Yoshimasa Miura, MD; Satoshi Shinozaki, MD, PhD; Alan Kawarai Lefor, MD, MPH, PhD, FACS; and Hironori Yamamoto, MD, PhD
Approximately 2 decades have passed since the introduction of endoscopic submucosal dissection (ESD) for the treatment of superficial gastrointestinal (GI) tract tumors.1 In Japan, ESD has become a standardized technique for resecting superficial tumors of the esophagus, stomach, and colorectum. However, there are some tumors that require sophisticated endoscopic resection techniques, and even experienced endoscopists frequently struggle during the procedure. Among others, ESD of lesions in the duodenum can be extremely difficult. In this chapter, we discuss some of the difficulties associated with ESD and some solutions to overcome these situations.
Factors That Define “Difficult” Endoscopic Submucosal Dissection
What factors affect the “difficulty” of performing ESD? The following outcome criteria are associated with difficult procedures: (1) low rate of en bloc resection, (2) long procedure time, and (3) high rate of perforation. Size, location, existence of submucosal fibrosis, and deep submucosal invasion (> 1000 µm) were identified as significant contributing factors to the difficulty of gastric ESD, which is defined by a long procedure time, R1 resection rate, and/or perforation.2 Takeuchi et al3 reported contributing factors to the difficulty of colorectal ESD. The rate of R1 resection was associated with low-volume centers, use of a snare, and poor lifting after submucosal injection.3 Long procedure time (> 2 hours) was associated with larger size, less-experienced endoscopists, a low-volume center, carbon dioxide insufflation, and the use of 2 or more electrosurgical ESD knives. Poor lifting after injection was reported to be the most significant contributing factor to perforation.3 Although multiple factors influence the difficulty associated with performing ESD, overall we categorize the important factors into 3 groups: (1) characteristics of the submucosa and muscularis under the tumor, (2) anatomical factors, and (3) the endoscopist. Taken together, these factors contribute to making ESD difficult (Table 22-1).
Characteristics of the Submucosa and Muscularis
Generally, thick perforating vessels from the muscularis to the submucosa enter the deep submucosa with a large diameter, and then branch off in the shallow submucosa. Therefore, the overall vascular density is higher in the shallow layer compared with the deep layer. If a hematoma forms in the submucosa, we encounter difficulty in performing ESD because of poor visualization. The submucosal fat is mainly distributed in the shallow layer compared with the deep layer. Dissection of submucosal fat causes staining of the lens, resulting in diminished visualization. To avoid these unfavorable conditions, avoid the high-density of blood vessels and fat in the shallow submucosa. Dissection should proceed in the deep submucosal layer, just above the muscularis. To do that, modulation of dissection depth and clear visualization of the submucosa are essential to accomplish safe ESD. It is especially important in tumors with abundant blood vessels such as those along the greater curvature of the gastric body. Even in such cases, however, bleeding during ESD is easily controlled as long as we select the appropriate plane of dissection and properly cauterize thick perforating vessels.
In some parts of the GI tract, the structure of the muscularis is so coarse that muscularis fibers can easily be misidentified as submucosal fibers. A false injection into the muscularis further increases the risk of misidentification, potentially leading to perforation. While performing a vertical approach to the muscularis, we should be especially careful in differentiating submucosal tissue from coarse muscle fibers.
Dense submucosal fibrosis also makes ESD difficult. There are mainly 2 types of fibrosis in gastric tumors. One is fibrosis associated with cancer and the other is fibrosis due to scarring from a previous ulcer. In the colon, laterally spreading tumors–nongranular, pseudo-depressed type frequently have associated submucosal fibrosis as part of the nature of the tumor. Another cause of fibrosis in colorectal tumors is prolapse associated with peristalsis often seen with large sessile tumors. This fibrosis is complicated, regardless of the type of lesion, adenoma or carcinoma. In resecting tumors with this kind of fibrosis, a circumferential mucosal incision induces folding of the mucosa toward the center of the tumor, which makes submucosal dissection difficult because the tip of the endoscope cannot get into the submucosal layer easily. Therefore, a routine circumferential incision prior to submucosal dissection is not recommended. We frequently encounter dense fibrosis in so-called salvage ESD procedures performed to resect recurrent tumors after chemoradiotherapy or previous endoscopic or surgical resections. To overcome this dense fibrosis, we expose the problematic area of fibrosis by dissecting the surrounding submucosal tissue. Then, divide the fibrotic area based on the estimated line.
