The management of refractory benign esophageal strictures (RBES) presents a formidable clinical challenge, necessitating frequent interventions to ameliorate symptoms and enhance the quality of life for affected individuals. Among the array of available endoscopic therapeutic modalities for RBES, esophageal dilation stands out as the primary treatment approach, with both balloon dilators and bougies demonstrating high rates of technical success and satisfactory clinical resolution. Despite its efficacy, approximately 30-40% of strictures recur following dilation, prompting exploration into adjunctive therapies such as steroid injections, incisional therapy, stent placement, and the application of mitomycin C. Triamcinolone injections have emerged as an option, reducing stricture recurrence rates and improving dysphagia scores, particularly in refractory anastomotic strictures. However, the literature reports conflicting findings regarding their efficacy, underscoring the need for further investigation. Similarly, stent placement, including the use of self-expanding metal stents (SEMS) and lumen-apposing metal stents (LAMS), offers viable alternatives, albeit with concerns regarding migration rates and adverse events. Furthermore, self-dilation, while rarely employed, presents a patient-centered approach that can be both safe and effective when appropriately implemented. Despite these advancements, several knowledge gaps persist, necessitating further research to refine treatment strategies, optimize clinical outcomes, and enhance the overall management of RBES. This literature review aims to synthesize existing evidence, identify areas of agreement and disagreement, and delineate avenues for future investigation to address these critical gaps in understanding and practice.

Dilation

Esophageal dilation remains the primary treatment for RBES as patients with RBES often require multiple dilations.^,,  Most strictures are successfully treated with endoscopic dilation, however approximately 30-40% recur. There are several methods of performing esophageal dilation. These vary by the type of dilator used and the way it is passed through the esophagus to the level of the stricture itself. Generally, dilation can be categorized as either balloon or mechanical (bougie-type). Balloon dilators can be passed through-the-scope (TTS) or over a guidewire. Placement can be verified by direct visualization via endoscopy, and/or via fluoroscopy.^1,4 TTS balloons come in a variety of sizes and are in widespread use. (Figure 1) The most common type of bougies in current use are Savary-Gilliard (SG) or Maloney dilators. Modern bougies, made of polyvinyl chloride, are generally passed over a wire, frequently with additional fluoroscopic guidance, across a stricture where they exert radial and longitudinal pressure on the stricture. It should be noted that using balloon dilation is technically easier, but the cost is higher as balloons are one time use devices. SG and Maloney dilators are not disposable and can be used repeatedly and are more cost effective over time.⁴ There is no statistical difference between the balloon dilation and SG dilators in terms of clinical resolution of esophageal strictures.^, Repeated dilation treatment by balloons and bougies was found to have an overall clinical success rate of 70.9% in a 2019 retrospective analysis.⁷ Another study found successful dilation, defined as the ability to expand the esophageal lumen to accommodate a 42F (14 mm wide) catheter, was attained in 93.5% of patients undergoing endoscopic dilation.¹⁰

Among the adverse events associated with dilation for benign esophageal strictures are perforation, bleeding, bacteremia, and (rarely) esophageal fistula. The perforation rate has been reported between 0.1 – 0.4%, which no clear evidence of different perforation rates for mechanical versus balloon dilators.¹ Significant bleeding and bacteremia are rare adverse events. Furthermore, data suggests no significant difference in adverse event rates between the use of balloon dilators and other methods, underscoring the safety and efficacy of both approaches in clinical practice.⁸ Numerous individuals encounter challenges with traditional interventions such as balloons and bougies in managing refractory strictures, necessitating the exploration of additional and alternative therapeutic modalities.

Steroid Injection

Triamcinolone, a long-acting and semi-viscous corticosteroid agent, has been utilized as an adjunctive therapy to enhance the efficacy of dilation in the treatment of refractory strictures, or as standalone therapy. Most investigators utilize triamcinolone acetate or acetonide at concentrations of 10 mg/mL, although higher concentrations of 40 mg/mL have also been employed. The volume of injection has varied across studies, ranging from 0.5 mL to 2.8 mL. Additionally, betamethasone and dexamethasone preparations have been utilized, with no discernible differences in outcomes reported among different steroid formulations. 

