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

Abstract

Endoscopic submucosal dissection (ESD) offers a curative, organ-preserving approach for early-stage gastrointestinal tumors, yet its global adoption remains inconsistent. This review examined the multifaceted challenges hindering wider use of ESD, including the steep technical learning curve, variability in training access, procedural time demands, and risk of complications. We explored recent innovations aimed at improving procedural outcomes and reducing operator dependency, such as enhanced dissection tools, traction techniques, and digital training platforms. In addition, emerging technologies, such as artificial intelligence, robotics, and image-guided systems, are reshaping the procedural landscape and may help streamline both decision-making and execution. Looking forward, addressing the current limitations of ESD will require technical refinement as well as broader investment in training infrastructure and system-level support. This article outlined key areas for development and provided a forward-looking perspective on how ESD may evolve into a more accessible and standardized therapeutic modality.

Key Words: Endoscopic submucosal dissection; Gastrointestinal neoplasms; Treatment outcome; Learning curve; Technological innovation; Future directions

Core Tip: Endoscopic submucosal dissection enables curative, organ-preserving treatment of early gastrointestinal neoplasia, but its adoption is limited by technical complexity, long procedure times, and uneven training opportunities. Recent advances including novel dissection tools, traction methods, and digital training along with emerging technologies such as artificial intelligence and robotics, have the potential to overcome these barriers. Future progress will depend on both technological innovation and system-level strategies to expand training and standardize practice worldwide.

INTRODUCTION

Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique first introduced in Japan in 1995[1]. Compared with conventional endoscopic mucosal resection (EMR), ESD enables en bloc removal of large superficial gastrointestinal (GI) tumors, providing precise histopathological assessment and reducing the risk of local recurrence[2]. Initially applied to gastric lesions, its use has now expanded to the esophagus, colorectum, and small intestine. Historical series also noted multiplicity patterns in gastric cancers[3].

Endoscopic resection (ER) represents a well-established, minimally invasive approach for premalignant and early malignant GI lesions when performed by trained endoscopists under appropriate indications. Over time ER has evolved from simple snare polypectomy to EMR and subsequently to ESD[4]. While EMR remains effective for small lesions, its snare-based design limits en bloc resection to approximately 1.5-2.0 cm and is unsuitable for non-lifting lesions, often requiring piecemeal resection and resulting in higher residual or recurrent neoplasia rates[5-7]. ESD was developed to overcome these limitations, enabling complete R0 resection of larger, fibrotic, or irregularly shaped lesions. Since its introduction in the late 1990s, continuous technological refinements, including novel lifting solutions, electrosurgical units, and specialized endo-knives, have standardized ESD as the preferred ER method for large superficial lesions in Japan and other Asian countries[4,6,7].

Accurate lesion characterization is essential before ESD. The Paris Classification provides a morphological framework for estimating submucosal invasion risk[8,9]. Additional systems, such as Kudo’s pit pattern[10], Sano’s vascular pattern[11], and the Narrow-Band Imaging (NBI) International Colorectal Endoscopic criteria, aid in grading dysplasia[8]. High-resolution and image-enhanced endoscopy further improve surface evaluation. Techniques such as chromoendoscopy and NBI help delineate lesion margins and assess mucosal patterns, guiding the suitability of EMR vs ESD[9-12]. Additional contrast-enhanced modalities such as optimal band imaging further improve lesion visualization[13]. Comprehensive endoscopic characterization, including Paris classification, lesion size, mucosal architecture (regular vs irregular), and surface morphology (granular, non-granular, or depressed types), is mandatory before proceeding with ESD.

INDICATIONS FOR ESD

Recent innovations in ESD is indicated for the en bloc resection of superficial GI neoplasms with a high likelihood of complete (R0) resection and low risk of lymph node metastasis. The specific indications vary according to the organ involved, histological type, and depth of invasion. In the esophagus ESD is recommended for squamous cell carcinoma confined to the mucosa, ranging from high-grade dysplasia (HGD) to well (G1) or moderately (G2) differentiated carcinoma. Lesions classified as Paris 0-II are appropriate for ESD. Absolute indications include lesions involving only the m1-m2 layer and extending to less than two-thirds of the esophageal circumference. Expanded indications may include lesions with m³ or superficial submucosal invasion, provided there is no evidence of lymphovascular invasion.

