Introduction
Stenosis is one of the most frequent local complications of Crohn’s disease (CD),
occurring in one of three patients within 10 years of diagnosis [1 ]. It happens as a result of chronic transmural inflammation with subsequent tissue
remodeling, and mesenchymal cell hypertrophy due to hyperplasia and fibrosis. It occurs
most frequently in the terminal ileum, ileocolonic anastomosis, and rectum, and is
considered clinically relevant when there is a steady narrowing of the lumen with
prestenotic dilatation and obstructive symptoms. More than 50 % of patients who require
ileal resection need a repeat operation after 15 years, and over 40 % have recurrence
of obstructive symptoms after 4 years, with the possibility in the long term of ending
up having to undergo several surgical interventions [2 ]. Strictures are more common in CD than in ulcerative colitis, and they are more
frequent when the disease is localized in the small intestine rather than in the colon
exclusively (64 % vs. 5 %, respectively). In different meta-analyses and systematic
reviews of the effectiveness of strictureplasty in patients with CD, a 25 % rate of
recurrence at the site of the stenosis was reported, with a median time of 46 months,
and with a considerable percentage of associated complications [3 ]
[4 ]
[5 ]. This suggests the need for conservative nonsurgical treatment; currently endoscopic
balloon dilatation (EBD) is the endoscopic treatment of choice [6 ]. Several uncontrolled observational studies have shown that EBD in selected patients
is a safe, effective alternative to surgery, with an overall success rate ranging
from 44 % to 58 % [7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ]. Within the limitations of these various published studies, we found heterogeneity
of technique, different endpoints, and small series of patients, among other characteristics.
And the complications related to the EBD technique are not negligible.
It is, therefore, critical to find alternative conservative measures to avoid or delay
surgery in CD patients with stenosis.
The technological evolution of stents in recent years and their effectiveness in malignant
stenosis of the gastrointestinal tract has allowed their use in benign diseases of
various localizations and origins, such as CD.
Stent types
Various expanding stents are commercially available (metal, plastic, and biodegradable),
with differing lengths, diameters and shapes, with partial or full silicone coverage,
and with differing transport and release systems, allowing placement anywhere in the
upper intestinal tract, colon and even terminal ileum ([Fig. 1 ]) [13 ]
[14 ]
[15 ]
[16 ]. Some have been designed specifically for benign intestinal stenosis and can be
placed throughout the working channel (TTS: Through-the-scope stents). Until now,
there has been no specific stent designed for IBD. Self-expanding metal stents (SEMS)
were initially uncovered and designed for colonic malignancy as palliative treatment
without the intention of removing them. Because of their efficacy in this indication,
they were subsequently covered in plastic, to be removed, for use in benign intestinal
pathologies. SEMS consist of metal mesh cylinders that exert self-expanding force
until they reach their maximum fixed diameter. They are packaged in a compressed form
and constrained on a delivery device. They are made of stainless steel and alloys
such as nitinol (nickel and titanium) and elgiloy (cobalt, nickel, and chromium).
The radial expandable forces and degree of shortening differ among stent types. To
prevent tissue ingrowth and facilitate removal, the interstices between the metal
mesh of SEMS may be fully (FCSEMS) or partially (PCSEMS) covered by a plastic membrane
or silicone [14 ]
[16 ].
Fig. 1 Different types of stents. a self-expanding metal stent fully covered – TTS (Niti-STM – Taewoong). b Plastic stent (Polyflex® – Boston Scientific). c Self-expanding metal stent partially covered – TTS (Hannaro stent® M.I.Tech). d Biodegradable stent (SX-ELLA BD stent® )
Tissue reactions to SEMS are well known. The stent material becomes incorporated into
both the tumour and surrounding tissue by pressure necrosis. At the edge of the stent,
above and below the stenosis, the stent lodges itself deep into the wall of the organ.
This reaction allows anchoring of the stent and helps to prevent stent migration.
