ORIGINAL ARTICLE
Endoscopic Balloon Dilatation of Crohn’s Disease Strictures: Results from a Large United Kingdom Series Mahesh Bhalme, MRCP,* Sanchoy Sarkar, FRCP, PhD,† Simon Lal, FRCP, PhD,‡ Keith Bodger, FRCP, MD,§,k Rose Baker, PhD, FRSS, FIMA, CStat, CMath,¶ and Robert P. Willert, FRCP, PhD**
Introduction: Stricturing is a common complication of Crohn’s disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. Methods: A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn’s strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Results: Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1–11; median 2) were carried out on 93 strictures (range, 1–5; median 1) over a median duration of 12 months (range, 1–84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn’s disease duration (P ¼ 0.03) and high C-reactive protein (P ¼ 0.008) were associated with an increased need for subsequent surgery.
Conclusions: EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn’s disease phenotype, and the role of concomitant medication to identify those best suited to EBD. (Inflamm Bowel Dis 2014;20:265–270) Key Words: stricture, Crohn’s disease, endoscopic balloon dilatation, surgery
C
rohn’s disease (CD) is a chronic inflammatory granulomatous disorder that can affect any part of the intestinal tract. Unfortunately, one-third of patients may develop structuring disease within 10 years of initial diagnosis,1 and up to 80% of patients eventually require at least 1 surgical resection within 10 years of diagnosis.2,3 Furthermore, up to 48% will require reoperation within
Received for publication October 7, 2013; Accepted November 14, 2013. From the *Royal Bolton Hospital, Bolton, United Kingdom; †Department of Gastroenterology and Hepatology, Royal Liverpool University Hospitals, Liverpool, United Kingdom; ‡Intestinal Failure Unit, Salford Royal Foundation Trust, Salford, United Kingdom; §Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; kDigestive Diseases Centre, Clinical Sciences Centre, Aintree University Hospital, Liverpool, United Kingdom; ¶School of Business, Salford University, Salford, United Kingdom; and **Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester, United Kingdom. Presented as part of CERT-N (Collaboration of Endoscopy Research and Training in Northwest England). The authors have no conflicts of interest to disclose. Reprints: Robert P. Willert, FRCP, PhD, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester M13 9WL, United Kingdom (e-mail: [email protected]). Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/01.MIB.0000439067.76964.53 Published online 26 December 2013.
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5 to 8 years, most often at the anastomosis, irrespective of whether the surgery was a stricturoplasty or a resection.4 Both de novo and postsurgical stricturing are often responsible for patients’ symptoms, repeated hospitalization, and surgeries. Inflammatory strictures may respond well to medical therapies, including immunomodulators and anti–tumor necrosis factor agents. However, predominantly fibrotic strictures are less amenable to medical therapy and are more likely to require surgical resection. Surgery, although effective in such circumstances, is not a permanent cure. Multiple surgical interventions carry the risk of causing short bowel syndrome and the risk of perioperative adverse events. Over 70% of patients who underwent operation will have new endoscopic lesions in the neoterminal ileum within a year and, 40% of patients will become symptomatic within 4 years after surgery.5 Therefore, bowel-preserving strategies, such as surgical stricturoplasty and endoscopic balloon dilatation (EBD) have been investigated as alternatives to resection. A number of uncontrolled observational studies indicate that EBD is a safe and efficacious alternative to bowel resection in selected patients with de novo and anastamotic strictures at colonoscopy6 and more recently using double-balloon enteroscopy (DBE) in the small intestine.7 However, there is paucity and heterogeneity of data on factors that may influence the safety and efficacy of this technique. Furthermore, the Global Rating www.ibdjournal.org |
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Scale framework that supports the accreditation of endoscopy services in the United Kingdom recommends that all units undertake quality assurance audit for low-volume therapeutic procedures. Our aim was to perform a retrospective multicenter audit to evaluate the outcomes and efficacy of EBD in symptomatic patients with CD strictures and identify factors that may predict EBD success.