For Barrett’s esophagus ESD is indicated in cases of HGD or moderately differentiated intramucosal carcinoma (T1a, m1-m3) that are ≥ 15 mm in size and not amenable to en bloc removal by EMR. It is also suitable for patients presenting with large or bulky nodular areas, equivocal histology prior to the procedure, suspected superficial submucosal invasion, recurrent dysplasia, or positive margins following EMR. In the stomach ESD is indicated for mucosal adenocarcinomas (or HGD lesions) of the intestinal type, G1 or G2 differentiation, less than or equal to 2 cm in size, and without ulceration.

Expanded indications include: (1) Intestinal-type adenocarcinoma (G1-G2), any size, without ulceration; (2) Intestinal-type adenocarcinoma (G1-G2) with submucosal invasion less than 500 μm (sm1); (3) Intestinal-type adenocarcinoma (G1-G2) up to 3 cm with ulceration; and (4) Diffuse-type adenocarcinoma (G3-G4), ≤ 2 cm, without ulceration. In the remnant stomach, ESD has also been reported as feasible for metachronous tumors after distal gastrectomy[14].

For the colon and rectum, ESD is primarily indicated for en bloc resection of lesions with features suggestive of submucosal invasive cancer, such as those with a type V Kudo pit pattern, depressed morphology (Paris 0-IIc), or complex morphology (0-Is or 0-IIa + Is). Lesions located in the rectosigmoid area, including nongranular laterally spreading tumors (LSTs) ≥ 20 mm and granular LSTs ≥ 30 mm, are appropriate candidates. ESD is also indicated for residual or recurrent colorectal adenomas following prior incomplete resections.

In contrast, EMR remains the first-line treatment for: Superficial lesions in Barrett’s esophagus; small gastric lesions (< 10 mm, Paris IIa) that are technically challenging for ESD; small duodenal lesions, given the risk of perforation; colorectal nongranular or nondepressed lesions < 20 mm,; or granular lesions < 30 mm in which piecemeal EMR can achieve complete removal safely. These evidence-based criteria, aligned with international consensus statements and the latest guidelines, ensure the optimal and safe application of ESD across GI organs[5] (Table 1).

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.

OVERVIEW

Over the past two decades, several refinements in instruments, traction methods, and closure techniques have enhanced the safety and efficacy of ESD. A single-channel colonoscope with a water-jet function is most commonly used while gastroscopes and balloon-assisted systems can aid maneuverability in challenging colonic segments[5,15]. The choice of devices and adjuncts is guided by lesion location, operator experience, and available technology rather than preference alone.

Endo-knives and distal attachments

Transparent hoods, particularly the small-caliber ST hood (Fujifilm, Tokyo, Japan), improve visualization and stability during submucosal dissection[15]. Numerous knives have been developed to optimize control, hemostasis, and efficiency. Short-needle monopolar knives (dual knife, hook knife, flush knife, splash needle, pro knife, Endosaber) are widely used due to simplicity and versatility[16,17] though they may risk tissue injury in less experienced hands. Scissor-type knives such as the SB Knife Jr. and Clutch Cutter provide greater safety and are ideal for beginners though they can prolong procedure time[18]. The IT-nano knife, Flex Knife, and Triangle Tip Knife offer enhanced precision in difficult locations[17-20]. Overall, hybrid knives with integrated water-jet functions allow continuous injection and have been linked to shorter procedure times and fewer perforations in randomized trials[17,21].

Advanced ESD techniques

Multiple technical modifications have been introduced to improve visualization and traction. The pocket creation method (PCM) enables a stable submucosal plane and has demonstrated higher completion rates in randomized controlled trials compared with conventional ESD[21]. The water pressure method, which uses dynamic saline flow to expand the submucosa, enhances dissection efficiency and visualization[22]. Traction-based approaches, including the clip-flap[23,24], clip-with-line[25-28], and pulley methods[29-31], provide controlled countertraction to shorten procedure time and improve safety. Comparative studies suggest that traction-assisted ESD yields higher en bloc resection rates and fewer perforations than conventional ESD, particularly in the colorectum[27,32].

