Endoscopic submucosal dissection: Challenges, innovations, and the road ahead

Table 1 Suggested indications for endoscopic submucosal dissection by the European Society of Gastrointestinal Endoscopy

Organ		Indications for ESD
Esophagus	Squamous cell carcinoma	HGD to well (G1) to moderately (G2) differentiated; Paris 0-II lesions; Absolute indications: M1-m2 involvement with 2/3 or less of the esophageal circumference; Expanded indications: M3 or sm
	Barrett’s esophagus	HGD to moderately (G1 or G2) differentiated T1a (m1-m3) lesions 15 mm (not amenable to en bloc resection by EMR); Patients with Barrett’s esophagus and the following features: Large or bulky area of nodularity; equivocal preprocedural histology; intramucosal carcinoma; suspected superficial submucosal invasion; recurrent dysplasia; and EMR specimen showing invasive carcinoma with positive margins
Stomach		Mucosal adenocarcinoma (and lesions with HGD), intestinal type, G1 or G2 differentiation, size < or 2 cm, no ulceration. Expanded indications: Adenocarcinoma, intestinal type, G1 or G2 differentiation, any size, without ulceration; adenocarcinoma, intestinal type, G1 or G2 differentiation, sm-invasive (< 500 μm); adenocarcinoma, intestinal type, G1 or G2 differentiation, 3 cm, with ulceration; and adenocarcinoma, diffuse type, G3 or G4 differentiation, size 2 cm, without ulceration
Colon and rectum		En bloc resection for lesions at risk for submucosally invasive cancer: Type V Kudo pit pattern, depressed component (Paris 0-IIc), complex morphology (0-Is or 0-IIaþIs), rectosigmoid location: Nongranular LST (adenomas), 20 mm in size granular LST (adenomas), 30 mm in size; Residual or recurrent colorectal adenomas

Endoscopic mucosal resection as first option for: Superficial lesion in Barrett esophagus; gastric (small lesion) < 10 mm, IIa, difficult for endoscopic submucosal dissection; duodenum colorectal nongranular/nondepressed < 20 mm or granular. ESD: Endoscopic submucosal dissection; LST: Laterally spreading tumor; HGD: High-grade dysplasia; EMR: Endoscopic mucosal resection; sm: Submucosal.

Table 2 Overview of innovative techniques in endoscopic submucosal dissection and their clinical advantages

Technique	Purpose/mechanism	Clinical benefit
Pocket creation method	Creation of a stable submucosal pocket before full incision	Maintains elevation, reduces perforation risk
Water pressure method	Saline infusion + water-jet pressure into submucosa	Enhances visibility, dissection precision
Clip-flap method	Endoclip replaces mucosal flap to open dissection plane	Improves access in fibrotic/complex lesions
Clip-with-line	Traction using string-connected endoclip	Enhances visualization, reduces procedure time
Pulley traction	Dual-directional clip system with external string redirection	Adjusts traction direction, useful in colorectal ESD
Loop clips/S-O clip	Loop with clip for traction without reinsertion	Simplifies complex ESD, effective for larger lesions
Line-assisted closure	Clip with nylon line to approximate tissue edges post-ESD	Enables complete defect closure in large ulcers
Loop clip closure	Loop structure aids in progressive closure with standard clips	Facilitates closure of wide defects
Clip-on-clip closure	Staggered clip placement to anchor and approximate tissue	Effective when standard clips slip
Mucosal incision around defect	Pre-incising around ulcer edges to improve clip grip	Improves clip fixation and wound approximation
Hand suturing (overstitch)	Endoscopic needle and suture system	Full-thickness closure, especially in difficult locations
Underwater clip closure	Closure performed under water immersion	Enhances tissue pliability and defect approximation

ESD: Endoscopic submucosal dissection.

Table 3 Summary of major endoscopic submucosal dissection innovations, evidence level, and clinical use

Category	Example/technique	Main advantages	Limitations	Supporting evidence	Best clinical use
Endo-knives	Dual knife, flush knife, hook knife, SB knife Jr., IT-nano	Precise cutting, hemostasis control	Risk of tissue injury, longer learning curve	RCTs and meta-analyses[11-16]	Standard ESD for upper and lower GI lesions
Traction methods	Clip-flap, clip-with-line, pulley, S-O clip	Shorter procedure time, improved visualization	May need device reinsertion, limited control direction	Multiple RCTs[18-28]	Complexor fibrotic colorectal lesions
Pocket creation method	Submucosal pocket dissection	Maintains lift, prevents fluid leakage	Technically demanding	RCT[16]	Large or fibrotic gastric/colorectal lesions
Water pressure- underwater ESD	Saline immersion with dynamic jet	Enhanced submucosal visibility	Requires water-jet function	Prospective trials[17]	Lesions with poor submucosal lift
Closure techniques	Line-assisted, loop clip, clip-on-clip, hand-suturing	Reduces perforation and PECS	Added time, cost	Observational and case series[35-42]	Large post-ESD defects, right colon

PECS: Post-endoscopic submucosal dissection coagulation syndrome; ESD: Endoscopic submucosal dissection; RCT: Randomized controlled trial; GI: Gastrointestinal.