“The pursuit for the better esophageal stent…”
In this issue, Dua et al
- Dua K.S.
- DeWitt J.M.
- Kessler W.R.
- et al.
A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).
publish their results of a phase 3, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve. This work was presented at Digestive Disease Week in 2018. Eight centers in the United States participated in this study. The study was funded and supported by the stent manufacturer.
Self-expanding esophageal metal stents have been extensively used over the past few decades in the palliative management of esophageal cancer and esophageal cancer–related adverse events such as fistulae and for the management of esophageal cancer–related treatment adverse events. There have been multiple designs for esophageal stents, combining various metal alloy compounds, mesh design, varying radial expansile forces, and other variables. One adverse event of these metal stents, when placed across the gastroesophageal junction, is the resulting gastroesophageal reflux, which can be significant and incapacitating.
The majority of esophageal adenocarcinomas affect the gastroesophageal junction on the basis of their predominant distal third location, resulting in stricture formation and secondary dysphagia. A majority of patients in whom esophageal adenocarcinoma develop have experienced long-standing GERD, and many continue to have heartburn even after they experience significant esophageal strictures, which in theory would decrease acid exposure.
The main purpose of the esophageal stent is the relief of dysphagia. The associated postesophageal stent placement–related GERD has been well studied and documented. The importance of such reflux is not so much the associated symptomatology of heartburn but the fact that it is mostly volume related and relates to gastric contents. Thus, it does not respond to management with any type of antacid or bile blocker and places patients at high risk for aspiration pneumonitis.
Therefore, it was only natural to develop an esophageal stent with some form of antireflux system, mostly same-design stents adapted with a distal valve of sorts. For the past 2 decades, there have been multiple publications on the use of antireflux stents. Some of these publications have included esophageal physiologic studies proving the efficacy of such stents. However, most of these studies included a small number of patients, the study design was poor, and patients were treated with antacid medication. Meta-analyses including only randomized controlled trials have not proved efficient in reducing gastroesophageal reflux after stent placement.
In this randomized trial, a laser-cut, nonforeshortening, silicone, fully covered nitinol stent was used, 1 stent with an antireflux valve versus 1 stent without a valve. The valve design is in a tricuspid shape and is located 3 cm proximal to the distal end of the stent. The same stent with no valve is already in use in the United States and abroad. The valve stent has been used in Europe. Placement of the stents and poststent recommendations, including diet and medications, were standard in current practice.
In this study, only patients with malignant strictures compromising the gastroesophageal junction were included, and none had received previous stent therapy. Neither the endoscopists nor the treating physicians were blinded to the stent used.
This was an intent-to-treat, noninferiority study, not designed for statistical significance. The main objective was the response to dysphagia. Secondary objectives were symptoms related to gastroesophageal reflux at 4 weeks, adverse events, technical success, and reinterventions. It was a 1:1 randomization; the baseline characteristics were similar in both groups. The technical success was 100% for both groups. Over half of the patients were dead or unable to cooperate during the anticipated follow-up period of 24 months.
When the 2 stents were compared, the primary endpoint of dysphagia resolution was similar between the 2 groups. One then can conclude that the valve stent was not inferior to the nonvalve stent in dysphagia resolution, despite the small number of patients and the short survival overall. One must note, however, as listed in the overall adverse events, that 4 patients (13.8%) experienced dysphagia in the valve stent group compared with none in the nonvalve stent group.
Gastroesophageal reflux–related symptoms also had a similar response between the 2 groups, with some improvement trends in favor of the valve stent. As the authors point out, over the years there have been multiple antireflux valve designs, including those with a tricuspid valve like the stent assessed in this study, all with reported mixed results. The authors provide various explanations for the lack of difference in reflux control between the 2 stents, most not related to the main issue of volume/content reflux. Perhaps the most critical feature in placing a valve in the stent is to prevent reflux of volume and gastric contents into the esophagus. By definition, the stent is a mechanical barrier with that function. The purpose is not really to decrease symptoms based on acid. First, patients may have acid sensations above the valve; second, all patients were (appropriately) using acid inhibitors. Furthermore, the questionnaire used to assess reflux response does not include any measure to assess volume-related reflux. It is mostly heartburn related. Thus, the anticipated results from a mechanical barrier were really not assessed or questioned. At least to me, based on the title of the study, as in going to the movies, I was anticipating a good antireflux outcome and stent performance; however, “the film did not deliver.” One must wonder whether asking patients after stent placement whether they have heartburn is the right question to ask. Is the use of a nonvalidated questionnaire used for patients with benign GERD appropriate for patients with malignant esophageal stricture?
Considering the time lapsed since we started using self-expanding metal stents for the management of malignant esophageal strictures, there have really not been any significant developments in stent technology. Stents continue to have significant adverse events and major complications. The authors describe the use of a novel stent. But we really do not have a novel stent. Novel is defined as “of a new kind; different from anything seen or known before.” We wish for that day when we will have a stent that is deployed flawlessly, that has a much lower rate of adverse events (hopefully none), and that prevents reflux of gastric contents. This has been proved to be quite difficult and elusive, including to some of the authors in the article who have devoted much time and effort in developing esophageal stents.
What do I (we) take home from this study? We know we can help our patients in the relief of dysphagia with stent placement. We can make their short survival a bit better. We can restore their capacity to take food by mouth and at least give them that pleasure. That is it. And we know that stents with an “antireflux valve” do not prevent reflux better than stents without a valve.
The pursuit for the better esophageal stent, at least for those used in the palliation of distal esophageal malignant strictures and reflux prevention, continues. I am certain we will get there.
The author disclosed no financial relationships relevant to this publication.
- Dua K.S.
- DeWitt J.M.
- Kessler W.R.
- et al.
A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).Gastrointest Endosc. 2019; 90: 64-74
© 2019 by the American Society for Gastrointestinal Endoscopy