Anatomical Factors: Lack of Endoscopic Stability
Unstable endoscopic maneuverability always frustrates endoscopists. The difficulty in approaching the lesion occurs in organs with a wide lumen. Typical examples include tumors in the gastric fundus, greater curvature of the gastric body, and incisura. Controlling the volume of gas insufflation (ie, carbon dioxide) is important to address this issue. Collapsing the lumen by aspirating the gas solves this problem in most cases. If it still does not resolve, an endoscope with a multibending function and/or a traction device such as a “clip and line” can be useful.
Difficult maneuverability frequently occurs in the proximal colon and distal duodenum. Resection of tumors in the proximal colon in an unstable situation is exceptionally challenging and requires stable maneuvering of the scope. Using an overtube-assisted device (ie, double-balloon endoscope) during ESD can remarkably stabilize the tip of the endoscope and improve maneuverability even in the proximal colon in an otherwise unstable situation.4 Duodenal ESD requires a highly sophisticated technique because the duodenum is fixed in the retroperitoneum but the endoscope shaft easily bends in the stomach. Therefore, 22% of patients required balloon-assisted endoscopy in our experience. In these patients, however, we have successfully completed distal duodenal ESD without complications.5
|CHARACTERISTICS OF THE SUBMUCOSA AND MUSCULARIS UNDER THE TUMOR|
|Abundant blood vessels|
Greater curvature of the gastric body
Rectum, perianal area
Lesion on an ulcer scar
Colon laterally spreading tumor, nongranular type, pseudo depressed
Giant semi-pedunculated polyp
Lesion on an anastomosis
Local recurrence after endoscopic resection
Greater curvature of the gastric body
Rectum, perianal area
|Difficult to approach|
Upper angle of the duodenum
Flexion part of the colon
Lesion on large colonic haustra
|Narrow working space|
Orifice of the appendix
Lesion in a diverticulum
|Level of experience||Less experience|
The vertical approach makes ESD difficult and increases the risk of perforation. It frequently occurs while resecting a tumor located on the greater curvature of the gastric body, in the cecum and the angled portions of the duodenum. Although the endoscopist tries to get a tangential approach by aspirating gas and/or changing the patient’s position to take advantage of gravity, the tangential approach cannot be obtained in some situations. In such difficult circumstances, a traction-assisted ESD device such as a clip-with-line or S-O clip (Zeon Medical), a scissors-type knife such as the SB Knife (Sumitomo Bakelite), or Clutch Cutter (Fujifilm) (Figure 22-1), and the pocket-creation method (PCM) (details described later) may be helpful.6 When a vertical approach is unavoidable, the SAFEKnife V (Fujifilm) is useful. As shown in Figure 22-2, it has a sandwich-like structure with a circular electrode. This design is useful to overcome difficulties associated with a vertical approach.
In many situations, ESD becomes more difficult because of complications that arise during the procedure. The most important factor is bleeding control. Endoscopists with less experience can easily encounter intraprocedural bleeding requiring aggressive hemostasis, which results in a lengthy procedure. Repeat attempts at hemostasis can cause charring from coagulation, which makes it difficult to see clearly. These conditions prevent the identification of blood vessel and the muscularis, resulting in a vicious cycle of bleeding and attempted hemostasis, and may increase the risk of perforation. Control of bleeding is the key to successful ESD. Clear visualization of vessels in the submucosa and accurate cauterization are most important to control intraprocedural bleeding. Lack of experience may lead to errors in basic strategy, converting an easy procedure into a difficult procedure. Case selection based on the endoscopist’s level of experience is very important to decrease the number of ESD procedures that are considered “difficult.”
The Dilemma of Endoscopic Submucosal Dissection
Even under the difficult circumstances as described above, an R0 resection must be accomplished. In the case of a positive lateral margin, it may be rescued by additional ESD after recurrence. However, positive deep margins are a more difficult problem. Incomplete (R1) resection with positive deep margins negates the benefit of ESD and often incurs an additional otherwise unnecessary surgical resection. Histopathological examination absolutely determines the quality of ESD and the necessity for further surgical resection. The important information that predicts the risk of lymph node metastases is in the submucosal layer, not the mucosal layer. Therefore, the resected specimen should have a thick submucosal layer, which is obtained by dissection of the deep submucosal layer just above the muscularis. However, unstable endoscopic control and/or severe fibrosis can easily lead to perforation. Further, a large or circumferential mucosal incision prior to the submucosal dissection destabilizes subsequent control of the endoscope.
