A minimally invasive treatment for early GI cancers

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Endoscopic submucosal dissection (ESD) allows curative resection of early malignant gastrointestinal (GI) lesions, potentially avoiding open surgery. Unfortunately, awareness of this technique is low, and many patients undergo surgery without consideration of ESD. This article reviews the indications for ESD and its advantages and limitations, and guides internists in their approach to patients with early GI cancer.


  • ESD is a minimally invasive endoscopic technique with curative potential for patients with superficial GI neoplasia.
  • ESD preserves the integrity of the organ while achieving curative resection of large neoplasms.
  • ESD is indicated rather than surgery in patients with early GI lesions with a negligible risk of lymph node metastasis.
  • Complications of the procedure include bleeding, perforation, and stenosis. Most of these respond to endoscopic treatment.
  • Successful ESD requires supportive teamwork among internists, gastroenterologists, pathologists, and surgeons.



The treatment of early esophageal, gastric, and colorectal cancer is changing.1 For many years, surgery was the mainstay of treatment for early-stage gastrointestinal cancer. Unfortunately, surgery leads to significant loss of function of the organ, resulting in increased morbidity and decreased quality of life.2

Endoscopic techniques, particularly endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have been developed and are widely used in Japan, where gastrointestinal cancer is more common than in the West. This article reviews the indications, complications, and outcomes of ESD for early gastrointestinal neoplasms, so that readers will recognize the subset of patients who would benefit from ESD in a Western setting.


Since the first therapeutic polypectomy was performed in Japan in 1974, several endoscopic techniques for tumor resection have been developed.3

EMR, one of the most successful and widely used techniques, involves elevating the lesion either with submucosal injection of a solution or with cap suction, and then removing it with a snare.4 Most lesions smaller than 20 mm can be removed in one piece (en bloc).5 Larger lesions are removed in multiple pieces (ie, piecemeal). Unfortunately, some fibrotic lesions, which are usually difficult to lift, cannot be completely removed by EMR.

ESD was first performed in the late 1990s with the aim of overcoming the limitations of EMR in resecting large or fibrotic tumors en bloc.6,7 Since then, ESD technique has been standardized and training centers have been created, especially in Asia, where it is widely used for treatment of early gastric cancer.3,8–10 Since 2012 it has been covered by the Japanese National Health Insurance for treatment of early gastric cancer, and since 2014 for treatment of colorectal malignant tumors measuring 2 to 5 cm.11

Adoption of ESD has been slow in Western countries, where many patients are still referred for surgery or undergo EMR for removal of superficial neoplasms. Reasons for this slow adoption are that gastric cancer is much less common in Western countries, and also that ESD demands a high level of technical skill, is difficult to learn, and is expensive.3,12,13 However, small groups of Western endoscopists have become interested and are advocating it, first studying it on their own and then training in a Japanese center and learning from experts performing the procedure.

Therefore, in a Western setting, ESD should be performed in specialized endoscopy centers and offered to selected patients.1


Ideal candidates for endoscopic resection are patients who have early cancer with a negligible risk of lymph node metastasis, such as cancer limited to the mucosa (stage T1a).7 Therefore, to determine the best treatment for a patient with a newly diagnosed gastrointestinal neoplasm, it is mandatory to estimate the depth of invasion.

The depth of invasion is directly correlated with lymph node involvement, which is ultimately the main predictive factor for long-term adverse outcomes of gastrointestinal tumors.4,14–17 Accurate multidisciplinary preprocedure estimations are mandatory, as incorrect evaluations may result in inappropriate therapy and residual cancer.18

Other factors that have been used to predict lymph node involvement include tumor size, macroscopic appearance, histologic differentiation, and lymphatic and vascular involvement.19 Some of these factors can be assessed by special endoscopic techniques (chromoendoscopy and narrow-band imaging with magnifying endoscopy) that allow accurate real-time estimation of the depth of invasion of the lesion.5,17,20–27 Evaluation of microsurface and microvascular arrangements is especially useful for determining the feasibility of ESD in gastric tumors, evaluation of intracapillary loops is useful in esophageal lesions, and assessment of mucosal pit patterns is useful for colorectal lesions.21–29

Endoscopic ultrasonography is another tool that has been used to estimate the depth of the tumor. Although it can differentiate between definite intramucosal and definite submucosal invasive cancers, its ability to confirm minute submucosal invasion is limited. Its use as the sole tumor staging modality is not encouraged, and it should always be used in conjunction with endoscopic evaluation.18

Though the aforementioned factors help stratify patients, pathologic staging is the best predictor of lymph node metastasis. ESD provides adequate specimens for accurate pathologic evaluation, as it removes lesions en bloc.30

All patients found to have risk factors for lymph node metastasis on endoscopic, ultrasonographic, or pathologic analysis should be referred for surgical evaluation.9,19,31,32


Before the procedure, the patient’s physicians need to do the following:

Determine the best type of intervention (EMR, ESD, ablation, surgery) for the specific lesion.3 A multidisciplinary approach is encouraged, with involvement of the internist, gastroenterologist, and surgeon.

Plan for anesthesia, additional consultations, pre- and postprocedural hospital admission, and need for special equipment.33

During the procedure

Figure 1. Endoscopic submucosal dissection, a minimally invasive treatment for early-stage cancers of the gastrointestinal system, involves the following steps: (A) marking the circumference of the tumor, (B) lifting the tumor by injecting saline or another inert substance beneath it, (C) cutting around the outside of the tumor margin, and (D) dissecting and removing the tumor.

The main steps of ESD are circumferential marking of the lesion, submucosal injection, circumferential incision, and submucosal dissection (Figure 1). The endoscopist must do the following:

Define the lateral extent of the lesion using magnification chromoendoscopy or narrow-band imaging. In the stomach, a biopsy sample should be taken from the worst-looking segment and from normal-looking mucosa. Multiple biopsies should be avoided to prevent subsequent fibrosis.33 In the colon, biopsy should be avoided.34

Identify and circumferentially mark the target lesion. Cautery or argon plasma coagulation can be used for making markings at a distance of 5 to 10 mm from the edges.33 This is done to recognize the borders of the lesion, because they can become distorted after submucosal injection.14 This step is unnecessary in colorectal cases, as tumor margins can be adequately visualized after chromoendoscopy.16,35

Lift the lesion by injecting saline, 0.5% hyaluronate, or glycerin to create a submucosal fluid cushion.19,33

Perform a circumferential incision lateral to the mucosal margins to allow for a normal tissue margin.33 Partial incision is performed for esophageal and colorectal ESD to avoid fluid leakage from the submucosal layer, achieving a sustained submucosal lift and safer dissection.16

Submucosal dissection. The submucosal layer is dissected with an electrocautery knife until the lesion is completely removed. Dissection should be done carefully to keep the submucosal plane.33 Hemoclips or hemostat forceps can be used to control visible bleeding. The resected specimen is then stretched and fixed to a board using small pins for further histopathologic evaluation.35

Postprocedural monitoring. All patients should be admitted for overnight observation. Those who undergo gastric ESD should receive high-dose acid suppression, and the next day they can be started on a liquid diet.19


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