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Learning objectives

Upon completion of this activity, participants should be able to:

1. Specify recommended stent types for the treatment of malignant esophageal strictures.
2. Describe the use of brachytherapy in the treatment of esophageal strictures.
3. Identify the most common cause of benign, simple esophageal strictures.
4. Describe the treatment of benign esophageal strictures.

Competing interests

The author declared no competing interests. Charles P Vega, the CME questions author, declared that he has served as an advisor or consultant to Novartis, Inc.

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Stents

Mid and distal esophageal cancer

So far, more than 130 patient series have reported on stent placement for the palliation of malignant dysphagia caused by mid or distal esophageal cancer. These studies have mainly dealt with one stent type only and, therefore, cannot be used to compare the effectiveness of different stent types. A few retrospective studies have compared different stent types;^{4, 5, 6} however, in these studies uncovered stents were used, and it has been convincingly shown that partially or fully covered stents give better long-term palliation of malignant dysphagia than uncovered stents.⁷

There have been few prospective studies that have directly compared stent types for the palliation of malignant esophageal strictures. In one study, 100 patients with inoperable mid and distal esophageal, or gastric cardia cancer were randomly allocated to have one of three commonly used stent types placed: the Ultraflex^™ stent (Ultraflex^™ Esophageal NG Stent System, Boston Scientific, Natick, MA), the Flamingo Wallstent (Boston Scientific) or the Z-stent (Wilson-Cook Medical, Winston-Salem, NC).⁸ Both the Ultraflex^™ stent and Flamingo Wallstent are made of nitinol and covered at their midsections with a polyester cover. The Z-stent is made of stainless steel and covered with polyethylene over its entire length. No statistically significant differences were found between the stents for dysphagia improvement, the occurrence of complications, such as perforation or hemorrhage, and the occurrence of recurrent dysphagia, as determined by stent migration or tissue overgrowth and ingrowth. A trend towards more complications with Z-stents was, however, observed; this difference would have been statistically significant if 150 patients instead of 100 patients had been randomized. Similar findings with regard to dysphagia improvement and complications were observed in another study, which was a randomized trial performed in the UK, in which Ultraflex^™ stents (n = 31) and Flamingo Wallstents (n = 22) were compared in patients with malignant dysphagia caused by distal esophageal cancer.⁹

An ongoing issue with stents is the occurrence of recurrent dysphagia because of stent migration (Figure 2A), tumoral (Figure 2B) or nontumoral (Figure 2C) tissue growth and food obstruction (Figure 2D). Recurrent dysphagia occurs in 30–40% of patients after a mean follow-up of 2–3 months.¹⁰ Reintervention for stent-related recurrent dysphagia is effective in more than 90% of patients.¹⁰ In our experience, the most effective treatment strategy for tissue overgrowth or ingrowth and stent migration is the placement of a second stent, or, in some cases of migration, stent repositioning. For cases of food obstruction, endoscopic stent clearance is an easy and effective strategy to employ. After treatment for recurrent dysphagia, the median survival of patients has been shown to be longer than 2 months.¹⁰ Nonetheless, reintervention is expensive because in many cases endoscopy, a new stent or even admission to hospital is required.

Figure 2 Examples of recurrent dysphagia after stent placement for a malignant stricture in the esophagus.

(A) Stent migration. (B) Tumoral growth. (C) Nontumoral growth. (D) Food bolus obstruction.

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In order to reduce the need for reinterventions, two new stent designs, the Polyflex^® stent (Boston Scientific) and the Niti-S double stent (Taewoong Medical, Seoul, Korea), have been developed. Polyflex^® stents are made of silicone and polyester, fully covered, and were designed to reduce nontumoral tissue overgrowth and ingrowth, which is mostly seen after the placement of partially covered stents made of nitinol because of hyperplastic tissue growth. By contrast, the Niti-S double stent was developed to reduce stent migration: it combines a flare at both ends and a double layer configuration, with an inner cover and an outer uncovered nitinol wire tube to allow the mesh of the stent to embed itself in the esophageal wall.

