These parameters cannot, at the present time, be determined by non-invasive imaging techniques.

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1 Endoscopic Mucosal Resection for Upper Gastrointestinal Lesions Kenneth K. Wang, M.D. Chairman, WEO Publication and Guidelines Committee Professor of Medicine, Mayo Clinic Rochester, Minnesota Upper gastrointestinal lesions should be described using a standard terminology in order for endoscopists to compare their results. In 2003 a paper was published from a meeting held in Paris to classify superficial neoplastic lesions of the esophagus, stomach, and colon. The proceedings of the meeting were published as a supplement to the journal, Gastrointestinal Endoscopy. This produced the so-called Paris classification for intraluminal lesions. In a more recent update, an international meeting was held to redefine this classification. All adenomas are benign, and by definition are confined to the epithelial component of the mucosa without invasion beyond the basement membrane. Another term for this is intraepithelial neoplasia. The detection of superficial intraepithelial neoplasms is currently performed endoscopically with white light, chromoendoscopy, or a variety of techniques for changing the wavelength of light to enhance the mucosal vascular characteristics. The Paris classification of superficial intraepithelial neoplasia is a strict hierarchical categorization, preceded by the number 0 in order to distinguish this from the Forrest classification of bleeding which uses the same Roman numerals but has no preceding digit such as "0" or "1". These indicate pedunculated or sessile polyps whose height is over 2.5 mm. If the elevation of sessile lesions above the surface of the mucosa is less than 2.5 mm, they are denoted as 0-IIa, and if absolutely flat, the descriptor is 0-IIb. If the lesion is depressed, it is termed 0-IIc, and if excavated or ulcerated, it is 0-III. Lesions larger than 10 mm that are spreading superficially across the mucosa are categorized as lateral spreading tumors. Following removal of any lesion, careful histological assessment is necessary to assess the completeness of resection as well as the possibility of malignancy. Histological classification of malignancy differs between the United States and European pathologists. In the United States, there is an requirement for invasion of the basement membrane versus the European view in which there is an assessment of nuclear cytoplasmic ratio, the cellular polarity, and pleomorphic changes for determination of carcinoma. The depth of penetration is the one of the most important assessments for prognosis. If a tumor invades through the muscularis mucosa, the mucosal lesion is termed submucosal, and the prognosis depends on the grade of the malignancy, the depth of invasion, and the presence or absence of lymphovascular invasion. 3 These parameters cannot, at the present time, be determined by non-invasive imaging techniques. EMR for UGI Lesions (Wang Paper; JDW Rewrite) 1

2 Although many superficial cancers of the GI tract can now be endoscopically treated for curative intent, an R0 resection must be performed, meaning that there is no residual malignancy following its removal. 4 In order to make this determination, sufficient tissue needs to be collect and sent for critical assessment by the pathologist so that the completeness of resection can be evaluated. Endoscopic mucosal resection (EMR) techniques have been developed for total en bloc removal of lesions in the 1-1.5cm diameter range. There are two primary techniques for removal of lateral spreading polyps in the upper intestinal tract. One involves a cap and snare technique, and the other is a band and snare procedure. Both techniques resect similar tissue sizes. The cap technique can be performed with large size caps that can hold and remove over 2 square cm of tissue. In performing EMR using the cap technique, it is important that fluid be injected into the submucosa to ensure that the mucosa under the polyp is free and not bound down to deeper tissue. If the tissue elevates well, it can usually be resected using the various mucosal resection techniques. The usual injection solution is a 1:200,000 dilute epinephrine solution. Some endoscopists prefer to add a drop or two of indigo carmine or methylene blue to the injected solution in order to provide a greater contrast between the pink polyp on a bed of blue fluid injected in the submucosal layer. Cap Technique The cap technique employs a short transparent cylindrical hood that is placed on to the tip of the endoscope prior to the procedure. On the inner edge of the hood (which contacts the tissue) there is a small lip that allows a snare to be seated around that orifice so that, when tissue is aspirated into the cap, closing the snare handle captures the tissue permitting transection through the mucosal layer. This technique is relatively inexpensive. The caps may have a straight end or can be slanted; the oblique caps are able to resect a greater amount of tissue during aspirationpolypectomy. Hard plastic caps can provide more control over the amount of tissue that is aspirated, but a soft plastic cap is easier to pass through the cricopharynx. The cap technique can be used to resect tissue that is difficult to remove such as residual neoplastic tissue after a prior mucosal resection. The snares used to perform the resection are single use and if another resection is to be performed, a separate snare needs to be employed as the snare becomes deformed with one use. Band Technique A variceal band ligator is used to form a pseudo-polyp by aspirating and then banding tissue in the same fashion as banding an esophageal varix. For this simple and effective technique, it is necessary to use an adapter that permits passage of a snare alongside the control strings for the band ligator. Band devices are available for in various sizes both therapeutic and diagnostic EMR for UGI Lesions (Wang Paper; JDW Rewrite) 2

