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Gastroenterology Research and Practice
Volume 2018, Article ID 1696849, 8 pages
https://doi.org/10.1155/2018/1696849
Review Article

Progress on the Prevention of Esophageal Stricture after Endoscopic Submucosal Dissection

1Medical School, Ningbo University, Ningbo, Zhejiang, China
2Gastroenterology Department, Ningbo First Hospital, Ningbo, Zhejiang, China

Correspondence should be addressed to Xiaoyun Ding; moc.621@gnidyyyd

Received 26 November 2017; Accepted 28 January 2018; Published 4 March 2018

Academic Editor: James H. Tabibian

Copyright © 2018 Peina Shi and Xiaoyun Ding. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective, minimally invasive treatment for superficial esophageal cancers. However, esophageal stricture often occurs in patients with large mucosal defects after ESD. In this review, we discuss various approaches recently researched to prevent esophageal strictures after ESD. These approaches can be classified as pharmacological treatments, esophageal stent treatments, and tissue engineering approaches. Most of the preventive approaches still have their limitations and require further research. With the improvement of current therapies, ESD can be more widely utilized as a minimally invasive treatment with minimal complications.

1. Introduction

Currently, endoscopic submucosal dissection (ESD) has been widely accepted as an effective, minimally invasive treatment for superficial esophageal cancers, including esophageal squamous cell carcinoma and Barrett’s adenocarcinoma [13]. Compared to endoscopic mucosal resection (EMR), ESD has substantially higher en bloc and curative resection rates, lower local recurrence rates, and more precise histopathologic assessment [4, 5]. However, esophageal stricture often occurs inevitably in patients who have large mucosal defects after ESD. Esophageal strictures cause nausea, vomiting, and varying degrees of dysphagia and may influence patients’ vocalization, severely decreasing the patient’s quality of life. Patients with esophageal strictures require multiple endoscopic balloon dilations (EBDs) or dilations with a bougie over a long period [6]. Multiple sessions of endoscopic dilation are painful and increase the risk of esophageal perforation [7, 8]. Therefore, various kinds of approaches to prevent esophageal strictures after ESD are necessary and useful.

Esophageal stricture after ESD can be structurally divided into two categories: (1) a simple stricture, meaning that the stricture is short, focal, and not angulated and has a diameter that will allow the endoscope to pass, and (2) a complex stricture, meaning that the stricture is long (>2 cm), irregular, and angulated or has a severely narrow diameter [9]. In clinical research, esophageal stricture after ESD often refers to the complex stricture, and the patient has a feeling of dysphagia or the stricture prevents the passage of a standard 9.2–10 mm diameter endoscope. Two main mechanisms can explain the esophageal stricture after ESD: (1) the loss of the esophageal epithelium, which means the loss of a barrier against saliva, gastric acid, microorganisms, and so on, and (2) inflammation, fibrosis, and scar formation in the process of wound healing [10]. The rate of stricture occurrence after near-circumference or whole-circumference ESD was reported to be 88–100% [2, 9, 11, 12]. Esophageal stents, extracellular matrix scaffolds, and cell-based therapy have been researched to address this problem. The severe inflammation is due to the stimulation of several physical and chemical factors, as well as to the after-effects of the heat damage caused by the use of a high-frequency wave snare [13]. This inflammation results in ulceration of the deep layer of the esophagus. Myofiber atrophy and fibrosis reactions gradually appear during the period of the wound recovery, which finally results in esophageal stricture [13, 14]. Steroids and some antifibrotic drugs have been reported to mitigate these types of reactions.

2. Pharmacological Treatment

2.1. Endoscopic Intralesional Injection of Steroid Therapy

Steroids can inhibit inflammation and fibrosis. The endoscopic intralesional injection of triamcinolone acetonide (TA) has been used for the treatment of benign and malignant esophageal strictures [15, 16]. Hashimoto et al. found that the endoscopic injection of TA after ESD in 41 patients with mucosal defects of three-quarters of the esophageal circumference was safe and effective to prevent esophageal stricture [17]. Twenty-one patients in the treatment group had an endoscopic injection of TA on the 3rd, 7th, and 10th days after ESD with a dose of 16–62 mg of TA for each treatment. The incidence of stricture in the treatment group (19.0%) was apparently lower than that in the control group without TA injection (75.0%), and the number of extra EBD procedures to treat the stricture decreased. Hanaoka et al. also reported a prospective study in 30 patients who had a single injection of 100 mg TA immediately after ESD [18]. The stricture rate was 10%, which is lower than that in the historical control group of 29 patients without TA injection (66%). However, Takahashi et al. showed that in patients with a circumferential mucosal defect of more than three-quarters of the circumference of the esophagus, it was difficult to prevent refractory stricture, despite the patients receiving TA injection after ESD [19]. The stricture rate was not significantly different, from 87.5% in the control group to 62.5% in the study group. Additionally, the perforation rate during dilatation procedures was 1.0% in the study group but 0.5% in the control group. Hanaoka et al. confirmed that a tumor extent greater than 75% of the esophageal circumference was an independent risk factor for complex stricture [20]. Nagami et al. reported in a retrospective matched case-control study of 602 patients that a single injection of TA after ESD effectively reduced the esophageal stricture rate and the number of EBD sessions [21]. However, the efficacy reduced in patients with entire circumferential mucosal defects. Steroid treatment concerns include the possibility of periesophageal abscess after steroid treatment and the increased risk of delayed perforation in the extra EBD procedures [22, 23].

