Dra. Carme Loras Alastruey
Hospital Universitari Mútua de Terrassa. Barcelona
INDICATIONS FOR STENTS IN CROHN’S DISEASES
Stenosis in Crohn’s disease (CD) is a consequence of chronic transmural inflammation with subsequent tissue remodelling, and hypertrophy of mesenchymal cells with hyperplasia and fibrosis. They tend to occur in the terminal ileum, at ileocolic anastomosis sites and in the rectum, and are considered clinically relevant when constant narrowing of the lumen occurs with prestenotic dilation and obstructive symptoms.
Stenoses appear in one third of patients with CD 10 years after diagnosis of the disease1. Over 50% of subjects who undergo ileal resection require further surgery within the next 15 years, and in 40%, symptoms reappear within the next four, with the possibility of ending up with short bowel syndrome in the long-term2.
Stenoses are more common in CD than in ulcerative colitis and in cases where the
disease is limited to the small intestine rather than restricted to the colon (64% vs 5%, respectively). In a meta-analysis that included 516 patients with CD and who underwent strictureplasty, 36% of stenoses were jejunoileal, 32% ileal and 24% jejunal
(Fig. 1), with stenotic recurrence observed at the strictureplasty site in 2.8 to 5% of cases3,4.
The need thus arises for a non-surgical conservative treatment, with pneumatic balloon dilation currently being the endoscopic treatment of choice. Various uncontrolled observational studies have shown that balloon dilation in selected patients is
a safe and effective alternative to surgery with a global success rate ranging from 44 to 58%5-7. Within the limitations of the different studies published, we find heterogeneity in the methods employed, different endpoints, small series of patients, etc., not to mention the non-negligible rate of complications associated with balloon dilation.
It is therefore imperative to find more conservative therapeutic alternatives to either prevent or delay possible surgical resection in patients with CD stenosis. Recent technological advances in self-expanding metal stents (SEMS), coupled with their clear effectiveness in treating malignant stenoses of the gastrointestinal tract, have allowed their use in benign diseases of any aetiology and in any location, including CD. Initially, uncovered SEMS were designed as a palliative treatment for malignant colonic diseases. These devices were not intended to be withdrawn. Given their effectiveness in this indication, fully covered SEMS were then devised for use in benign intestinal diseases and subsequent removal. A wide range of stents are now available (fully or partially covered, wide matrix and asymmetrical, biodegradable, plastic, metal, etc.), some of which are specifically designed for the treatment of benign intestinal stenosis and can be inserted via a working channel (these are known as “through the scope” [TTS] stents).
The first reference in the literature concerning the possible use of SEMS in CD appeared in a letter to the editor of Gastrointestinal Endoscopy published in 19968. A gastroenterologist’s son, whose mother had CD, who had been doing a rotation in a hospital for his final-year project observed a oesophageal and biliary stenting procedure and thought that there was no reason why this kind of treatment should not be used in the intestinal tract.
Until only recently, information regarding the effectiveness and safety of SEMS in treating CD stenosis was limited. To date, only 12 case reports9-17 and four small patient series18-21 have been published, between 1997 and 2012.
Early experiences found in the literature on the use of SEMS in CD were published in the form of case reports9-17 (Table I). A total of nine studies were published, which included 12 patients who received a total of 20 stents. Given the great heterogeneity of the type of patients included and stents used, and that in half of all cases, treatment was a bridge to surgery, it is difficult to draw firm conclusions.
The first small series of patients published are still very recent: 2012. The first is a retrospective study of five patients with refractory ileocolonic anastomotic stenoses secondary to resection for CD18.
In all cases, uncovered SEMS were used that were not subsequently removed. Treatment was successful in four patients, two of whom underwent long-term follow-up (one of them for nine years). The most noteworthy aspect of this study, and probably the reason for the high success rate obtained, was the homogeneity
in terms of the type of patients included, with the same type of stent used in the same clinical situation (anastomotic stenosis after surgical resection).
That same year, we found a longer series of 11 patients with intestinal stenosis (two of them naive to surgery and nine with a prior history of ileocolonic or ileocaecal resection) treated with fully covered SEMS 19. In only one case (9%) was the procedure considered a completely satisfactory (stent removed and a disappearance of obstructive symptoms); however, in three other cases the patients were free of symptoms for more than one year after spontaneous migration of the stent. As such, the procedure could have been deemed satisfactory in these cases too. Two cases (18%) required emergency surgery, and generally speaking, spontaneous stent migration was the norm.
