Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection

Journal Pre-proof Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection Yuichiro Suzuki, Tokuma Tanuma, Masanori Nojima, Masakazu Akahonai, Gota Sudo, Hidetaka Hamamoto, Hironori Aoki, Taku Harada, Akio Katanuma, Hiroshi Nakase PII:

S0016-5107(19)32218-7

DOI:

https://doi.org/10.1016/j.gie.2019.08.042

Reference:

YMGE 11742

To appear in:

Gastrointestinal Endoscopy

Received Date: 3 April 2019 Accepted Date: 25 August 2019

Please cite this article as: Suzuki Y, Tanuma T, Nojima M, Akahonai M, Sudo G, Hamamoto H, Aoki H, Harada T, Katanuma A, Nakase H, Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection, Gastrointestinal Endoscopy (2019), doi: https://doi.org/10.1016/ j.gie.2019.08.042. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2019 by the American Society for Gastrointestinal Endoscopy

Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection

Yuichiro Suzuki1, Tokuma Tanuma1, Masanori Nojima3, Masakazu Akahonai1, Gota Sudo1, 2, Hidetaka Hamamoto1, Hironori Aoki1, Taku Harada1, Akio Katanuma1, Hiroshi Nakase2

1

Center for gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan

2

Department of Gastroenterology and Hepatology, Sapporo Medical University School

of Medicine, Sapporo, Japan. 3

Center for Translational Research, The institute of Medical Science Hospital, The

University of Tokyo, Japan.

Correspondence to Tokuma Tanuma, MD, PhD. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan 1-40-12-1, Maeda, Teine-ku, Sapporo 006-8555, Japan

Tel: +81-11-681-8111 Fax: +81-11-685-2998 E-mail: [email protected]

Word count: 2174 words

Conflicts of Interest The authors declare no conflict of interest.

Abstract Background and aims: Traction methods have been reported to speed up endoscopic submucosal dissection (ESD). We used multiloop (M-loop) method as traction method for colorectal ESD and recorded its submucosal dissection time (SDT), and submucosal dissection speed (SDS). Methods: From January 2018, we used M-loop method during all of colorectal ESD and timed its duration until August 2018 and recorded its outcomes. The study included 2 experts and 8 nonexperts, and was carried out at a tertiary endoscopic center in Japan. Results: A total of 50 patients were treated by colorectal ESD using M-loop method in the study. The mean SDT and SDS were 42.1 ± 4.16 minutes and 28.0 ± 2.89 mm2/minutes, respectively. The mean SDS was 38.9±6.9 mm2/minutes for experts and 25.3±3.1 mm2/minutes for nonexperts. En bloc resection was achieved in 100% of the cases. There were 3 adverse events and unfavorable outcomes. Conclusions: Traction by M-loop method improved the SDS in the colorectal ESD. The method can be an effective tool to assist colorectal ESD. Further evaluation of the usefulness of M-loop is required in direct comparison with conventional ESD.

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Introduction Endoscopic submucosal dissection (ESD) is one of the effective methods for treating large superficial colorectal neoplasms, for its ability to increase curative resection rate compared to endoscopic mucosal resection (EMR) [1, 2]. The clinical issue is the longer procedure time, which makes standardization of colorectal ESD more difficult. Methods to create traction have been developed as a useful tool to overcome this difficulty [3, 4]. Traction creates tension in submucosal plane allowing quicker identification of line of dissection and blood vessels. For this property, traction can speed up colorectal ESD and reduce burden on both patient and physician. Several techniques of traction, which includes clip with line method [3], clip and snare method [5], and S-O clip method [6] have been reported. These methods facilitate dissection, but they either require additional maneuvers such as reinsertion of the endoscope, or require costly adjunct devices that are not available in some institutions. On the other hand, nontraction method such as pocket-creation method (PCM) has been invented by Hayashi et al [7]. It involves creation of submucosal pocket into which the tip of the endoscope is inserted to directly visualize the submucosa. PCM does not require reinsertion of the endoscope nor does it require adjunct devices. It stabilizes the view of the submucosal dissection plane, and has been reported to have fewer adverse events than the conventional method

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of colorectal ESD [8]. However, PCM is still difficult for many nonexperts. We have previously reported a new traction technique called multiloop (M-loop) method, which requires only endoscopic clips and one surgical suture [9]. The materials used to make M-loop are cheap and accessible in any institutions. Furthermore, the loop is easy to make. In this case series study, we investigated the dissection speed of M-loop method for colorectal ESD.

