Mucosectomy in the Colon with Endoscopic Submucosal Dissection

• Objectives
• Basic Principles
• Material Used
• Injecting Fluid
• Injection Needle
• Electrosurgical Knife
• Hood
• Electrosurgical Current Generator
• Hemostatic Forceps
• Clip
• Description of Procedure
• Strategy for ESD
• Mucosal Incision
• Submucosal Dissection
• Limitations and Success Rate
• Complications and Safety
• Bleeding
• Perforation
• Indications
• Necessary
• Appropriate
• Inappropriate
• References

Objectives

The most important factor which predicts the probability of metastasis in early-stage cancers of the colon is the depth of cancer invasion. The probability of lymph node metastasis is minimal if cancer invasion is limited to within the mucosal layer. For superficial-type cancers, the size of the lesion is not as important as the depth of invasion in determining the risk of lymph node involvement. Large superficial tumors, so-called “laterally spreading tumors” (LST), in the colon have little tendency to vertical growth despite their lateral extension. Therefore, they are best removed by endoscopic mucosal resection (EMR). To ensure the curativeness of the EMR, accurate histopathologic assessment of the resected specimens is essential, because a significant amount of submucosal invasion of the tumor suggests considerable risk of lymph node metastasis, which necessitates additional surgery.

The objectives of performing endoscopic submucosal dissection (ESD) are to ensure reliable en bloc resections of superficial neoplastic lesions and to confirm the completeness of the resection with an accurate histopathologic assessment. ESD offers a reliable and curative treatment with minimum invasiveness.

Basic Principles

To ensure a reliable en bloc resection, the margin of the tumor is delineated by spraying it with indigo carmine dye, and a mucosal incision and a submucosal dissection are then made with an electrosurgical knife to resect the entire lesion in one piece without resorting to the use of a polypectomy snare.

It is important to note that some of the ESD techniques used for lesions in the stomach could be risky if applied to lesions in the colon, because the colonic wall is thinner and softer than the stomach wall. For ESD in the colon, it is important to use a dissecting technique that allows direct visualization of the submucosal tissue, and to use a long-lasting injecting fluid [1].

Material Used

Injecting Fluid

Normal saline is the most popular injecting fluid for conventional EMR. However, the mucosal protrusion created with injection of normal saline does not last long enough to provide sufficient time for submucosal dissection [2].

In order to create a long-lasting mucosal protrusion, several other fluids have been used for ESD; among those, sodium hyaluronate is the most effective fluid for maintaining mucosal protrusion [2] [3]. Sodium hyaluronate has high viscosity and has been approved for clinical use in intra-articular injections for osteoarthritis. It is harmless to the injected tissue because of its isotonicity, despite its high viscosity [2]. It is also able to retain epinephrine locally.

The sodium hyaluronate products intended for intra-articular injections are too viscous to inject through an endoscopic injection needle. Therefore, they are diluted when used for ESD [4] [5] [6]. For example, 1.0 % sodium hyaluronate solution with an average molecular weight of 800 kDa (Artz 1 %; Kaken Pharmaceutical Co., Tokyo, Japan; derivative type, rooster comb) is diluted to 0.5 % by mixing with the same volume of normal saline solution. Higher molecular weight sodium hyaluronate (Suvenyl 1 %, Chugai Pharmaceutical Co., Tokyo, Japan, average 1900 kD) is diluted to 0.25 % by mixing with normal saline or to 0.125 % with dextrose [7]. A mixture with a small amount of epinephrine (0.001 %) is effective for control of bleeding during the procedure. A mixture of indigo carmine dye (0.004 %) is optional. A small caliber syringe such as a 5-ml syringe and a high flow injection needle should be used to minimize the resistance to injection.

To inject sodium hyaluronate solution into the appropriate submucosal layer of the thin wall of the colon, pre-injections of normal saline into the submucosal layer are useful. The injected sodium hyaluronate remains localized, even after the injected normal saline is dispersed.

