Introduction. Piecemeal EMR (EPMR) Symposium

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1 Symposium Symposium II - Lower GI : Colonoscopy Issues in 2015 Resection of Large Polyps Using Techniques other than Endoscopic Submucosal Dissection: Piecemeal Resection, Underwater Endoscopic Mucosal Resection, and Hybrid Endoscopic Submucosal Dissection Hyun Gun Kim Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea Introduction Theoretically, the majority of colorectal adenomas and high-grade dysplasias which include carcinoma in situ, intramucosal cancer, and superficial submucosal (SM) carcinoma with negligible risk of lymph node (LN) metastasis due to location in the superficial submucosal layer less than 1000 μm from the muscularis mucosae can be treated by endoscopic resection, including endoscopic mucosal resection (EMR). 1 Endoscopic submucosal dissection (), which enables en bloc resection, was introduced in the early 2000s initially in Japan and is an attractive endoscopic treatment method for large colorectal tumors. 2,3 In a previous large-scale study of colorectal s, the en bloc resection rate was 91-98%, and the curative resection rate was 87-91%. 4,5 Colorectal is widely accepted as a standard procedure for the treatment of large (2-5 cm) lateral spreading tumors (LSTs), especially those suspected to involve SM invasion. 6 However, this procedure has several disadvantages, such as greater technical difficulty, longer procedure time and increased risk of complications (including perforation and bleeding) compared with conventional EMR. Several methods of endoscopic treatment for the resection of large polyps, such as hybrid and underwater EMR (UEMR), are used in Western countries, where the most frequently performed procedure is piecemeal EMR (EPMR). This review focuses on the procedures used for resection of large polyps other than, including classic EPMR, UEMR and hybrid. Piecemeal EMR (EPMR) EPMR is frequently performed for the treatment of large colorectal adenomas. Because lesions smaller than 2 cm can be removed en bloc using a snare, EPMR is applied mostly to large polyps (>2 cm) suspected to be adenomas. Compared with, this procedure is relatively simple and easy to learn, which results in a low complication rate and reduced procedure time. However, EPMR may be associated with incomplete resection and local recurrence. Because the lesion is separated into several pieces during the procedure, accurate histological evaluation can be difficult. Early data from Western countries revealed a high recurrence rate of up to 28%. 7 Recent studies of EPMR used for large colorectal tumors reported recurrence rates of 12-19%, 8-10 and piecemeal resection was associated with a threefold higher risk of local recurrence than that of en bloc resection in a large-scale Japanese study. 11 In particular, the risk of local recurrence was 19-fold higher in patients in whom piecemeal resection was performed during compared with en th Congress of the Korean Society of Gastrointestinal Endoscopy November 28, 2015

2 Hyun Gun Kim bloc. 11 Interestingly, the risk of local recurrence increased with the number of pieces resected and was threefold higher in the group in whom the tumor was resected into five or more pieces. 10,11 Because of the risk of remnant tissue or local recurrence, close surveillance is generally recommended. Repeat colonoscopy may be performed within as little as 4-6 weeks to ensure that all dysplastic tissue has been removed. For these reasons, the indications for EPMR should be limited to lesions with a low probability of superficial SM invasion, such as lateral spreading tumors greater than 2 cm and of the homogenous granular type and lesions not showing a V-type pit pattern. 12 Underwater EMR Submucosal injection is an integral part of all therapeutic endoscopic procedures, including EMR and. However, paradoxically, it may render snare capture of a flat polyp more difficult or impossible. 13 Moreover, there has been concern over an increased risk of needle tracking of neoplastic cells into deeper wall layers when injecting through the lesion. 14 A few years ago, a novel full water immersion EMR technique without submucosal injection was reported by Binmoeller et al. in the US. 15 This method may be considered a modified EPMR technique, and eliminating the need for submucosal injection before resection could be useful, particularly in Western countries where is not performed frequently. This technique was inspired by the observation during EUS that, when filled with water, the colonic muscularis propria remains circular. The folds of a nondistended colon consist of involutions of the mucosa, and submucosa floats away from the deeper muscularis layer during water immersion. Table 1. UEMR as the primary endoscopic treatment for large colorectal lesions. Binmoeller (n=62) 15 Wang (n=43) 16 Uedo (n=11) 17 Curcio (n=72) 18 Size (mm) Mean 33.8 Mean 25 Median 20 Mean 18.7 Procedure time (min) Complication rate 5%* 4.8%* 0% 0% Recurrence rate 1.9% - - 0% *Delayed bleeding. Studies of UEMR from several Western countries other than the US, including Sweden and Italy, were published recently; however, most involved a small number of cases In published reports, the total number of cases who underwent UEMR as the primary endoscopic treatment for large colorectal lesions is only The mean lesion size in these studies was mm, and the procedure time was min. Two studies that evaluated the recurrence or residual tumor rate after UEMR on surveillance colonoscopy reported a lower recurrence rate (-1.9%) compared with previous studies of EPMR (Table 1). 15,18 Also, complications during the procedure were infrequent, and although bleeding occurred during the procedure, it usually ceased spontaneously within 1 min with continuous irrigation. Delayed bleeding occurred in up to 5% of cases, and no perforation was reported. The pathologic findings of resected specimens revealed a deep SM resection margin 1600 μm from the muscularis mucosa, 18 and UEMR resulted in a free deep margin for removal of superficial intraepithelial lesions not invading the deep SM layer. Interestingly a duckbill snare has been used during UEMR (15 mm AcuSnare; Cook Medical Inc., Bloomington, IN, USA). 15 This snare, which resembles a duckbill mouse, facilitates capture of mucosa floating in water rather than capture lifted lesion after submucosal injection. However, this is not designed specifically for UEMR but is usually used for resection of small November 28, th Congress of the Korean Society of Gastrointestinal Endoscopy 29