The Polyflex^® stent, the Niti-S double stent and the Ultraflex^™ stent (the most commonly used stent type worldwide) were recently compared in a randomized trial including 125 patients with esophageal or gastric cardia cancer.¹¹ The improvement of dysphagia and complications was similar for the three stents, but, overall, it was found that recurrent dysphagia occurred more frequently with Ultraflex^™ stents (n = 22 [52%]) than with Polyflex^® stents (n = 15 [37%]) or Niti-S stents (n = 13 [31%]; P = 0.03). Of the main causes of recurrent dysphagia, stent migration was most commonly seen with Polyflex^® stents (n = 12 [29%] vs Ultraflex^™ stents: n = 7 [17%] and Niti-S stents n = 5 [12%]). Tissue ingrowth and overgrowth was more frequent with Ultraflex^™ stents (n = 13 [31%] and, to a lesser degree, Niti-S stents n = 10 [24%] vs Polyflex^® stents: n = 4 [10%]). Finally, food obstruction occurred frequently with Ultraflex^™ stents (n = 10 [24%]) vs Polyflex^® stents (n = 2 [5%]) vs Niti-S stents (n = 1 [2%]).

In conclusion, Flamingo Wallstents and Niti-S stents are both appropriate for the palliation of dysphagia from esophageal cancer. The same is probably true for Ultraflex^™ stents, although recurrent dysphagia caused by tissue ingrowth and overgrowth or food obstruction occurs more frequently with this stent design. By contrast, Z-stents and Polyflex^® stents seem less preferable in these patients, because, compared with the other stents, Z-stents are likely to be associated with a higher risk of complications, and Polyflex^® stents are more prone to migrate; in addition, placement of this device is technically demanding.

Proximal esophageal cancer

Esophageal cancer that is located close to the upper esophageal sphincter (i.e. 7–10% of all esophageal cancers) has traditionally been regarded as too difficult to manage with stents. The reason for this belief is that placing stents at this location was thought to be associated with a high risk of complications, such as perforation, aspiration pneumonia, proximal migration, and patient intolerance caused by pain and foreign body sensation. Over the last few years, this view has begun to change. Two studies that included 22 and 104 patients, respectively, reported the results of stent placement in the proximal esophagus.^{12, 13} In the latter study, 44 patients had a malignant stricture within 4 cm of the upper esophageal sphincter.¹³ Endoscopic visualization and/or fluoroscopic monitoring were used to control for precise positioning of the proximal stent end just below the upper esophageal sphincter (Figure 3). Dysphagia improved in most patients, and the occurrence of complications and recurrent dysphagia was comparable to that in patients who underwent stent placement in the mid and distal esophagus. In total, 5–15% of patients had foreign body sensation; however, in none of the patients was stent removal indicated.

Figure 3 Endoscopic management of a malignant stricture close to the upper esophageal sphincter.

(A) A malignant stricture close to the upper esophageal sphincter. (B) A metal stent was placed to relieve symptoms.

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In our experience, Ultraflex^™ stents, which have a relatively low radial force and flexible mesh compared with other stent designs, are the preferred stent type for patients with a malignant stricture that is close to the upper esophageal sphincter.

Extrinsic compression of the esophagus

Apart from being caused by primary cancer, dysphagia can also be caused by malignancies compressing the esophageal lumen, such as lung cancer or metastatic mediastinal lymph nodes. Until the past few years, it was generally believed that dysphagia due to extrinsic compression should be treated with an uncovered stent to prevent stent migration.^{14, 15}

We treated 39 patients with extrinsic compression of the esophagus with partially covered or fully covered stent types (PD Siersema, unpublished data). In our experience, dysphagia improvement and the occurrence of complications and recurrent dysphagia were no different in patients with extrinsic compression of the esophagus than in patients with primary esophageal cancer. Only one (3%) stent migrated to the stomach (PD Siersema, unpublished data). These positive results need to be balanced with the poor overall prognosis of this patient group, with one-third dying from progressive disease within 30 days after treatment (PD Siersema, unpublished results).

It can be concluded that covered stents can also be used to palliate dysphagia caused by extrinsic compression. It seems logical, therefore, to have a small selection of stent types available in an endoscopy unit and to become well acquainted with their characteristics, as these devices should not only be able to palliate dysphagia from primary esophageal cancer, but also from extrinsic malignant compression. In this regard, it is important to realize that various stents differ in characteristics such as radial force, buckling characteristics, shortening or no shortening on deployment, and releasing proximally or distally. Moreover, the selection of stent type is also influenced by stricture characteristics, such as being straight or angulated, fully or semi-circumferential, intrinsic or extrinsic, and location in the esophagus.