Injection Needle

For the injection of sodium hyaluronate solution, a high flow injection needle with a large inner lumen should be used to minimize injecting resistance. We use a disposable Teflon sheath injection needle of 23 G (NM-200L-0423; Olympus, Tokyo, Japan).

Electrosurgical Knife

Several kinds of electrosurgical knives have been developed for ESD.

Needle knife. The needle knife (KD-10Q-1; Olympus) has a fine tip and a small contact area, which allows a sharp incision (Figure [1] a). Since it is very sharp, operators should be careful to prevent perforation or bleeding when they use this type of knife. To use this needle knife safely, it is advisable to employ a transparent endoscopic hood at the same time, and to use sodium hyaluronate as an injecting fluid.

Hook knife. At the end of the hook-type knife (KD-620LR; Olympus), 1 mm of the tip is bent, forming a right angle (Figure [1] b). Operators can hook and pull the submucosal tissue before they incise it, which improves safety. Safety is further enhanced if operators use a transparent hood at the same time, so that they pull the tissue into the hood before cutting it. This knife has a rotating function so that operators can select any direction for hooking.

A hook knife is useful to prevent bleeding. Operators can cut small vessels, 1 mm or less in size, without bleeding if they use argon plasma coagulation (APC) mode (60 W). Also, if bleeding should be caused, hemostasis is possible by coagulation with the back of this hook knife [8].

Flex knife. The point of the flex knife (KD-630L; Olympus) (Figure [1] c) is rounded with a twisted wire like a snare. The sheath is soft and flexible. A flex knife is less likely than a needle knife to cause perforation when it reaches the muscular layer, since the point of the flex knife is round, and the entire knife is soft and flexible. In addition, the length of the knife is adjustable according to circumstances. Operators can therefore use it with relative safety. Since the tip of the sheath is thick and functions as a stopper, operators can control the depth of incision very easily [9]. It is very important to use a transparent hood for a better visualization of the operating field.

Insulated-tip knife. An insulated-tip knife (KD-610L; Olympus) is a needle-knife that is equipped with a ceramic ball at its point. This type of knife was developed for safe performance of ESD, as the point is blunted and insulated to prevent perforation. The insulated-tip knife is most frequently used for ESD of the stomach, and special care should be taken when it is used for ESD of the colon. When operators dissect the submucosal layer using an insulated-tip knife, they can only incise in a direction from the outside to the inside of the tumor. The wall of the colon has a thin and soft muscular layer and creases easily. If operators incise a tumor of the colon with the wall creased, they could perforate the wall with the knife.

Hood

To perform ESD safely, it is strongly recommended that, according to the situation, a straight or a small-caliber-tip transparent hood (ST hood) should be attached to the tip of the endoscope. The edge of the hood can be used like a surgical forceps to open an incised wound to obtain a surgical field, or to gently hold the tissue to help control a knife during an incision.

The ST hood (DH-16CR; Fujinon, Saitama, Japan) (Figure [2]) has a hood aperture small enough to make it easy to widen an incised wound using the edge of the hood, and to allow more accurate adjustment of the depth of incision by the knife point. By using this ST hood, operators can keep the tip of the knife near the center of the hood aperture. Therefore, they can easily dissect the submucosal tissue at the desired incision line within the submucosal layer, regardless of which direction the lesion is located in the endoscopic field [10]. It is very useful especially for the needle knife.

Electrosurgical Current Generator

To keep the risk of bleeding to a minimum during the ESD procedure, it is important to select the appropriate high frequency electrosurgical current generator and to set it appropriately. The Erbotom ICC200 (Erbe, Tübingen, Germany) is used as a high frequency generator for ESD in most facilities. The generator is usually set to “Endo Cut” mode for mucosal incision, and to “forced coagulation” mode for submucosal dissection. The optimal output settings for mucosal incision and submucosal dissection depend upon the type of knives used: Endo Cut mode, at effect 3, 120 W, is used for the needle knife and the hook knife, and at effect 2, 60 W, for the flex knife; forced coagulation mode is used at 25 - 30 W for the needle knife and at 40 W for the flex knife and the hook knife.