2.2. Steroid Gel Therapy

An improper endoscopic intralesional injection carries the risk of bleeding and myofiber atrophy because TA must be injected in the submucosa. Therefore, Mori et al. changed the application method of TA by a prospective study [24]. Twenty patients received a 17.5 mL TA gel treatment applied to the ulcer floor and 5 minutes of balloon dilatation to permeate the steroid on the 5th, 8th, 12th, and 15th days after ESD. The control group accepted TA injection and balloon dilatation after ESD. The stricture rate had no significant difference between the two groups. The TA gel application is safe and effective to prevent esophageal stricture after ESD, but visibly, it has too many operation procedures.

2.3. Oral Administration of Steroid Therapy

The oral administration of steroids has also been widely researched to prevent esophageal stricture due to their anti-inflammatory effects. Yamaguchi et al. reported the effectiveness for stricture prevention in the study of 41 patients who underwent more than three-quarters of circumference circular ESD [25]. Twenty-one patients in the study group received oral prednisolone starting on the third day after ESD. The dose of prednisolone was 30 mg/d for the first two weeks, 25 mg/d for the next two weeks, and then was gradually decreased to 5 mg/d each week over the next four weeks until termination, eight weeks after ESD. The stricture rate in the study group (5.3%) was lower than that in the control group (31.8%). The control group performed preemptive EBD twice a week for 8 weeks after ESD. Isomoto et al. reported similar conclusions in patients with complete, circular ESD [26]. Sato et al. evaluated a retrospective cohort study and found that early administration of oral prednisolone combined with EBD is an effective method to prevent esophageal stricture after ESD and early steroid administration is better than late administration or no steroid therapy [27]. However, it is possible for some systemic problems to appear after long-time oral steroid therapy, such as peptic ulcers, immune suppression, metabolic disturbances, and psychiatric symptoms. Kataoka et al. shortened the period of steroid use in their research [28]. Seventeen patients in the study group underwent prednisolone treatment from the third day after ESD, at a dose of 30 mg/d during the first one week. Then, the dose was gradually decreased to 10 mg/d every week for the next two weeks until termination, three weeks after ESD. The patients in the two groups showed no significant differences, but the incidence of esophageal stricture was lower in the study group than in the ESD-alone group (17.6% versus 68.7%, resp.). Recent studies showed that oral administration of steroids has little adverse events or serious complications. However, there is a study that reported a nocardiosis infection in an elderly patient who received oral steroid treatment after ESD [29].

2.4. Antifibrotic Drug Therapy

Some antifibrotic drugs have been studied in the prevention of esophageal stricture. Antifibrotic drugs inhibit the proliferation of fibrous scars. 5-Fluorouracil (5-FU) is an antineoplastic drug. 5-FU combined with TA was researched in regard to the reduction of strictures that occur after subepiglottic surgery [30]. Mizutani et al. reported that 5-FU can be used as an antiscarring agent [31]. In their research, 5-FU was combined with liposome and mixed with atelocollagen, for sustained release. It was effective in preventing esophageal strictures after ESD in a canine model, by reducing submucosal fibrosis.

Tranilast is an antiallergic drug that can inhibit the release of transforming growth factor-beta (TGF-β1), prostaglandin-E2 (PGE2), and interleukin-1 (IL-1), which reduces collagen synthesis and fibrosis [32]. Tranilast was used to treat keloids and hypertrophic scars in an animal study [33]. Uno et al. reported a pilot study that demonstrated the availability and safety of oral tranilast with EBD to prevent esophageal strictures after ESD [34].

N-acetylcysteine is an antioxidant that inhibits TGF-β1. However, the use of N-acetylcysteine failed to reduce the formation of esophageal fibrogenesis after circumferential ESD in a pig model [35].

Botulinum toxin type A (BXT-A) is a neurotoxin that inhibits the deposition of collagen fibers and improves hypertrophic scars [36]. Wen et al. proved that BTX-A can reduce esophageal strictures in patients who underwent more than two-thirds of circumference circular ESD [37]. The endoscopic intralesional injection of BTX-A after ESD can reduce stricture rates to 6.1%, compared with 32.4% in the control group.