Triamcinolone injections are indicated for refractory strictures where conventional dilation techniques have proven ineffective. The precise mechanism of action of triamcinolone in stricture management remains unclear. However, studies suggest that corticosteroids decrease the fibrotic healing that appears to occur after dilation.⁹ Triamcinolone injections have shown potential results in reducing stricture recurrence rates and improving dysphagia scores, particularly in patients with refractory anastomotic strictures.^9, Meta-analysis has not demonstrated consistent improvement in dysphagia scores among patients receiving steroid injections, but the interpretation of these findings is limited due to the high heterogeneity of the data. Studies have reported a significant decrease in the Periodic Dilation Index (PDI), which is defined as the number of dilations required/duration of time in months, among patients receiving intralesional steroid injections alongside dilation therapy.¹¹ Triamcinolone may prove beneficial in managing RBES, potentially reducing the frequency of necessary dilations. There is currently no standardized protocol for the number of triamcinolone injection sessions. The optimal dosing regimen and injection technique may vary based on the specific characteristics of the stricture and individual patient factors.⁹ The literature presents conflicting results regarding the efficacy of triamcinolone injection in the management of patients with RBES. Pereira-Lima et al. reported a significant increase in the number of dysphagia-free patients after 6 months and an improvement in dysphagia scores in a double-blind randomized study consisting of 19 patients. In contrast, the double-blind study of 60 patients conducted by Hirdes et al. failed to replicate these results. 

While endoscopic triamcinolone injections are generally well-tolerated, adverse events may include intramural infection, yeast esophagitis, and perforation. Due to the low number of adverse events, statistical analysis was not possible in a 2018 meta-analysis that analyzed the effect of intralesional steroid injections in addition to endoscopic dilation of benign refractory esophageal strictures.¹¹ 

Incisional Therapy

Incisional therapy represents an additional option for patients with RBES. This therapeutic approach entails the use of electrocautery or mechanical devices to directly incise or cauterize the fibrotic stricture itself. The fundamental principle underlying this modality mirrors that of dilation, involving the disruption or displacement of circumferential fibrotic tissue and collagen fibers to facilitate the restoration of a satisfactory lumen diameter and prevent reformation of scar tissue. 

Needle knife incision is the most commonly employed technique. This technique employs a needle-knife catheter, widely used for ERCP, to perform electrosurgical incisions in a radial manner around the stricture. (Figure 2) The determination of the length and quantity of incisions is tailored to each specific stricture. Typically, an average of 4-12 radial incisions is required for ideal treatment.¹³ Optimal outcomes are typically observed with short-segment strictures measuring less than 1 cm such as Schatzki rings or anastomotic strictures. With long segment strictures, complete removal of the stricture rim may not always be feasible. In a prospective outcome study, 87.5% of patients had neither subjective dysphagia nor endoscopic recurrence at a 24 month follow up after incisional therapy.

Potential adverse events associated with incisional therapy include pain, bleeding, and perforation. The perforation or hemorrhage rate associated with balloon or bougie dilation ranges from 0.1% to 0.4%,¹ while the perforation rate with endoscopic incision therapy falls within the range of 0% to 3.5%, with no reported evidence of significant bleeding.¹³

Stents

Self-Expanding Metal Stents

Endoscopic stent placement has emerged as mainstay of treatment for managing RBES. It is widely recognized as a safe procedure and is frequently used as a first-line therapy option. Stents commonly employed in therapy include partially covered self-expanding metal stents (PCSEMS), fully covered self-expanding mental stents (FCSEMS), LAMS, and biodegradable stents (where they are commercially available). Stents are deployed under endoscopic and/or fluoroscopic guidance, depending on the patient and the type of stent used, with placement confirmation via endoscopy. Alternatively, direct visualization can guide stent placement without fluoroscopic assistance.

