Gastric polypectomy was developed by Niwa and Tsuneoka et al in 1968, followed by Wolff and Shinya1Wolff W.I. Shinya H. Polypectomy via the fiberoptic colonoscope. Removal of neoplasms beyond reach of the sigmoidoscope.N Engl J Med. 1973; 288: 329-332Crossref PubMed Scopus (175) Google Scholar in 1969, who first reported colon polypectomy. In 1971, Karita et al2Karita M. Tada M. Okita K. et al.Endoscopic therapy for early colon cancer: the strip biopsy resection technique.Gastrointest Endosc. 1991; 37: 128-132Abstract Full Text PDF PubMed Scopus (219) Google Scholar and Dyehle et al3Deyhle P. Jenny S. Fumagalli I. Endoscopic polypectomy in the proximal colon. A diagnostic, therapeutic and preventive? intervention.Dtsch Med Wochenschr. 1973; 98: 219-220Crossref PubMed Scopus (36) Google Scholar reported endoscopic mucosal resection (EMR), and Inoue et al4Inoue H. Endo M. Takeshita K. et al.A new simplified technique of endoscopic esophageal mucosal resection using a cap-fitted panendoscope (EMRC).Surg Endosc. 1992; 6: 264-265Crossref PubMed Scopus (147) Google Scholar developed EMR using a cap for the treatment of early esophageal cancer. During EMR, lesions of ≤2 cm in diameter can be resected en bloc; for lesions that are >2 cm, the only options were piecemeal resection or surgery. Endoscopic submucosal dissection (ESD) is a minimally invasive and effective technique for the en bloc resection of early-stage cancers or precancerous lesions in the gastrointestinal tract that are >2 cm in size. In the 1980s, Hirao et al5Hirao M. Masuda K. Asanuma T. et al.Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic saline-epinephrine.Gastrointest Endosc. 1988; 34: 264-269Abstract Full Text PDF PubMed Scopus (312) Google Scholar developed a technique called endoscopic resection with a local injection of hypertonic saline-epinephrine solution. In this procedure, a circumferential incision is made with a needle knife and the submucosa is dissected. Later, in the 1990s, Ono et al6Ono H. Kondo H. Gotoda T. et al.Endoscopic mucosal resection for treatment of early gastric cancer.Gut. 2001; 48: 225-229Crossref PubMed Scopus (1332) Google Scholar at National Cancer Center Hospital developed an insulated tipped knife and started gastric ESD. At about the same time, Oyama7Oyama T. Esophageal ESD: technique and prevention of complications.Gastrointest Endosc Clin N Am. 2014; 24: 201-212Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar started gastric ESD using the prototype of the hook knife, which they created by bending a needle knife, and Yahagi et al. used the snare tip (later the flex knife and then the dual knife) for ESD. After >20 years, esophageal and colorectal ESD can now be safely performed by experts. However, ESD cannot be performed safely and reliably without appropriate indications, devices, and a well-thought-out strategy. Furthermore, the first step is to properly identify and diagnose lesions using image-enhanced endoscopy8Tajiri H. Niwa H. Proposal for a consensus terminology in endoscopy: how should different endoscopic imaging techniques be grouped and defined?.Endoscopy. 2008; 40: 775-778Crossref PubMed Scopus (67) Google Scholar that are amenable to ESD. Obtaining adequate histological specimens for detailed pathologic evaluation with high-quality ESD is also a minimum requirement. The purpose of this article is to provide tips and strategies for performing high-quality ESD in the gastrointestinal tract, using a variety of organ-specific figures in an easy-to-understand manner. A number of devices should be available for the conduct of ESD, including a water-jet scope, CO2 insufflation, distal attachments, submucosal injection solution, electrocautery generator, hemostat forceps, and clip device. Esophageal ESD is technically challenging because the narrow lumen of the esophagus makes countertraction owing to gravity less effective, the resected specimen retracts distally, making it difficult to maintain good traction and orientation, and the thin wall of the esophagus increases the risk of perforation.7Oyama T. Esophageal ESD: technique and prevention of complications.Gastrointest Endosc Clin N Am. 2014; 24: 201-212Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar To overcome these challenges, the following are technical tips and tricks to achieve high-quality esophageal ESD. Because esophageal ESD is normally performed in the left lateral position, the left side is gravity dependent. A partial circumferential incision is preferred to prevent the escape of fluid from the submucosal layer.9Aadam A.A. Abe S. Endoscopic submucosal dissection for superficial esophageal cancer.Dis Esophagus. 2018; 31: 1-9Crossref Scopus (28) Google Scholar Therefore, a C-shaped mucosal incision is normally performed followed by submucosal dissection to maintain the lesion away from the water-pooling area, thereby enhancing visualization (Figure 1).10Abe S. Oda I. Suzuki H. et al.Insulated tip knife tunneling technique with clip line traction for safe endoscopic submucosal dissection of large circumferential esophageal cancer.VideoGIE. 2017; 2: 342-345Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar In addition, suction of air thickens the submucosal cushion and facilitates a safe and effective mucosal incision. Tissue traction to expose the submucosal space plays a key role during high-quality esophageal ESD. Among several reported traction methods,11Abe S. Wu S.Y.S. Ego M. et al.Efficacy of current traction techniques for endoscopic submucosal dissection.Gut Liver. 