With the use of a covered stent, this integration does not always occur and a higher
rate of stent migration is seen. Therefore, partially covered stents have been developed
with flared uncovered segments at both ends to anchor in the tissue.
Regarding biodegradable stents, they are made of polydioxanone and are spontaneously
degraded in 10 to 12 weeks. There are no biodegradable TTS stents and they would only
be considered in distal intestinal tubes such as recto-sigma. Moreover, the effect
of polydioxanone degradation on the tissue of an IBD patient is unknown [17 ].
Methods
A Medline search including the terms “stricture,” “stenosis,” “stent” and “Crohn’s
disease” was performed. In some cases, the patients were identified reviewing one
specific paper that mentioned them. The inclusion criteria were all the patients that
have been treated with a stent for a stricture in CD. We didn’t exclude any article
or patient where we had found that the stent was used to treat the stenosis.
Scientific evidence about self-expanding metal stents
Information regarding the efficacy and safety of SEMS in the treatment of strictures
in CD is limited. The first reference in the literature to the usefulness of SEMS
in CD was published as a letter to the editor of Gastrointestinal Endoscopy in 1996 [18 ]. The son of a gastroenterologist, whose mother suffered from CD, spent 2 weeks in
a hospital in the setting of a high school independent study project, learning about
expandable wire stents for the treatment of obstructive esophageal and biliary tract
disease. He wondered whether this sort of stent could feasibly be placed in the intestinal
tract and what complications might prevent the safe placement of such a stent.
Since 1997 a total of 12 case reports [19 ]
[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]
[27 ] and 4 small series of patients (ranging from 5 to 17 patients) have been published
([Table 1 ]) [28 ]
[29 ]
[30 ]
[31 ].
Table 1
Summary of Crohn’s disease patients reported in the literature with SEMS.
Author/Year
Nº of patients
Location
Length
Previous treatment
Stent type
Technical/Clinical success (rate[1 ])
Durantion of stenting
Outcome
Matsuhashi 1997 /2000 [17 ]
2
Colon
–
EBD
FCSEMS (15 × 50 mm)
Yes/Yes
4 w (SM)
Symptom free at 3 years
IC anastomosis
EBD
3 FCSEMS?
Yes/Yes
22 w (SM)
Symptom free at 4.5 years
Whole 1998 [18 ]
1
colon
–
No
TB-UC
Yes/Yes
3 w
BS[2 ]
Suzuki 2004 [19 ]
2
Colon
–
–
UCSEMS
Yes/No
13 w
Fistula terminal ileum → surgery
2 UCSEMS
Yes/Yes
104 w
Recurrence → stent
Wada 2005 [20 ]
1
Colon
–
No
UCSEMS
Yes/Yes
139 w
Perforation and fistula
Bickston 2005 [21 ]
1
Ileocecal
–
EBD
2 UCSEMS (10x60 mm)
Yes/Yes
8 w
Symptom free at 2 months
Dafnis 2007 [22 ]
1
Colon
5 cm
No
4 UCSEMS (22x90 mm)
Yes/Yes
82 w
Death from lung cancer
Martines 2008 [23 ]
1
IC anastomosis
6 cm
EBD
FCSEMS (18 /24x80 mm)
Yes/Yes
1 w
BS[2 ]
Small 2008 [24 ]
1
Rectum
–
No
2 PCSEMS (30x117 – 57)
Yes/Yes
1 w
BS[2 ]
Keranen 2010 [25 ]
2
Anastomosis
–
No
FCSEMS
Yes/Yes
6 w
BS[2 ]
UCSEMS
Yes/Yes
221 w
Perforation
Levin 2012 [26 ]
5
IC anastomosis
< 6 cm
EBD (2 patients)
UCSEMS
Yes (100 %)/Yes (80 %)
3 w – 9 years
Symptom free in 4 /5 patients
Attar 2012 [27 ]
11
IC anastomosis
1 – 4 cm
EBD (9 patients)
FCSEMS
Yes (90 %)/Yes (36 %)
1 – 28 days (8 stents SM)
Symptom free in 4 /11 patients ≥ 1 year. 2 complications
Branche 2012[28 ]
7
IC anastomosis
< 5 cm
EBD
PCSEMS
Yes (100 %)/Yes (71,4 %)
1 w
Symptom free in 5/7 patients, mean follow-up 10 months.