PCM

In 2014 Hayashi et al[21] introduced the PCM for the first time. The successful execution of the PCM involves forming a substantial submucosal pocket beneath the lesion using a transparent hood equipped with a small-caliber tip. PCM preserves a thick submucosal layer with minimal mucosal incision, thus preventing the leakage of the injection solution. A recent randomized controlled trial showed that PCM achieved a higher completion rate for ESD compared with conventional ESD. After the mucosal incision the patient’s position is adjusted so that the lesion is closer to the ground, facilitating assistance from water. Various fluids are used to elevate the submucosa effectively[21].

Water pressure method

Previously referred to as underwater ESD or saline-pocket ESD, this technique involves a series of specific steps[22,24]. After making the mucosal incision, the patient’s position is adjusted to bring the lesion as close to the ground as possible, allowing for the insertion of water. Subsequently, a saline solution is injected into the submucosal layer, and the water-jet function of the colonoscope is employed to apply dynamic pressure to the submucosa. This technique combines the buoyant force of the saline solution with the added benefit of actively applying pressure to the submucosa, akin to underwater ESD or saline-pocket ESD. It improves the visibility of the submucosa and enhances the effectiveness of submucosal dissection[22].

Clip flap method

Yamamoto et al[23] introduced the clip-flap method for mucosal construction, a technique that plays a crucial role in the effectiveness of ESD. In this technique the endoclip acts as a substitute for the mucosal flap during its full formation. The procedure begins by applying an endoclip to secure the edge of the excised mucosa, followed by inserting a distal attachment beneath the clip. This approach improves the visibility of the submucosal layer, aiding in the creation of the flap. The clip-flap method has shown considerable effectiveness, particularly in cases of unexpected fibrosis or when a vertical approach is required[23,25].

Traction

ESD is typically conducted using a single endoscope, allowing for single-handed operation. In contrast, most surgical procedures, including laparoscopic surgery, involve the use of two or more hands, utilizing traction techniques. When performing colorectal ESD, gravity serves as the simplest form of traction, and changing the patient’s position is relatively straightforward. However, for ESD procedures involving upper GI lesions, achieving traction become more challenging. In this section we will discuss different methods and devices employed to provide additional traction during ESD[23].

Clip-with-line

A new technique has been developed to provide traction during upper GI ESD, involving the attachment of an endoclip to a string[25,26]. However, this technique has been found to be unsuitable for colonic ESD due to the need to reinsert the colonoscope to attach the endoclip secured to the string. In response to this issue, a new method called traction-assisted colorectal ESD was developed[27]. This approach involves pre-inserting a long string through the accessory channel of the colonoscope, enabling the use of the clip-with-line technique after the mucosal incision without the need for reinserting the colonoscope. Randomized trials have demonstrated the efficacy of this method, including shorter procedure times and higher self-completion rates[28]. Additionally, successful resection of lesions involving diverticula has been accomplished[33].

Pulley method

Although the traction-assisted colorectal ESD discussed earlier is generally effective, it has the limitation of providing traction solely towards the anal side and may not always be optimal. Alternative approaches, referred to as “pulley” techniques, have been described for upper GI ESD[29-31]. In our publications we presented a video case report and a case series illustrating the use of “pulley” traction-assisted colorectal ESD[31,33].

Clip with loop

Several traction methods involving a loop connected to a clip, such as the S-O clip and loop-attached rubber band, have been documented in the literature. These techniques offer the advantage of providing traction without requiring reinsertion of the colonoscope. Additionally, the pulley technique can be employed to adjust the direction of the applied force and increase its intensity. Following the surgical removal of lesions, it is essential to use a cutting loop to properly separate the excised lesions from the colonic wall[34,35].

Stitching

A large defect resulting from colorectal ESD can lead to complications such as perforation and post-ESD coagulation syndrome. Previous studies have indicated that complete closure of these defects may help reduce the risk of such complications[36,37]. However, achieving complete closure of large defects can present technical challenges. Therefore, we will explore various closure methods, as ESD ulcers can occasionally be large, making simple closure with clips difficult[36].

Line-assisted complete closure

We have developed a novel closure technique known as “line-assisted complete closure”, which combines the use of a clip and a nylon line. The procedure involves inserting an endoclip with an attached long nylon line through the accessory channel and placing it on the healthy mucosa just before the ESD ulcer[38]. An additional endoclip without a line is placed on the opposite side of the healthy mucosa, and the clips are brought together by gently pulling the nylon line through the accessory channel. Further endoclips with or without a line are then applied until complete closure is achieved[39,40].

