From EMR to ESD: Evolution of Minimally Invasive Oncologic Endoscopy
Endoscopic treatment of early gastrointestinal neoplasia has undergone a major transformation over the past two decades. Endoscopic mucosal resection (EMR) was the initial standard for removing superficial esophageal and gastric lesions, especially in Western practice. However, EMR is inherently limited by piecemeal resection for larger lesions, which compromises histological assessment and increases the risk of local recurrence. To address these limitations, endoscopic submucosal dissection (ESD) was developed in Japan in the early 2000s, primarily for early gastric cancer. ESD enables en bloc removal of larger or ulcerated lesions, allowing for precise histologic evaluation of margins and depth of invasion. The technique quickly expanded to the esophagus and duodenum, supported by robust outcome data from high-volume Asian centers.
Today, ESD is considered the standard of care for resectable early-stage upper GI cancers in appropriate candidates. Guidelines from societies such as the ASGE and JGES now include ESD as a first-line option in specific clinical scenarios, particularly when curative resection without surgery is possible. As tools and training improve, ESD is being adopted more broadly, offering patients organ-preserving, minimally invasive oncologic therapy.
Patient Selection and Absolute vs. Expanded Indications
Appropriate patient selection is the cornerstone of safe and effective ESD for early upper gastrointestinal cancers. The primary objective is to achieve curative en bloc resection in lesions with negligible risk of lymph node metastasis, thereby avoiding more invasive surgical interventions.
Absolute indications for ESD, particularly in early gastric cancer, include differentiated-type adenocarcinomas ≤2 cm in size, confined to the mucosal layer (M1 or M2), and without ulceration. These criteria are associated with a lymph node metastasis risk of less than 1%, making ESD a curative intent procedure.
Over time, guidelines, especially those from Japan, have adopted expanded indications based on large observational cohorts. These include:
- Differentiated-type cancers >2 cm without ulceration
- Lesions ≤3 cm with ulceration
- Superficial submucosal invasion (SM1, ≤500 μm)
- Select undifferentiated-type lesions within strict size and depth limits
Accurate staging with high-resolution endoscopy, narrow-band imaging, and sometimes endoscopic ultrasound (EUS) is essential before ESD to assess lesion morphology, invasion depth, and ulceration. Biopsy confirmation of histology is also critical.
Multidisciplinary input, especially for borderline lesions, ensures optimal decision-making. ESD is not appropriate in patients with deep submucosal invasion (SM2), poor differentiation, or signs of lymphovascular involvement, who require surgery with lymphadenectomy.
Technical Essentials: Knives, Traction Devices, Electrosurgical Settings
Endoscopic submucosal dissection (ESD) is a technically demanding procedure that requires mastery of specialized tools and procedural techniques. The success of ESD, defined by en bloc resection, clear margins, and minimal complications, depends heavily on the operator’s familiarity with dissection knives, traction methods, and energy settings.
Knives and Injection Agents
Several types of ESD knives are available, each with unique cutting characteristics. Common options include the Dual knife, IT (insulated tip) knife, and Hook knife. The choice depends on lesion location, operator preference, and dissection stage. For example, the Dual knife allows for both marking and cutting, while the Hook knife offers precise control near vessels or fibrotic tissue.
Submucosal injection is critical for lifting the lesion and creating a safe dissection plane. Solutions such as glycerol, hydroxypropyl methylcellulose, or sodium hyaluronate provide lasting elevation and reduce the risk of perforation. Colored dyes (e.g., indigo carmine) enhance visualization of the submucosal layer.
Traction Techniques
Traction improves exposure of the dissection plane and reduces procedure time. Techniques include clip-with-line, pulley methods, and multiloop traction devices, which allow the mucosal flap to be lifted away from the muscle layer. The pocket-creation method (PCM) is another approach that stabilizes the working space and minimizes thermal injury.
Electrosurgical Settings and Ancillary Tools
Electrosurgical units (e.g., ERBE VIO) are programmed for precise cutting and coagulation. Common settings use Endo Cut Q or Swift Coag modes. The choice of settings must balance effective dissection with minimal bleeding and thermal injury. CO₂ insufflation is standard to reduce post-procedure discomfort and air embolism risk.
Adjunct tools such as hemostatic forceps, coagulation graspers, and distal caps further support procedural safety and precision.
Outcomes: En Bloc/Curative Resection Rates, Adverse Events, Long-Term Survival
One of the defining advantages of endoscopic submucosal dissection (ESD) over piecemeal endoscopic mucosal resection (EMR) is its ability to achieve high en bloc and curative resection rates, even for larger and ulcerated lesions. In expert centers, particularly in Japan and South Korea, en bloc resection rates for early gastric cancers exceed 95%, while curative resection, defined as en bloc removal with negative horizontal and vertical margins, and without lymphovascular invasion, is reported in up to 90% of cases for absolute indication lesions.
Adverse events, though relatively infrequent in experienced hands, remain important considerations. Bleeding occurs in approximately 5–10% of gastric ESDs and can usually be managed endoscopically. Perforation rates range from 1–5%, depending on the lesion location and operator experience, and are also amenable to endoscopic closure in most cases. In esophageal ESD, post-procedure strictures may develop in 10–20% of cases when large mucosal defects are created, often necessitating serial balloon dilation or steroid therapy.
