of the specimen, tumor location in the middle third of the stomach, hypertension, high body mass index (≥ 25 kg/m2)
Miyahara et al[29]	Japan	3.7%	6.9%	-
		RFs: Tumor location, massive submucusal invasion, endoscopists’ experience of 100-149 cases and hypertension	RFs: Tumor location, tumor size, and scarred lesion
Toyokawa et al[30]	Japan	2.4%	5.0%	-
		RFs: Location in the upper area of the stomach	Risk factors: Age ≥ 80 years, long procedure time
Nam et al[31]	South Korea	-	4.1%	-
			RFs in the first 24 hours: Age ≤ 65 years, resection size ≥ 30 mm, procedure time ≥ 20 minutes, lower third of the stomach, erosion, clopidogrel use
			RFs after 24 hours: The middle to upper third of the stomach, undifferentiated carcinoma, erosion, high risk of stigma during second-look endoscopy, history of early PEB, clopidogrel use
Sumiyoshi et al[155]	Japan	-	-	Cardia: 21.3%
				Antrum: 3.2%
				RFs: More than 75% of the circumferential extent (both locations)
Coda et al[156]	Japan	-	-	Cardia: 17%
				Pyloric: 7%
				RF: Circumferential extent > 75%, longitudinal extent > 5 cm

RFs: Risk factors; P2Y12RA: Receptor antagonist; DOAC: Direct oral anticoagulants; PEB: Post-endoscopic submucosal dissection bleeding.

Table 4 Risk factors of postprocedural bleeding after gastric endoscopic submucosal dissection

Number	Risk factors of postprocedural bleeding after gastric ESD
1	Antithrombotic therapy (OR = 1.63)
2	Male sex (OR = 1.25)
3	Cardiopathy (OR = 1.54)
4	Cirrhosis (OR = 1.76)
5	Chronic kidney disease (OR = 3.38)
6	Tumor size > 20 mm (OR = 2.70)
7	Resection size > 30 mm (OR = 2.85)
8	Location in the lesser curvature (OR = 1.74)
9	Flat/depressed morphology (OR = 1.43)
10	Carcinoma histology (OR = 1.46)
11	Ulceration (OR = 1.64)
12	Procedure duration > 60 minutes (OR = 2.05)

ESD: Endoscopic submucosal dissection; OR: Odds ratio.

Table 5 Complication rates and risk factors in colorectal endoscopic submucosal dissection

Ref.	Country of origin	Perforation	Delayed bleeding
Albouys et al[59]	France	-	8.0%
			Risk factors: Age > 74 years, use of antihrombotics, rectal location, size > 50 mm, ASA score III or IV
Seo et al[60]	South Korea	-	2.9%
			Risk factors: Tumor location in the rectosigmoid colon, tumor size ≥ 30 mm, use of antiplatelet agents except for aspirin alone
Lim et al[91]	-	4%-8%	-
Tanaka et al[157]	-	4.7%	-
Kim et al[15]	-	20.4% risk factors: Tumor size, fibrosis	-
Saito et al[158]	-	Intraprocedural: 4.9%	-
		Delayed: 0.4%
		Risk factor: Tumor size > 5 cm
Akintoye et al[153]	-	Intraprocedural: 4.2%	2.1%
		Delayed: 0.22%

ASA: Acetylosalicylic acid.

Table 6 Management of immediate perforations - summary

Location and size	Management/device
Esophagus, < 2 cm	TTSCs
	OTSCs
Esophagus, > 2 cm	Endoscopic suturing
	Stenting with SEMS (only when primary closure is not possible)
Stomach, < 2 cm	TTSCs
	OTSCs
Stomach, > 2 cm	Endoscopic suturing
	Combined method: TTS clips + endoloop
Duodenum (type 2) diagnosed at the time of ERCP	TTSCs
	Consider additionally placing stent (fully covered SEMS) into the bile duct across the ampulla
Colon	TTSCs
	OTSCs
	Endoscopic suturing

TTSCs: Through-the-scope clips; OTSCs: Over-the-scope clips; SEMS: Self-expandable metallic stent; TTS: Through-the-scope; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 7 Specifications of endoscopic closure devices