2020; 14: 673-684Crossref PubMed Scopus (12) Google Scholar clip-line traction is commonly used in the esophagus. An Endoclip with a thread is applied to the proximal edge of the lesion. The thread is then pulled through the mouth proximally and gentle pressure is applied to the string; this maneuver invariably optimizes visualization of the submucosal layer during dissection. A randomized controlled trial by Yoshida et al12Yoshida M. Takizawa K. Nonaka S. et al.Conventional versus traction-assisted endoscopic submucosal dissection for large esophageal cancers: a multicenter, randomized controlled trial (with video).Gastrointest Endosc. 2020; 91: 55-65.e2Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar demonstrated that clip line traction-assisted ESD significantly decreased the procedure time compared with conventional ESD (44.5 minutes vs 60.5 minutes; P < .001). More important, no adverse events, such as intraoperative perforation, were noted using this technique. This traction technique is recommended by Japanese ESD/EMR guidelines.13Ishihara R. Arima M. Iizuka T. et al.Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer.Dig Endosc. 2020; 32: 452-493Crossref PubMed Scopus (41) Google Scholar Thereafter, submucosal dissection can be performed by manipulating the knife from inside to outside (Figure 2). This technique facilitates visualization of the left edge of the submucosal plane and muscle direction, allowing for safe and efficient esophageal ESD. With experience and improvement in endoscopists’ skills and the availability of various ESD devices, gastric ESD has now become standard for early gastric cancer with a negligible risk of nodal metastasis.13Ishihara R. Arima M. Iizuka T. et al.Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer.Dig Endosc. 2020; 32: 452-493Crossref PubMed Scopus (41) Google Scholar,14Ono H. Yao K. Fujishiro M. et al.Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition).Dig Endosc. 2021; 33: 4-20Crossref PubMed Scopus (27) Google Scholar A recent multicenter prospective cohort study showed en bloc and R0 resection rates of 99.2% and 91.6%, respectively. However, the procedural time was >120 minutes in 25.9% of patients.15Suzuki H. Takizawa K. Hirasawa T. et al.Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: ‘real-world evidence' in Japan.Dig Endosc. 2019; 31: 30-39Crossref PubMed Scopus (50) Google Scholar The main factors associated with long procedure time were lesions located in the upper or middle one-third of the stomach, a large tumor, and ulcerated lesions.15Suzuki H. Takizawa K. Hirasawa T. et al.Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: ‘real-world evidence' in Japan.Dig Endosc. 2019; 31: 30-39Crossref PubMed Scopus (50) Google Scholar,16Yano T. Hasuike N. Ono H. et al.Factors associated with technical difficulty of endoscopic submucosal dissection for early gastric cancer that met the expanded indication criteria: post hoc analysis of a multi-institutional prospective confirmatory trial (JCOG0607).Gastric Cancer. 2020; 23: 168-174Crossref PubMed Scopus (10) Google Scholar The following techniques are recommended to perform a safe and high-quality gastric ESD and to overcome technical difficulties. Gastric ESD is technically less demanding than esophageal and colorectal ESD and can be a starting point for nonexpert endoscopists. The relative ease can be attributed to the thick stomach wall and the ability to obtain a stable scope position. However, intraoperative bleeding commonly hinders the procedure owing to the presence of large vessels, particularly in the anterior and posterior walls of the middle and upper one-third of the stomach. These large vessels normally penetrate the muscle layer vertically and then inflow horizontally at the level of the middle submucosal layer, forming a ramified vascular network. A layer containing fewer vessels and fibrotic tissue exists just above the muscularis propria.17Toyonaga T. Nishino E. Man I.M. et al.Principles of quality controlled endoscopic submucosal dissection with appropriate dissection level and high quality resected specimen.Clin Endosc. 2012; 45: 362-374Crossref PubMed Scopus (45) Google Scholar Thus, the appropriate submucosal dissection depth is the avascular stratum immediately above the muscle layer. It is also important to maintain an appropriate dissection level and identify the left and right edges of the submucosa as well as the muscle direction (Figure 3). This process is applicable to ESD of EGC with ulceration. These techniques allow us to perform safe and efficient gastric ESD and to obtain a high-quality specimen containing the entire submucosal layer. As mentioned elsewhere in this article, gastric ESD is a battle against intraprocedure bleeding, particularly for lesions located in the middle and upper one-third of the stomach. It is challenging to identify the source of bleeding and subsequent hemostasis efforts if a circumferential mucosal incision is performed from the far to the near side in the retroflexed view. To avoid this challenging situation, the near-side approach was developed.18Mori G. Nonaka S. Oda I. et al.Novel strategy of endoscopic submucosal dissection using an insulation-tipped knife for early gastric cancer: near-side approach method.Endosc Int Open. 2015; 3: E425-431Crossref PubMed Google Scholar In this approach, a step-by-step incision is made followed by submucosal dissection from the near side to open the incision space quickly and to facilitate hemostasis (Figure 4). The near-side approach combines the use of an insulated and needle-type knife strategies to decrease the risk of making the bleeding points difficult to recognize and does not impair the advantages of the insulated knife as a safe and fast method. Colorectal ESD is an excellent minimally invasive treatment for early-stage colorectal cancer or precancerous lesions larger than 2 cm, which are usually difficult to resect en bloc by EMR.19Saito Y. Fukuzawa M. Matsuda T. et al.Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection.Surg Endosc. 2010; 24: 343-352Crossref PubMed Scopus (412) Google Scholar, 20Saito Y. Uraoka T. Yamaguchi Y. et al.A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video).Gastrointest Endosc. 2010; 72: 1217-1225Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar, 21Tanaka S. Kashida H. Saito Y. et al.JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection.Dig Endosc. 2015; 27: 417-434Crossref PubMed Scopus (299) Google Scholar The main advantage of en bloc resection is that it can accurately assess submucosal and lymphovascular invasion and in case of submucosal invasion, en bloc specimens can reliably determine whether the resection is curative or noncurative. Second, because the risk of local recurrence is extremely low, frequent surveillance for recurrence may not be necessary. 1.For ESD, a basic skill involves using the left hand for all angle operations, and this is critical to gain expertise for this procedure. It is not recommended for endoscopists to use the right hand to handle the up-down and right–left knobs.2.Colorectal ESD does not involve a full circumferential incision, but a partial incision that is followed by immediate submucosal dissection (Figure 5, A–D). After the flap is created, it is important to use a short-type tapered hood to adequately penetrate the submucosal layer (Figure 5, D).22Saito Y. Sylvia Wu S.Y. et al.Colorectal endoscopic submucosal dissection with use of a bipolar and insulated tip knife.VideoGIE. 2019; 4: 314-318Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar3.If a retroflexed position is possible, it is advisable to commence ESD in this position as it stabilizes the colonoscope and allows for a horizontal approach to the submucosal layer.4.Proceed with a partial incision and submucosal dissection in both directions using either the pocket creation method or tunneling method (Figure 5, E, F), and continue with the dissection without making incisions on both lateral sides until the end of the ESD. In general, dissection of the lower one-third of the submucosal layer is recommended without exposing the muscularis propria. Leaving a thin submucosal layer is also necessary to avoid intraprocedural or delayed perforation.5.Once the dissection has progressed to some extent, marginal incision and dissection are commenced at the opposite side (Figure 5, G, H). The process of partial incision and dissection of the submucosal is repeated in the same way (Figure 5, I–K).6.Once the tunnel is open in the middle (Figure 5, L), the tunnel is then widened in either direction using an insulated knife (Figure 5, M–O).22Saito Y. Sylvia Wu S.Y. et al.Colorectal endoscopic submucosal dissection with use of a bipolar and insulated tip knife.VideoGIE. 2019; 4: 314-318Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The risk of perforation is estimated to be higher when submucosal fibrosis is severe. In such cases, it is necessary to use the appropriate traction method in addition to the basic strategy as described (Figure 5, M, N).11Abe S. Wu S.Y.S. Ego M. et al.Efficacy of current traction techniques for endoscopic submucosal dissection.Gut Liver. 2020; 14: 673-684Crossref PubMed Scopus (12) Google Scholar Clips and nylon line traction can be used in the distal colon. In the proximal colon, SO clips or multitraction loops should be used,8Tajiri H. Niwa H. Proposal for a consensus terminology in endoscopy: how should different endoscopic imaging techniques be grouped and defined?.Endoscopy. 2008; 40: 775-778Crossref PubMed Scopus (67) Google Scholar especially for cecal ESD owing to the thin muscle layer and vertical approach to the submucosal layer. Unlike simple gastric ESD, for colorectal ESD, it is important to repeat submucosal dissection through a partial incision instead of creating a full circumferential incision at the start. The basic principles of using the insulated knife along with the different steps are detailed in Figure 6. The key to safe and reliable ESD using the insulated knife is to perform submucosal dissection from both sides (left and right) while considering the effect of gravity, and to lift the dissected specimen using the sheath of the insulated knife after confirming the incision line before proceeding with the next dissection. Herein, we have described tips for efficient and appropriate ESD of the esophagus, stomach, and colon. A high-quality ESD enables detailed pathologic diagnosis and reliable completion even in situations with severe fibrosis or those lesions in a difficult anatomic location. It is essential to apply this technique after detecting lesions that are amenable to ESD by image enhanced endoscopy and appropriately diagnose intramucosal neoplasia using magnification endoscopy. Finally, it is equally important to prevent complications but take appropriate measures in the event of a complication.