3. Esophageal Stent Treatment

3.1. Esophageal Self-Expandable Stents

Metallic esophageal stents function to expand the esophagus. Metallic esophageal stents were initially researched for the interventional treatment of esophageal fistulas and esophageal strictures caused by malignant esophageal neoplasms [38, 39]. The application of metallic esophageal stents in benign esophageal strictures is controversial, due to common adverse reactions such as bleeding, esophageal perforation, stent migration, or stricture recurrence [39, 40]. Comparatively speaking, temporary self-expandable metallic stents are more suitable to be used in the treatment of benign esophageal strictures [41, 42]. A positive aspect of these stents is that they can be removed easily; however, a negative aspect is the high recurrence rate after stent removal [40, 43]. Several studies reported that elderly patients with refractory cicatricial strictures after ESD had temporary self-expandable metal stents placed, which resulted in successful esophageal treatment without complications (i.e., fever, chest pain, or stricture recurrence) [44, 45]. The efficacy of circumferential esophageal stents for the prevention of stricture formation after ESD has been reported by Wen et al. [46]. In their randomized controlled trial, 22 patients with a circumferential mucosal defect of more than three-quarters of the esophageal circumference were included. The study group had esophageal stents for 8 weeks and had a significantly lower stricture rate (18.2%) than the no-stent group (72.7%). The complication of stent migration into the stomach still occurred, which markedly reduced the expansion effect of the stents and required a repeat endoscopy operation to reposition the stent. The long-term stricture-preventing effects after the removal of the stents were unknown.

3.2. Biodegradable Stents

Some researchers attempted to use biodegradable stents to treat benign esophageal strictures [47]. Compared to metallic or plastic stents, biodegradable stents have the advantages that they do not need to be removed and have sufficient radial force to expand esophagus [44, 48]. Poly-L-lactic acid (PLLA) is one kind of biodegradable stent that was reported to prevent restricture in two patients after near-circumference ESD [49]. Lua et al. reported on biodegradable stents made of carboxymethyl cellulose (CMC) [50]. Seven patients with mucosal defects of three-quarters of the esophageal circumference had endoscopic placement of CMC stents after ESD. This research had no control group. The stricture rates were approximately 57%. Compared to the other research, the preventing efficacy of CMC esophageal stents appears to be limited.

Polyglycolic acid (PGA) sheets have been used in implantation surgeries to reinforce sutures [51]. In recent years, PGA sheets have been used to repair mucosal defects, prevent scar contracture, and alleviate postoperative pain [5254]. The combination of PGA sheets and fibrin glue as an endoscopic tissue shielding method has been used in the colon and duodenum, with few postoperative adverse events [50, 55]. Iizuka et al. demonstrated the potential of PGA and fibrin glue for the prevention of stricture after ESD [56]. Fifteen patients with defects greater than half of the circumference after ESD were included in the study, and 6 weeks later, the esophageal stricture rate was 7.7%. The small PGA sheets (15 × 7 mm) were placed on an artificial ulcer without overlapping, and fibrin glue was sprayed to affix the PGA. Limitations of this method include that the small sheets take a long time to place and are easy to drop. Thus, Ono et al. reported a novel technique called “the clip and pull method”, using a whole PGA sheet to shield an artificial ulcer [57]. This method was used in eight patients with a circumferential mucosal defect of more than three-quarters after ESD [58]. The stricture rate was 37.5%, and the number of EBD sessions was 0.8 ± 1.2. Additionally, Kataoka et al. reported a case of an elderly patient that did not suffer dysphagia after circumferential ESD, by the treatment of the steroid injection, shielding the ulcer with PGA and fibrin glue [59]. The combination therapy of intralesional steroid injection and PGA sheets also showed positive effects on ten patients after near-circumference ESD [60]. Although further research is needed to confirm these findings, the results from these studies increase the interest in the combination therapy of PGA sheets and other treatments.

4. Tissue Engineering Approaches

4.1. Extracellular Matrix Scaffold Therapy

Extracellular matrix (ECM) scaffolds can support the growth of epithelial cells, are compatible with perivascular stem cells, and promote wound recovery and esophageal structure remodeling [6163]. The ECM scaffolds derived from the small intestinal submucosa or urinary bladder submucosa were reported to achieve reconstruction of the esophagus in a dog model [64]. Then, Badylak et al. reported that the ECM scaffolds can minimize stricture and promote esophageal remodeling in five male patients after endoscopic inner-layer circumferential resection [65]. The actual esophageal remodeling mechanisms in patients were unclear, but the study showed that cryptic peptides formed in scaffold degradation maybe the potential factor. Nieponice et al. researched a dog model to evaluate the potential of urinary bladder ECM tubular scaffolds for the prevention of esophageal stricture [66]. Five dogs had endoscopic ECM scaffold placement after circumferential esophageal EMR, while another five dogs only had circumferential esophageal EMR. As a result, histological assessment of the ECM treatment group showed a continuous, intact, regenerate esophageal mucosa with no inflammation or necrosis, while histology of the control group showed an immature epithelial layer with inflammation and severe scarring. A surgical adhesive was used in this study to prevent scaffold migration, but the influence of this adhesive on esophageal mucosal remodeling was unclear. Additionally, the efficacy of the ECM scaffold was controversial. Schomisch et al. reported an unsuccessful study on the prevention of stricture formation using three ECM scaffolds: the small-intestine submucosa, acellular dermal matrix, and urinary bladder matrix [67]. The major influencing factors of the study included the preparation technique of the scaffold and the use of a self-expanding stent rather than the use of surgical adhesive to attach the scaffold. Future biological ECM research may focus on novel materials and proper techniques to promote the recovery of the esophagus.