Loop clip

The loop clip is made up of a metal clip that is looped around a nylon thread in order to create a loop. The loop clip has the capability to be passed through the instrument channel of the endoscope. In accordance with the ESD protocol, the loop clip is secured to the margins of the mucosal lesion, situated roughly at the halfway point between the distal and proximal sides. Following that, further standard clips are employed one by one to attain complete closure[34,41].

Clip-on-clip closure method

The first clip is positioned on the intact mucosa, slightly away from the mucosal lesion, and the second clip is attached to the handle of the first clip. Next, the teeth of the third clip are inserted into the gap between the teeth of the second clip, creating an anchorage mechanism. The third clip is then pulled across the defect and secured to the opposite side of the mucosal defect. Verification is performed to ensure the third clip is firmly attached to the mucosa on the contralateral side of the defect. Additional clips are applied to achieve complete closure of the mucosal defect[42,43].

Mucosal incision around the mucosal defect

A needle-type knife used in ESD is employed to make a small incision around the mucosal defect. These incisions enhance the adherence of conventional clips, reducing the risk of slippage and helping lift the adjacent mucosa in the presence of a defect. This approach effectively reduces the size of the defect and allows for the easy placement of additional clips[43].

Hand-suturing

Uninterrupted endoscopic suturing of the mucosal defect after colorectal ESD with an absorbable barbed suture and a through-the-scope needle holder has been reported[42]. Although it is technically challenging and requires an extended procedure time (median: 56 min), further modification of the technique and devices could lead to clinical use[44]. The Overstitch System is also reportedly feasible and safe. If the procedure becomes easier, widespread use is expected[42].

Underwater clip closure

Studies have demonstrated that underwater EMR provides a higher en bloc resection rate for medium-sized polyps compared to conventional EMR. Furthermore, when ESD is performed underwater, it facilitates effective wound closure with clips, leading to a reduction in the size of the mucosal defect[42,43].

CLOSURE AND PREVENTION OF COMPLICATIONS

ESD has a significant advantage in achieving en bloc resection of large or complex lesions[45]. This capability reduces recurrence rates, improves histopathological diagnostic accuracy, and allows curative treatment for early invasive malignancies. Systematic reviews and meta-analyses consistently demonstrate higher en bloc resection rates with ESD: 88% to 92% compared with 35% to 63% achieved with EMR[46-48].

The low local recurrence rates associated with ESD are largely attributed to its high en bloc resection success even for large lesions. Regardless of the resection method, piecemeal resection remains a major predictor of recurrence[2,49]. Long-term follow-up studies confirm higher recurrence rates after piecemeal EMR approaches[50]. A meta-analysis identified piecemeal resection as the only independent risk factor for local recurrence. En bloc resection also ensures a more accurate histopathologic diagnosis, particularly in cases of adenocarcinoma. Thus, ESD provides both curative resection and precise histological assessment for early neoplastic lesions[51].

Bleeding is one of the major complications of ESD, occurring both intraoperatively and postoperatively. Prophylactic coagulation and timely management are essential to minimize risks. Different endoscopic knives offer variable hemostatic capabilities depending on generator settings. The Coagrasper and Argon Plasma Coagulation are effective tools for controlling bleeding sites. However, the routine use of clamps is generally discouraged. The reported incidence of significant bleeding varies among studies but typically ranges from 0.50% to 2.75%[46,52,53].

Perforation is another major risk, occurring more frequently in ESD than in EMR. Even experienced Japanese endoscopists initially reported perforation rates of 10%-12% in early series[54,55]. When complete closure is achieved, most intraprocedural perforations can be managed conservatively using endoclips without the need for surgery. However, delayed perforations may lead to peritonitis and often require immediate surgical intervention. These typically present within 48 h after ESD with symptoms such as fever and severe abdominal pain[54,55].

Hospitalization is generally required for ESD, especially in expert centers in Japan. Despite efforts to reduce hospital stay through optimized care pathways, the average duration remains around 5 days[56,57]. By contrast, EMR is usually performed as an outpatient, day-case procedure[58].

