Esophageal stent BD-Covered for refractory benign esophageal strictures: a safety and efficacy study

A benign esophageal stricture is a narrowing of the esophagus that causes
difficulty to swallow, and endoscopically is defined by the inability to cross
it with an endoscope of 9 mm of diameter. Clinical symptoms may be dysphagia,
odynophagia, weight loss and regurgitation of food.

Benign esophageal strictures are relatively common in clinical practice. In the
past, peptic stricture secondary to gastroesophageal reflux, were the most
frequent, whereas at present are mainly secondary to caustic ingestion and
radiotherapy (1). In recent years they have also been described as a result of
advanced endoscopic therapy in the esophagus: endoscopic circumferential
mucosal resection and submucosal dissection.

Generally, most benign strictures respond well to endoscopic dilation, but in
25-30% of cases, multiple sessions of dilation are necessary. Moreover, there
are also "complex" benign strictures refractory to endoscopic dilatation (2).

Postsurgical stenosis secondary to ingestion of caustic, and those caused by
radiation treatments, have a low response rate to endoscopic treatment, where
over 40% of cases tend to recur. Additionally, a hypopharyngeal location of a
stenosis, regardless of the cause, is usually refractory to endoscopic dilation.

In view of this situation, a definition of "refractory strictures" has been
proposed when: 1) absence of inflammatory response or motor disorder at the
level of the stenosis is observed; 2) failure to maintain an esophageal
diameter * 14mm after 2 dilation sessions conducted at intervals of two weeks;
and 3) if there is failure to maintain an esophageal diameter * 14mm 4 weeks
after reaching a diameter of 14mm (recurrent stenosis) (3).

Parallel to dilation, other treatments have been proposed, such as steroid
injection (triamcinolone) or section of fibrotic ring with needle diathermy,
with a very low success rate, leaving as the only option for patients with
refractory strictures, the implantation of expandable esophageal stent (EES),
since it achieves a sustained expansion of the esophageal lumen (4,5).

Esophageal Stent Types

a) Self-expanding Plastic Stents (SEPS)

The SEPS (Polyflex*) are usually placed under radiological control. Regularly,
a SEPS takes a length of 2-4 cm over the stenosis to achieve an extension of
1.2 cm above and below it. These stents have usually slow expansion, reaching
their maximum diameter after several hours or days (6). However, the main
drawback of these stents is their high rigidity, and is sometimes very
difficult to implement, as it requires that the patient place the neck in a
hyperextended position. Likewise, the need for a stiff guide wire, increases
the risk of esophageal perforation, mainly in angled strictures (7). A
systematic review of the recent literature, including 10 studies with a total
of 130 patients, shows that the SEPS acquire a 98% of technical success,
clinical efficacy of 52%, an early migration rate (<4 weeks) of 24% and a
complication rate of 9% (7).

b) Partially covered self-expanding metallic stents (PCSEMS)

Using this type of stent in benign pathology, given the risk of proliferation
of granulation tissue at the ends that are not covered (proximal and distal),
is inadvisable, making removal difficult. This is why patients with this type
of stent present a restenosis rate of 41%, with an incidence of migration of
31%, and the occurrence of complications in 21% of cases (8).

c) Fully covered self-expanding metallic stents (FCSEMS)

The FCSEMS have the advantage that they can be removed after a certain period
of time, but leads to an increase in the rate of migration. To try to relieve
this problem, there are different types of FCSEMS in the market, so that the
endoscopist can choose the most appropriate one for each patient. With this
type of stent, a resolution of dysphagia in 29% of cases is achieved, with a
migration rate of 36% (9).

d) Uncovered self-expanding biodegradable stent (USEBS)

The USEBS (SX-ELLA Stent Esophageal Degradable BD / BD Stent), ELLA - CS,
s.r.o., Hradec Kralove, Czech Republic) are available for clinical use since
2008. The radial force of the stent is maintained for 6-8 weeks after
implantation. Degradation of stent occurs in 11-12 weeks. This type of stent
achieve a significant improvement of dysphagia in 45% of patients after a
follow-up period of 53 weeks, with a migration rate of 9.5% (10, 11).

The main advantage of biodegradable stents is that its removal is not required;
furthermore, another advantage is that it can be more effective in resolving
the stenosis. In this sense, to try to obtain an increase of the radial force
of the BD Stent, and that it can also be effective in esophageal fistulas, that
are occasionally associated with stenosis, were developed the Covered SEBS
(Esophageal Stent BD-Covered/ BD-Covered), which supposed a significant
improvement in the treatment, with this type of stent.

The main objective of this study is to evaluate, in an exploratory study, the
safety and efficacy of implanting the Esophageal Stent BD-Covered (BD-Covered)
in patients with refractory benign esophageal strictures, i.e. who has been
treated with a minimum of 2 and no maximum of esophageal dilation sessions to
the minimal diameter of 15 mm, using a balloon dilator or Savary bougie.

Other (secondary) objectives are to assess: the effect of the stent of the
study on the quality of life of the subject (Health Questionnaire SF-36), the
presence of hyperplastic reaction after implantation of the stent and the
functional complications.

Non-randomized prospective clinical study, in a single centre (Radboudumc), to
evaluate the safety and efficacy of endoscopic implantation of a BD-Covered
Esophageal Stent (BD-Covered) in patients with refractory benign esophageal
strictures.

Implantation of the BD-Covered esophageal self expanding stent via an
endoscopic procedure

Participation in the study does not cause any additional charge to patients.
The stent implantation and follow-up are not different from the usual in
clinical practice.

The main advantage of the BD-Covered stents is that its removal is not
required; Moreover, another advantage is that it can be more effective in
resolving the stenosis.

The risk classification is determined as negligible based on the guideline of
the *Nederlandse Federatie van Universitair Medische Centra*. The risks
associated with the participation in the study are similar to the risks of
treatment with esophageal stent, and not different from the complications
arising from the use of other expandable stent, migration, perforation and
development of hyperplasia/ granulation tissue. However, bleeding and
perforation are rare complications.

Risk of esophageal stent implantation:
- Migration of the stent;
- Esophageal perforation;
- Gastrointestinal bleeding;
- Chest Pain;
- Food impaction;
- Bacteremia/ fever.