SEMS were introduced into clinical practice approximately three decades ago. PCSEMS and FCSEMS have both been evaluated for treatment of RBES. Presently, temporary placement of SEMS is commonplace in the management of RBES. (Figure 3) It has been recommended by one study that FCSEMS should be left in place for up to 12 weeks to minimize the risk of hyperplastic tissue and stent embedment, but in practice many patients require longer stent indwell times and treatment should be individualized. Both PCSEMS and FCSEMS were found to have a high technical success rate and short-term clinical efficacy. There was no statistical difference between PCSEMS and FCSEMS. Adverse events linked to PCSEMS encompass stent migration and tissue ingrowth. Conversely, FCSEMS primarily presents stent migration as the main adverse event. Stent migration persists as a significant concern and represents a primary factor prompting re-intervention with SEMS. 

Migration rates were observed to be 17.6% for PCSEMS post-placement and 17.4% for FCSEMS, as reported in a 2015 retrospective case review.¹⁸ A different 2016 multicenter study reported stent migration in 44.4% of patients with SEMS. Additionally, a literature review published in 2017 documented stent migration in 11.9% of patients treated with SEMS, while 20.3% experienced tissue in-growth or overgrowth. Another multicenter study conducted in 2016 reported a notable stent migration rate of 44.4% among patients receiving SEMS.  It should be stressed that stent migration is not always an adverse event per se. If the stricture responds to stenting, and the lumen opens up appropriately, there may no longer be a stenosis there to help anchor the stent in place. 

Biodegradable stents have emerged as a potential solution to address adverse events associated with SEMS and self-expandable polymer stents (SEPS), although these devices are not currently available in the United States. Two main types of biodegradable stents have been developed: knitted poly-L-lactic acid monofilaments, although no longer available, and the SX-ELLA BDS composed of semicrystalline biodegradable polymer known as polydioxanone. These stents offer constant radial force over a period of 4-5 weeks, allowing sufficient time for treating underlying esophageal diseases, while their progressive hydrolysis-mediated self-degradation prevents tissue overgrowth.²² Notably, their complete dissolution within 11-12 weeks obviates the need for endoscopic removal. Adverse events such as bleeding and chest pain have been reported. It is worth noting that BDS are associated with a higher incidence of major adverse events (28.6%) compared to FCSEMS and SEPS (10.6% and 14.3% respectively).²² Further prospective randomized trials are warranted to compare the clinical effectiveness of BDSs with FCSEMS. These trials should aim to determine the optimal duration of stent placement, evaluate the value of repeat stenting over extended periods, and assess the cost-effectiveness alongside patient satisfaction. A 2012 prospective multicenter study comparing FCSEMS, SEPS, and BDS revealed no significant differences in the clinical success of all three stent types. However, BDSs and FCSEMS demonstrated superiority over SEPS in several variables, including the dysphagia-free period, long-term improvement, and the number of reinterventions required.¹⁶ It should be noted that SEPS are no longer in clinical use. 

Lumen-apposing metal stents (LAMS)

LAMS were initially designed for the management of pancreatic fluid collections, chosen for their anti-migratory property attributed to their saddle-shaped design. Over time, their clinical applications have expanded greatly beyond their initial indications, owing to several benefits such as offering multiple different diameters, short stent lengths, and facilitating simple stepwise deployment, which enhances technical success. These devices can be used effectively to treat short-segment RBES. (Figure 4) Comparative effectiveness studies have demonstrated that LAMS procedures are both feasible and safe, yielding good clinical outcomes. Technical and clinical success rates have been reported at 98.6% and 79.7%, respectively.²³ Notably, the migration rate with LAMS stands at 10.6%, significantly lower than that observed with SEMS.²⁴ Moreover, LAMS have exhibited superior clinical outcomes compared to FCSEMS and BDS. However, adverse events associated with LAMS include perforation, discomfort prompting early removal, stent migration, bleeding, and stricture reformation. 

