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3. Gastric and Duodenal Endoscopic Mucosal Resection
Keywords
Submucosal normal saline injectionCap-assisted endoscopic mucosal resection (EMRC)Endoscopic aspiration mucosectomy (EAM)Ligation-assisted EMRUnderwater EMR (UEMR)Introduction
Endoscopic mucosal resection (EMR), previously known as mucosectomy, is a minimally invasive procedure currently being recommended as treatment for early malignant lesions of the gastrointestinal tract [1]. Endoscopic removal of tumors has been reported as early as 1973 when polypectomy was performed using electrocautery [2], but EMR for early gastric cancer was pioneered by the Japanese in 1983 [3]. The techniques and devices used for EMR have come a long way since Tada’s strip biopsy using saline injection into the mucosa [4], but this method is still being used up to this day. This chapter will focus on EMR for gastric and duodenal lesions. This chapter will focus on the following domains: (i) indications, (ii) endoscopic techniques, (iii) contraindications, (iv) benefits and clinical outcomes, and (v) adverse events associated with EMR.
Clinical Indications
This treatment option for GI malignancy is enticing, but meticulous selection of patients must be done before considering EMR. Because this technique should be utilized to remove mucosal lesions, this technique should be limited to lesions that are within the mucosal layer (lesions that do not breach the muscularis mucosa). A review by Soetikno and colleagues published in 2003 [5] acknowledged the importance of the estimation of depth of the lesion, as well as the limitations of the technology they were using at the time. In the current ASGE technical review [1], EMR is a treatment option for the definitive management of premalignant and early-stage (T1N0) malignant lesions and should not be performed in lesions which are deeper than the mucosa. The Japanese gastric cancer treatment guidelines [6] state that lesions that are amenable to endoscopic resection are those with no evidence of lymph node or vascular involvement and well-differentiated T1a lesions not bigger than 3 cm if with ulcerations or more than 2 cm in size without ulceration. If the lesion is undifferentiated, it may still be resected endoscopically if it is non-ulcerative and not larger than 2 cm. These guidelines, however, recommend the performance of endoscopic submucosal dissection (ESD) over EMR to avoid incomplete resection.
The non-lifting sign, which is a predictor of depth of invasion of the tumor [7, 8], is useful in determining whether or not a lesion is amenable to EMR. Failure of a lesion to completely lift after submucosal injection, unless thought to be secondary to fibrosis from a previous biopsy, usually means that the tumor has invaded deep into the submucosa or beyond. Endoscopic ultrasound (EUS) is currently the best diagnostic tool for locoregional staging . While some authors will point out that nodal metastases are better diagnosed with cross-sectional imaging, it cannot be contested that EUS is better in T staging, especially in small gastric tumors, which becomes more relevant because it is concerned more about tumor depth than size. However, the best diagnostic approach is a combination of these imaging modalities.
Recently, endoscopic methods like high-resolution magnification and mucosal enhancement technologies are increasingly used to identify suitable lesions for EMR. Clinical application of such endoscopic image technologies to determine depth of lesions before the removal procedure will be discussed in other chapters.
Endoscopic Techniques
Injection Assisted
As previously mentioned, submucosal normal saline injection was the first technique employed to perform EMR. Several solutions are now being used as “lifting” agents, but the idea remains the same: an endoscopic needle is passed through the working channel and directed onto multiple points surrounding the area in question to provide a cushion between the mucosal lesion and the deeper submucosa to facilitate an easier and safer endoscopic resection. At this day, en bloc resection of lesion is preferred over piecemeal resection, if possible.
Normal saline is still very commonly used as a lifting solution , but the main problem is that the cushion it provides usually subsides within a few minutes. Other solutions being used are 3.75% NaCl, 20% dextrose water, glycerin-fructose solution, and sodium hyaluronate [9]. Yamamoto has shown that a 0.4% hyaluronic acid solution provides a longer-lasting cushion which results in significantly steeper lifts and less reinjections [10]. In a systematic review of literature, however, Ferreira et al. have found that sodium hyaluronate solutions clinically perform just as well as normal saline and may not be cost-effective [11].
