Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2017; 23(6): 931-934
Published online Feb 14, 2017. doi: 10.3748/wjg.v23.i6.931
Prophylactic stenting for esophageal stricture prevention after endoscopic submucosal dissection
Ke-Da Shi, Feng Ji
Ke-Da Shi, Feng Ji, Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
Author contributions: Shi KD and Ji F equally contributed to the analysis of the literature and writing of the manuscript.
Conflict-of-interest statement: Both authors declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Feng Ji, MD, PhD, Deputy Director, Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Rd., Hangzhou 310000, Zhejiang Province, China. jifeng1126@sina.com
Telephone: +86-571-87236568 Fax: +86-571-87236568
Received: August 28, 2016
Peer-review started: September 1, 2016
First decision: September 20, 2016
Revised: October 6, 2016
Accepted: November 12, 2016
Article in press: November 13, 2016
Published online: February 14, 2017

Abstract

Endoscopic submucosal dissection (ESD) of superficial esophageal cancer has been increasingly used as an alternative to surgery because it is minimally invasive and has a high rate of en bloc resection. However, a high rate of esophageal stricture is observed after ESD for large lesions, which can dramatically decrease the patient’s quality of life. Stricture prevention is necessary to allow for endoscopic therapy to expand. We, herein, review the most recent evidence and discuss the role of the metallic self-expandable stent and the biodegradable stent in esophageal stricture prevention. Limited studies suggested that prophylactic stenting could reduce the stricture rate without increasing the number of complications. In addition, the number of bougie dilation procedures was significantly lower with stent placement. Esophageal stenting is a promising option for post-ESD stricture prevention. However, current evidence is too preliminary to formulate practice standards. Future studies are needed to further validate the efficacy and safety of prophylactic stenting and determine the best strategy for stricture prevention. Stent migration is the most common complication. A new stent that has advantages of a low migration rate and minimal tissue reaction will need to be developed. Therefore, randomized controlled trials with long-term follow-up periods are required before prophylactic stenting could be considered a valid option to prevent post-ESD stricture.

Key Words: Biodegradable stent, Stricture prevention, Esophageal stricture, Metallic self-expandable stent, Endoscopic submucosal dissection

Core tip: Esophageal stenting is a promising option for esophageal stricture prevention. Current evidence is too preliminary to formulate practice standards. Randomized controlled trials with long-term follow-up periods and cost-effective studies are required before prophylactic stenting could be considered a valid option to prevent post-endoscopic submucosal dissection stricture.



INTRODUCTION

Endoscopic submucosal dissection (ESD) of superficial esophageal cancer has been increasingly used as an alternative to surgery because it is minimally invasive and has a high rate of en bloc resection. Despite these advantages, a high rate of esophageal stricture is observed after ESD for large lesions, which can dramatically decrease the patient's quality of life[1-3]. The rate of strictures after endoscopic resection for circumferential or near-circumferential lesions can be as high as 88%[4]. Although oral steroids were administered in one study, 45% of patients still suffered from stricture[5]. Therefore, post-ESD esophageal stricture prevention is needed to allow for endoscopic therapy to expand. In this editorial, we discuss the use of prophylactic stenting in the prevention of post-ESD stricture and include a discussion of our future vision related to this topic. PubMed and Web of Science were searched using the following search strategy: (ESD OR endoscopic resection) AND esophageal stricture AND stent, until 31 August 2016. Studies investigating the role of stent placement after esophageal ESD were included. We searched the reference lists of the relevant studies to identify other studies on the same topic. Currently, no conclusive recommendation is evident in the literature related to the type of stent to use in stricture prevention. According to the current studies, the self-expandable metallic stent and the biodegradable stent are two potential options.