3 Resection of Large Polyps Other Than : Piecemeal Resection, Underwater EMR, and Hybrid pieces and fibrotic lesions. According to these published studies, UEMR was efficacious, with a high success rate of removal of large, flat lesions with a short procedure duration. 16 However, hot biopsy forceps and argon plasma coagulation for residual islands of neoplasia during UEMR were required in 11.6% and 16.3% of cases, respectively; the need for these additional procedures was associated positively with lesion size. 16 It should be noted that the total number of UEMR procedures reported in the literature is still small, and further studies are needed to determine its usefulness and safety for the treatment of large colorectal lesions. Two studies on the usefulness of UEMR were published recently, one pertaining to resection of recurrent lesions after EPMR and the other pertaining to lesions on the appendiceal orifice. 19,20 Considering the scant published data and lack of a standard strategy, UEMR may be effective for salvage endoscopic treatment of recurrent adenomas after EPMR. 19 EMR with pre-cut incision and hybrid En bloc resection is important for complete R0 resection and prevention of recurrence. Although colonic is the optimal procedure for en bloc resection of large lesions, standardization is difficult, and adoption of the technique remains slow. EMR with pre-cut incision is a modified method that enables en bloc resection during EMR. As there is no standard term for this procedure, various names have been used, including EMR with pre-cut incision, EMR with circumferential incision (EMR-CI), -universal, with snaring, and hybrid. 21,22 The term EMR with pre-cut incision or EMR-CI is used to describe EMR with circumferential mucosal incision without partial submucosal dissection. The mucosal incision can facilitate optimal snare positioning and improve the ability to grasp the entire lesion with the snare. However, only circumferential mucosal incision may not facilitate en bloc resection of large lesions (>4 cm) unless the lifting tension was maintained. Very limited published studies on EMR-CI have reported clinical outcomes, yielding an en-bloc resection rate of approximately 66~67% for 2~4 cm colorectal lesions. 23,24 The indications for EMR-CI could thus be similar to those for hybrid, but for smaller lesions. To increase en-bloc resection rate, partial submucosal dissection following mucosal incision could be performed before snaring to facilitate capture. Terms such as hybrid, -universal, and with snaring are used to describe snaring after partial dissection following circumferential mucosal incision. 22 The results of were superior to those of hybrid in terms of complete resection rate and safety (Table 2). 22,25,26 Table 2. Outcomes of hybrid versus. Byeon 22 Toyonaga 25,27 Yoshida 26 (n=74) (n=163) (n=44) (n=468) (n=22) (n=466) Mean size (mm) * Procedure time (min) 35 49* En bloc resection (%) 64 87* R0 resection (%) 57 75* Complications (%) Immediate bleeding Delayed bleeding Perforation , hybrid th Congress of the Korean Society of Gastrointestinal Endoscopy November 28, 2015