Given the poor results obtained in terms of stent migration, the same authors subsequently published an initial experience involving partially covered SEMS; Seven patients with ileocolic anastomoses under 5 cm were treated with partially covered SEMS, which were removed after seven days. 71.4% of the patients remained asymptomatic with a median follow-up of 10 months, and no cases of stent migration or adhesion20.
Finally, we have the largest patient series to date, which evaluated the effectiveness and safety of using SEMS in the treatment of symptomatic stenosis refractory to medical treatment and/or endoscopy in patients with CD21. A total of 25 stents (four partially covered and 21 fully covered) were placed in 17 patients with colonic and ileocolonic anastomotic stenoses (<8 cm) in six different hospitals; Thirteen individuals had a history of surgery at the site of the stenosis, and all but three cases had previously been unsuccessfully treated with endoscopic dilatation. Clinical success (defined as remaining free of obstructive symptoms at the end of follow-up or for at least one year after the procedure, with no major complications) was obtained in 64.7% of patients (11/17) after a mean follow-up period of 67 weeks (11–272) with a technical success rate of 92% (23/25 stents) (Fig. 2). The follow-up period and clinical outcome of each of these patients are detailed in Table II21. In four cases (16%), stent removal was technically difficult due to its adhesion to the lumen (Fig. 4). Two of these cases had a partially covered SEMS (50% of the partially covered SEMS) and the other two had fully covered SEMS (9.5% of the fully covered SEMS were maintained for 8 to 16 weeks, a long period that is probably what caused the adhesion). Only one patient presented an adverse effect considered serious, secondary to proximal migration of the stent during its insertion, since its endoscopic removal was prevented by colonic angulation, despite the proper insertion of another stent during the same procedure. Despite being asymptomatic, the patient required surgery for removal of the first stent which migrated proximally four months after insertion. 52% (13/25) of the stents spontaneously migrated distally, and the stenosis resolved in most cases (11/13, 84.6%), so this was regarded as an adverse incident rather than an adverse effect. All patients could be treated as outpatients.
For all these reasons, we can conclude that the use of SEMS has a clear indication in all refractory cases where endoscopic balloon dilation has either failed or could not be performed, and that it can thus help either avoid or delay a future surgical intervention. In addition, taking into account the results of this latest study21 conducted in patients at high risk of refractoriness to a previous endoscopic treatment, the overall success rate of SEMS was equal to, or even higher than, that reported in the literature with respect to balloon dilation. Therefore, pending further studies or future comparative research, the indications for SEMS could be expanded in some cases and SEMS could be considered a good alternative to endoscopic balloon dilation, or even the best first-line endoscopic treatment. In financial terms, although treatment with SEMS is initially more expensive than balloon dilation, it should be borne in mind that in most patients, an average of 2.2 dilations are required for good results. A study comparing the cost-effectiveness of the two techniques is thus required, which should take into account not only the cost of the equipment used, but also the overall cost of the procedures (number of admissions, complications, etc.).
BIODEGRADABLE STENTS AND CROHN’S DISEASE
A review of the literature appears to show that the power of biodegradable stents to reverse stenoses is limited22,23. One of the studies with the largest patient population22, in which biodegradable stents were used for the treatment of benign oesophageal stenoses, found a success rate of 45% (9/21) with a mean follow up of 53 weeks (25–88). Neither are the results of the only study in patients with CD very encouraging24. It included a total of 11 patients with short stenoses (≤50 mm) in different locations (small intestine, colon, ileocolic anastomoses). There was one instance of faulty placement, three migrations (two of which occurred within two days) and one patient relapsed at four months, requiring placement of a new stent. Despite the difficulty in calculating the overall success rate of the procedure, based on the data reported in the article, we can estimate an overall success rate of 54–63% with a median follow up of 17 months (12–29 months). In addition to these results, one must take into account the technical difficulties in accessing the most proximal stenoses, to which end it was necessary to create an insertion system akin to a balloon overtube for radiology-guided insertion of the stent. In addition, asymptomatic patients did not undergo a follow-up colonoscopy and, as mentioned by the same authors, it was not possible to assess the possible mucosal hyperplastic reaction as a secondary complication after insertion of the biodegradable stent, as described in previous articles.