SELF-EXPANDABLE METALLIC STENTS

Temporary placement of a self-expandable metallic stent is increasingly used in practice to prevent post-ESD stricture. Ye and colleagues reported on their application of fully-covered stent placement after circumferential endoscopic resection of esophageal lesions[6]. More information about the stent used can be found in Table 1. A total of 23 patients were included in this prospective study. During the follow-up period, 4 patients had stent migration, and 3 of those 4 patients developed esophageal strictures. The stricture rate in this study was 17.3% (4/23), which was significantly lower than the stricture rate reported in previous studies. However, only one endoscopist from a high-volume center performed the study, which raises concerns about potential bias. Because the post-ESD stricture rate could be affected by the experience and operative skills of the endoscopist, the results of this study may not be generalizable. Another limitation of this study was the absence of sham control to further validate the advantage of stent placement. The only randomized controlled trial (RCT) to date to investigate this question was conducted by Wen and his colleagues[7]. In this study, patients who had mucosal defects that exceeded 75% of the circumference of the esophagus after ESD treatment were randomized in a 1:1 fashion to either a group that received treatment with a fully-covered esophageal stent or an observation group. The study showed a significantly lower rate of stricture in the group that received stent placement compared to the observational group (18.2% vs 72.7%, respectively, P < 0.05). Moreover, the number of bougie dilation procedures was significantly lower in the stent placement group compared to the observational group (mean 0.45, range 0-3 vs mean 3.9, range 0-17, respectively, P < 0.05). In addition, complications were comparable between the two groups. Interestingly, the two patients who developed stricture in the stent group both had stent migration. The stent migration rate could be affected by the design of the stents. Different types of stents have their own characteristics. A small portion of exposed bare metal at both ends of the partially covered metallic stent helps to prevent migration. However, the granulation tissue ingrowth at the ends of the stent could lead to stent-induced strictures. In contrast, fully-covered stents do not have any exposed bare metal, but they are more prone to migration. A new stent that has advantages of both a low migration rate and minimal tissue reaction will need to be developed. Is successful stent placement without migration enough for stricture prevention? The answer may be "no". Bhat and colleagues reported a 28% stricture rate after stent removal or migration[8]. The circumferential lesion left at the ends of the stent after stent removal is prone to forming strictures. In addition, the potential pro-inflammatory action of the implanted stent makes it unlikely to be the single best choice for esophageal stricture prevention. Although the results in previously mentioned studies are inspiring, the studies involved a small sample size and a short-term follow-up period; therefore, the results need to be confirmed in future larger trials. A recent meta-analysis conducted by Oliveira and his colleagues demonstrated that the use of preventive therapy after extensive ESD reduces the risk of stricture without increasing the number of complications[9]. Moreover, the placement of a fully-covered stent and the use of local corticosteroid injections have the most promising results in reducing post-ESD stricture among different types of strategies. It is worth mentioning that these results were based on three small RCTs and several retrospective studies. The high degree of heterogeneity across the included studies raises additional concerns about the potential bias of this analysis. Therefore, RCTs with larger sample sizes comparing different treatment strategies are still needed to clarify this issue. In endoscopy, the advancement of a new concept could be affected by the availability and cost-effectiveness of technology. Since stents are associated with a high cost, evidence on cost-effectiveness is required in future studies.

Table 1 Studies using esophageal stenting to prevent post-endoscopic submucosal dissection stricture.
Ref.Type of studyPopulationType of stentTime of removalStricture rateStent migration rate
Ye et al[6], 2016CohortcircumferentialFully-covered self-expandable metallic stents (CZES stent; Sigma, China)12 wk17.4%17.4%
Wen et al[7], 2014RCTmucosal defect > 3/4Fully-covered self-expandable metallic stents (CZES stent; Sigma, China)8 wk18.2%18.2%
Saito et al[11], 2008Case reportmucosal defect > 3/4PLLA esophageal stent (Tanaka-Marui stent; Marui Textile Machinery Co., Japan)Self-degradable00
Saito et al[10], 2007Case reportmucosal defect > 3/4PLLA esophageal stent (Tanaka-Marui stent; Marui Textile Machinery Co., Japan)Self-degradable077.0%
BIODEGRADABLE STENTS

Saito et al[10] reported the successful application of biodegradable stents to post-ESD esophageal stricture prevention. Despite having a high rate of early stent migration, the efficacy of stricture prevention reached 100%, but caution should be taken as the data are based on short-term follow-up case reports[10]. This group also reported 2 cases of successful application of biodegradable stents in the prevention of re-stricture formation after balloon dilatation of post-ESD strictures[11]. Experience in using these types of stents is learned from animal model-based experiments[12,13]. Biodegradable stents have the potential to mitigate stent-related complications and do not require removal. The main limitations of biodegradable stents are a hyperplastic tissue reaction and stent migration. The poly-L-lactic acid (PLLA) stent and the polydioxanone stent are two types of biodegradable stents that are currently available. The PLLA-biodegradable stent has a high rate of early stent migration, which makes it unlikely to be the best choice for stricture prevention[10,14]. Meanwhile, polydioxanone stents have a migration rate of 20%, but they could induce a severe hyperplastic tissue reaction[15,16]. A hyperplastic tissue reaction delays the healing of the mucosa and poses a challenge when removing the stent. Moreover, it might prevent adequate surveillance for local recurrence. Although the ideal stent has not yet been developed, possible options to minimize tissue hyperplasia after biodegradable stent placement should be considered in future studies. These options include steroid injection, consumption of a drug-eluting layer, and coverage with biodegradable membranes or extracellular matrix scaffolds.