Materials and Methods Patients All ESDs were planned according to Japanese guidelines for ESD and EMR of colorectal cancer [10]. Antithrombotic agents were stopped before ESD according to the current guideline [11]. Beginning in January 2018, M-loop method (a novel traction method) was used to treat all cases of colorectal ESD from which point procedural time for all ESDs were recorded until August 2018. All informed consent processes for this study were conducted in accordance with the guideline of the Teine Keijinkai Hospital Institutional Review Board. Lesions with submucosal invasion were excluded from the study.

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M-loop design M-loop was created and used in a same manner as our previous video (Fig. 1) [9]. A 3-0 silk suture thread (Sterilized Matsuda Suture; Matsuda) was reeled once around a 2.5 mL syringe and made a knot. We then reeled the thread back around the syringe to tie a second knot. By repeating this process, we can adjust the number of loops depending on the diameter of the colonic lumen. The redundant thread is then trimmed (Fig. 2A). Figures 2A to C show creation of M-loop with double loops, whereas Figures 3C and 4A show M-loop with triple loops to demonstrate the versatility of M-loop. The loop was stored for later use for ESD. The loop was attached onto a clip and housed within delivery sheath right before its use (Fig. 2B and 2C).

ESD procedure All patients were sedated under intravenous midazolam or propofol. Intravenous pethidine was used for analgesic on an as-needed basis. Colorectal ESD was performed using a single channel endoscope with jet function (PCF-H290AZI; Olympus Medical Systems, Tokyo, Japan). A transparent short hood was attached to the endoscope tip (TOP co, Tokyo, Japan). Hook knife (KD-620QR; Olympus Medical Systems, Tokyo, Japan) was used for all cases of colorectal ESD. We have used coagrasper (FD-411QR;

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Olympus Medical Systems, Tokyo, Japan) for arterial bleeding that cannot be controlled with the hook knife. Sodium hyaluronate solution mixed with indigo carmine was used as injectate and was injected to lift the lesion. As with M-loop method, we attached M-loop onto an opening-and-closing clip (EZ Clip, Olympus Medical Systems, Tokyo, Japan), which was introduced into colorectal lumen via working channel. The M-loop is clipped onto the edge of the exfoliated mucosa right after circumferential incision. We then introduced another clip in to attach the free end of the loop onto the contralateral wall. As a result, we obtained excellent traction and visualization of the submucosal layer (Fig. 2 and 3) [9]. During dissection of larger lesions, the traction sometimes become slack and insufficient. In such cases, a new clip is hooked onto the knot in between the loops and re-attached onto the contralateral wall. This brings the lesion closer to the contralateral wall, which strengthens the traction to better expose the submucosa (fig 4). After completion of dissection the loop was cut by the same electrosurgical knife used for dissection. The tissue was sent for pathological analysis by experienced pathologist independently of the endoscopists.

Outcomes

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As the primary outcome of this study, the mean submucosal dissection speed (SDS), submucosal dissection time (SDT), and the mean time and the rate of successful clip attachment was recorded for colorectal ESD with M-loop method. For the secondary outcome, the en bloc resection rate, curative resection rate, rate of perforation, and delayed bleeding were investigated.

Definitions The submucosal dissection time (SDT) for the M-loop method was defined as the time from the creation of first traction of M-loop to completion of tumor dissection. We have defined the time taken for M-loop attachment as the time taken from introduction and opening of the M-loop-attached clip in the colon to successful attachment of the M-loop onto the contralateral wall by another clip. SDT was defined as the time from when the first traction of M-loop is created until completion of tumor dissection. The specimen area was calculated by multiplying length and width of the specimen. We calculated SDS by dividing the area of the resected specimen by SDT. En bloc resection was defined as 1-piece resection of the tumor with free margins. The curative resection was defined as having free horizontal and vertical margins, and no lymphovascular invasions. Submucosal fibrosis was determined visually and grouped

