Esophageal squamous epithelial cells are rich in glycogen, hence turn brown when sprayed with Lugol’s iodine liquid. Abnormal area such as columnar change, or with inflammatory edema, atrophy, atypical hyperplasia, or cancer lead to glycogen depletion resulting in absent or reduced staining (pale) with iodine (Fig. 4.1). Thus Lugol iodine staining helps to identify the margin of lesion clearly. Lugol iodine is irritant and not used routinely in tumor screening.

NBI is a novel optical technique that enhances the diagnostic ability of endoscope by highlighting the intraepithelial papillary capillary loop (IPCL) using narrow bandwidth filters [5]. The NBI filter sets (415 and 540 nm) are selected to obtain fine images of the microvascular structure. Because 415 nm is the hemoglobin absorption band, capillaries on the mucosal surface can be seen most clearly at this wavelength. NBI is able to represent more clearly both capillary patterns and the boundary between different types of tissue, which are necessary for diagnosing a tumor in its early stage. This improves the visibility of superficial capillaries and mucosal structures, which allows clear visualization of the lesion and predication of the invasion depth, hence facilitates targeted biopsies (Fig. 4.2). In combination with magnifying endoscopy, NBI is useful to demarcate the lesion margin.

IPCL: As demonstrated by Inoue et al., magnifying endoscopic findings were classified into five types according to the degree of change in IPCL pattern. Changes include dilatation, tortuosity, and/or caliber change of individual IPCL, or multiple IPCLs of various shapes. Type I is a normal IPCL pattern. Squamous mucosa with this type is usually well stained by iodine solution. Type II is minimal dilatation and elongation of IPCL, and stains lightly by iodine-dye chromo endoscopy. This finding corresponds to esophagitis. In Type III, minimal changes in IPCL are observed, and the lesion is shown by iodine-dye chromoendoscopy as an unstained area. In Type IV, three of the four abnormal IPCL patterns are present at magnifying endoscopy, and the mucosa is unstained by iodine. Types III and IV correspond to, respectively, mild and severe dysplasia. In Type V, all four abnormal IPCL factors are present and distinct; the Type V pattern signifies the presence of cancer. Among the lesions of Type V, Type V_I exhibits severe changes in all four patterns, which corresponds to m3 or sm1 invasion. In Type V_N, the structure of the IPCL is completely destroyed and abnormal vessels are present. This type of lesion, cancer invades deeply into the submucosal layer (Fig. 4.3) [6].

To ensure en bloc resection, the first step of ESD is to mark the resection margin clearly. For superficial lesion with a clear border, we directly mark the margin. For lesion without a clear border, lugol iodine staining or NBI is used to visualize the margins. Marking points are made 2–5 mm outside the demarcation of the lesion using APC or tip of ESD knife (Fig. 4.5).

Submucosal bleb is formed, using a 23-gauge needle, with saline mixture [7]. To lift the lesion, multi-point injections are made to separate the lesion from muscular layer. This makes the dissection easier, and reduces the risk of perforation and bleeding. The esophageal lumen is narrow, hence excessive injection is avoided to operating space. We use injection 2 ml is injected at each point to left the entire lesion (Fig. 4.6). Sometimes, it is easier to start mucosal precutting after part of lesion has been injected and lifted. We avoid deep needle insertion to prevent spilling of solution into mediastinum. Lesions with no lifting sign after sumucosal injection may be not suitable for ESD treatment because of either severe inflammation or submucosal invasion.

In view of the limited endoscopic view in the esophagus, it is very important to determine the starting point of incision. The anal half of the incision is completed first, followed by the oral half. Incision of the left-wall is carried out first, otherwise lesion is submerged with fluid due to gravity, that can lead to hinderance of endoscopic views. After lifting the lesion with submucosal injection part of the mucosa along the lateral border of marked points is incised using ESD knife first. Then a circumferential mucosal incision is made around the lesion using the IT knife [8] (Fig. 4.7). The tip of the knife should be less than 2 mm. Multiple ESD knives have been developed and used, such as Flex knife, TT knife and needle knife.

During the incision, bleeding can often be treated by forced coagulation using the tip of the knife or a hemostatic forceps. Perforation is often due to the inadequate submucosal injection or too deep cutting [9].

After separating the lesion from the muscular propria by submucosal injection, the submucosal connective tissue, including the whole marked outer circumference of the target lesion, is cut, and the target lesion, is carefully dissected from the submucosal layer under direct vision. Dissection of the submucosa is begun from the oral end to the anal end. Both sides of the lesions should be dissected at the same time, to facilitate the dissection and ensure en block resection (Fig. 4.8). A transparent cap is used lift the mucosal flap to expose the submucosal layer and to provide space to facilitate dissection. Injections are repeated as needed during the procedure to ensure total removal of the lesion (Fig. 4.9).