In summary, ESD represents a minimally invasive yet technically demanding method for treating early GI neoplasia. While it achieves superior en bloc and curative resection rates compared with EMR, challenges such as bleeding, perforation risk, and procedural complexity persist, underscoring the need for continuous refinement of technique, technology, and training. Meta-analyses confirmed that ESD achieved higher en bloc resection rates (88%-92%) than EMR (35%-63%) with lower recurrence[46-48]. Although bleeding (0.5%-2.7%) and perforation (10%-12%) remain concerns[46,52-55], most are managed conservatively. Recent closure innovations have further reduced delayed adverse events and shortened hospitalization[56-58] (Tables 2 and 3).

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.

CHALLENGES IN THE GLOBAL ADOPTION OF ESD

Technical limitations

ESD represents a technically advanced yet demanding procedure, and there are situations in which achieving en bloc resection may not be feasible due to several patient-related or lesion-related factors. These include the large size of the lesion, patient frailty, comorbidities that limit procedural duration, deeply scarred or fibrotic lesions from prior resection attempts, or limited operator expertise in ESD. In cases of invasive adenocarcinoma, malignant components are typically located beneath the largest nodule or within depressed regions[59,60].

Compared with the stomach, the colon and rectum present distinct technical challenges for ESD. Several lesion-related and technical factors have been associated with difficult gastric ESD[61]. Their narrower tubular lumen, sharper angulations, and thinner muscularis layer reduce endoscopic stability and increase the risk of perforation. Consequently, endoscopic control and precise submucosal dissection are more difficult in these areas. Treating lesions in anatomically complex sites, such as the esophagogastric junction, duodenum, or anorectum, with standard ESD techniques can therefore be particularly challenging and may result in incomplete resection[62].

A recent study published in the Journal of Gastroenterology and Hepatology highlighted the technical limitations encountered during ESD for large colorectal lesions, reporting that lesions exceeding 5 cm and those located in the rectum were associated with a significantly higher risk of incomplete resection[62]. Similarly, the duodenal wall, characterized by its high vascularity, thin muscularis propria, and exposure to gastric acid, bile, and pancreatic secretions, carries a substantial risk of both immediate and delayed bleeding or perforation during duodenal ESD[5]. Therefore, duodenal ESD should be performed only by highly experienced endoscopists with advanced technical proficiency and surgical backup readily available[63,64].

In contrast, data regarding ESD at the terminal ileum remain limited, making it difficult to draw firm conclusions about safety or efficacy in this segment. Lesions involving the cecum or appendiceal orifice are particularly challenging due to submucosal fibrosis related to peristaltic stress or previous appendicitis. Furthermore, the confined space and tangential view of these lesions make en face visualization difficult. The risk of perforation is heightened as the knife tip often lies perpendicular to the dissection plane, and paradoxical endoscope movement further complicates control[65,66].

The anorectal region introduces additional complexity. Detailed knowledge of the anorectal neurovascular anatomy is essential for safe dissection in this area[67]. Abundant venous plexuses increase the risk of systemic bacteremia, and hemorrhoids further predispose to bleeding[68]. The presence of somatic sensory nerves below the dentate line increases procedural discomfort and pain while the narrow lumen proximal to the anal sphincter compromises visualization and instrument maneuverability[67,69]. Lesions that extend to the dentate line or anal canal thus remain among the most technically demanding for endoscopic management.

Nevertheless, despite these anatomical and procedural challenges, ESD continues to demonstrate high safety and efficacy in expert hands. Even in difficult areas such as the anorectum, ESD allows curative resection with minimal bleeding and low recurrence rates, provided that careful case selection, optimized technique, and adequate operator experience are ensured[70,71].

Training and education challenges

ESD is a complex procedure that demands advanced endoscopic skills and knowledge. Training and educating surgeons and endoscopists to master ESD techniques, which require precise tissue dissection and manipulation with specialized equipment, present considerable challenges. Several studies have underscored the importance of structured training programs and standardized curricula to improve endoscopist proficiency in ESD[65,72]. For example, a study published in Digestive Endoscopy demonstrated the effectiveness of a comprehensive training program that included didactic sessions, hands-on practice, and proctoring. This program resulted in improved technical competence and a reduction in procedural complications among trainees, highlighting the importance of standardized training to meet this unmet need[73].

