Treatment of refractory benign esophageal strictures: it is all about being “patient”

Benign esophageal strictures are seen frequently and are caused by a variety of esophageal injuries, such as gastroesophageal reflux, radiotherapy, corrosive substance ingestion, eosinophilic esophagitis, after esophageal resection, and as an adverse event of ablation. Most benign strictures are effectively treated by bougie or balloon dilation, which usually takes 1 or only a few sessions.1de Wijkerslooth L.R. Vleggaar F.P. Siersema P.D. Endoscopic management of difficult or recurrent esophageal strictures.Am J Gastroenterol. 2011; 106: 2080-2089Crossref PubMed Scopus (84) Google Scholar However, in a small subset of patients (<10%), at least 5 dilations to at least 14 mm fail to establish adequate and persistent food passage. These strictures are defined as refractory benign esophageal strictures (RBES).2Kochman M.L. McClave S.A. Boyce H.W. The refractory and the recurrent esophageal stricture: a definition.Gastrointest Endosc. 2005; 62: 474-475Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar Over the last decade, the therapeutic options for RBES have increased. If dilation alone is not successful, dilation combined with 4-quadrant steroid injections or electrocautery incisions should be considered as second step in the treatment algorithm.1de Wijkerslooth L.R. Vleggaar F.P. Siersema P.D. Endoscopic management of difficult or recurrent esophageal strictures.Am J Gastroenterol. 2011; 106: 2080-2089Crossref PubMed Scopus (84) Google Scholar Dilation with steroid injections has been shown to be effective for strictures caused by gastroesophageal reflux and for those after (extended) ablation therapy. A subgroup of patients with anastomotic strictures is also responsive to treatment with electrocautery incisions or dilation with steroid injections. If patients are still symptomatic after up to 3 sessions with incisions and/or dilation with steroids, placement of a self-expanding metal stent (SEMS) or biodegradable stent can be considered as a third step in the treatment algorithm. Biodegradable stents are of interest for treating RBES because they gradually dissolve, which eliminates the need for endoscopic removal.3Repici A. Hassan C. Sharma P. et al.Systematic review: the role of self-expanding plastic stents for benign oesophageal strictures.Aliment Pharmacol Ther. 2010; 31: 1268-1275Crossref PubMed Scopus (79) Google Scholar If stent placement is not successful, self-dilation is an option in a subgroup of patients, whereas surgery is the ultimate remedy when all previous options have not resulted in stricture resolution.1de Wijkerslooth L.R. Vleggaar F.P. Siersema P.D. Endoscopic management of difficult or recurrent esophageal strictures.Am J Gastroenterol. 2011; 106: 2080-2089Crossref PubMed Scopus (84) Google Scholar In this issue of Gastrointestinal Endoscopy, Repici et al4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar report a 15-year experience of treating RBES in 2 academic centers in Milan, Italy and Philadelphia, Pennsylvania. In particular, the use of dilation and stents was evaluated for resolution of dysphagia, adverse events, and long-term outcome. Seventy patients were included. Stricture resolution was achieved in some patients (31%). Remarkably, success was less-frequently observed in patients treated with a stent (mean dysphagia-free period of 72 days in the stent group vs 99.5 days in the dilation group). The authors concluded that the long-term outcome for treatment of RBES was disappointing, whereas stents had no additive effect on the natural history of RBES. Repici et al4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar are to be congratulated for summarizing the long-term follow-up data on the natural history and management of RBES. As of now, only limited data on the long-term follow-up of this group of patients is available. Most patients included in the study had an esophageal stricture caused by a caustic, postsurgical, postradiotherapy, or mixed etiology. More than 40% of the strictures were located in the cervical esophagus, whereas the stricture length was 2 cm or longer in most of those in whom stricture length was known. The authors found that clinical resolution, defined as >6 months dysphagia-free without the need for further intervention, tended to be lower in patients with a cervical stricture. It is known from a previous systematic review that the success of stent placement is significantly lower in patients with a cervical stricture and in those with a stricture longer than 2 cm.4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar The patients in the study by Repici et al4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar were therefore not simple stricture patients who required 1 or only a few dilations but rather patients with highly refractory strictures referred to tertiary care centers for treatment. One of the major findings of the study by Repici et al was that after a mean follow-up of 43.9 months, only 22 patients (31.4%) had achieved clinical stricture resolution. This is indeed disappointingly low. Hirdes et al5Hirdes M.M. Siersema P.D. van Boeckel P.G. et al.Single and sequential biodegradable stent placement for refractory benign esophageal strictures: a prospective follow-up study.Endoscopy. 2012; 44: 649-654Crossref PubMed Scopus (58) Google Scholar reported similar findings in 28 patients with RBES, according to the Kochman criteria. Patients were followed for a median of 21 months and previously treated with combinations of multiple dilations and SEMS placement, followed by sequential placement of 1 or more biodegradable stents. Clinical resolution of the stricture was achieved in 7 patients (25%). The authors concluded that (sequential) stent placement, either with a SEMS or biodegradable stent, is an option to be considered in patients with RBES to avoid serial dilations. Nonetheless, both the results of Repici et al4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar and Hirdes et al5Hirdes M.M. Siersema P.D. van Boeckel P.G. et al.Single and sequential biodegradable stent placement for refractory benign esophageal strictures: a prospective follow-up study.Endoscopy. 2012; 44: 649-654Crossref PubMed Scopus (58) Google Scholar show that there is a subgroup of RBES patients who are difficult to treat and for whom prolonged time and patience are required from both the patient and the treating physician before stricture resolution is achieved. Based on their long-term follow-up results, Repici et al4Repici A. Small A.J. Mendelson A. et al.Natural history and management of refractory benign esophageal strictures.Gastrointest Endosc. 