Long-term data from Asia show excellent oncologic outcomes, with 5-year disease-specific survival approaching 98% for curatively resected mucosal cancers. Recurrence is rare when curative criteria are met, underscoring the importance of meticulous technique and appropriate patient selection.
Regular surveillance endoscopy is recommended post-ESD to detect metachronous lesions, particularly in patients with underlying mucosal atrophy or intestinal metaplasia.
As global expertise grows and Western centers gain experience, these outcomes are increasingly reproducible outside of Asia, provided appropriate training and infrastructure are in place.
Training Curves and Western Adoption Barriers
Despite its proven efficacy, endoscopic submucosal dissection (ESD) remains underutilized in Western countries due to a combination of technical complexity, training limitations, and systemic barriers. Mastery of ESD typically requires 30 to 50 supervised cases to reach procedural competency, and significantly more to manage complex or fibrotic lesions safely. However, opportunities for hands-on experience are limited outside of East Asia, where high case volumes support early training and specialization.
In contrast, Western trainees often face low procedure volumes, making it difficult to progress beyond the learning curve. Animal model courses, international fellowships, and proctoring by visiting experts have helped bridge this gap, but sustained institutional commitment is essential. Societies such as ASGE and ESGE now support structured ESD training pathways, including simulator-based learning and validated assessment tools.
Beyond training, reimbursement issues remain a major deterrent. In many healthcare systems, ESD is time-consuming and poorly reimbursed relative to surgical alternatives, creating disincentives for both endoscopists and institutions. Concerns about medico-legal liability, particularly for rare but serious adverse events like perforation, further limit adoption. Cultural and organizational factors also play a role. In the West, early cancers are often referred directly to surgery, bypassing endoscopic staging or treatment options. Building multidisciplinary collaboration between gastroenterologists, pathologists, and surgical oncologists is key to expanding ESD access.
Despite these barriers, growing recognition of ESD’s oncologic value is prompting efforts to centralize care in high-volume centers of excellence, with the goal of replicating the safety and efficacy observed in Asian cohorts.
Future Innovations: Hybrid ESD, Robotic & Full-Thickness Platforms
As ESD adoption expands globally, several technological innovations aim to simplify procedures, reduce complication rates, and broaden accessibility beyond expert centers. One such development is hybrid ESD, which combines mucosal incision and limited submucosal dissection with snare resection. This technique shortens procedure time and reduces perforation risk, making it appealing for non-expert endoscopists or lower-risk lesions. However, it may compromise en bloc rates in larger or fibrotic tumors.
Robotic endoscopy platforms are another emerging frontier. Systems with articulated instruments and haptic feedback are under development to enhance precision and ergonomics during dissection. These platforms could democratize ESD by shortening the learning curve and improving operator control, particularly in technically demanding anatomical regions like the esophagus or duodenum.
Full-thickness resection devices (FTRD) provide a single-step solution for lesions with submucosal fibrosis or uncertain invasion depth. Although primarily used in the colon, adaptations for upper GI applications are in early stages.
Advances in AI-driven image analysis may soon assist in real-time margin delineation and submucosal plane visualization, further refining ESD safety and accuracy. Together, these innovations point toward a future in which minimally invasive endo-oncology becomes more scalable, standardized, and globally accessible.
Key Practice Points
- ESD offers curative, organ-preserving treatment for selected early esophageal and gastric cancers with high en bloc and R0 resection rates.
- Training and case volume remain critical barriers to Western adoption, though structured programs and hybrid innovations are bridging the gap.
- With continued technological refinement and multidisciplinary integration, ESD is poised to become a cornerstone of minimally invasive GI oncology worldwide.
References
1. ASGE Standards of Practice Committee. (2023). ASGE guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers. American Society for Gastrointestinal Endoscopy. https://www.asge.org/docs/default-source/guidelines/asge-guideline-on-endoscopic-submucosal-dissection-for-the-management-of-early-esophageal-and-gastric-cancers-summary-and-recommendations.pdf
2. Fu, K., Yamada, M., & Matsumoto, T. (2024). Recent advances and future directions of endoscopic submucosal dissection in upper gastrointestinal neoplasia. World Journal of Gastrointestinal Endoscopy, 16(11), 4402–4416. https://www.wjgnet.com/1948-5204/full/v16/i11/4402.htm
3. Pimentel-Nunes, P., Libânio, D., Bastiaansen, B. A. J., Biermann, K., Bisschops, R., Coron, E., … & Dumonceau, J. M. (2022). Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) guideline — Update 2022. Endoscopy, 54(03), 232–254. https://doi.org/10.1055/a-1719-3156
4. Libânio, D., Pimentel-Nunes, P., Rodrigues, J. P. N., & Dinis-Ribeiro, M. (2023). Long-term outcomes of gastric ESD: A European perspective. Digestive Endoscopy, 35(1), 43–51. https://doi.org/10.1111/den.14418
5. Oyama, T., Yahagi, N., & Fujishiro, M. (2023). ESD training and dissemination in the West: Strategies to overcome barriers. Clinical Endoscopy, 56(2), 137–144. https://doi.org/10.5946/ce.2022.090