MATERIALS AND METHODS Audit Design We undertook a multicenter retrospective case series analysis of CD patients with strictures treated with EBD. Patients presenting between 1998 and 2011 were identified from endoscopy databases across 4 large National Health Service Teaching Hospitals (Central Manchester University Hospital, Salford Royal Foundation Trust, Royal Liverpool and Broadgreen University Hospital, and Aintree University Hospital) in the Northwest of England as part of the CERT-N (Collaboration of Endoscopy Research and Training in Northwest England). Patient information was anonymized and exchanged through a secure National Health Service server for final analysis and interpretation. We had approval from clinical audit department across all of the participating hospitals.
Data Collection Data were collected using a standard proforma, which recorded information acquired from medical case notes, hospital electronic endoscopy databases, and patients electronic records. Details included patient demographics, disease characteristics, smoking status, medications, C-reactive protein (CRP), endoscopic findings, EBD technical details including adverse events, and subsequent surgery at follow-up. Radiological assessment (computed tomography, magnetic resonance imaging, and/or barium study) was used to define stricture length, location, degree of stenosis, any angulation, and associated complications (e.g., fistulation). Only patients with a minimum of 3-month follow-up, data after EBD were included in the audit. Success of EBD was defined as symptomatic improvement without need for surgery at follow-up.
Dilatation Procedure All EBD procedures were carried out in a dedicated endoscopy unit by experienced endoscopists. When possible conscious sedation was preferred using a combination of midazolam and opiate (e.g., pethidine or fentanyl). The use of gastroscope, colonoscopy, or DBE was determined by stricture accessibility. A single experienced endoscopist performed all DBE procedures. Fluoroscopy was not used routinely. A mixture of de novo and anastomotic strictures was dilated using a throughthe-scope CRE wire-guided balloon catheter device developed by Boston Scientific (Boston Scientific Corporation, One Boston Scientific Place, Natick, MA). The balloon was positioned across the stricture and filled with sterile water under direct vision until the desired diameter was achieved. The desired diameter (limited
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to a maximum of 20 mm) was achieved in a 3-step increment of size. The maximum duration of stretch at each increment was variable but mostly around 1 minute with apposition of the clear transparent balloon to the tip of the endoscope allowing direct visualization of the dilatation process. If patients complained of any significant abdominal pain during the dilatation, then a further increment in diameter was avoided. At the end of each balloon dilatation, an attempt was made to pass the endoscope through the dilated stricture to define the technical success of the dilatation. Patients were observed in endoscopy recovery for at least 2 hours after EBD. If there were any concerns, patients were admitted to hospital for observation and further tests as necessary.
End Points Four end points were evaluated:
1. Technical success at index EBD (defined as passage of scope through the dilated stricture), 2. Clinical success at index EBD (defined as symptomatic improvement with no need for further EBD or surgery at follow-up), 3. Avoidance of surgical intervention for stricture-related problems at follow-up (after the first and subsequent EBDs), and 4. Severe adverse events8 (e.g., bowel perforation, significant bleeding needing blood transfusion, and procedure-related death).
Statistical Analysis The relationships between potential prognostic factors (such as age, sex, duration of CD, current or past smoking, stricture length, maximum balloon dilatation diameter, number of dilatations, CRP, stricture location, stricture type, and disease activity) and end points 2 and 3 described above were assessed using Cox regression (the proportional hazards model). Here, the hazard of an event is the “baseline” hazard, multiplied by the exponential of a regression term linear in the predictor variables. Thus, the logarithm of the hazard is linear in the predictor variables. The hazard of the next event occurring (another EBD or surgery) timed from the first EBD was modeled using each covariate (such as duration of CD) separately. The censoring event was the time of data collection.