4.2. Cell-Based Therapy

Cell transplantation is applied to esophageal mucosal defects, inducing early reepithelization and promoting scarless wound healing. The efficacy of implantation of autologous keratinocytes or adipose stromal cells was proven in several animal model studies [6870]. However, the long-term efficacy of the direct injection of the cells was unknown. The cells that migrated after injections were difficult to trace for prolonged periods. Additionally, the real mechanism of the reepithelization is still uncertain.

A new approach using endoscopic transplantation of cultured autologous cell sheets overcame the limitations of cell migration and low viability rates of transplanted cells. The cell sheets are fabricated on a temperature-responsive culture surface and can be easily harvested. The sheets can be transplanted to the target sites without the use of sutures or adhesives [71]. The transplantation of cell sheets after ESD can contribute to early epithelium regeneration and mild fibrosis. However, much of this area of research was performed in animal models. Kanai et al. proved that the epidermal cell sheets can reduce the symptom of dysphagia in patients who underwent circumferential ESD [72]. Perrod et al. reported that adipose tissue-derived stromal cell sheets can reduce the stricture rate after ESD [73, 74]. In animal and clinical research, cultured autologous oral epithelial cell sheets can suitably cover ulcer areas and effectively reduce the degree of stricture [7578]. Ohki et al. demonstrated that transplantation of autologous oral epithelial cell sheets can safely and effectively prevent esophageal stricturing and promote epithelial healing after ESD without the need for additional treatments for complications [76, 78]. The growth factors, cytokines, and the source of regenerated epithelia may be related to the early reconstruction of the esophageal surface [75]. In further studies, more clinical evaluation and long-term follow-up should be performed to ensure the safety and reproducibility of the cell sheet technique. The high cost of fabrication and rapid adhesion warrants further research of methods to facilitate the transplantation of the cell sheets. In addition, some methods demonstrate the potential of cell-based therapy for the prevention of postoperative strictures. Mizushima et al. showed that the application of conditioned medium obtained from mesenchymal stem cells, combined with the injection of steroids, can significantly decrease inflammation and fibrosis of the animal esophagus after ESD [79].

5. Conclusion

In brief, we reviewed recent publications on the prevention of esophageal stricture after ESD, all of which inevitably have their own limitations and cannot be widely accepted in clinical application (Table 1). The steroid therapies have been effective in many clinical trials but cannot completely prevent stricture in some high-risk patients. The reduced efficacy of these therapies to prevent stricture after near-circumference or whole-circumference ESD is an ongoing problem. Thus, a sufficient evaluation before endoscopic surgery and a prolonged assessment after preventive therapy are essential to current comprehensive treatment. The combination of different therapies should be evaluated in future studies.

Table 1: Treatments for the prevention of esophageal stricture after endoscopic submucosal dissection.

In recent years, many innovative therapies have shown appreciable feasibility, but they still require controlled clinical research to confirm effectiveness. Some single case reports lack consensus, needing more evidence to sufficiently confirm safety. After the improvement of current therapies, ESD can be more widely utilized as a minimally invasive treatment with minimal complications.

Conflicts of Interest

The authors declare no conflict of interests.

Authors’ Contributions

All authors equally contributed to this paper.

Acknowledgments

This study was supported by grants from the Natural Science Foundation of Ningbo (nos. 2016A610158 and 2014A610226) and the Scientific Benefit for People Project of Ningbo (no. 2014C51001).

