Esophageal strictures: in search of the Goldilocks solution

In this issue of Endoscopy, Walter et al. report on a multicenter exploratory study on the use of biodegradable stents in the treatment of benign esophageal strictures [1]. The authors conclude that biodegradable stents delay the need for retreatment due to recurrent dysphagia compared with dilation therapy alone. Walter et al. should be given accolades for this valuable contribution to the growing literature on biodegradable endoprosthetics and for studying a difficult and heterogeneous patient population.

The biodegradable endoprosthetic represents an evolutionary technology that has clear theoretical benefits over other treatments for esophageal strictures. In benign refractory esophageal strictures, endoscopic resource utilization could potentially be reduced if biodegradable stents are placed, and subsequent replacement or dilation is performed only when dysphagia recurs. One of the most attractive features of the biodegradable stent, as demonstrated in the Walter et al. study, is that there were no reports of hyperplastic tissue growth or secondary stricture formation as may be seen with self-expandable metal stents (SEMS). Although the biodegradable stent is not a disruptive technology, it represents incremental innovation and appears to provide valuable improvements over existing endoprosthetic technologies for selected indications. In order to push the boundaries of innovation and patient care further, we must critically evaluate this study in order to assist in the evolution of this technology and to define the patient population that will most benefit from it.

“For now, the use of protocolized dilation will remain the gold standard, but depending upon the individual patient situation, strategies utilizing biodegradable stents or self-bougienage may be appropriate.”

When placing the use of a new technology into clinical perspective, it is important to evaluate both the pathologic disease process to which the technology will be applied and also the technology itself. In the case of benign esophageal strictures, defining refractory and recurrent strictures is necessary to better delineate the exact patient population enrolled. Benign refractory strictures are those that cannot be remediated to a diameter of 14 mm over the course of five sessions at 2-week intervals [2]. Conversely, recurrent esophageal strictures are those in which the luminal diameter cannot be maintained once the 14 mm dilation threshold has been reached [2].

The esophageal strictures in the Walter et al. study did not uniformly meet criteria for either recurrent or refractory esophageal strictures. The majority of the strictures were anastomotic in etiology, but there were also multiple other types of stricture included in the study. Although these permissive inclusion criteria in terms of prior interventions and stricture etiology allowed the authors to capture a broad study population and bring the study to conclusion, they may have prevented observation of a more significant effect (and signal) than if a well defined and reproducible population had been evaluated, such as previously untreated anastomotic strictures or refractory anastomotic strictures.

An appraisal of the characteristics of the biodegradable stent as a technology is warranted. The stents are able to maintain radial force for approximately 8 weeks and their eventual degradation eliminates the need for endoscopic removal [3]. In this study, radiographic examination for the presence of the biodegradable stent’s gold markers was performed at 12 weeks. The timing of this evaluation (8 weeks vs. 12 weeks) can be debated, but of equal importance is the relevance of the gold markers: does their presence actually indicate that the stent continues to maintain its expansile force and is indeed providing any remediation? The major finding of the study – that biodegradable stents are associated with a longer period of time until repeat dilation of the stricture – could potentially be explained by the stent maintaining its force and remaining intact for a longer period than is presumed. Additionally, the observation that the strictures were not uniformly remediated and subsequently required dilation after biodegradable stent placement should not come as a surprise. Prior studies utilizing self-expandable plastic stents for refractory benign esophageal strictures observed remediation in less than a quarter of patients treated, and similar results have been observed with the use of SEMS and biodegradable stents, reflecting the pathophysiology of the disease process [4] [5] [6] [7].

Overall, the heterogeneity of the esophageal strictures and the interventions employed add a great deal of complexity to the interpretation of the study results. The strictures were of varying etiologies, the initial luminal diameters of the strictures differed, the dilation protocols both pre- and post-study were not defined, and the diameter of the biodegradable stent placed was based upon the endoscopist’s judgment. With such heterogeneity of patient and device characteristics, a relevant regression analysis could not be performed.

The biodegradable stent represents an evolutionary technology with great promise that needs a clearly defined patient population to maximize its potential. Traditionally, endoprosthetics are utilized for one of two purposes: remediation (e. g. for leaks or fistulas) or palliation (e. g. in the setting of malignancy), and such devices have not demonstrated significant efficacy for remediation in the setting of benign refractory strictures. If biodegradable stents are unable to permanently remediate benign strictures, then perhaps their best use is for palliation of benign strictures. In the future, a randomized trial with crossover occurring at clinical failure could address the use of biodegradable stents for palliation of refractory benign esophageal strictures; such a trial would likely also demonstrate improved resource utilization and cost-effectiveness outcomes.

Existing treatments for esophageal strictures are numerous and diverse, with the biodegradable stent being a valuable addition to the armamentarium. The future is even brighter as innovators continue to perfect current treatments and conceive disruptive technologies, ideally with the goal of reversing the underlying pathologic process. For now, however, the use of protocolized dilation will remain the gold standard, but depending upon the individual patient situation, strategies utilizing biodegradable stents or self-bougienage may be appropriate. A Goldilocks solution that can effectively be employed for all benign esophageal strictures may not yet exist [8], but until one is found, the vast majority of patients will find a solution that works for them by minimizing inconvenience and maximizing quality of life.

• References

• 1 Walter D, van den Berg MW, Hirdes MM. et al. Dilation or biodegradable stent placement for recurrent benign esophageal strictures: a randomized controlled trial. Endoscopy 2018; 50: 1146-1155
• 2 Kochman ML, McClave SA, Boyce HW. The refractory and the recurrent esophageal stricture: a definition. Gastrointest Endosc 2005; 62: 474-475
• 3 Repici A, Vleggaar FP, Hassan C. et al. Efficacy and safety of biodegradable stents for refractory benign esophageal strictures: the BEST (Biodegradable Esophageal Stent) study. Gastrointest Endosc 2010; 72: 927-934
• 4 Holm AN, de la Mora Levy JG, Gostout CJ. et al. Self-expanding plastic stents in treatment of benign esophageal conditions. Gastrointest Endosc 2008; 67: 20-25
• 5 Kochman ML. Removable endoprosthetics in the management of esophageal pathology: all strictures and fistulae are not created equal. Gastrointest Endosc 2008; 67: 26-27
• 6 Oh YS, Kochman ML, Ahmad NA. et al. Clinical outcomes after self-expanding plastic stent placement for refractory benign esophageal strictures. Dig Dis Sci 2010; 55: 1344-1348
• 7 Repici A, Small AJ, Mendelson A. et al. Natural history and management of refractory benign esophageal strictures. Gastrointest Endosc 2016; 84: 222-228
• 8 The Goldilocks principle. Available from: https://en.wikipedia.org/wiki/Goldilocks_principle