Hemostatic Forceps

Although bleeding during incision from small blood vessels may be stopped by coagulation using knives, bleeding from blood vessels whose diameters are larger than the tip of the needle knife should be treated with hemostatic forceps (HDB2422W; Pentax, Tokyo, Japan) (Figure [3]) before incision. The generator is set to soft coagulation mode (50 - 80 W) for hemostatic forceps. Operators should be cautious about overcoagulation: too much coagulation may cause delayed perforation, even in soft coagulation mode. Therefore it is important for operators to pinch a blood vessel precisely, retract it, and coagulate with a minimal contact area. The use in combination of hemostatic forceps and water-jet furnished endoscopes (Pentax and Olympus, Tokyo; Fujinon, Saitama) is very useful for the visualization of bleeding vessels.

Clip

If bleeding cannot be controlled with hemostatic forceps, use a clip. It is better to apply a clip (HX-6UR-1; Olympus) as far as possible from the incised mucosa so as not to hamper the dissecting procedures that follow hemostasis. It may be necessary to make a further small incision to identify and expose the site of bleeding before hemostasis. In addition, a clipping device is indispensable in cases of perforation. Operators have to close perforated holes immediately after the perforation, before any leakage of intestinal fluid, in order to prevent severe peritonitis.

Description of Procedure

Strategy for ESD

To perform ESD of the colon successfully, it is important to create a strategy that includes the order of incisions and dissections of the mucosa and submucosa. The wall of the colon is so thin that it becomes very difficult to dissect it if submucosal thickening disappears. Therefore, the strategy should allow operators to complete their dissection with submucosal thickening that lasts for the duration of the procedure.

The operators should elevate the mucosal area to be dissected by injecting a sufficient amount of sodium hyaluronate into the submucosa. The mucosal incision should be made only for the area to be dissected and then dissection of the submucosa from the incised part must be started promptly. If operators perform circumferential mucosal incision and postpone submucosal dissection, even viscous sodium hyaluronate will eventually drain from the incised wound, resulting in loss of submucosal thickening, which makes completion of the procedure difficult.

The following is an example of such a strategy. Start with an incision, and dissect from the most distant edge of the tumor, to make the end point of dissection from the proximal edge. Make an incision and dissect the proximal part of the tumor along the uppermost side of the tumor, in terms of gravity. When dissection has progressed to the central part of the tumor from the upper side, reverse the position of the patient so that the side of the tumor that had been lower is now at the higher level, in terms of gravity. Keep a sufficient mucosal protrusion by making an additional injection of fluid into the submucosa, if necessary, and then resume incision and dissection of the mucosa covering the remaining part of the tumor. When enough dissection has been done, complete the dissection from the direction of easiest approach (if the direction of dissection before positional change is easier, then change the patient’s position back to the original one and complete the dissection from the previous direction). This strategy prevents drainage of the submucosal fluid cushion that could make dissection very difficult. Even if dissection takes a long time and injected fluid diffuses out, it is still possible to give additional injections at any time as long as the mucosa remains to be incised.

Mucosal Incision

After a sufficient protrusion of the mucosa is produced, mucosal incision around the tumor is made with a needle knife or a flex knife. A transparent hood, 8 mm in length and attached at the endoscope tip, should be used to ensure the safety of a mucosal incision. The transparent hood at the endoscope tip can halt unintentional movements of the colonic wall toward the knife and prevent perforation. Endo Cut mode, according to the previously mentioned settings, is used for the mucosal incision. Submucosal dissection should be done immediately after the mucosal incision of that area. Mucosal incision all around the tumor before starting submucosal dissection should be avoided unless the tumor is small.