References

  1. C. V. Lopes, M. Hela, C. Pesenti et al., “Circumferential endoscopic resection of Barrett’s esophagus with high-grade dysplasia or early adenocarcinoma,” Surgical Endoscopy, vol. 21, no. 5, pp. 820–824, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. S. Ono, M. Fujishiro, K. Niimi et al., “Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms,” Gastrointestinal Endoscopy, vol. 70, no. 5, pp. 860–866, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Repici, C. Hassan, A. Carlino et al., “Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series,” Gastrointestinal Endoscopy, vol. 71, no. 4, pp. 715–721, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Ishihara, H. Iishi, N. Uedo et al., “Comparison of EMR and endoscopic submucosal dissection for en bloc resection of early esophageal cancers in Japan,” Gastrointestinal Endoscopy, vol. 68, no. 6, pp. 1066–1072, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Oka, S. Tanaka, I. Kaneko et al., “Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer,” Gastrointestinal Endoscopy, vol. 64, no. 6, pp. 877–883, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Ezoe, M. Muto, T. Horimatsu et al., “Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection,” Journal of Clinical Gastroenterology, vol. 45, no. 3, pp. 222–227, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Kishida, N. Kakushima, N. Kawata et al., “Complications of endoscopic dilation for esophageal stenosis after endoscopic submucosal dissection of superficial esophageal cancer,” Surgical Endoscopy, vol. 29, no. 10, pp. 2953–2959, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Takahashi, Y. Arimura, S. Okahara et al., “Risk of perforation during dilation for esophageal strictures after endoscopic resection in patients with early squamous cell carcinoma,” Endoscopy, vol. 43, no. 3, pp. 184–189, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. R. J. Lew and M. L. Kochman, “A review of endoscopic methods of esophageal dilation,” Journal of Clinical Gastroenterology, vol. 35, no. 2, pp. 117–126, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Nonaka, M. Miyazawa, S. Ban et al., “Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model,” BMC Gastroenterology, vol. 13, no. 1, p. 72, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Katada, M. Muto, T. Manabe, N. Boku, A. Ohtsu, and S. Yoshida, “Esophageal stenosis after endoscopic mucosal resection of superficial esophageal lesions,” Gastrointestinal Endoscopy, vol. 57, no. 2, pp. 165–169, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Ono, M. Fujishiro, K. Niimi et al., “Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms,” Endoscopy, vol. 41, no. 8, pp. 661–665, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Honda, T. Nakamura, Y. Hori et al., “Process of healing of mucosal defects in the esophagus after endoscopic mucosal resection: histological evaluation in a dog model,” Endoscopy, vol. 42, no. 12, pp. 1092–1095, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Radu, P. Grosjean, C. Fontolliet, and P. Monnier, “Endoscopic mucosal resection in the esophagus with a new rigid device: an animal study,” Endoscopy, vol. 36, no. 4, pp. 298–305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Kochhar and G. K. Makharia, “Usefulness of intralesional triamcinolone in treatment of benign esophageal strictures,” Gastrointestinal Endoscopy, vol. 56, no. 6, pp. 829–834, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. J. I. Ramage Jr., A. Rumalla, T. H. Baron et al., “A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures,” The American Journal of Gastroenterology, vol. 100, no. 11, pp. 2419–2425, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Hashimoto, M. Kobayashi, M. Takeuchi, Y. Sato, R. Narisawa, and Y. Aoyagi, “The efficacy of endoscopic triamcinolone injection for the prevention of esophageal stricture after endoscopic submucosal dissection,” Gastrointestinal Endoscopy, vol. 74, no. 6, pp. 1389–1393, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. N. Hanaoka, R. Ishihara, Y. Takeuchi et al., “Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: a controlled prospective study,” Endoscopy, vol. 44, no. 11, pp. 1007–1011, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. H. Takahashi, Y. Arimura, S. Okahara et al., “A randomized controlled trial of endoscopic steroid injection for prophylaxis of esophageal stenoses after extensive endoscopic submucosal dissection,” BMC Gastroenterology, vol. 15, no. 1, p. 1, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Hanaoka, R. Ishihara, N. Uedo et al., “Refractory strictures despite steroid injection after esophageal endoscopic resection,” Endoscopy International Open, vol. 4, no. 3, pp. E354–E359, 2016. View at Publisher · View at Google Scholar
  21. Y. Nagami, M. Shiba, M. Ominami et al., “Single locoregional triamcinolone injection immediately after esophageal endoscopic submucosal dissection prevents stricture formation,” Clinical and translational gastroenterology, vol. 8, no. 2, article e75, 2017. View at Publisher · View at Google Scholar · View at Scopus