Nonetheless, the development of biodegradable stents seems promising and in the future, technological advances will most likely give rise to modified stents that exert greater radial force and have a TTS delivery system, which will help to improve current results.
ADVANTAGES AND DISADVANTAGES OF CURRENT STENTS
Based on all the above, we drew up a schematic outline of the advantages and disadvantages of the stents currently available for the treatment of CD:
• Allow for a more consistent and longer-lasting dilation of the intestinal lumen than the balloon method.
• Can be inserted via the scope channel (TTS), thus allowing access to more proximal stenoses.
• Provide a possible treatment option for refractory stenoses that are ineligible for other endoscopic treatments (e.g. longer stenoses).
• Can either prevent or delay a possible surgical resection of the stenosis.
• The use of fully covered SEMS allows their subsequent removal, preventing their adherence to the intestinal mucosa.
• The use of partially covered SEMS can prevent possible stent migration.
• The use of biodegradable stents can save us from having to remove them, while providing a more prolonged dilation.
• The cost of treatment with SEMS is presumably higher than that of current endoscopic treatment, and significantly higher still when using biodegradable stents.
• Fully covered SEMS are susceptible to migration.
• Partially covered SEMS are susceptible to adherence.
• Current stents are not specifically designed for the treatment of CD stenosis.
• The success rate of current biodegradable stents is low, and it is inconclusive whether they cause a mucosal hyperplastic reaction in patients with CD.
• Biodegradable stents can not be inserted through the working channel, making access to proximal stenoses difficult or even impossible.
In conclusion and despite the limited information available to date, the placement of a SEMS may constitute a safe and effective alternative to endoscopic balloon dilation and/or surgery in the treatment of short stenoses in patients with CD. These could have the same indications as balloon dilation (e.g. long or complex stenosis), so inserting a fully covered stent for an average of four weeks may be the best treatment option. Future prospects involve improving the design of stents specifically adapted for inflammatory bowel disease, including biodegradable and/or drug-eluting stents. Well-designed prospective randomised studies are needed on the use of stents in inflammatory bowel disease that compare
the different endoscopic techniques in order
to establish a proper treatment algorithm.
PRACTICAL CONSIDERATIONS FOR STENT INSERTION
I. Before performing endoscopic stenting
in a CD stenosis, it is essential to conduct a thorough study of the disease activity and the stenosis. Imaging techniques are required for proper characterisation and to rule out any associated complications.
First, it is necessary to conduct an assessment of the clinical and endoscopic disease activity (Table III) and then another of the number and extent of the stenoses (Table IV).
II.All the above allows us to choose the right kind of stent, particularly in terms of its length and diameter.
III. Whenever possible, it is preferable to have access to fluoroscopy for radiological and endoscopic monitoring. If fluoroscopy is not available, a preliminary dilation may optionally be performed to ensure proper positioning of the stent, although this dilation may later promote the early migration of the stent (Video 1).
IV. The endoscope is advanced to the stenosis, and the stent can then be inserted after introduction of a long and soft guide.
V. Optionally, clips ± tissue adhesives may be placed at the distal end of the stent to prevent early migration (Video 2).
VI. Once the stent has been placed, no attempts should be made to thread the endoscope through it, as this could cause the stent to move.
VII.As long as the patient is wearing the stent, a diet with plenty of fluid intake and no insoluble fibre is recommended in order
to avoid stent occlusion.
1. Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002; 8: 244-50.
2. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990; 99: 956-63.
3. Hommes DW, van Deventer SJ. Endoscopy in inflammatory bowel diseases. Gastroenterology. 2004; 126: 1561-73.
4. Tichansky D, Cagir B, Yoo E, Marcus SM, Fry RD. Strictureplasty for Crohn’s disease: meta-analysis. Dis Colon Rectum. 2000; 43: 911-9.
5. Hassan C, Zullo A, de Francesco V, Ierardi E, Giustini M, Pitidis A, et al. Systematic review: Endoscopic dilatation in Crohn’s disease. Aliment Pharmacol Ther. 2007; 26: 1457-64.
6. Van Assche G, Thienpont C, D’Hoore A, Demedts I, Bisschops R, Coremans G, et al. Long-term outcome of endoscopic dilatation in patients with Crohn’s disease is not affected by disease activity or medical therapy. Gut. 2010; 59: 320-4.