Loras 2012 [29 ]
17
IC anastomosis (10 patients)/colon (7 patients)
< 8 cm
EBD (14 patients)
PCSEMS (4)/FCSEMS (21)
Yes (92 %)/Yes (64.7 %)
Mean 28 days (1 – 112) (13 stents SM)
Symptom free in 11/17 patients, mean follow-up 67 w. 1 complication.
Abbreviations: C, ileocolonic; EBD, endoscopic balloon dilatation; FCSEMS, fully covered
self-expanding metal stent; UCSEMS, uncovered self-expanding metal stent; PCSEMS,
partially covered self-expanding metal stent; TB, tracheo-bronchial; SM, spontaneous
migration.
1 Rate** when is applicable.
2 BS*, bridge to surgery; w, weeks
The earliest experiences found in the literature with the use of SEMS in CD were published
as case reports [19 ]
[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]
[27 ]. These consisted of a total of nine studies involving 12 cases and with the placement
of 20 stents. It is difficult to draw conclusions regarding efficacy from these studies,
given the wide heterogeneity of patients included, the type of stents used, and the
fact that in half of the cases the stent placement was a bridge therapy to surgery.
In 2012, a retrospective series of five refractory ileocolonic postoperative anastomotic
strictures was published [28 ]. In all cases uncovered SEMS were used without stent removal. The procedure was
successful in four patients, two of them with long-term follow-up (one of them for
9 years). The homogeneity of patients included with the same type of stent used in
a similar clinical setting (anastomosis recurrence after surgery) was probably responsible
for the high rate of success.
A larger series of 11 patients with intestinal stenosis (two naïve to surgery and
nine with previous ileocolonic or ileocecal resection) was published the same year;
all were treated with FCSEMS [29 ]. The procedure was considered completely satisfactory (stent removal and disappearance
of obstructive symptoms) in only one patient (9 %), but in another three cases the
patients were free of symptoms for more than 1 year after the spontaneous migration
of the stent. So spontaneous migration should not be considered a technique failure
if a patient remains free of obstructive symptoms for a long period of time. In two
cases (18 %) major morbidity requiring urgent surgery was noted and spontaneous migration
of the stent was generally the rule.
From the same group, and given the poor results related to stent migration, a further
study using PCSEMS was published [30 ]. Seven patients with ileocolonic anastomosis (< 5 cm) were treated with PCSEMS removed
at 7 days. Some 71.4 % of patients remained asymptomatic with a median follow-up of
10 months, with no cases of migration or adhesion of the stent observed.
Finally, the largest series of CD patients treated with SEMS was recently published
[31 ]. This was a retrospective multicenter (six hospitals) Spanish cohort, in which the
efficacy and safety of SEMS in the treatment of symptomatic strictures refractory
to medical and/or endoscopic treatment in patients with CD was evaluated. A total
of 25 stents (four PCSEMS and 21 FCSEMS) were placed in 17 patients with stenosis
(< 8 cm) in the colon and ileocolonic anastomosis. Thirteen patients were operated
on before the stent placement and in all but three cases previous endoscopic dilation
had been unsuccessful. Clinical success (defined as remaining free of obstructive
symptoms at the end of the follow-up of at least 1 year after the procedure, without
major complications) was achieved in 64.7 % of patients (11 of the 17 patients) with
a mean follow-up period of 67 weeks (11 – 272). The technical success rate for stent
placement was 92 % (23 of the 25 stents). In four cases (16 %) the removal of the
stent was technically difficult, two of them PCSEMS (50 % of the PCSEMS) and two FCSEMS
(9.5 % of the FCSEMS). In these latter cases the SEMS were maintained for 8 and 16
weeks, respectively, with this long period probably being responsible for the adherence.