3 endoscopes. The six band cap permits that many resections per session. Tissue pre-injection is not necessary although many utilize it to increase the level of safety of the procedure. Once a lesion is identified, the tissue is suctioned deep into the cap and a ligation band placed around the captured tissue base. A snare, which can be reused for multiple resections, is then used to resect the lesion. From a technical viewpoint, this is the simplest technique for mucosal resection. Endoscopic Submucosal Dissection Endoscopic submucosal dissection (ESD) has the ability to remove larger lesions. The technique requires submucosal injection under one end of the lesion and then to incise the mucosa adjacent to the lesion, gradually tunneling underneath the lesion, using frequent reinjections to maintain a submucosal cushion until the lesion has been totally resected. This procedure takes considerably longer than the EMR method, and the dissection must be performed very carefully in order to prevent dissection deep through the muscularis propria. An assortment of dissecting tools is used for the ESD technique, and they are basically electrosurgical devices. The injection solution for ESD is usually a long lasting compound such as hyaluronate, glycerol, or hydroxypropyl methylcellulose. The hydroxypropyl methylcellulose is the same ingredient as in moisturizing eye drops such as Artificial Tears or Gonak but is also sold under a variety of other names. The solution is sterile and is injected in a 1:2 dilution. Other solutions can be injected and include 50% glucose, hypertonic saline, collagen, and blood, all of which have been used and appear to work similarly with a submucosal cushion sustained for a considerably longer interval than saline injection. The injection solution is often mixed with a small amount of indigo carmine or methylene blue to permit the endoscopist to determine the location of the submucosal space by the color of the solution. This procedure is best conducted in the stomach where the neoplastic tissue can be approached en face, but ESD can be performed at the cardioesophageal junction and in the gastric cardia in retroflex position which actually is more stable to perform ESD. This technique requires great expertise, and should only be performed by individuals who have been trained in the technique. The dissection requires identification and cautery of bleeding lesions as well as understanding the location of the submucosa and muscularis mucosa. The appropriate lesions for EMR are those that are usually flat or slightly elevated, less than 20-25mm in diameter, and those that have low or high grade dysplasia or low grade carcinoma and are limited to the mucosa. 5 Ulcerated lesions can be approached with EMR, but then it is more difficult to perform and there is a higher rate of neoplasia recurrence following EMR. During the initial approach to a mucosal intraepithelial neoplasm is the best opportunity to completely resect an area of neoplasia. I suggest the band procedure as the first attempt to eradicate these lesions. After any attempt, subsequent EMR is more difficult due to scarring from healing of the EMR for UGI Lesions (Wang Paper; JDW Rewrite) 3

4 ulcers produced as a result of the first procedure. Post EMR strictures are not a problem when the resected area is less than 75% of the circumference of the esophagus. However, certain individuals seem to produce scar tissue more readily than others. In my personal experience, I have seen a stricture following an EMR where less than 30% of the circumference was removed along with the intraepithelial neoplasm. High cervical esophageal lesions seems to have a greater risk for a stricture than the distal tubular esophagus. When removing a small segment of Barrett esophagus in its entirety, band EMR is the usually the best technique. This so-called widespread EMR, or radical EMR, can be used to completely remove Barrett s esophagus, but is associated with a stricture rate in 50% of patients. 6 EMR with a cap is more controlled in terms of removing a precise area of a lesion since the lesion can be suctioned in the cap several times to ensure that it is appropriately centered in the cap and that all of the lesion is included. Endoscopic Submucosal Dissection (ESD) ESD is reserved for larger neoplastic lesions that are still confined to the mucosa. The problem is that one cannot be certain if these lesions are only limited to the mucosa until they are removed and examined by the pathologist. In Japan, where these techniques originated, there appears to be a large amount of superficial spreading gastric cancers that can be large in diameter and yet do not penetrate through the mucosal layer. In Western countries, these lesions are less common. The preponderance of the evidence strongly suggests that lesions greater than 1.5cm in size should be removed en bloc by ESD and are associated with a decreased recurrence rate The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon. Gastrointest Endosc. 2003; 58: S Lambert R, Kudo SE, Vieth M, et al. Pragmatic classification of superficial neoplastic colorectal lesions. Gastrointest Endosc. 2009; 70: Badreddine RJ, Prasad GA, Lewis JT, et al. Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma. Clinical Gastroenterology & Hepatology 2010; 8: Wang KK, Prasad G, Tian J. Endoscopic mucosal resection and endoscopic submucosal dissection in esophageal and gastric cancers. Current Opinion in Gastroenterology 2010; 26: Ell C, May A, Gossner L, et al. Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus. Gastroenterology 2000; 118: Pouw RE, Seewald S, Gondrie JJ, et al. Stepwise radical endoscopic resection for eradication of Barrett s esophagus with early neoplasia in a cohort of 169 patients. Gut 2010; 59: EMR for UGI Lesions (Wang Paper; JDW Rewrite) 4

5 7. Yamaguchi Y, Katusmi N, Aoki K, et al. Resection area of 15 mm as dividing line for choosing strip biopsy or endoscopic submucosal dissection for mucosal gastric neoplasm. Journal of Clinical Gastroenterology 2007; 41: EMR for UGI Lesions (Wang Paper; JDW Rewrite) 5