Although there is no standard approach to ESD training in the United States, it is common to begin by participating in ESD courses that provide steadily in-depth exposure[74]. In the United States appropriate lesions for initiating ESD are typically found in the rectum, given the relative rarity of early gastric cancer. While there is no consensus on the exact definition of an experienced ESD endoscopist, a feasibility study on colorectal ESD suggested that it can be performed safely and effectively after completing more than 100 colorectal ESD procedures[75,76]. The availability of expert endoscopists with ESD experience is particularly crucial in Western practice, and ensuring adequate training opportunities in this context presents an additional challenge.

In Japan well-established training pathways begin with technically simpler and safer procedures in the stomach, gradually progressing to the esophagus, rectum, and colon. However, upper GI lesions suitable for ESD are less common in Western countries. Concerns about the impact on interventional endoscopy services, longer procedure durations, and the risk of complications have contributed to the slower adoption of ESD in Western practice. Early Western studies on colorectal ESD reported significant complication rates, which further hindered its widespread use. Nevertheless, evidence suggests a clear learning curve with complications decreasing as experience grows as shown in Western settings. A recent nationwide population-based study confirmed stable outcomes and increasing procedural use at the national level[77]. Emerging data from Europe indicate comparable en bloc resection and perforation rates to those seen in Eastern practice[74,78]. Large prospective multicenter studies from North America also demonstrate improving outcomes as operator experience increases[4].

In addition, Western health systems face specific barriers: Limited dedicated ESD lists and institutional support, often restricting procedure time; reimbursement challenges since ESD is time-consuming but not adequately compensated; medico-legal concerns surrounding perforation and bleeding risk; and low case volume of suitable early neoplasia, limiting exposure for trainees.

To address these disparities the European Society of Gastrointestinal Endoscopy and the Japan Gastroenterological Endoscopy Society have proposed stepwise curricula and certification standards to define competence and quality assurance. Recent advances in simulation-based and animal-model training (ex vivo porcine stomach, three dimensional printed models, and virtual-reality ESD simulators) allow repetitive, risk-free practice and are rapidly gaining acceptance as core components of modern training pipelines.

Overall, the establishment of structured international mentorship programs, validated assessment tools, and global credentialing will be key to overcoming regional disparities. Addressing these unmet needs in ESD can enhance the procedure, improve patient outcomes, and foster advancements in endoscopic techniques. Investing in training programs, technological innovations, research initiatives, and patient-centered approaches will support the evolution of ESD, leading to safer and more effective treatments for patients with GI lesions[75,76].

Patient selection challenges

The selection of appropriate candidates for ESD is essential for optimizing outcomes. Currently, there is no standardized approach to determine which patients are suitable for the procedure. Factors such as lesion characteristics (size, location, and histology) and patient comorbidities must be considered when assessing eligibility for ESD. Patient frailty and multiple comorbidities may limit procedural duration and tolerance[79-81]. A study published in Gastrointestinal Endoscopy discussed the challenges of patient selection for ESD in early gastric cancer. The authors found that certain patient factors, such as age and comorbidities, were linked to a higher risk of adverse outcomes. They emphasized the need for more refined criteria and risk stratification models to help clinicians make well-informed decisions regarding ESD eligibility[10,60,82].

Considering the advantages and efficacy of both ESD and EMR, it is important to adopt a pragmatic, guideline-based approach to patient and lesion selection. International consensus statements, including those from the European Society of Gastrointestinal Endoscopy, Japan Gastroenterological Endoscopy Society, and American Society for Gastrointestinal Endoscopy, recommend the following: (1) EMR is preferred for small, non-fibrotic lesions (< 20 mm) that can be resected en bloc with clear margins; (2) ESD is indicated for lesions > 20 mm, non-lifting or fibrotic lesions, superficial submucosal invasion, or high-grade intraepithelial neoplasia; (3) Surgical resection should be considered for lesions showing deep submucosal invasion, non-lifting sign despite adequate injection, or poor endoscopic visualization; (4) Lesions exhibiting clear signs of deep invasive adenocarcinoma, such as a Vn pit pattern or endoscopic ultrasound finding of deep invasion, should not be considered for ER; (5) Magnification chromoendoscopy, NBI, and colonoscopic ultrasound, when available, remain valuable for assessing lesion margins, vascular architecture, and invasion depth[82]; and (6) LSTs-non-granular, particularly pseudodepressed types and those showing a Vi pit pattern, should preferentially undergo ESD, especially if > 2 cm. Even smaller LST-non-granular lesions in which EMR might be compromised due to submucosal fibrosis can benefit from ESD.