Only one patient had a severe complication due to proximal stent migration during
insertion. Endoscopic removal was not possible due to colonic angulation, even though
another stent was correctly inserted during the same procedure. Although the patient
was asymptomatic, he required a programmed surgical intervention 4 months later for
stent removal. Thirteen of the 25 stents (52 %) presented spontaneous distal migration,
due to resolution of stenosis in the majority of cases (11 of the 13 patients, 84.6 %).
This was not considered an adverse effect but rather an incident that could be treated
in all patients on an outpatient basis.
Scientific evidence about biodegradable stents
Regarding the use of biodegradable stents in CD patients, to date only a one small
series of patients (n = 11) [32 ] and 2 case reports [33 ]
[34 ] have been published ([Table 2 ]).
Table 2
Summary of Crohn’s disease patients reported in the literature with biodegradable
stents.
Author/Year
No. of patients
Location
Length
Previous treatment
Stent type
Technical/clinical success (rate[1 ])
Time degradation
Outcome
Rejchrt 2011 [30 ]
11
Small intestine, colon, IC anastomosis
≤ 5 cm
EBD (7 patients)
Polydioxanone biodegradable stent
Yes (90 %) / Yes (63 %)
4 months
Symptom free in 6 – 7 /11 patients, median follow-up 17 months
Rodrigues 2013 [31 ]
1
Colon
6 cm
No
Polydioxanone biodegradable stent
Yes/Yes
4 months
Symptom free at 16 months
Karstensen 2014 [32 ]
1
Small-bowel stricture in the ascending limb of an ileoanal J-pouch
12 cm
EBD
Custom-made biodegradable polydioxanone monofilament stent
Yes / Yes
–
Symptom free at 3 months
Abbreviations: IC, ileocolonic; EBD, endoscopic balloon dilatation.
1 Rate* when is applicable.
In reviewing the literature it seems that these devices have a low likelihood of reversing
stenosis when used for other indications [17 ]
[35 ]
[36 ]. In one of the studies with a large number of patients [35 ] in which biodegradable stents were used to treat benign esophageal strictures, an
efficacy of 45 % (9 of 21 patients) was observed with a mean follow-up of 53 weeks
(25 – 88). Also less than encouraging were the results obtained in the only study
performed in patients with CD [32 ]. A total of 11 patients with short stenosis ( ≤ 50 mm) at various locations (small
intestine, colon, ileocolonic anastomosis) were included. They had one faulty insertion,
three migrations (two of them in two days), and one relapse at 4 months requiring
the placement of a new stent. Despite the difficulty in determining the overall efficacy
of the technique from the reported data, we estimate an overall success rate of 54 %
to 63 % with a median follow-up of 17 months (12 – 29 months). In addition to these
results we have to take into account the technical difficulties in reaching the proximal
stenosis, for which a system of introduction with an over-tube balloon for stent insertion
with radiology had to be devised. Moreover, in the asymptomatic patients, a follow-up
colonoscopy was not performed. As noted by the authors, it was not possible to assess
the possible hyperplastic reaction of the mucosa as a secondary complication after
insertion of a biodegradable stent, as reported in previous studies.
Recently, two case reports were published in which a biodegradable stent was successfully
placed in CD patients. One was inserted with 16 months of follow-up in a woman with
CD and colonic stenosis of 6 cm in length [33 ]. In the other case, a custom-made biodegradable polydioxanone monofilament stent
was specially manufactured and successfully placed, with 3 months of follow-up, in
a man with an inflamed 12-cm small-bowel stricture in the ascending limb of an ileoanal
J-pouch [34 ].