Brachytherapy

Brachytherapy can be carried out as an outpatient procedure and is performed with a 10 mm applicator (Bonvoisin-Gérard Esophageal Applicator, Nucletron, Veenendaal, The Netherlands) that is passed down into the esophagus over a guidewire. The most frequently used source for brachytherapy is iridium (¹⁹²Ir). Brachytherapy can be delivered at different dose rates; however, high-dose-rate (HDR) brachytherapy is increasingly being used, delivering a dose of 12 Gy or more per hour. Different treatment schedules have been used for the palliation of dysphagia, with doses of 7.5–20 Gy given in one to three fractions. No differences in outcome have been reported for esophageal squamous cell carcinoma or adenocarcinoma.¹⁶

The complication rate after brachytherapy has been reported to be low, with the complications mainly consisting of fistula formation, mild retrosternal pain and radiation esophagitis (Figure 4).¹⁶ Recurrent dysphagia after brachytherapy occurs in 10–40% of patients and is most commonly caused by tumor persistence, tumor recurrence or, rarely, benign stricture formation.¹⁷ Tumor persistence and recurrence are the predominant causes of additional treatment after brachytherapy, which mostly consists of stent placement. Patients with stenotic tumors that cannot be bypassed without dilation and, to a minor extent, those who previously underwent chemotherapy have an increased risk of developing tumor persistence or recurrence.¹⁸

Figure 4 Examples of radiation esophagitis after brachytherapy for a malignant stricture of the esophagus.

(A) early radiation esophagitis (5 days) (B) Late radiation esophagitis (3 weeks).

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Brachytherapy versus stent

In the past 4 years, two randomized trials have been published that compared brachytherapy with stent placement for the palliation of dysphagia caused by incurable esophageal cancer.^{19, 20} In the largest study, 209 patients were randomly allocated to 12 Gy brachytherapy or Ultraflex^™ stent placement.¹⁹ Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Complications occurred less frequently after brachytherapy, with hemorrhage, in particular, being significantly less common after brachytherapy than after stent placement (5% vs 13%). There was no difference between the treatment groups for the occurrence of persisting or recurrent dysphagia, or for median survival (brachytherapy 155 vs stent placement 145 days). After brachytherapy, however, patients had better quality of life scores after a follow-up of at least 3 months. Finally, there was no difference between the two treatment modalities for the total cost of treatment, follow-up and any additional procedures. It was concluded that single dose brachytherapy was preferable to stent placement as the initial treatment for patients with progressive dysphagia caused by incurable esophageal carcinoma.

The findings in the above-mentioned trial²⁰ and additional nonrandomized data on stent placement and brachytherapy from the Erasmus MC–University Medical Center Rotterdam, The Netherlands, resulted in the development of a prognostic model to identify patients with a poor prognosis, in whom stent placement should be at least equivalent to brachytherapy in terms of dysphagia-adjusted survival.³ A simple score was developed that included age, gender, tumor length, WHO performance score, and the presence of metastases. A total score based on these factors was able to separate patients with a poor, intermediate or relatively good prognosis (Table 1). It was found that in the group with a poor prognosis, the difference in dysphagia-adjusted survival was 23 days in favor of stent placement compared with brachytherapy (77 vs 54 days). For the groups with an intermediate (68 days [stent] vs 98 days [brachytherapy]) or relatively good (104 days [stent] vs 138 days [brachytherapy]) prognosis, the use of brachytherapy resulted in a better dysphagia-adjusted survival.

Table 1 Results of brachytherapy versus stent placement by prognostic risk group.³

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On the basis of this model, it is recommended that stents be placed in patients who have dysphagia caused by esophageal or gastric cardia cancer and a calculated life expectancy of 3 months or less. Brachytherapy should be reserved for patients who have a life expectancy longer than 3 months.

Dilation

Simple strictures

Three types of dilators are currently in use. These include bougies filled with mercury or tungsten (e.g. Maloney dilators [Medovations, Inc., Germantown, WI]), wire-guided polyvinyl dilators (e.g. Savary-Gilliard^® [Wilson-Cook Medical]) and Through-The-Scope (TTS) balloon dilators (Controlled Radial Expansion [CRE^™] dilation balloon, with or without guidewire [Boston Scientific]).¹ Of these, the Savary-Gilliard^® and TTS balloon dilators are currently by far the most frequently used.² The main difference between these two dilators is their mechanism of action. A Savary-Gilliard^® dilator exerts a radial force as it is passed down, but some of its dilating force is transmitted longitudinally because of its shearing effects. By contrast, longitudinal forces are not transmitted with balloon-type dilators.²⁴ Nonetheless, no clear advantage has been demonstrated for either one of these two dilator types.^{25, 26, 27, 28} The only exceptions include conditions in which a longitudinal shearing force should be avoided, such as strictures caused by epidermolysis bullosa,²⁹ or in cases in which a tracheoesophageal puncture voice prosthesis is present. Savary-Gilliard^® dilators are more cost-effective as they can be re-used, whereas TTS balloon dilators are intended for single use only.