If local ESD expertise is unavailable, patients should be referred to tertiary centers with trained personnel. Individualized management remains crucial as lesion characteristics and patient tolerance vary. While ESD may be indicated based on pathology, it may not always be optimal for frail or elderly patients unable to withstand prolonged procedures or deep sedation. Endoscopic ultrasound prior to resection helps assess depth and margins, guiding treatment planning[83].

A major advantage of ESD is its ability to provide a single, well-oriented specimen for precise pathological margin assessment, ensuring accurate staging and optimal oncologic follow-up[83]. Thus, applying guideline-based selection criteria, integrating advanced imaging, and fostering multidisciplinary decision-making improve both safety and long-term outcomes.

FUTURE PERSPECTIVES IN ESD

Improved training and skill development

Standardizing training programs for ESD remains a fundamental goal as no universally accepted framework currently exists. Establishing consensus-based curricula would streamline learning for endoscopists and ensure procedural safety and quality. Training should integrate comprehensive cognitive preparation with supervised, hands-on experience, emphasizing both technical skill and clinical decision-making[84].

Before training begins minimum competency benchmarks and expected outcomes for each level should be clearly defined. Structured programs combining didactic instruction, simulation-based practice, and expert proctoring have markedly improved both safety and efficiency. A consensus statement from European experts recommends that ESD training begin with animal or ex vivo models before progressing to human procedures[85].

Standardized training and certification frameworks would foster quality assurance and reduce inter-center variability. Reports from Western centers show that with appropriate mentorship and structured curricula outcomes comparable with Eastern programs can be achieved[85,86].

Simulation models

Because of the steep ESD learning curve, simulation models have become indispensable teaching tools. They accurately reproduce GI anatomy and tissue resistance, enabling endoscopists to practice hand-eye coordination, dissection control, and complication management in a risk-free setting[87].

Realistic artificial tissue simulators now provide ethical and sustainable alternatives to live animal training. These models can be reused and objectively evaluated, bridging the gap between video instruction and animal work[88]. Despite their advantages simulator cost and limited anatomical variety remain obstacles to widespread implementation. As manufacturing costs fall, however, simulation will likely become an essential component of competency-based ESD education worldwide.

Advanced endoscopic imaging technologies

Innovations in visualization have transformed the precision of ESD. Recent reviews summarize advances in image-enhanced endoscopy, including dye-based and virtual chromoendoscopy modalities[89]. High-definition endoscopy allows superior lesion delineation while NBI enhances contrast between vasculature and mucosa, facilitating early cancer detection[90]. Nevertheless, interobserver variability and the need for additional training may limit reproducibility.

Virtual chromoendoscopy systems such as FICE and i-scan reproduce dye effects without staining, reducing procedure time and patient discomfort[91,92]. Although these tools improve diagnostic accuracy, their use is restricted by equipment cost, availability, and operator experience. Standardized training and cost-sharing strategies are necessary to expand their accessibility across healthcare systems.

Artificial intelligence and computer-aided diagnosis

Artificial intelligence (AI) is rapidly reshaping diagnostic endoscopy. Machine learning algorithms can analyze live images to provide real-time lesion detection, classification, and margin evaluation, thereby improving both accuracy and efficiency[93]. The WISENSE system, for example, significantly reduced blind spots compared with conventional endoscopy (5.9% vs 22.4%, P < 0.001)[93]. Similarly, the GRAIDS trained on over a million images-showed diagnostic sensitivity comparable to expert endoscopists[94]. However, despite its promise AI faces several limitations: (1) Generalizability varies across platforms, populations, and imaging standards; (2) Implementation costs and data privacy requirements remain high; and (3) Regulatory and medico-legal frameworks are still evolving. Therefore, while AI should be viewed as a powerful adjunctive tool, widespread autonomous application awaits large-scale validation in diverse clinical environments[95].

