Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it: injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en-bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects: (1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.

Application of endoscopic resection (ER) to gastrointestinal (GI) neoplasms is limited to lesions with no risk of nodal metastasis. Either polypectomy or endoscopic mucosal resection (EMR) is beneficial for patients because of its low level of invasiveness. However, to ensure the curative potential of these treatment modalities, accurate histopathologic assessment of the resected specimens is essential because the depth of invasion and lymphovascular infiltration of the tumor is associated with considerable risk for lymph node metastasis. For accurate assessment of the appropriateness of the therapy, en bloc resection is more desirable than piecemeal resection. For a reliable en bloc resection of GI neoplasms, a new method of ER called endoscopic submucosal dissection (ESD) has been developed. In this article, an outline of the current status of ESD will be discussed.

The ESD technique has developed from one of the EMR techniques, namely endoscopic resection after local injection of a solution of hypertonic saline-epinephrine (ERHSE)[1]. Initially, the ESD technique was called by various names such as cutting EMR, exfoliating EMR, EMR with circumferential incision etc. However, a new name was proposed to this technique in 2003, as a treatment positioned between EMR and laparoscopic surgery, since this technique is innovative and enables complete resection of neoplasms that were impossible to resect en bloc by EMR.

At present, numerous electrosurgical knives such as insulation-tipped diathermic knife (IT-knife)[2–6], needle knife[7], hook knife[8], flex knife[9–11], triangle-tipped knife[12], flush knife[13], mucosectomy[14], splash needle[15] and a special device called a small-caliber tip transparent (ST) hood[7] are available for this technique. One or two of these electrosurgical knives are used in combination with a high frequency electrosurgical current (HFEC) generator with an automatically controlled system (Endocut mode, Erbotom ICC200, ICC350, VIO300D, ERBE, Tubingen, Germany) (PSD-60, Olympus, Tokyo, Japan). New types of endoscopes are available for ESD, such as an endoscope with a water jet system (EG-2931, Pentax, Tokyo, Japan, GIF-Q260J, Olympus, Tokyo, Japan), an endoscope with a multi-bending system (M-scope: XGIF-Q240M, R-scope: XGIF-2TQ240R, Olympus, Tokyo, Japan) to facilitate the ESD procedure[16–19]. As another approach to successful ESD, investigations of submucosal injection solutions have been actively done. It was reported that a hyaluronic acid solution makes a better long-lasting submucosal cushion without tissue damage than other available solutions[720–23]. As a further improvement of hyaluronic acid solution, usefulness of a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar has also been reported[2425].

ESD is characterized by three steps: injecting fluid into the submucosa to elevate the lesion from the muscle layer, circumferential cutting of the surrounding mucosa of the lesion, and subsequent dissection of the connective tissue of the submucosa beneath the lesion. Major advantages of this technique in comparison with polypectomy or EMR are as follows. The resected size and shape can be controlled, en bloc resection is possible even in a large neoplasm, and neoplasms with submucosal fibrosis are also resectable. So this technique can be applied to the resection of complex neoplasms such as large neoplasms, ulcerative non-lifting neoplasms, and recurrent neoplasms. The disadvantages of this technique are the requirement of two or more assistants, it is time-consuming, there is a higher risk of bleeding and perforation than EMR. In Japan, ESD is now gaining acceptance as the standard endoscopic resection technique for stomach neoplasms in an early stage, especially for large or ulcerative neoplasms. Recently, the ESD technique is applied to esophageal or colorectal neoplasms in some institutions, although it is still controversial considering the technical difficulty, associated risks, and favorable outcomes by EMR.

In Japan, ESD is performed on hospitalized patients. After ESD, eating is usually started on the next or 2 d after ESD if there is no complication, and the patient may be discharged within a few days. Antacids are usually administered to gastric and esophageal ESD patients to relieve pain, prevent postoperative bleeding and promote ulcer healing. A recent study showed that proton pump inhibitors more effectively prevented bleeding from the gastric ulcer created after ESD than did H2-receptor antagonists[58]. Ulcers after ESD are reported to heal within 6 to 8 wk in the esophagus, stomach and colorectum[59–63].

Endoscopic surveillance should be carried out in patients after ESD not only to detect local recurrence but also metachronous cancer especially in the esophagus and stomach. A recent study showed that the average time to detect a first metachronous gastric cancer (MGC) was 3.1 ± 1.7 years after EMR/ESD, and the cumulative 3-year incidence was 5.9%[64]. In order to detect MGC at an early stage to perform a successful ER, annual endoscopic surveillance program may be practical for post-ER patients.

Long-term outcomes after ESD for gastric cancers within the expanded indication are currently under investigation. Survival data is still lacking in the literature, however in the 2007 annual meeting of Japanese gastroenterological endoscopy society (JGES), a symposium was held upon long-term outcomes after gastric and esophageal ESD. For gastric ESD, 3-year disease free survival rate was reported as 90%-92%, local recurrence rate was reported as 0.8%-12%. For lesions within the criteria of node negative cancers, there were no reports of distant metastasis. Metachronous gastric cancer detection rate during follow-up was reported as 3.4%-10.2%. In comparison, long-term outcomes after EMR for small differentiated mucosal EGC less than 20 mm in diameter have been reported as comparable to those after gastrectomy. The disease-specific 5- and 10-year survival rates were 99% and 99%[65]. For esophageal ESD, in the 2007 JGES meeting, 3-year survival rate for m1-2 cancer and m3-sm1 cancer were 95.1% and 86.7%, respectively. According to colorectal ESD, there is still no long-term data at present.

With the development of ESD, more than half of GI cancers in the early stage are removed by ER in advanced institutions in Japan. En bloc retrieval of lesions is essential for detailed histopathologic studies, which form the basis for stratification of treatment outcomes and patient’s prognosis. ESD theoretically offers greater histopathological accuracy than conventional EMR methods or piecemeal resection. However, ESD requires highly skilled endoscopists, and a suitable training program is demanded for permeation of this technique. For trainees starting ESD, skills of routine endoscopy and colonoscopy, target biopsy, endoscopic hemostasis techniques and simple EMR techniques should be required. A trainee would gain early proficiency of ESD after 30 cases under supervision of a mentor[3266]. On the other hand, serious complications such as delayed perforation have been reported, and a thorough patient care before and after ESD is essential. At present, selection of a lesion within the criteria for ER, selection of the patient with adequate general function should be well considered. It is important to share the information and experience among endoscopists to skill up and avoid serious complications. The ESD technique is still not a treatment at ease, and further refinements of the technique is required to popularize ESD as a safe and reliable, less invasive treatment for patients with GI neoplasms.