  22. E. Rajan, C. Gostout, A. Feitoza et al., “Widespread endoscopic mucosal resection of the esophagus with strategies for stricture prevention: a preclinical study,” Endoscopy, vol. 37, no. 11, pp. 1111–1115, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Yamashina, N. Uedo, M. Fujii et al., “Delayed perforation after intralesional triamcinolone injection for esophageal stricture following endoscopic submucosal dissection,” Endoscopy, vol. 45, article E92, Supplement 2, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Mori, K. Rafiq, H. Kobara et al., “Steroid permeation into the artificial ulcer by combined steroid gel application and balloon dilatation: prevention of esophageal stricture,” Journal of Gastroenterology and Hepatology, vol. 28, no. 6, pp. 999–1003, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. N. Yamaguchi, H. Isomoto, T. Nakayama et al., “Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma,” Gastrointestinal Endoscopy, vol. 73, no. 6, pp. 1115–1121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. H. Isomoto, N. Yamaguchi, T. Nakayama et al., “Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma,” BMC Gastroenterology, vol. 11, no. 1, p. 46, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Sato, H. Inoue, Y. Kobayashi et al., “Control of severe strictures after circumferential endoscopic submucosal dissection for esophageal carcinoma: oral steroid therapy with balloon dilation or balloon dilation alone,” Gastrointestinal Endoscopy, vol. 78, no. 2, pp. 250–257, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Kataoka, S. Anzai, T. Shirasaki et al., “Efficacy of short period, low dose oral prednisolone for the prevention of stricture after circumferential endoscopic submucosal dissection (ESD) for esophageal cancer,” Endoscopy International Open, vol. 3, no. 2, pp. E113–E117, 2015. View at Publisher · View at Google Scholar
  29. T. Ishida, Y. Morita, N. Hoshi et al., “Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection,” Digestive Endoscopy, vol. 27, no. 3, pp. 388–391, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. D. R. Ingrams, P. Ashton, R. Shah, J. Dhingra, and S. M. Shapshay, “Slow-release 5-fluorouracil and triamcinolone reduces subglottic stenosis in a rabbit model,” Annals of Otology, Rhinology, and Laryngology, vol. 109, no. 4, pp. 422–424, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Mizutani, A. Tadauchi, M. Arinobe et al., “Novel strategy for prevention of esophageal stricture after endoscopic surgery,” Hepato-Gastroenterology, vol. 57, no. 102-103, pp. 1150–1156, 2010. View at Google Scholar
  32. H. Suzawa, S. Kikuchi, K. Ichikawa, and A. Koda, “Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages,” Japanese Journal of Pharmacology, vol. 60, no. 2, pp. 85–90, 1992. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Shigeki, T. Murakami, N. Yata, and Y. Ikuta, “Treatment of keloid and hypertrophic scars by iontophoretic transdermal delivery of tranilast,” Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, vol. 31, no. 2, pp. 151–158, 1997. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Uno, K. Iijima, T. Koike et al., “A pilot study of scheduled endoscopic balloon dilation with oral agent tranilast to improve the efficacy of stricture dilation after endoscopic submucosal dissection of the esophagus,” Journal of Clinical Gastroenterology, vol. 46, no. 9, pp. e76–e82, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Barret, F. Batteux, F. Beuvon et al., “N-Acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model,” Fibrogenesis & Tissue Repair, vol. 5, no. 1, p. 8, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. Z. Xiao, F. Zhang, and Z. Cui, “Treatment of hypertrophic scars with intralesional botulinum toxin type A injections: a preliminary report,” Aesthetic Plastic Surgery, vol. 33, no. 3, pp. 409–412, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Wen, Z. Lu, E. Linghu et al., “Prevention of esophageal strictures after endoscopic submucosal dissection with the injection of botulinum toxin type A,” Gastrointestinal Endoscopy, vol. 84, no. 4, pp. 606–613, 2016. View at Publisher · View at Google Scholar · View at Scopus
  38. J. H. Shin, H. Y. Song, G. Y. Ko, J. O. Lim, H. K. Yoon, and K. B. Sung, “Esophagorespiratory fistula: long-term results of palliative treatment with covered expandable metallic stents in 61 patients,” Radiology, vol. 232, no. 1, pp. 252–259, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. J. H. Kim, H. Y. Song, J. H. Shin et al., “Palliative treatment of unresectable esophagogastric junction tumors: balloon dilation combined with chemotherapy and/or radiation therapy and metallic stent placement,” Journal of Vascular and Interventional Radiology, vol. 19, no. 6, pp. 912–917, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Y. Song, S. I. Park, Y. S. Do et al., “Expandable metallic stent placement in patients with benign esophageal strictures: results of long-term follow-up,” Radiology, vol. 203, no. 1, pp. 131–136, 1997. View at Publisher · View at Google Scholar · View at Scopus
  41. R. P. Wadhwa, R. A. Kozarek, R. E. France et al., “Use of self-expandable metallic stents in benign GI diseases,” Gastrointestinal Endoscopy, vol. 58, no. 2, pp. 207–212, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. S. Cheng, M. H. Li, W. X. Chen, N. W. Chen, Q. X. Zhuang, and K. Z. Shang, “Temporary partially-covered metal stent insertion in benign esophageal stricture,” World Journal of Gastroenterology, vol. 9, no. 10, pp. 2359–2361, 2003. View at Publisher · View at Google Scholar