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according to categories proposed by Matsumoto et al, which is classified by the presence and extent of white thread directly after submucosal injection [12]. Expert endoscopist was defined as an operator who performed more than 80 ESD cases, and nonexpert was defined as those who performed less than 80 ESD cases before this study [13]. This study involved 2 experts who treated 10 cases, and 8 nonexperts who treated 40 cases. In principle, a nonexpert was supervised by expert endoscopists who had taken over the procedure in difficult cases of colorectal ESD. Perforation was defined as full-thickness defects of the colorectal wall, which were recognized by the operator as a state in which connective tissue, adipose tissue, and/or serosa was visible through the defect. Delayed bleeding was defined as the presence of marked bloody stool after treatment or the requirement for hemostasis after treatment [11]. To assess unfavorable outcomes efficiently, we defined unfavorable outcome as non-en bloc resection, noncurative resection, perforation, or delayed bleeding.

Results A total of 51 patients with 54 lesions were treated by colorectal ESD between January 2018 and August 2018 at Teine Keijinkai hospital, a tertiary endoscopic center. 1 case was excluded because ESD was aborted due to deep submucosal invasion. When

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multiple lesions are dissected in one specimen, the lesion was counted as one. After exclusion, 50 patients with 50 lesions were treated by colorectal ESD. Characteristics of patients treated with M-loop method are shown on Table 1. The average age of the patient was 72 years old, and 72% of the patients were male. In this study, the percentage of lesions located in the right and left colon segments were 66% and 34%, respectively. Eighty percent of the operators participating in this study were nonexperts. Eight cases of ESD by nonexpert endoscopists required the assistance of expert endoscopists, but other cases were completed independently. Eighty-eight percent of the lesions were flat type. The mean size of the lesion was 873.2 mm2. The mean length and width of the lesion was 35.8 mm and 28.9 mm, respectively. As for the attachment of M-loop, the mean time of successful clip attachment was 2 minutes and 54 seconds. The success rate was 98% because of one case failing due to the loosening of the loop. Table 2 demonstrates the primary and secondary outcomes. The mean SDT for M-loop method was 42.1±4.16 minutes, and the mean SDS was 28.0±2.89 mm2/minutes. With regard to secondary outcomes, en bloc resection was achieved in 100% of the cases. There were 3 cases with unfavorable outcomes; 1 case with perforation, 1 case with noncurative resection, and 1 case with both perforation and noncurative resection. Table 3 shows that the mean SDS was 38.9±6.9 mm2/minute for

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experts and 25.3±3.1 mm2/minute for nonexperts.

Discussion This study first demonstrated that the M-loop method in colorectal ESD is simple, safe, and cost-effective. Therefore, we strongly consider that this new traction method is a new therapeutic approach for colorectal ESD. ESD helps patients with large superficial colorectal neoplasms to avoid surgery. On the other hand, variation in size and location of the polyps in colon affect the difficulty of performing colorectal ESD. Therefore, many methods and devices have been developed to overcome such issues, examples of which includes ring thread traction method [14], S-O clip method [6], and clip and thread method [15]. By calculating the SDS in reference to their procedure time and the size of colorectal lesions from respective studies, we found that the SDS by ring thread traction method, S-O clip, and clip and thread method were 23.5mm2/minute [14], about 23.0 mm2/minute [6], and about 29.0 mm2/minute [15], respectively. On the other hand, nontraction method such as PCM has advantage over conventional methods of ESD because it helps to stabilize the view when the endoscope is inserted into the pocket, which spontaneously fixes the endoscope and becomes effective even when there is extensive submucosal fibrosis [16].

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In the recent retrospective study comparing SDS for PCM and conventional ESD, the SDS was greater for PCM (23.5±11.6 vs 20.9±13.6mm2/minute; p<0.001) [17]. When compared with other methods of traction, advantage of PCM is that neither adjunct devices nor complicated maneuvers are required for its safe execution in comparison with most of the ESD traction methods. However, the PCM has a disadvantage in the point of making the submucosal pocket that is a very hard technique for nonexperts. Therefore, the PCM may not be suitable for ESD training especially in institutions without expert attendings with knowledge of using PCM. In this regard, we considered that any feasible methods for all endoscopists were required as an alternative to the aforementioned methods. M-loop method, which we already have reported [9] can be easily made with surgical thread and clip within a few minutes, which makes it accessible to any endoscopist. Our present data indicated that the attachment time to the lesion with M-loop (approximately 2 minutes 54 seconds) was similar to that with S-O clip for colorectal lesion (2 minutes). In addition, this study demonstrated that the mean SDS using M-loop was 28.0 (mm2/minute), which was not in the least inferior to those using previous traction and nontraction methods, although we did not compare directly the usefulness of M-loop in