Procedure description and practical aspects
Step 1: Before endoscopic placement of an enteral stent for the treatment of CD stenosis,
a thorough study of the disease activity and the length and location of stenosis is
in order. This requires imaging techniques to obtain a good characterization of the
stenosis so as to rule out any possible associated complication. We recommend endoscopic
(colonoscopy, enteroscopy) and radiological studies, preferably cross-sectional imaging
techniques. Magnetic resonance imaging (MRI) enterography and computed tomography
(CT) are the modalities of choice. Barium small-bowel follow through (SBFT) or enteroclysis
are alternative techniques when the above are not available. The aim is to assess
the anatomy, length, and number of the stenosis; the degree of obstruction; disease
activity; and the presence of local complications (abscesses and fistulae). The presence
of a certain degree of activity does not contraindicate stent placement. By contrast,
fistulae and abscesses are formal contraindications.
Step 2: The results of step 1 above allow for appropriate choice of the stent to use,
above all in terms of length and diameter. The stent chosen should be at least 3 to
4 cm longer than the obstruction to allow an adequate margin of stent on either side
of the stricture, as all stents show a degree of shortening, ranging from 5 % to 40 %.
Step 3. During stent insertion it is preferable to perform fluoroscopy to maintain
endoscopic and radiologic control at the same time. If fluoroscopy is not available,
a prior dilation to ensure proper placement of the stent is recommended. However,
this technique may subsequently encourage early migration of the stent.
Step 4. The endoscope must be advanced to the stenosis; after introduction of a long,
soft guide-wire (usually hydrophilic biliary guide-wire), the stent can be placed.
It is important to recognize the correct position of the wire passing into an air-filled
distal bowel loop. Once this is done, a catheter or a Fogarty balloon can be passed
over the wire. Radiographic contrast has to be injected to confirm both proper position
and luminal patency before actually placing the stent. Contrast can be injected into
the stent to assess complete patency ([Fig. 2 ] and [Fig. 3 ]). Optionally, clips can be positioned with or without adhesive tissue at the distal
end of the stent to prevent early migration. After placing the stent, it is important
not to pass through it as this maneuver could dislodge it.
Fig. 2 Placement of an FCSEMS in stenosis of CD patient in terminal ileum. a and b Endoscopic images of the scarred cecum making it very difficult to identify the ileocecal
valve and the stenosis in terminal ileum. c Passage of the guidewire through the stricture with fluoroscopic guidance. d and e . Total deployment of the stent.
Fig. 3 Placement of FCSEMS in stenosis of ileocolonic anastomosis in CD patient. a Endoscopic image of the stenosis. b Passage of the guidewire through the stricture. c The whole process of stent deployment with fluoroscopic and endoscopic guidance.
Image provided by Dr. Joan B Gornals, Hospital Universitari de Bellvitge.
Step 5. While the stent is in place, a diet with plenty of fluid intake without insoluble
fiber is recommended to prevent occlusion of the device. We recommend maintaining
the stent for a period not longer than 4 weeks.
Advantages and disadvantages and safety of current stents
Advantages and disadvantages
Endoscopic treatment of a short stricture of CD can avoid or delay a surgical resection.
Thus, both EBD and SEMS should be considered before surgery is undertaken. An advantage
of stents is that they allow constant dilation of the lumen over a longer period of
time than EBD and, at least theoretically, could be more effective. To date no comparative
studies have been published to assess this possibility. However, an on-going randomized
clinical trial (clinical trial NCT 02395354) will provide an answer to this question.
At any rate, stent placement is an alternative to endoscopic treatment that has demonstrated
efficacy in short strictures refractory to EBD. Moreover it is a feasible treatment
in patients who are not candidates for EBD (those with stenosis longer than 4 cm or
complex strictures).
The ideal type of stent is another unresolved issue, and in fact, current stents are
not specifically designed for the treatment of stenosis in the CD. FCSEMS prevent
adherence to mucus membrane and are thus easier to remove, but this also increases
the likelihood of distal migration. By contrast, PCSEMS can prevent possible distal
migration, but the increased chance of firm adherence to the mucosa makes their removal
more difficult. The very limited experience with biodegradable stents does not allow
a recommendation, but because their removal is unnecessary, they could theoretically
have a longer effect. However, current biodegradable stents show low efficacy in other
types of strictures and could produce a hyperplastic reaction in the mucosa of a patient
with CD. The technical difficulties of biodegradable stent insertion through the endoscope
channel, with difficult or impossible access to proximal stenosis, makes the procedure
very unattractive at present.