  43. J. H. Kim, H. Y. Song, E. K. Choi, K. R. Kim, J. H. Shin, and J. O. Lim, “Temporary metallic stent placement in the treatment of refractory benign esophageal strictures: results and factors associated with outcome in 55 patients,” European Radiology, vol. 19, no. 2, pp. 384–390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Matsumoto, H. Miyatani, Y. Yoshida, and M. Nokubi, “Cicatricial stenosis after endoscopic submucosal dissection of esophageal cancer effectively treated with a temporary self-expandable metal stent,” Gastrointestinal Endoscopy, vol. 73, no. 6, pp. 1309–1312, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Yamasaki, T. Tomita, M. Takimoto et al., “Esophageal stricture after endoscopic submucosal dissection treated successfully by temporary stent placement,” Clinical Journal of Gastroenterology, vol. 9, no. 6, pp. 337–340, 2016. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Wen, Z. Lu, Y. Yang et al., “Preventing stricture formation by covered esophageal stent placement after endoscopic submucosal dissection for early esophageal cancer,” Digestive Diseases and Sciences, vol. 59, no. 3, pp. 658–663, 2014. View at Publisher · View at Google Scholar · View at Scopus
  47. T. Tanaka, M. Takahashi, N. Nitta et al., “Newly developed biodegradable stents for benign gastrointestinal tract stenoses: a preliminary clinical trial,” Digestion, vol. 74, no. 3-4, pp. 199–205, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. P. G. A. van Boeckel, F. P. Vleggaar, and P. D. Siersema, “A comparison of temporary self-expanding plastic and biodegradable stents for refractory benign esophageal strictures,” Clinical Gastroenterology and Hepatology, vol. 9, no. 8, pp. 653–659, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. Saito, T. Tanaka, A. Andoh et al., “Novel biodegradable stents for benign esophageal strictures following endoscopic submucosal dissection,” Digestive Diseases and Sciences, vol. 53, no. 2, pp. 330–333, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. G. W. Lua, J. Tang, F. Liu, and Z. S. Li, “Prevention of esophageal strictures after endoscopic submucosal dissection: a promising therapy using carboxymethyl cellulose sheets,” Digestive Diseases and Sciences, vol. 61, no. 6, pp. 1763–1769, 2016. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Nakamura, Y. Shimizu, S. Watanabe et al., “New bioabsorbable pledgets and non-woven fabrics made from polyglycolide (PGA) for pulmonary surgery: clinical experience,” The Thoracic and Cardiovascular Surgeon, vol. 38, no. 2, pp. 81–85, 1990. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Shinozaki, R. Hayashi, M. Ebihara, M. Miyazaki, and T. Tomioka, “Mucosal defect repair with a polyglycolic acid sheet,” Japanese Journal of Clinical Oncology, vol. 43, no. 1, pp. 33–36, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. Y. Tsuji, K. Ohata, T. Gunji et al., “Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to cover wounds after colorectal endoscopic submucosal dissection (with video),” Gastrointestinal Endoscopy, vol. 79, no. 1, pp. 151–155, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Takeuchi, H. Suzuki, M. Murata et al., “Clinical evaluation of application of polyglycolic acid sheet and fibrin glue spray for partial glossectomy,” Journal of Oral and Maxillofacial Surgery, vol. 71, no. 2, pp. e126–e131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Takimoto, Y. Imai, and K. Matsuyama, “Endoscopic tissue shielding method with polyglycolic acid sheets and fibrin glue to prevent delayed perforation after duodenal endoscopic submucosal dissection,” Digestive Endoscopy, vol. 26, Supplement 2, pp. 46–49, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. T. Iizuka, D. Kikuchi, A. Yamada, S. Hoteya, Y. Kajiyama, and M. Kaise, “Polyglycolic acid sheet application to prevent esophageal stricture after endoscopic submucosal dissection for esophageal squamous cell carcinoma,” Endoscopy, vol. 47, no. 4, pp. 341–344, 2015. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Ono, Y. Tsuji, M. Fujishiro, S. Kodashima, N. Yamamichi, and K. Koike, “An effective technique for delivery of polyglycolic acid sheet after endoscopic submucosal dissection of the esophagus: the clip and pull method,” Endoscopy, vol. 46, Supplement 1, pp. E44–E45, 2014. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Sakaguchi, Y. Tsuji, S. Ono et al., “Polyglycolic acid sheets with fibrin glue can prevent esophageal stricture after endoscopic submucosal dissection,” Endoscopy, vol. 47, no. 4, pp. 336–340, 2015. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Kataoka, Y. Tsuji, Y. Sakaguchi et al., “Preventing esophageal stricture after endoscopic submucosal dissection: steroid injection and shielding with polyglycolic acid sheets and fibrin glue,” Endoscopy, vol. 47, Supplement 1, pp. E473–E474, 2015. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Nagami, M. Shiba, K. Tominaga et al., “Hybrid therapy with locoregional steroid injection and polyglycolic acid sheets to prevent stricture after esophageal endoscopic submucosal dissection,” Endoscopy International Open, vol. 4, no. 9, pp. E1017–E1022, 2016. View at Publisher · View at Google Scholar