Personalized medicine

Personalized or precision medicine aims to tailor treatment using molecular and genetic profiling. Identification of tumor-specific biomarkers and mutations enables prediction of recurrence risk and guides individualized surveillance or therapy (ESD candidacy, adjuvant management, or follow-up). By considering patient-specific factors such as genetic variations, immune status, and molecular signatures, clinicians can forecast procedural outcomes and optimize therapy. This paradigm will ultimately reposition ESD as a key element in precision GI oncology, improving both safety and long-term efficacy.

Telemedicine and remote consultation

Telemedicine offers an effective means to bridge expertise gaps between tertiary and peripheral centers. Through live video support expert mentors can review images, provide guidance, and deliver real-time procedural feedback. This model has already shown value in complex polypectomy and early ESD mentoring. Yet its routine use is constrained by network reliability, data-security standards, and medico-legal jurisdiction. With continued refinement tele-mentoring could democratize advanced endoscopic training and reduce global disparities in ESD access.

Robotics and robotic-assisted ESD

Robotic systems enhance dexterity and control, compensating for the limitations of conventional flexible endoscopes. The evolution of robotic platforms continues to reshape minimally invasive surgery[96]. Articulating robotic wrists and haptic feedback enable precise submucosal dissection with improved stability[97,98]. Novel platforms such as REXTER have demonstrated feasibility and safety in preclinical porcine models[99].

Nevertheless, robotic ESD currently faces significant constraints: High capital cost; complex setup; limited availability; and the absence of large-scale human data. Although robotics could shorten learning curves and improve ergonomics, its clinical readiness remains limited until cost, accessibility, and standardization barriers are resolved[2,98].

Therapeutic agents and techniques

Combining ESD with molecular-targeted therapies or photodynamic therapy may enhance oncologic outcomes. Agents such as monoclonal antibodies or tyrosine kinase inhibitors can address residual microscopic disease while photodynamic therapy selectively destroys malignant cells under specific light activation[100]. These hybrid approaches remain experimental and increase procedural complexity and cost. Prospective multicenter trials are needed to determine their safety, efficacy, and cost-effectiveness before integration into standard ESD protocols.

Noninvasive diagnostics

Emerging liquid-biopsy technologies enable detection of circulating tumor DNA, microRNA, and proteins for early diagnosis, surveillance, and recurrence monitoring. Molecular imaging with fluorescent probes enhances intraprocedural visualization and may predict invasion depth or malignancy potential. In parallel, AI-driven predictive models combining clinical, radiologic, and molecular data can stratify recurrence risk and guide treatment selection. Despite these advances validation across populations, reproducibility, and affordability remain key challenges before these tools become part of everyday clinical practice.

ESD for complex lesions and non-GI applications

Ongoing technological progress now allows ESD to manage increasingly complex and fibrotic lesions. Enhanced traction devices and closure techniques facilitate complete resection in anatomically challenging sites, such as the esophagogastric junction or anorectal region.

Beyond the GI tract ESD principles are being adapted for airway, bladder, and urologic lesions with early reports confirming feasibility. Concurrently, advanced closure devices, including over-the-scope clips, suturing systems, and bioengineered materials-permit secure defect closure, promoting scarless healing.

Emerging regenerative medicine strategies using stem cell scaffolds or tissue engineered matrices may accelerate mucosal recovery and minimize fibrosis. While still experimental these innovations represent the next frontier in minimally invasive therapeutic endoscopy.

CONCLUSION

ESD has emerged as an effective and minimally invasive technique for the resection of early GI neoplasms. However, several challenges and unmet needs still exist in the field. Innovations in endoscopic devices, such as improved knives and energy sources, are necessary to enhance the efficiency and safety of the procedure. Additionally, the development of advanced imaging techniques, such as AI-assisted endoscopy, can aid in accurate lesion identification and characterization, further improving the success rate of ESD. Training and expertise in ESD are crucial and standardized training programs should be established to ensure proficiency among practitioners. Long-term follow-up studies are needed to evaluate the oncological outcomes of ESD and guide clinical decision-making.

Looking ahead, the integration of advanced technologies, such as robotic assistance and virtual reality, holds potential in improving the precision and outcomes of ESD procedures. The application of ESD beyond the GI tract also presents exciting possibilities for expanding its clinical utility. In summary, addressing the challenges in ESD technology, training, long-term studies, and integrating advanced technologies are key to enhancing the safety, efficacy, and clinical applicability of ESD. By doing so ESD has the potential to revolutionize endoscopy and improve patient outcomes.