Device Assisted
Several devices are developed to make EMR easier. Probably the most common of these devices is the cap or hood, which is a transparent plastic extension fitted onto the tip of the endoscope for the purpose of applying suction and lifting the mucosa with the lesion while being able to easily apply a cutting or ligating tool no different with the principle of endoscopic band ligation. Cap-assisted endoscopic mucosal resection (EMRC) or endoscopic aspiration mucosectomy (EAM) begins with marking the border of the lesion with an electrocautery device followed by injection of the lifting solution into the submucosa to raise the lesion. A cap is then fitted onto the scope tip, and a snare is opened and positioned in a groove within the cap. The cap is then positioned over the raised lesion where suction is applied retracting the mucosa toward the tip of the scope within the cap where the snare is used to guillotine the mucosa using electrocautery.
Ligation-assisted EMR is similar to cap-assisted EMR. But as the name implies, this method is similar to what is done during variceal endoscopic band ligation. A cap is fitted onto the tip of the endoscope and positioned over the mucosa of the lesion. The mucosa is lifted by suction into the cap without the need for submucosal injection. After deployment of the ligator, a pseudopolyp is then produced, and resection of the mucosa will be completed by a snare with electrocautery just like a standard snare polypectomy.
Underwater EMR
First described in 2012 by Binmoeller [12], underwater EMR (UEMR) is more commonly used for endoscopic resection of large colorectal lesions [13–16]. There is a report from 2014 about the performance of UEMR for removal of large duodenal adenomas [17]. The rationale of performing EMR underwater is the muscularis propria floats into the bowel lumen without the compression effect of air allowing it to be static independent of the changes of the mucosa and submucosa, even during peristaltic contractions [16]. This means that submucosal injection is not necessary before resection with a snare. Since this technique is usually employed in large lesions, as well as lesions in which prior EMR failed to achieve complete resection [1], the lesion is usually removed in a piecemeal fashion. A low-profile cap is likewise attached onto the tip of the endoscope similar to cap-assisted EMR, but its purpose is to facilitate visualization of the lesion rather than providing room for mucosa that is being “lifted” toward the endoscope.
Contraindications
The obvious clinical contraindication of performing EMR is the presence of a more advanced tumor. The lesions that are amenable to this procedure have been discussed above, and those that are more advanced than the aforementioned lesions are therefore not good candidates for EMR. Procedural contraindications to other endoscopic procedures also apply to EMR.
Clinical Outcomes
Long-term results of endoscopic resection of early gastric cancer in carefully selected patients show that complete remission is achieved by endoscopic therapy in 97% of patients over one to three endoscopic therapy sessions spread in an average of 3.5 months [18]. In an earlier trial, the complete remission rate was 89% and required one to four endoscopy sessions [19]. However, despite this good numbers, the fact remains that despite en bloc resection, it does not eliminate the possibility of metachronous or synchronous lesions, which can be present in about 3.2% and 35%, respectively [20, 21]. Also, the local recurrence post-endoscopic treatment is 4.1%, with only one of those patients needing a repeat endoscopic resection [21].
Adverse Events
In general, the most common complication of EMR is bleeding, which occurs in an average of 10% of cases [1]. The risk of bleeding increases with the size of the tumor being resected, from 4% on subcentimeter lesions to 32% on lesions larger than 3 cm [19]. However, the risk of bleeding from gastric and duodenal EMR ranges from 0% to 16% [1, 22], and the risk of delayed bleeding is 5% [22]. Perforation is the most serious complication of endoscopic mucosal resection. Perforation risk in gastric and duodenal EMR is about 1% and 2%, respectively [23, 24].
Conclusions
As with any advanced endoscopic technique, the risk of adverse events is inversely related to endoscopist experience. It is therefore recommended that these techniques be performed by expert endoscopists with an equally experienced endoscopy team or a novice therapeutic endoscopist under close supervision by an expert until the learning curve is overcome.