Device	Specifications
TTS clip[78,94]	Intermediate strength
	Fast application but may be challenging in large defects
	Easy to deliver (beneficial in the right colon and in difficult locations)
	Good choice in defects smaller that 2-3 cm
	Alternative and combined methods are available
	Cost-effectiveness depends on the number of clips used but is usually well maintained
OTS clip[78,94,107,159]	Intermediate strength in 15 mm defects
	Low strength in 30 mm defects
	Medium prolonging of the procedure but its rather easy to apply after proper training
	The diameter of the tip of the scope is increased with additional device (16.5-21 mm) that has irregular edges - it may cause difficulty in an introduction of the scope through the larynx and strictures of all origins (including radiation)
	Poor visibility due to bleeding may make the application not possible
	May lead to stenosis
	Allows only one attempt to close the defect
	May inadvertently capture structures beyond the gastrointestinal wall as seen in the reports of unintended inclusion of organs and vessels adjacent to the target site
	The newly introduced OTSC cutting device (remOVE system; Ovesco) allows for the removal of a deployed OTSC. When cutting OTSC, the electric DC impulses are delivered by a special electric generator connected to the grasping device
	However, it is important to note that the OTSC cutting device has a 10- to 15-minute warm-up time before it can be used. Therefore, removing a misdeployed OTSC and deploying a second OTSC on the misfired location would entail a significant time lag
EHS[78]	Appropriate for defects larger than 2-3 cm
	Feasible in various locations and depths
	High strength and secure closure
	Takes more time and is difficult to perform (extensive training is appropriate)
Overstitch[94]	High strength and secure closure
	Takes more time and is difficult to perform (extensive training is appropriate)
	May inadvertently capture structures beyond the gastrointestinal wall as seen in the reports of unintended inclusion of organs and vessels adjacent to the target site
	Is significantly more expensive than other devices
X-tack Helix[94]	Most beneficial in superficial defects smaller than 3 cm, but can be applied in more advances ones
	Low strength
	Medium prolonging of the procedure
	Application may be challenging
	May be removed with fully rotatable rat tooth forceps
	Cost-effective in specific indications

TTS: Through-the-scope; OTS: Over-the-scope; OTSC: Over-the-scope clip; DC: Direct current; EHS: Endoscopic hand suturing.

Table 8 Characteristics of the most common through-the-scope clips

Clip and brand	Brand	Arms span	Reopening/repositioning	360 degree rotation	Retention period	MR safety	Additional information
Resolution™	Boston Scientific, Marlborough, MA, United States	11 mm	5 times	-	4-8 weeks	+	-
Resolution™ 360		11 mm	5 times	+	4-8 weeks	+	Nurse/technitian controlled rotation using control knob and physician controlled rotation using a braided catheter
Resolution™ 360 Ultra		17 mm	5 times	+	4-8 weeks	+
QuickClip2™	Olympus, Tokyo, Japan	9 mm	No repositioning	+	9.4 days	Unsafe	-
QuickClip Pro™		11 mm	5 times	+	1-2 weeks	Conditional	-
Retentia™		9 mm/12 mm/16 mm	Unlimited	+	No data (new device)	Conditional	-
EZ Clip™		7 mm/9.5 mm/11 mm	No repositioning	+	-	Conditional	Reloadable clip applicator
Instinct Plus™ Clip	Cook Medical, Bloomington, IN, United States	16 mm	5 times	+	1-3 weeks	Conditional	-
LOCKADO™	MicroTech Endoscopy, Micro-Tech, Ann Arbor, Michigan, United States	8 mm/11 mm/16 mm/(22 mm)	Unlimited	+	Limited data, probably 1-3 weeks	+	Indications: Mucosal and submucosal defects smaller than 30 mm, bleeding ulcers and polyps smaller than 15 mm, luminal perforations smaller than 20 mm in the GI that can be treated without surgery
SureClip™		8 mm/11 mm/16 mm	Unlimited	+	2-4 weeks	Conditional	A shorter stem
EcoClip		8 mm/11 mm/16 mm	Unlimited	+	1-2 weeks	Conditional	-
DuraClip	Conmed Corporation, Utica, NY, United States	11 mm/16 mm	Unlimited	+	1-3 weeks	Conditional	A shorter stem (deployed part is 10 mm long)

MR: Magnetic resonance; GI: Gastrointestinal.

Table 9 Indications for through-the-scope clips

Number	Indications for TTS clips
1	Endoscopic marking
2	Hemostasis for: Mucosal/sub-mucosal defects < 3 cm, bleeding ulcers, arteries < 2 mm, polyps < 1.5 cm in diameter, diverticula in the colon, prophylactic clipping to reduce the risk of delayed bleeding post lesion resection
3	Anchoring to affix jejunal feeding tubes to the wall of the small bowel
4	Anchoring to affix fully covered esophageal self-expanding metal stents to the wall of the esophagus in patients with fistulas, leaks, perforations, or disunion
5	As a supplementary method, closure of GI tract luminal perforations < 20 mm that can be treated conservatively

TTS: Through-the-scope; GI: Gastrointestinal.