Submucosal Dissection

For the submucosal dissection, forced coagulation mode, according to the previously mentioned settings, is selected. When using the flex knife, a straight transparent hood is necessary for a better view of the incision line. On the other hand, when making a submucosal incision with a needle knife, it is safer to widen the incised wound using the ST hood, visually recognize submucosal connective tissue fibers, and then slide the knife from the center of the tumor toward the mucosal incision at the side, while hooking submucosal fibers with the knife. Submucosal dissection should be done parallel to the muscular layer, along a plane superficial by one-third of the submucosal thickness to the interface between the submucosa and the muscular layer. If the operator cannot get sufficient submucosal thickness, or if it is difficult to get a good field of view of the dissection plane, then the operator should gently dissect the submucosa little by little by hooking submucosal fibers using a hook knife.

A sample case of ESD in the colon is shown in Figure [4].

Limitations and Success Rate

The success rate depends mostly on the skill of operators. Although skilled operators can perform ESD regardless of the location or size of the colonic lesions, it is only safe for novices to perform ESD for rectal lesions. Large lesions may take a considerable time to dissect, but we can cure even large lesions consistently, and we can make more accurate judgments about therapy based on pathological assessments. In our experience, we have succeeded in performing en bloc resection in over 90 % of large lesions.

Complications and Safety

Bleeding

In ESD, postoperative bleeding is rare despite the fact that we perform mucosal excision from a relatively wide area, probably because we carry out hemostasis together with dissection. In less than 1 % of our cases we have encountered postoperative bleeding that required hemostatic procedures. This postoperative bleeding ratio is much less than that of gastric ESD, probably because the size of the blood vessels of the colon is much thinner than that of the stomach.

Perforation

Perforation is a major concern as a possible complication of ESD, especially for large superficial lesions of the colon. In endoscopic submucosal dissection using sodium hyaluronate, perforation can be prevented by ensuring sufficient thickening of the submucosa by proper injection with sodium hyaluronate and careful selection of the incising layer. Even if this complication occurs during the procedure, the perforation made by a knife is usually tiny and recognized immediately; therefore, the perforation can be closed with endoscopic clip placement and can be managed conservatively. The perforation rate in our recent cases is less than 1 %.

Indications

Necessary

• A necessary indication is early superficial carcinoma for which the standard snaring method is not feasible due to its size and location, or because of insufficient lifting with submucosal injections.

Appropriate

These include:

• large superficial benign adenoma for which en bloc resection is not feasible with the standard snaring method; and

• small submucosal tumor, including carcinoid tumor, located within the submucosal layer.

Inappropriate

These include:

• small adenomas for which en bloc resection with the standard snaring method can be easily performed;

• advanced cancer; and

• submucosal tumors originating from the proper muscle layer.

References

• 1 Yamamoto H, Sunada K, Miyata T. et al . Endoscopic submucosal dissection using sodium hyaluronate for large superficial tumors in the colon.  Dig Endosc. 2004;  16 178-181
  CrossrefPubMedSearch in Google Scholar
• 2 Yamamoto H, Yube T, Isoda N. et al . A novel method of endoscopic mucosal resection using sodium hyaluronate.  Gastrointest Endosc. 1999;  50 251-256
  CrossrefPubMedSearch in Google Scholar
• 3 Fujishiro M, Yahagi N, Kashimura K. et al . Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.  Endoscopy. 2004;  36 579-583
  Thieme ConnectPubMedSearch in Google Scholar
• 4 Yamamoto H, Koiwai H, Yube T. et al . A successful single-step endoscopic resection of a 40 millimeter flat-elevated tumor in the rectum: endoscopic mucosal resection using sodium hyaluronate.  Gastrointest Endosc. 1999;  50 701-704
  CrossrefPubMedSearch in Google Scholar
• 5 Yamamoto H, Sekine Y, Higashizawa T. et al . Successful en bloc resection of a large superficial gastric cancer by using sodium hyaluronate and electrocautery incision forceps.  Gastrointest Endosc. 2001;  54 629-633
  CrossrefPubMedSearch in Google Scholar
• 6 Yamamoto H, Kawata H, Sunada K. et al . Success rate of curative endoscopic mucosal resection with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate.  Gastrointest Endosc. 2002;  56 507-512
  CrossrefPubMedSearch in Google Scholar
• 7 Fujishiro M, Yahagi N, Kashimura K. et al . Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.  Endoscopy. 2004;  36 584-589
  Thieme ConnectPubMedSearch in Google Scholar
• 8 Oyama T, KikuchiY . Aggressive endoscopic mucosal resection in the upper GI tract - hook knife method.  Minim Invasive Ther Allied Technol. 2002;  11 291-295
  PubMedSearch in Google Scholar
• 9 Yahagi N, Fujishiro M, Imagawa A. et al . Endoscopic submucosal dissection for the reliable en bloc resection of colorectal mucosal tumors.  Dig Endosc. 2004;  16 S89-S92
  CrossrefPubMedSearch in Google Scholar
• 10 Yamamoto H, Kawata H, Sunada K. et al . Successful en bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood.  Endoscopy. 2003;  35 690-694
  Thieme ConnectPubMedSearch in Google Scholar