Endoscopic treatment of a CD stenosis with SEMS is more expensive to begin with than
EBD, which is particularly true of biodegradable stents. However, a cost-benefit comparison
of EBD versus SEMS has not yet been carried out. The above-mentioned trial (clinical
trial NCT 02395354) should provide valuable information in this regard.
Safety
In general, placement of a stent is a safe procedure, but we have to take into account
several issues associated with this technique.
The first point is the difficulty of insertion. In some cases, this step can be very
laborious or impossible depending on the location and angle of the stenosis. Moreover,
during placement, it is imperative to be careful to avoid proximal migration of the
stent [31 ].
The second point is the adherence of the stent to the mucus membrane of the bowel.
Depending on the type of SEMS (FCSEMS or PCSEMS), it is important not to leave the
stent in place for more than 4 to 6 weeks (less time for PCSEMS) to avoid complications
during removal [31 ]. Hyperplastic mucosal reaction to a foreign body is unlikely with a shorter period
of time ([Fig. 4 ]).
Fig. 4 Adherence of the stent in the mucosal membrane of the bowel making the removal procedure
difficult. a Beginning of the removal. b and c Removal of the stent remains. d Post-removal of the stent.
The third point is the possibility of perforation. This complication has been described
mostly in malignant disease due to mucosal erosion at the ends of the stents when
they are not removed [37 ]. In IBD patients, this complication has never been reported when the stent was used
as a temporary treatment. Avoiding excessive angling of the stent and using flexible
stents are two measures that help minimize risk.
The last point that has to be mentioned is the frequent spontaneous distal migration
of the stent [29 ]
[31 ]. Usually this occurs because the stenosis is resolved by the stent and for that
reason, it is considered an incident rather than a complication. Moreover, the patient
may spontaneously eject the stent, obviating the need to take it out endoscopically.
Otherwise, the stent usually migrates to the rectum and may thus be easily removed
with a forced biopsy.
Conclusions
For the time being, we can conclude that the use of stents is clearly indicated in
refractory cases of failure of endoscopic treatment with EBD and in cases in which
EBD does not eliminate the need for immediate or future surgery. Moreover, taking
into account results of the largest study [31 ] conducted in patients at high risk of refractoriness to prior endoscopic therapy,
the overall efficacy of SEMS was equal to or even greater than that reported in the
literature for EBD. Thus, SEMS could also be considered an alternative endoscopic
treatment to EBD in some cases. In cost-effective terms, although treatment with SEMS
is initially more expensive when compared with EBD, we must bear in mind that in most
patients a mean of 2.2 dilations to achieve good efficiency is required. Therefore
a comparative study of cost-effectiveness of the two techniques is required, considering
not only the cost of the materials used, but also the overall cost of the procedures
(number of admissions, complications, etc.).
At present, despite the limited information we have to date, placing a SEMS may be
a safe and effective alternative to EBD and/or surgical intervention in the treatment
of short stenosis in patients with CD. It may have the same or possibly more indications
than does EBD (such as longer or complex strictures). With the current information,
it seems that the best treatment option may be the placement of a fully covered stent
for a mean time of 4 weeks. Moreover, development of biodegradable stents in the future
seems promising given the advancement in technology. We can expect that modified stents
that exert greater radial strength and a TTS placement system will help improve current
results.
With the currently available information, we propose a therapeutic algorithm in which
stents could play a role ( [Fig.5 ]). Nevertheless, well-designed prospective randomized studies on the use of stents
in IBD comparing the different endoscopic techniques are required in order to establish
the correctness of this algorithm.
Fig. 5 Therapeutic algorithm proposed for strictures in Crohn’s disease patients. *complicated:
fistula abcess; **optional ± injection of substances.
Future development of this treatment will see improvement in the design of stents
specifically adapted for IBD, biodegradable stents, and/or stents that release medication.