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colorectal ESD with that of other methods. It should be noted that the mean SDS using M-loop by expert and nonexpert was 38.9 and 25.3 (mm2/minute), respectively. These data also indicate that M-loop methods could contribute to the improvement of endoscopic performance for not only experts but also nonexperts. M-loop is also as safe as the conventional method of colorectal ESD because the rate of perforation and delayed bleeding evens previously reported data for adverse events of colorectal ESD in Asian countries which was 4.5% and 2.7%, respectively [18]. When compared with other traction methods, M-loop has more advantages as follows: (1) no necessity of reinserting the endoscope, (2) it is applicable in segments with large lumen such as cecum and rectum by adding the number of loops, [9] and (3) the cheap cost. For example, the cost of one S-O clip is 45 U.S. dollars (5000 JPN yen), whereas the cost of making 3 M-loops, which requires one 3-0 thread, is about 20 cents (23.3 JPN yen). These properties make M-loop method a simple and cost-effective ESD assisting method. This study has limitations. First, this study was carried out in single center alone because M-loop method, which we first invented, has not yet been spread through many facilities. Therefore, the multicenter study will be required to confirm the usefulness of M-loop method. Second, we have not yet performed the head to head comparison study

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regarding SDT and SDS between the M-loop method and other nontraction method. In this regard, a prospectively randomized control trial is necessary in the future.

In conclusion, traction method by M-loop method is an effective tool in improving SDS and additionally shortening SDT especially even for nonexperts. Further prospective studies in comparison with other methods of colorectal ESD is necessary.

Figure legends Figure 1. The traction applied during colorectal ESD. The M-loop is attached to the lesion and the wall on the contralateral side of the lesion by 2 clips, which pulls the lesion in a manner that gives traction during ESD. Figure 2. The design of M-loop. (A) The thread is reeled around a 2.5cc syringe to make 2 knots. (B, C) The M-loop is then hooked onto the clip, then housed into the delivery sheath for its use during ESD. Figure 3. Attaching the M-loop during colorectal ESD. Circumferential incision is made to a LST-NG 60mm in size located in the ascending colon (A). M-loop attached to a clip is introduced into colon via working channel and attached to the exfoliated mucosa (B). A second clip is introduced and hooked onto the free loop of the M-loop, and clipped onto the slightly anal side of the contralateral wall (C). The traction

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provided excellent view of the submucosa (D). Figure 4. The strengthening of traction during colorectal ESD. The traction has become slack during dissection (A). To intensify loosened traction, a new clip was introduced via working channel, and hooked onto the second loop and attached to contralateral wall, which gave additional traction that again effectively exposed submucosal layer. (B, C, D) The lesion was dissected successfully.

Reference [1] Saito Y, Fukuzawa M, Matsuda T, Fukunaga S, Sakamoto T, Uraoka T, et al. Clinical outcome of endoscopic submucosal dissection versus endoscopic mucosal resection of large colorectal tumors as determined by curative resection. Surgical endoscopy. 2010;24:343-52. [2] Terasaki M, Tanaka S, Oka S, Nakadoi K, Takata S, Kanao H, et al. Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm. J Gastroenterol Hepatol. 2012;27:734-40. [3] Oyama T. Counter traction makes endoscopic submucosal dissection easier. Clin Endosc. 2012;45:375-8. [4] Uraoka T, Parra-Blanco A, Yahagi N. Colorectal endoscopic submucosal dissection: is it suitable in western countries? J Gastroenterol Hepatol. 2013;28:406-14.