H. Yamamoto; M.D.

Department of Internal Medicine · Division of Gastroenterology · Jichi Medical School

3311-1 Yakushiji · Minamikawachi, Tochigi, 329-0498 · Japan

Fax: +81-285-448297·

Email: yamamoto@jichi.ac.jp

References

• 1 Yamamoto H, Sunada K, Miyata T. et al . Endoscopic submucosal dissection using sodium hyaluronate for large superficial tumors in the colon.  Dig Endosc. 2004;  16 178-181
  CrossrefPubMedSearch in Google Scholar
• 2 Yamamoto H, Yube T, Isoda N. et al . A novel method of endoscopic mucosal resection using sodium hyaluronate.  Gastrointest Endosc. 1999;  50 251-256
  CrossrefPubMedSearch in Google Scholar
• 3 Fujishiro M, Yahagi N, Kashimura K. et al . Comparison of various submucosal injection solutions for maintaining mucosal elevation during endoscopic mucosal resection.  Endoscopy. 2004;  36 579-583
  Thieme ConnectPubMedSearch in Google Scholar
• 4 Yamamoto H, Koiwai H, Yube T. et al . A successful single-step endoscopic resection of a 40 millimeter flat-elevated tumor in the rectum: endoscopic mucosal resection using sodium hyaluronate.  Gastrointest Endosc. 1999;  50 701-704
  CrossrefPubMedSearch in Google Scholar
• 5 Yamamoto H, Sekine Y, Higashizawa T. et al . Successful en bloc resection of a large superficial gastric cancer by using sodium hyaluronate and electrocautery incision forceps.  Gastrointest Endosc. 2001;  54 629-633
  CrossrefPubMedSearch in Google Scholar
• 6 Yamamoto H, Kawata H, Sunada K. et al . Success rate of curative endoscopic mucosal resection with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate.  Gastrointest Endosc. 2002;  56 507-512
  CrossrefPubMedSearch in Google Scholar
• 7 Fujishiro M, Yahagi N, Kashimura K. et al . Different mixtures of sodium hyaluronate and their ability to create submucosal fluid cushions for endoscopic mucosal resection.  Endoscopy. 2004;  36 584-589
  Thieme ConnectPubMedSearch in Google Scholar
• 8 Oyama T, KikuchiY . Aggressive endoscopic mucosal resection in the upper GI tract - hook knife method.  Minim Invasive Ther Allied Technol. 2002;  11 291-295
  PubMedSearch in Google Scholar
• 9 Yahagi N, Fujishiro M, Imagawa A. et al . Endoscopic submucosal dissection for the reliable en bloc resection of colorectal mucosal tumors.  Dig Endosc. 2004;  16 S89-S92
  CrossrefPubMedSearch in Google Scholar
• 10 Yamamoto H, Kawata H, Sunada K. et al . Successful en bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood.  Endoscopy. 2003;  35 690-694
  Thieme ConnectPubMedSearch in Google Scholar

H. Yamamoto; M.D.

Department of Internal Medicine · Division of Gastroenterology · Jichi Medical School

3311-1 Yakushiji · Minamikawachi, Tochigi, 329-0498 · Japan

Fax: +81-285-448297·

Email: yamamoto@jichi.ac.jp