The less-experienced endoscopist is especially concerned with the risk of perforation and may hesitate to adequately dissect into the deep submucosal layer. Dissection of the shallow layer causes bleeding by damaging finely branched vessels resulting in a submucosal hematoma preventing clear visualization. Dissection of the shallow layer also increases the risk of damaging the resected specimen, which may limit precise pathological evaluation because of the lack of information from the submucosa. Endoscopists always suffer from this dilemma (Figure 22-3).
What Is an Ideal Submucosal Dissection?
Open surgical dissection at laparotomy is performed by a surgeon and an assistant, dividing tissue while providing both traction and countertraction simultaneously so the operator recognizes blood vessels, cutting in the precisely desired plane. Ideal dissection always requires both appropriate traction and countertraction, allowing tissue to be adequately extended and safely dissected.
In the world of ESD, endoscopists have tried to obtain traction on tissue. However, traction during an endoscopic resection is quite difficult because the working channel is occupied by the resection device. Several traction devices including double endoscopes and external grasping forceps have been reported.7–10 Simple and reasonable methods include traction-assisted ESD using the clip-with-line method or the S-O clip method.
Traction-Assisted Endoscopic Submucosal Dissection Using the Clip-With-Line
This method is frequently used in ESD of esophageal and rectal lesions because the endoscope is easily moved and extracted during the ESD procedure. With this technique, dental floss with an endoclip is used to provide traction during dissection. ESD of gastric lesions using dental floss with a clip has been associated with shortened procedure time and reduced costs compared with conventional ESD.11
Traction-Assisted Endoscopic Submucosal Dissection Using the S-O Clip
The S-O clip has a spring and is applied to the wall, opposite the tumor. Interestingly, the spring continues to provide traction on the tumor so the submucosal layer is always exposed. A prospective study reported the usefulness of this device.12 This strategy can be applied to ESD throughout the GI tract.
The Pocket-Creation Method
Outline of the Procedure
After submucosal injection and mucosal elevation, the initial mucosal incision is minimal, while most of the mucosa surrounding the tumor remains intact. The tip of the endoscope enters the submucosa layer and dissection proceeds at the appropriate level, just above the muscularis. After completely dissecting the submucosa under the tumor, the surrounding mucosa is incised. This eliminates the need for a retroflex maneuver.
Strengths of the Pocket-Creation Method
The tip of the endoscope is stabilized by entering a submucosal pocket. It can be synchronized with, and less influenced by, cardiac and respiratory movements. Consequently, the endoscopist can select the level of dissection in the submucosal pocket. As described earlier, dissection of the deep submucosal layer in the pocket provides a comfortable ESD without the bleeding associated with fine-branched vessels and the abundant fat in the shallow submucosal layer. A resected specimen with a thick submucosal layer facilitates precise pathological diagnosis. A minimal mucosal incision is the key point in performing PCM. This prevents dispersion of the injected solution and maintains adequate mucosal elevation. Re-elevation is readily obtained by reinjection. Even with an initial vertical approach, once the tip of endoscope gets into the pocket, a tangential approach to the muscularis is easily obtained by entering the pocket. Because the pocket is a closed space, the endoscopist obtains countertraction as well as traction via the transparent hood. PCM provides “ultimate” traction without the need for special devices.
PCM always provides similar visualization in the pocket regardless of the level of experience of the endoscopist once the tip of endoscope enters the pocket. PCM can be used universally and is useful for ESD in difficult situations (Figure 22-4).
Development of the Pocket-Creation Method
We began performing endoscopic mucosal resection with a circumferential incision using the needle knife13,14 to precisely determine the lateral margin in 1998. However, we soon realized the importance of the deep margin rather than the lateral margin for reliable curative resections. To obtain a negative deep margin, we first reported15 submucosal dissection with clear visualization using a small-caliber-tip transparent hood (ST hood) in 2003 (Figure 22-5). Although we developed a tunneling method to accomplish safe submucosal dissection by making a tunnel, the main objective of this method is to dissect the submucosal layer under the tumor rather than making a tunnel.16 After continued improvement, we established PCM and reported it17,18 in 2014. We first reported its use for the ESD of a giant colorectal semi-pedunculated neoplastic lesion with rigid fibrosis.17 Since then, we have further reported the usefulness of PCM for gastric, colorectal, and duodenal ESD.5,19,20