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[5] Yamada S, Doyama H, Ota R, Takeda Y, Tsuji K, Tsuji S, et al. Impact of the clip and snare method using the prelooping technique for colorectal endoscopic submucosal dissection. Endoscopy. 2016;48:281-5. [6] Ritsuno H, Sakamoto N, Osada T, Goto SP, Murakami T, Ueyama H, et al. Prospective clinical trial of traction device-assisted endoscopic submucosal dissection of large superficial colorectal tumors using the S-O clip. Surgical endoscopy. 2014;28:3143-9. [7] Sakamoto H, Hayashi Y, Miura Y, Shinozaki S, Takahashi H, Fukuda H, et al. Pocket-creation method facilitates endoscopic submucosal dissection of colorectal laterally spreading tumors, non-granular type. Endosc Int Open. 2017;5:E123-e9. [8] Kanamori A, Nakano M, Kondo M, Tanaka T, Abe K, Suzuki T, et al. Clinical effectiveness of the pocket-creation method for colorectal endoscopic submucosal dissection. Endosc Int Open. 2017;5:E1299-e305. [9] Sudo G, Tanuma T, Suzuki Y, Nakase H. Multiloop method for traction during colorectal endoscopic submucosal dissection. VideoGIE. 2019;4:11-3. [10] Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23:1-34.

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[11] Tanaka S, Kashida H, Saito Y, Yahagi N, Yamano H, Saito S, et al. JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2015;27:417-34. [12] Matsumoto A, Tanaka S, Oba S, Kanao H, Oka S, Yoshihara M, et al. Outcome of endoscopic submucosal dissection for colorectal tumors accompanied by fibrosis. Scand J Gastroenterol. 2010;45:1329-37. [13] Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47:829-54. [14] Mori H, Kobara H, Nishiyama N, Fujihara S, Matsunaga T, Masaki T. Novel effective and repeatedly available ring-thread counter traction for safer colorectal endoscopic submucosal dissection. Surgical endoscopy. 2017;31:3040-7. [15] Yamasaki Y, Takeuchi Y, Uedo N, Kanesaka T, Kato M, Hamada K, et al. Efficacy of traction-assisted colorectal endoscopic submucosal dissection using a clip-and-thread technique: A prospective randomized study. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2018;30:467-76. [16] Shinozaki S, Hayashi Y, Lefor AK, Yamamoto H. What is the best therapeutic

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strategy for colonoscopy of colorectal neoplasia? Future perspectives from the East. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2016;28:289-95. [17] Takezawa T, Hayashi Y, Shinozaki S, Sagara Y, Okada M, Kobayashi Y, et al. The pocket-creation method facilitates colonic endoscopic submucosal dissection (with video). Gastrointest Endosc. 2019;89:1045-53. [18] Fuccio L, Hassan C, Ponchon T, Mandolesi D, Farioli A, Cucchetti A, et al. Clinical outcomes after endoscopic submucosal dissection for colorectal neoplasia: a systematic review and meta-analysis. Gastrointest Endosc. 2017;86:74-86.e17.

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Table 1. Characteristics of the patients treated by colorectal ESD with M-loop method.

M-loop (n=50) Age Gender Location Fibrosis

Operator Morphology 2

Specimen size, mm

Specimen length, mm Specimen width, mm

Mean

72

Median

74

M

36

F

14

Right

33

Left

17

F0

40

F1

8

F2

2

Expert

10

Non-expert

40

Flat

44

Elevated

6

Mean

873.2

Median

760.7

Mean

35.8

Median

34.5

Mean

28.9

Median

28

ESD: endoscopic submucosal dissection, M-loop: multiloop

Table 2. The average submucosal dissection speed for colorectal ESD with M-loop method.

M-loop (n=50) Procedure time, min Submucosal dissection time, min 2

Submucosal dissection speed, mm /min

Mean

69.9±4.95

Median

57

Mean

42.1±4.16

Median

32

Mean

28.0±2.89

Median

21.4

en-bloc resection, n(%)

50(100%)

Curative resection, n(%)

48(96%)

Perforation, n(%)

2(4%)

Delayed bleeding, n(%)

0(0%)

Total unfavorable outcome, n(%) ESD: endoscopic submucosal dissection, M-loop: multiloop 1

One patient had both perforation and non-curative resection.

3(6%)*1

Table 3. The submucosal dissection speed (mm2/min) of ESD using M-loop in experts and non-experts.

Operator Expert

M-loop (n=10) Mean

38.9±6.9

Median

33.8 M-loop (n=40)

Non-expert

Mean

25.3±3.1

Median

19.5

M-loop: multiloop

Acronyms and Abbreviations EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; M-loop, multiloop; PCM, Pocket Creation Method; SDS, submucosal dissection speed; SDT, submucosal dissection time