2016; 84: 222-228Google Scholar concluded that stents have no effect on the long-term natural history of RBES. The latter is not surprising because the main advantage of stent placement is prolonged, continuous dilation, whereas stents offer no cure for the underlying process of stricturing, with varying underlying causes such as ischemia (anastomotic stricture) and transmural injury (caustic ingestion).5Hirdes M.M. Siersema P.D. van Boeckel P.G. et al.Single and sequential biodegradable stent placement for refractory benign esophageal strictures: a prospective follow-up study.Endoscopy. 2012; 44: 649-654Crossref PubMed Scopus (58) Google Scholar The comparison between ongoing dilation and stent placement in the Repici et al study was, however, retrospective and, as pointed out by the authors, prone to confounding and selection bias. Walter et al6Walter D. van den Berg M.W. Hirdes M.M. et al.A randomized trial comparing biodegradable stent placement and endoscopic dilation for recurrent benign esophageal strictures (Destiny study).United Eur Gastroenterol J. 2015; 3: A24Google Scholar recently reported the results of a multicenter, randomized study comparing biodegradable stent placement with ongoing dilation in 66 patients with RBES. The primary outcome was the number of endoscopic dilations for recurrent dysphagia during follow-up. In addition, quality of life and ability to swallow of treated patients were regularly evaluated. Time to the first episode of recurrent dysphagia requiring intervention was significantly longer in the biodegradable stent group compared with the dilation group (median, 95 days vs 30 days). Quality of life and performance were also significantly better in the biodegradable stent group compared with the ongoing dilation group. These results confirm that stent (either biodegradable or SEMS) placement should be considered as a valuable treatment option for RBES. Moreover, because stent placement prolongs the time between visits to the hospital for dilation or makes visits no longer needed, this positively affects patients’ quality of life, one of the most important treatment outcome parameters in RBES management. In total, 7 patients (10%) developed a serious adverse event, specifically perforation (n = 3; caused by dilation) and fistula formation (n = 4; caused by dilation [n = 2] or stent placement [n = 2]). In the study by Walter et al,6Walter D. van den Berg M.W. Hirdes M.M. et al.A randomized trial comparing biodegradable stent placement and endoscopic dilation for recurrent benign esophageal strictures (Destiny study).United Eur Gastroenterol J. 2015; 3: A24Google Scholar 4 patients (6%) developed a perforation (n = 2; caused by dilation) or fistula formation (n = 2; caused by stent placement). The mortality rate because of the treatment of RBES was 2.8% in the Repici et al series. In our experience of endoscopic treatment of 168 patients with RBES, mortality was similar (ie, 1.7%). This mortality rate falls within the currently acceptable range when esophageal resection is performed. In addition, it also shows that RBES is a serious disorder with a significant risk of morbidity and mortality. Is it possible to further improve the endoscopic management of RBES? It can be foreseen that in the future, novel fully covered (biodegradable) stents will be developed with optimal characteristics for RBES management, which means these stents will have a sufficiently high radial force and elasticity to reduce the risk of stent migration and tissue ingrowth, but also a low axial force, reducing other severe adverse events, such as perforation and fistula formation.7Hirdes M.M. Vleggaar F.P. de Beule M. et al.In vitro evaluation of the radial and axial force of self-expanding esophageal stents.Endoscopy. 2013; 45: 997-1005Crossref PubMed Scopus (79) Google Scholar Alternatively, local application of mitomycin C, which inhibits DNA synthesis and reduces fibroblastic collagen formation, has been suggested to be effective for the treatment of RBES.8Rustagi T. Aslanian H.R. Laine L. Treatment of refractory gastrointestinal strictures with mitomycin C: a systematic review.J Clin Gastroenterol. 2015; 49: 837-847Crossref Scopus (15) Google Scholar Furthermore, a combination of currently available treatment modalities should be considered. Promising results have been reported when endoscopic electrocautery incisions and esophageal stenting are combined.9Liu D. Tan Y. Wang Y. et al.Endoscopic incision with esophageal stent placement for the treatment of refractory benign esophageal strictures.Gastrointest Endosc. 2015; 81: 1036-1040Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar In conclusion, endoscopic treatment according to a well-defined algorithm, including stent placement, should be the primary treatment approach for RBES. It is, however, important to discuss with the patient that the endoscopic treatment of RBES is not without a small but increased risk of developing a (severe) adverse event. Of similar importance, both patients and physicians should realize that a long treatment time with repeat sessions and visits to the hospital is needed for an effective treatment of RBES. This means patience, but with the guarantee that most RBES resolve with endoscopic treatment only, and do not require surgery. The author disclosed financial relationships relevant to this publication: Consultant for Boston Scientific and Ella-CS; research support recipient from Boston Scientific and Cook Medical. Natural history and management of refractory benign esophageal stricturesGastrointestinal EndoscopyVol. 84Issue 2PreviewThe natural history of refractory benign esophageal strictures (RBES) is unclear, and surgery or percutaneous endoscopic gastrostomy (PEG) may be the only viable long-term options. The aim of the present study was to assess the long-term outcomes of patients with RBES. Full-Text PDF Esophageal self-dilations as a treatment for refractory benign esophageal stricturesGastrointestinal EndoscopyVol. 85Issue 4PreviewIt was with great interest that we read the study by Repici et al1 on refractory benign esophageal strictures (RBES) and the accompanying editorial by Dr Siersema.2 This study should be commended for reporting a long-term follow-up in RBES treated with endoscopic dilation, self-expandable metallic stents, biodegradable stents, and steroid injections. The study was also comprehensive in analyzing the treatment effect on strictures that differ in location, length, and cause. Ultimately, the study found only a 31.4% rate of clinical resolution for patients with RBES; patients treated with endoprostheses had even a lower rate of successful outcome. Full-Text PDF