It is extremely important to prevent and stop bleeding during dissection. Once bleeding starts, the endoscopic view is hampered and any blind hemostasis attempt may eventually lead to perforation. Immediate minor bleeding can be treated successfully by grasping the bleeding vessels with Coag forceps. Direct coagulation with the tip of knife can be done for small vessels in the submucosa. Metallic clips are often deployed for more brisk bleeding (Fig. 4.10). Because of very thin esophageal wall, there is risk of perforation with coagulation hemostasis. The water-jet system is used to identify visible bleeding vessels for targeted hemostasis to prevent esophageal perforation. Blind coagulation hemostasis increases the risk of perforation (Fig. 4.11). The esophageal wound is carefully inspected to ensure the complete resection (Fig. 4.11).

After complete resection, all visible blood vessels and potential bleeding sites are coagulated using Coag forceps and argon plasma coagulation and large vessels are clipped. Small wound can be closed with clips to prevent delayed perforation.

The resected specimen is stretched smoothly by several pins on a cork board. After taking an endoscopic image, the specimen is fixed with 10 % formalin for further pathological examination. Paraffin-embedded tumor specimens are sectioned and stained with hematoxylin and eosin. Tumor resection is deemed microscopically complete when both lateral and deep resection margins are negative for tumor tissue.

The esophagogastric junction (EGJ) is regarded as a difficult and risky location for ESD due to its narrow lumen, sharp angle and very rich small vessels (Fig. 4.14).

For lesions at the EGJ, a small initial incision is often made with a hook knife at the antral side under direct view for insertion of the tip of the IT knife into the submucosal layer. Then a circumferential mucosal incision is made from the anal side of the lesion using the IT knife, with retroflex manipulation of the scope. The ceramic ball prevents perforation of the muscle layer. Submucosal dissection is then continued from the oral side of the lesion. The solution can be injected into the submucosa during dissection to raise the submucosal layer [12, 13] (Fig. 4.15).

In general, the gastric antrum is regarded as an easy location for ESD due to its thick wall, large space, hence with more operating space. Thus, the beginners often start ESD training from this location. Posterior wall of the antrum more difficult than the anterior wall, and the lesser curvature side more difficult than the greater curvature because of gravitational effect of fluid cushion. Changing body position is sometimes necessary for separating lesions from the liquid. Submucosal vascular bed at the antrum is also rich, so it is particularly important to prevent and stop bleeding quickly (Fig. 4.16).

Lesions located in the pyloric area are difficult to resect; ESD is technically difficult and should be carried out by experienced endoscopist. If the pre-pyloric tumor extended to the pyloric channel, ESD using scope retroflexion is often then attempted within the duodenum to evaluate tumor extension and resect the lesion from the pyloric area to the duodenal bulb [14–16]. Retroflexion in the duodenum is done in the same manner as is done in rectum. However, retroflexion may not be possible in the case of bulb deformity or duodenal ulcer. After endoscopic evaluation of pyloric lesion, marking is performed at the pre-pyloric antrum and the duodenal bulb with the endoscope retroflexed in the duodenum; then, precutting in the antral and duodenal sides is done. Subsequently, dissection using conventional and in retroflexed position and is carried out (Fig. 4.17).

The gastric wall at the angle is very thin and the clear view of the angle is usually possible after adequate insufflation during gastroscopy. Because the gastric angle includes the antral and gastric body side, we pay close attention to the direction of the knife tip and cut tangentially to the submucosal layer to prevent perforation, especially when the lesion locates at the notch. The lesion also can be resected using forward view technique when it is located anteriorly at the lesser curve (Figs. 4.18 and 4.19).

In view of large operating space and clear view, the gastric body is also regarded relatively easy location for ESD. The forward and retroflexion view can be used and switched at any time to facilitate the resection (Figs. 4.20 and 4.21). The lesion at the lesser curve and proximal side are technically difficult to resect.

In the past it was difficult to resect ulcerated gastric lesions or recurrent EGC after EMR by conventional endoscopic resection techniques because submucosal fibrosis preventing adequate lifting of the mucosal lesion with submucosal injection. ESD allows the removal of such lesions because the submucosal layer can be dissected under direct view. If the tissue did not lift during or after submucosal injection, the ulcerated tissues can be carefully dissected along the plane of the submucosa using a hook or IT knife (Figs. 4.22 and 4.23). The key to avoid perforation is to hold the endoscope stably and dissect the lesion along the base of scar using a tangential movement.

Serious heart and lung disease and coagulation disorders. The patients who take anticoagulants should stop it for 5 days prior to ESD treatment. The relative contraindication is the lesion with invasion depth of more than sm1.