CONCLUSION

All patients with extensive esophageal ESD should receive some type of preventive treatment. Esophageal stenting is a promising option for esophageal stricture prevention, especially when corticosteroid treatment is contraindicated in certain patients. Current evidence is too preliminary to formulate practice standards. RCTs with long-term follow-up periods are required before prophylactic esophageal stenting could be considered as a valid option to prevent post-ESD stricture.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): 0

Grade C (Good): C, C, C, C

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Iizuka T, Kim GH, Tsuji Y, Wang HP S- Editor: Gong ZM L- Editor: A E- Editor: Liu WX

References
1.  Katada C, Muto M, Manabe T, Boku N, Ohtsu A, Yoshida S. Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions. Gastrointest Endosc. 2003;57:165-169.  [PubMed]  [DOI]
2.  Ono S, Fujishiro M, Niimi K, Goto O, Kodashima S, Yamamichi N, Omata M. Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms. Endoscopy. 2009;41:661-665.  [PubMed]  [DOI]
3.  Ono S, Fujishiro M, Niimi K, Goto O, Kodashima S, Yamamichi N, Omata M. Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. Gastrointest Endosc. 2009;70:860-866.  [PubMed]  [DOI]
4.  van Vilsteren FG, Pouw RE, Seewald S, Alvarez Herrero L, Sondermeijer CM, Visser M, Ten Kate FJ, Yu Kim Teng KC, Soehendra N, Rösch T. Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett’s oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. Gut. 2011;60:765-773.  [PubMed]  [DOI]
5.  Tang B, Bai JY, Zhao XY, Fan CQ, Yang X, Deng L, Yang SM, Yu J. Endoscopic submucosal dissection for superficial esophageal cancer with near-circumferential lesions: our experience with 40 patients. Surg Endosc. 2015;29:2141-2148.  [PubMed]  [DOI]
6.  Ye LP, Zheng HH, Mao XL, Zhang Y, Zhou XB, Zhu LH. Complete circular endoscopic resection using submucosal tunnel technique combined with esophageal stent placement for circumferential superficial esophageal lesions. Surg Endosc. 2016;30:1078-1085.  [PubMed]  [DOI]
7.  Wen J, Lu Z, Yang Y, Liu Q, Yang J, Wang S, Wang X, Du H, Meng J, Wang H. Preventing stricture formation by covered esophageal stent placement after endoscopic submucosal dissection for early esophageal cancer. Dig Dis Sci. 2014;59:658-663.  [PubMed]  [DOI]
8.  Bhat YM, Kane SD, Shah JN, Hamerski CM, Binmoeller KF. Single-session circumferential EMR and metal stent placement for the treatment of long-segment Barrett’s esophagus with high-grade intraepithelial neoplasia. Gastrointest Endosc. 2014;80:331.  [PubMed]  [DOI]
9.  Oliveira JF, Moura EG, Bernardo WM, Ide E, Cheng S, Sulbaran M, Santos CM, Sakai P. Prevention of esophageal stricture after endoscopic submucosal dissection: a systematic review and meta-analysis. Surg Endosc. 2016;30:2779-2791.  [PubMed]  [DOI]
10.  Saito Y, Tanaka T, Andoh A, Minematsu H, Hata K, Tsujikawa T, Nitta N, Murata K, Fujiyama Y. Usefulness of biodegradable stents constructed of poly-l-lactic acid monofilaments in patients with benign esophageal stenosis. World J Gastroenterol. 2007;13:3977-3980.  [PubMed]  [DOI]
11.  Saito Y, Tanaka T, Andoh A, Minematsu H, Hata K, Tsujikawa T, Nitta N, Murata K, Fujiyama Y. Novel biodegradable stents for benign esophageal strictures following endoscopic submucosal dissection. Dig Dis Sci. 2008;53:330-333.  [PubMed]  [DOI]
12.  Barret M, Pratico CA, Camus M, Beuvon F, Jarraya M, Nicco C, Mangialavori L, Chaussade S, Batteux F, Prat F. Amniotic membrane grafts for the prevention of esophageal stricture after circumferential endoscopic submucosal dissection. PLoS One. 2014;9:e100236.  [PubMed]  [DOI]
13.  Pauli EM, Schomisch SJ, Furlan JP, Marks AS, Chak A, Lash RH, Ponsky JL, Marks JM. Biodegradable esophageal stent placement does not prevent high-grade stricture formation after circumferential mucosal resection in a porcine model. Surg Endosc. 2012;26:3500-3508.  [PubMed]  [DOI]
14.  Tanaka T, Takahashi M, Nitta N, Furukawa A, Andoh A, Saito Y, Fujiyama Y, Murata K. Newly developed biodegradable stents for benign gastrointestinal tract stenoses: a preliminary clinical trial. Digestion. 2006;74:199-205.  [PubMed]  [DOI]
15.  Hair CS, Devonshire DA. Severe hyperplastic tissue stenosis of a novel biodegradable esophageal stent and subsequent successful management with high-pressure balloon dilation. Endoscopy. 2010;42 Suppl 2:E132-E133.  [PubMed]  [DOI]
16.  Orive-Calzada A, Alvarez-Rubio M, Romero-Izquierdo S, Cobo Martin M, Juanmartiñena JF, Ogueta-Fernández M, Molina-Alvarez E, Eraña-Ledesma L. Severe epithelial hyperplasia as a complication of a novel biodegradable stent. Endoscopy. 2009;41 Suppl 2:E137-E138.  [PubMed]  [DOI]