4 Hyun Gun Kim * p < 0.05 Lesions subjected to hybrid were smaller than those subjected to ; hybrid has typically been used for lesions less than 4 cm in diameter. 22,25,26 Hybrid has a shorter procedure duration, and the en bloc resection rate is significantly lower than that of, especially for lesions larger than 20 mm in diameter. 22 The en bloc resection rate was 64-91% and differed markedly among individual endoscopists, possibly due to lesion size and the degree of partial submucosal dissection before snaring. Capturing large lesions using a snare became easier as the frequency of submucosal dissection increased. Interestingly, hybrid is not safer than. Albeit without statistical significance, possibly due to the small number of cases with complications, the rate of complications during hybrid, such as perforation and delayed bleeding, was similar to or higher than that of. These facts suggest hybrid to be a good option for lesions that can be fully removed by piecemeal resection, but lesions smaller than 3-4 cm are often unsuitable for. 25 Conclusion Colorectal is a good option for endoscopic treatment of large lesions suspicious for early stage cancer, but its adoption is hampered by its technical difficulty, prolonged duration and high complication rate. EPMR could be considered an old-fashioned procedure but is still widely performed for LST with a low probability of SM invasion. However, the high rate of recurrence and short-term surveillance after EPMR are disadvantages of this technique. Hybrid, including -CI, could overcome this disadvantage of EPMR and provide a good introductory step to. UEMR is another option to replace EPMR but is not commonly performed in Korea, where the use of is increasing. Further studies are needed to establish its safety and clinical effectiveness, including the rate of recurrence. Thus the procedure for resection of large colorectal lesions should be selected according to the individual lesion. References 1. Lambert R, Kudo SE, Vieth M, et al. Pragmatic classification of superficial neoplastic colorectal lesions. Gastrointest Endosc 2009;70: 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: Fujishiro M, Yahagi N, Kakushima N, et al. Outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms in 200 consecutive cases. Clin Gastroenterol Hepatol 2007;5:678-83; quiz Saito Y, Sakamoto T, Nakajima T, Matsuda T. Colorectal : current indications and latest technical advances. Gastrointest Endosc Clin N Am 2014;24: Lee EJ, Lee JB, Lee SH, et al. Endoscopic submucosal dissection for colorectal tumors--1,000 colorectal cases: one specialized institute's experiences. Surg Endosc 2013;27: Saito Y, Otake Y, Sakamoto T, et al. Indications for and technical aspects of colorectal endoscopic submucosal dissection. Gut Liver 2013;7: Walsh RM, Ackroyd FW, Shellito PC. Endoscopic resection of large sessile colorectal polyps. Gastrointest Endosc 1992;38: Saito Y, Fukuzawa M, Matsuda T, et al. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection. Surg Endosc 2010;24: Terasaki M, Tanaka S, Oka S, et al. Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm. J Gastroenterol Hepatol 2012;27: Sakamoto T, Matsuda T, Otake Y, Nakajima T, Saito Y. Predictive factors of local recurrence after endoscopic piecemeal mucosal resection. J Gastroenterol 2012;47: Oka S, Tanaka S, Saito Y, et al. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol 2015;110: November 28, th Congress of the Korean Society of Gastrointestinal Endoscopy 31

5 Resection of Large Polyps Other Than : Piecemeal Resection, Underwater EMR, and Hybrid 12. Kim BC, Chang HJ, Han KS, et al. Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance. Endoscopy 2011;43: Nelson DB. Techniques for difficult polypectomy. MedGenMed 2004;6: Zarchy T. Risk of submucosal saline injection for colonic polypectomy. Gastrointest Endosc 1997;46: Binmoeller KF, Weilert F, Shah J, Bhat Y, Kane S. "Underwater" EMR without submucosal injection for large sessile colorectal polyps (with video). Gastrointest Endosc 2012;75: Wang AY, Flynn MM, Patrie JT, et al. Underwater endoscopic mucosal resection of colorectal neoplasia is easily learned, efficacious, and safe. Surg Endosc 2014;28: Uedo N, Nemeth A, Johansson GW, Toth E, Thorlacius H. Underwater endoscopic mucosal resection of large colorectal lesions. Endoscopy 2015;47: Curcio G, Granata A, Ligresti D, et al. Underwater colorectal EMR: remodeling endoscopic mucosal resection. Gastrointest Endosc 2015;81: Kim HG, Thosani N, Banerjee S, Chen A, Friedland S. Underwater endoscopic mucosal resection for recurrences after previous piecemeal resection of colorectal polyps (with video). Gastrointest Endosc 2014;80: Binmoeller KF, Hamerski CM, Shah JN, Bhat YM, Kane SD. Underwater EMR of adenomas of the appendiceal orifice (with video). Gastrointest Endosc Sanchez-Yague A, Kaltenbach T, Raju G, Soetikno R. Advanced endoscopic resection of colorectal lesions. Gastroenterol Clin North Am 2013;42: Byeon JS, Yang DH, Kim KJ, et al. Endoscopic submucosal dissection with or without snaring for colorectal neoplasms. Gastrointest Endosc 2011;74: Sakamoto T, Matsuda T, Nakajima T, Saito Y. Efficacy of endoscopic mucosal resection with circumferential incision for patients with large colorectal tumors. Clin Gastroenterol Hepatol 2012;10: Hong YM, Kim HW, Park SB, Choi CW, Kang DH. Endoscopic mucosal resection with circumferential incision for the treatment of large sessile polyps and laterally spreading tumors of the colorectum. Clin Endosc 2015;48: Toyonaga T, Man IM, Morita Y, Azuma T. Endoscopic submucosal dissection () versus simplified/hybrid. Gastrointest Endosc Clin N Am 2014;24: Yoshida N, Yagi N, Naito Y. Hybrid techniques for colorectal tumor. Intestine 2013;17:51-8 [in Japanese with English abstract]. 27. Toyonaga T, Man-i M, Fujita T, et al. Retrospective study of technical aspects and complications of endoscopic submucosal dissection for laterally spreading tumors of the colorectum. Endoscopy 2010;42: th Congress of the Korean Society of Gastrointestinal Endoscopy November 28, 2015