In a 2020 multicenter study comparing 15 mm and 20 mm stents, stent migration (15.6%) was the most common adverse event with 15 mm LAMS, but pain (14.3%) was the most common adverse event with 20 mm LAMS. Moving forward, future research endeavors aim to provide more extensive data on long-term outcomes and explore the utility of LAMS in managing refractory strictures, thereby guiding device refinement, and enhancing clinical practice.

Mitomycin C

Mitomycin C, a chemotherapeutic agent primarily employed in the treatment of malignancies such as esophageal, anal, breast, and bladder cancer, possesses pharmacological properties that make it a potential candidate for scar modulation.³ In the context of esophageal strictures, mitomycin C is administered either topically at the site of the stricture or injected directly into the stricture following dilation. The typical dosing regimen involves diluting 0.4 mg/mL of mitomycin C in 1 mL of saline, which is then divided into aliquots of 0.5 mL each. These aliquots are injected into the four quadrants of the narrowest part of the stricture.³ Despite its potential benefits, the administration of mitomycin C is not without risks, as adverse events such as intense pain, necrosis, and ulceration have been reported. However, while no longer widely practiced, there is published literature reporting the use of this agent in patients with corrosive esophageal strictures refractory to repeated endoscopic dilation.

Self-Dilation

Self-dilation represents a patient-centered approach to the management of strictures, aiming to empower patients with the ability to actively participate in their own care. Self-dilation is offered to patients with esophageal strictures refractory to other treatments such as endoscopic dilation, incisional therapy, or stent placement.²⁸ Techniques for safe and effective self-dilation typically involve educating patients either in the clinic or during their hospital stay, if admitted, within 48 hours following endoscopic dilation. Patients are instructed to begin self-dilation with a Maloney dilator that is either the same size or one size smaller than the dilator used during their typical endoscopic dilation procedure. Patient selection criteria include those with recurrent strictures after dilation, many of which are proximal, and individuals who have failed previous treatments such as Savary or balloon dilation, or those who have undergone dilation combined with intralesional steroid injections or incisional therapy.^, Despite the potential benefits, patients may exhibit reluctance to engage in self-dilation due to concerns regarding pain or perforation. Nevertheless, self-dilation offers a safe, effective, and cost-efficient treatment option for appropriately selected patients with refractory strictures. In a 2013 small retrospective study, esophageal self-dilation was successful in treatment of 90% of patients. Another 2018 retrospective study showed comparable results, with a technical success rate of 94% and median number of endoscopic dilation procedures dropping from 17 over a median period of 9 months to 1.5 procedures after initiation of self-dilation. Further research is needed to refine patient selection criteria and optimize the implementation of self-dilation protocols in clinical practice.

Conclusion

The management of RBES continues to pose a significant clinical challenge, often requiring repeated interventions to alleviate symptoms and improve quality of life for affected individuals. The array of endoscopic therapeutic modalities available for RBES includes dilation, steroid injections, incisional therapy, stent placement, and the use of mitomycin C. While each approach offers distinct advantages and potential drawbacks, several key agreements and disagreements have emerged from the existing body of literature. Endoscopic dilation, whether performed with balloon dilators or bougies, remains the primary treatment modality for RBES, demonstrating high rates of technical success and an acceptable rate of clinical resolution. Triamcinolone injections have shown promise in reducing stricture recurrence rates and improving dysphagia scores, particularly in refractory anastomotic strictures. However, conflicting findings regarding the efficacy of triamcinolone injection underscore the need for further research to elucidate its true effectiveness. Discrepancies in reported stent migration rates highlight the necessity for standardized protocols and further investigation into optimal stent selection and placement techniques. Self-dilation is rarely undertaken although when appropriately implemented this approach offers a safe, effective, and cost-efficient treatment option for selected patients with refractory strictures. Overall, while significant progress has been made in the endoscopic management of RBES, several knowledge gaps persist, warranting additional research to refine treatment strategies and optimize clinical outcomes in this challenging patient population. 

References

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