7. Gustavsson A, Magnuson A, Blomberg B, Andersson M, Halfvarson J, Tysk C. Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn’s disease. Aliment Pharmacol Ther. 2012; 362: 151-8.
8. Leichter J. Potential for expandable stents in Crohn’s disease. Gastrointest Endosc. 1996; 44: 637-8.
9. Matsuhashi N, Nakajima A, Suzuki A, Yazaki Y, Takazoe M. Long-term outcome of non-surgical strictureplasty using metallic stents for intestinal strictures in Crohn’s disease. Gastrointest Endosc. 2000; 51: 343-5.
10. Wholey MH, Levine EA, Ferral H, Castaneda-Zuniga W. Initial clinical experience with colonic stent placement. Am J Surg. 1998; 175: 194-7.
11. Suzuki N, Saunders BP, Thomas-Gibson S, Akle C, Marshall M, Halligan S. Colorectal stenting for malignant and benign disease: outcomes in colorectal stenting. Dis Colon Rectum. 2004; 47: 1201-7.
12. Wada H, Mochizuki Y, Takazoe M, Matsuhashi N, Kitou F, Fukushima T. A case of perforation and fistula formation resulting from metallic stent for sigmoid colon stricture in Crohn’s disease. Tech Coloproctol. 2005; 9: 53-6.
13. Bickston SJ, Foley E, Lawrence C, Rockoff T, Shaffer HA Jr, Yeaton P. Terminal ileal stricture in Crohn’s disease: treatment using a metallic enteral endoprosthesis. Dis Colon Rectum. 2005; 48: 1081-5.
14. Dafnis G. Repeated coaxial colonic stenting in the palliative management of benign colonic obstruction. Eur J Gastroenterol Hepatol. 2007; 19: 83-6.
15. Martines G, Ugenti I, Giovanni M, Memeo R, Iambrenghi OC. Anastomotic stricture in Crohn’s disease: bridge to surgery using a metallic endoprosthesis. Inflamm Bowel Dis. 2008; 14: 291-2.
16. Small AJ, Young-Fadok TM, Baron TH. Expandable metal stent placement for benign colorectal obstruction: outcomes for 23 cases. Surg Endosc. 2008; 22: 454-62.
17. Keränen I, Lepistö A, Udd M, Halttunen J, Kylänpää L. Outcome of patients after endoluminal stent placement for benign colorectal obstruction. Scand J Gastroenterol. 2010; 45: 725-31.
18. Levine RA, Wasvary H, Kadro O. Endoprosthetic management of refractory ileocolonic anastomotic strictures after resection for Crohn’s disease: Report of nine-year follow-up and review of the literature. Inflamm Bowel Dis. 2012; 18: 506-12.
19. Attar A, Maunoury V, Vahedi K, Vernier-Massouille G, Vida S, Bulois P, et al; the GETAID. Safety and efficacy of extractible self-expandable metal stents in the treatment of Crohn’s disease intestinal strictures: A prospective pilot study. Inflamm Bowel Dis. 2012; 18: 1849-54.
20. Branche J, Attar A, Vernier-Massouille G, Bulois P, Colombel JF, Bouhnik Y, et al. Extractible self-expandable metal stent in the treatment of Crohn’s disease anastomotic strictures. Endoscopy. 2012; 44(Suppl 2 UCTN): E325-6.
21. Loras C, Pérez-Roldan F, Gornals JB, Barrio J, Igea F, González-Huix F, et al. Endoscopic treatment with self-expanding metal stents for Crohn’s disease strictures. Aliment Pharmacol Ther. 2012; 36: 833-9.
22. Repici A, Vleggaar FP, Hassan C, van Boeckel PG, Romeo F, Pagano N, et al. Efficacy and safety of biodegradable stents for refractory benign esophageal strictures: the BEST (Biodegradable Esophageal Stent) study. Gastrointest Endosc. 2010; 72: 927-34.
23. Van Hooft JE, van Berge Henegouwen MI, Rauws EA, Bergman JJ, Busch OR, Fockens P. Endoscopic treatment of benign anastomotic esophagogastric strictures with a biodegradable stent. Gastrointest Endosc. 2011; 73: 1043-7.
24. Rejchrt S, Kopacova M, Brozik J, Bures J. Biodegradable stents for the treatment of benign stenoses of the small and large intestines. Endoscopy. 2011; 43: 911-7.