The main complications associated with esophageal dilation include perforation, hemorrhage and bacteremia. The reported rate of perforation and massive bleeding is 0.3%: this risk is higher when complex strictures³⁰ and caustic strictures²² are dilated. It is generally believed that the risk of perforation is minimal if the 'rule of three' is applied, meaning that dilation diameters should not increase by more than 3 mm per session.² Pre-dilation diameter and stricture length are established factors that influence the number of dilations required for symptom relief and the need for additional dilations.³¹

Various investigators have examined whether the injection of steroids into the stricture can prevent recurrence of dysphagia.^{32, 33, 34} Most of these studies, however, were, small, uncontrolled and involved strictures with a diverse etiology. One randomized trial has been published in full.³⁵ A total of 30 patients with recurrent peptic stricture were randomly allocated to TTS dilation to 15–18 mm followed by 4-quadrant 0.5 cm triamcinolone injections (40 mg/cm³) or to TTS dilation to 15–18 mm alone. After a follow-up of at least 1 year, two patients in the steroid group (13%) and nine in the sham group (60%) required repeat dilations. This finding suggests that steroid injections could have a role in patients with recurrent peptic strictures after prior dilation therapy. The utility of intralesional injections for strictures with a different etiology needs further elucidation.

Complex strictures

Circular or nearly circular benign esophageal strictures are most frequently seen after radiation therapy for malignancies in the chest, head or neck. Most of these strictures are amenable to dilation, although fluoroscopic guidance is often required to monitor guidewire passage through the stricture. Endoscopic management of these strictures can, however, be challenging, particularly when a guidewire cannot be advanced, which sometimes occurs in the proximal esophagus. In these cases, an 'endoscopic rendezvous' approach can be employed.^{36, 37} This is accomplished by introducing a small-diameter endoscope through a mature PEG tract and advancing it in a retrograde fashion into the esophagus until the stricture is identified. In some patients, the guidewire, be it stiff or floppy, can be passed through the stricture, but in others a thin membrane is present that precludes its passage. In these patients, the guidewire, or a needle knife, can be used to puncture the membrane. The puncture should be aided by a second flexible endoscope³⁶ or rigid laryngoscope³⁷ approaching the stricture in an antegrade fashion. Subsequently, the stricture is dilated over the guidewire using a balloon dilator (retrograde) or Savary-Gilliard^® dilator (antegrade). As these post-radiation strictures need repeat dilations, a nasogastric feeding tube should be placed to maintain luminal access for future dilations.

Stents

It is not surprising that the successful application of metal stents for the palliation of esophageal malignancies indicated that there might be a role for these devices in the management of recurrent benign strictures. In the initial clinical series of patients with benign esophageal strictures refractory to conventional therapy, however, the partially uncovered self-expandable metal coil stents used were associated with some major complications.³⁸ The most common of these complications was the ingrowth of (benign) granulation tissue through the stent mesh as a reaction to the radial force placed by the stent onto the esophageal wall, and this ingrowth started to occur as early as 2–6 weeks after stent placement. This ingrowth of granulation tissue resulted in recurrent obstruction in up to 40% of patients.³⁹

To prevent recurrence due to ingrowth of granulation tissue, the completely covered Polyflex^® stent made of silicone and polyester was evaluated in three retrospective series.^{40, 41, 42} In the first two series,^{40, 41} the experience was favorable. In one series, relief of dysphagia occurred in 17 of 21 patients (81%) after a median follow-up of 21 months, especially in those with caustic and hyperplastic (due to partially covered stent placement) strictures;⁴⁰ in the other series, relief occurred in 12 of 15 patients (80%) with caustic, post-radiation, anastomotic or peptic strictures after a median follow-up of 22.7 months.⁴¹ No complications were mentioned in the first series,⁴⁰ whereas in the other study recurrent dysphagia was seen in 33% of patients, which was due to mucosal hyperproliferation in four patients and stent migration in one patient,⁴¹

Less optimistic results on Polyflex^® stents have since been reported. Holm et al.⁴² placed 84 Polyflex^® stents in 20 patients, most with benign or anastomotic strictures. Migration was the most frequent complication, noted in 18 of 29 patients (62%) and for 53 of 83 stent placements (64%). In addition, hyperplastic tissue growth and stricture formation around the stent was seen in 5 patients (17%) after 15 procedures (18%). Remarkably, only 5 of 83 procedures (6%) resulted in long-term symptom relief after stent removal, which is in line with the experience at my institution.