  61. B. Brown, K. Lindberg, J. Reing, D. B. Stolz, and S. F. Badylak, “The basement membrane component of biologic scaffolds derived from extracellular matrix,” Tissue Engineering, vol. 12, no. 3, pp. 519–526, 2006. View at Publisher · View at Google Scholar
  62. S. F. Badylak, D. A. Vorp, A. R. Spievack et al., “Esophageal reconstruction with ECM and muscle tissue in a dog model,” The Journal of Surgical Research, vol. 128, no. 1, pp. 87–97, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. T. J. Keane, R. Londono, R. M. Carey et al., “Preparation and characterization of a biologic scaffold from esophageal mucosa,” Biomaterials, vol. 34, no. 28, pp. 6729–6737, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Badylak, S. Meurling, M. Chen, A. Spievack, and A. Simmons-Byrd, “Resorbable bioscaffold for esophageal repair in a dog model,” Journal of Pediatric Surgery, vol. 35, no. 7, pp. 1097–1103, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. S. F. Badylak, T. Hoppo, A. Nieponice, T. W. Gilbert, J. M. Davison, and B. A. Jobe, “Esophageal preservation in five male patients after endoscopic inner-layer circumferential resection in the setting of superficial cancer: a regenerative medicine approach with a biologic scaffold,” Tissue Engineering Part A, vol. 17, no. 11-12, pp. 1643–1650, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Nieponice, K. McGrath, I. Qureshi et al., “An extracellular matrix scaffold for esophageal stricture prevention after circumferential EMR,” Gastrointestinal Endoscopy, vol. 69, no. 2, pp. 289–296, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. S. J. Schomisch, L. Yu, Y. Wu et al., “Commercially available biological mesh does not prevent stricture after esophageal mucosectomy,” Endoscopy, vol. 46, no. 2, pp. 144–148, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. T. Sakurai, S. Miyazaki, G. Miyata, S. Satomi, and Y. Hori, “Autologous buccal keratinocyte implantation for the prevention of stenosis after EMR of the esophagus,” Gastrointestinal Endoscopy, vol. 66, no. 1, pp. 167–173, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. B. F. Zuercher, M. George, A. Escher et al., “Stricture prevention after extended circumferential endoscopic mucosal resection by injecting autologous keratinocytes in the sheep esophagus,” Surgical Endoscopy, vol. 27, no. 3, pp. 1022–1028, 2013. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Honda, Y. Hori, A. Nakada et al., “Use of adipose tissue-derived stromal cells for prevention of esophageal stricture after circumferential EMR in a canine model,” Gastrointestinal Endoscopy, vol. 73, no. 4, pp. 777–784, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. R. Takagi, M. Yamato, D. Murakami et al., “Fabrication and validation of autologous human oral mucosal epithelial cell sheets to prevent stenosis after esophageal endoscopic submucosal dissection,” Pathobiology, vol. 78, no. 6, pp. 311–319, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Kanai, M. Yamato, T. Ohki, M. Yamamoto, and T. Okano, “Fabricated autologous epidermal cell sheets for the prevention of esophageal stricture after circumferential ESD in a porcine model,” Gastrointestinal Endoscopy, vol. 76, no. 4, pp. 873–881, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Perrod, G. Rahmi, L. Pidial et al., “Cell sheet transplantation for esophageal stricture prevention after endoscopic submucosal dissection in a porcine model,” PLoS One, vol. 11, no. 3, article e0148249, 2016. View at Publisher · View at Google Scholar · View at Scopus
  74. G. Perrod, L. Pidial, S. Camilleri et al., “ADSC-sheet transplantation to prevent stricture after extended esophageal endoscopic submucosal dissection,” Journal of Visualized Experiments, vol. 10, no. 120, article e55018, 2017. View at Publisher · View at Google Scholar · View at Scopus
  75. T. Ohki, M. Yamato, D. Murakami et al., “Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model,” Gut, vol. 55, no. 12, pp. 1704–1710, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. T. Ohki, M. Yamato, M. Ota et al., “Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets,” Gastroenterology, vol. 143, no. 3, pp. 582–588.e2, 2012. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Takagi, D. Murakami, M. Kondo et al., “Fabrication of human oral mucosal epithelial cell sheets for treatment of esophageal ulceration by endoscopic submucosal dissection,” Gastrointestinal Endoscopy, vol. 72, no. 6, pp. 1253–1259, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. T. Ohki, M. Yamato, M. Ota et al., “Application of regenerative medical technology using tissue-engineered cell sheets for endoscopic submucosal dissection of esophageal neoplasms,” Digestive Endoscopy, vol. 27, no. 2, pp. 182–188, 2015. View at Publisher · View at Google Scholar · View at Scopus
  79. T. Mizushima, S. Ohnishi, H. Hosono et al., “Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs,” Gastrointestinal Endoscopy, vol. 86, no. 3, pp. 542–552.e1, 2017. View at Publisher · View at Google Scholar · View at Scopus