The management of patients who have refractory hypopharyngeal strictures after chemoradiation and/or surgery can be unsatisfactory as normal diameter stents placed in this location can cause a foreign body sensation, severe pain, fistula formation or perforation. Patients with refractory hypopharyngeal strictures who have undergone stent placement sometimes end up with a feeding tube, but experience difficulties in degutting saliva. To prevent the need for a feeding tube and to allow patients to eat, a cervical Niti-S stent was developed that has a body diameter of 10 mm, 12 mm or 14 mm. This stent is available with or without a flare that is 2 mm wider than the body diameter and is covered or uncovered. This stent effectively improved dysphagia in a small series of seven patients.⁴³ As six of the seven patients developed stent migration and/or granulation tissue ingrowth or overgrowth, additional new stents were placed a median of 3 months after the previous stent placement. Hypopharyngeal strictures have a high recurrence rate, and prolonged stent placement with periodic stent exchanges at intervals of 6 weeks to 3 months is, therefore, indicated.

In conclusion, Polyflex^® stents have originally been advocated to be a promising stent type for the treatment of complex benign strictures. However, recent experience has questioned this optimistic view and further studies are required to select the most optimal patient population. Apart from stent migration, another disadvantage of using Polyflex^® stents is that the stent applicator is large and stiff compared with the applicators used for metallic stents. Dilation before stent placement is, therefore, often required. Another drawback to using Polyflex^® stents is the need to load the stent into the introduction catheter to avoid prolonged folding of the stent and prevent it from becoming deformed. For these reasons, at my institution we also use metal stents, particularly partially covered Ultraflex^™ stents, to treat benign esophageal strictures, and retrieve the stents 4–6 weeks after placement. In our experience, Ultraflex^™ stents have the advantage that they are less likely to migrate than Polyflex^® stents. For patients with complex hypopharyngeal strictures, my group prefers to use the modified Niti-S stents. In our experience, the best results can be obtained with the 10 or12 mm cervical Niti-S stent types that are flared and fully covered.

A recommended technique of stent removal is to grasp the nylon loop that is attached to the proximal end of most stents. This decreases the stent diameter and facilitates pulling the stent out. Yoon et al.⁴⁴ designed a special hook to grasp this loop and to remove the stent under fluoroscopic control. Although they reported that this technique was successful in the removal of 127 of 130 stents (98%), it is the experience at my institution that these loops quite often break during stent removal. We therefore prefer to grasp the proximal end of the stent with a polyp snare, or a rat-toothed forceps if a fully covered type of stent, such as the Polyflex^® stent, has been used. Partially covered stents, such as the Ultraflex^™ stent, can be removed more easily by grasping the distal end of the stent with rat-toothed forceps, which will result in invagination of the stent into itself.

Incisional therapy

Refractory anastomotic strictures that occur after gastrointestinal surgery are common, with a reported incidence of 2–30%.^{23, 45, 46} Anastomotic strictures usually are secondary to tissue ischemia, leakage or radiation therapy.^{23, 45} As an alternative to repeat dilation therapy, incisional therapy using electrocautery,⁴⁷ argon plasma coagulation in combination with electrocautery,⁴⁸ or endoscopic scissors⁴⁹ have been reported to be successful in patients with anastomotic strictures. In the largest reported series,⁴⁷ 20 patients with persisting anastomotic strictures after three endoscopic dilations were treated with a session of needle knife electrocautery until the endoscope could easily pass the stricture (Figure 6). Twelve patients who had a stricture shorter than 1 cm were free of dysphagia after a single treatment. In the remaining eight patients who had a stenosis of 1.5–5 cm, a mean of three electrocautery sessions was required for them to become symptom free. No complications such as perforation and hemorrhage were observed. In patients with recurrent Schatzki's rings, the same technique was also reported to be moderately successful after a median of three endoscopic dilations.⁵⁰ These results show that in patients with a firm fibrotic stricture, such as can be found at an anastomotic site, incisional therapy could be a safe alternative treatment modality in cases refractory to endoscopic bougie or balloon dilation.

Figure 6 Endoscopic management of an anastomotic stricture in a gastric tube interposition.⁴⁸

(A) An anastomotic stricture in a gastric tube interposition. (B) The stricture after treatment with needle knife cautery. Permission obtained from the American Society for Gastrointestinal Endoscopy © Hordijk ML et al. (2006) Electrocautery therapy for refractory anastomotic strictures of the esophagus. Gastrointest Endosc 63: 157–163.

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