RESULTS Patient and Disease Characteristics Data from 79 patients were available for analysis. Of these, 75 patients had their index EBD from year 2005 onwards and the remaining 4 underwent index EBD between 1998 and 2004. The median duration of follow-up (time from the first dilatation to the end of follow-up or to surgery) was 26.8 months (interquartile ratio, 12–62). Baseline patient demographics and disease characteristics are summarized in Table 1. The median number of strictures per patient was 1 (range, 1–5). The stricture characteristics are
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TABLE 1. Patient with EBD Demographics, CD Characteristics, and Immunomodulation Details N Patients Female, N (%) Age, median (range), yr Positive smoking history, N (%) Duration of CD, median (range), yr Disease location, N (%) Ileal (L1) Colonic (L2) Ileocolonic (L3) Upper GI (L4) Panenteric (L1–4) L3 + L4 Previous surgery, N (%) Concomitant medications in combinations, N Corticosteroids Azathioprine/6-MP/Methotrexate/Tacrolimus Biologics (infliximab or adalimumab) 5-ASA None Duration of follow-up, median (IQR), mo
47 48 33 17
79 (60) (17–85) (42) (0–64)
21 8 45 1 3 1 64
(27) (10) (57) (1) (4) (1) (81)
10 41 23 22 14 26.8 (12–62)
TABLE 2. The Characteristics of CD Stricture and the Details of Balloon Dilatation Procedure P*
0.832 0.532 0.620 0.036 0.574
NA 0.358
NA
*Significances are based on Wald tests (N ¼ number of patients; P-values are for Cox regressions, modeling the hazard of the next intervention, i.e., another dilatation or surgery). NA, not applicable; 6-MP, mercaptopurine; 5-ASA, aminosalicylic acid; IQR, interquartile ratio.
summarized in Table 2. For those patients undergoing repeat dilatations (n ¼ 45), we used the duration between these dilatations to find median time to the next dilatation. Based on the 112 durations between these dilatations, the median time to the next dilatation was 36.5 weeks (interquartile ratio, 12.6–97). Just over 5% repeat dilatations were within 4 weeks of the previous dilatation and 0.9% were within 2 weeks. The regression coefficients are not shown, and most were not statistically significant, but abnormal CRP at the time of dilatation and the duration of CD was significant (P ¼ 0.036) with longer duration giving a higher hazard of further interventions.
N No. of dilatations, N (median, range) 191 (2, 1–11) Type of stricture, N Anastomotic 48 De novo 31 Duration of dilatations, median 12 (1–84) (range), mo No. of strictures, N (median, range) 93 (1, 1–5) Location of strictures Anastomotic 48 Oesophageal 1 Duodenum 9 Jejunum 15 Terminal ileum 9 Colon 11 Length of stricture, median (range), cm 2 (0.5–7) Disease activity at anastomotic strictures i0 (no lesions) 15 i1 (,5 aphthous lesions) 11 i2 (.5 aphthous lesions with normal 15 intervening) i3 (diffuse aphthous ileitis with 2 diffusely inflamed mucosa) i4 (diffuse inflammation with large 3 ulcers, nodules, and/or narrowing) Unknown 2 Disease activity at de novo strictures Mild 7 Moderate 11 Severe 8 Unknown 5 Maximum diameter of balloon dilatation, median (range), mm Index dilatation 15 (10–20) Subsequent dilatations 18 (10–20) Time to the next dilatation, median 36.5 (12.6–97) (IQR), wk CRP (median, range) Index dilatation 5 (1–188) Subsequent dilatations 22.5 (3–382)
P* NA 0.521
NA NA NA
0.990 0.343
0.225
0.422 NA NA 0.008
Procedure The balloon dilatation procedure details are summarized in Table 2. Sixty-six patients had EBD performed at colonoscopy, 11 were performed at DBE (9 antegrade and 2 retrograde), and 2 at gastroscopy. Only 2 patients had EBD done under general anesthetic, and both these patients had distal jejunal small bowel strictures requiring an antegrade DBE procedure. The remaining patients had their procedures done using a combination of midazolam (median, 3.5 mg; range, 1–20 mg) and fentanyl (median, 100 mg; range, 25–200 mg) or pethidine (median, 50 mg; range, 25–50 mg), respectively.
*Significances are based on Wald tests (N ¼ number of patients; P-values are for Cox regressions, modeling the hazard of the next intervention, i.e., another dilatation or surgery). NA, not applicable; IQR, interquartile ratio.
Outcomes Technical success at index EBD was 95% (75 patients). Of the 4 cases where index EBD was technically unsuccessful, 3 had subsequent success after further attempts at EBD and avoided www.ibdjournal.org |
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surgery, whereas 1 required surgical resection after another EBD attempt with technical success. Clinical success at index EBD was 34% (27 patients), whereas another 43% (34 patients) achieved long-term symptomatic relief from further episodes of EBDs and avoided surgery at follow-up (Fig. 1). The Lexis diagram (Fig. 2) plots the medical interventions by calendar time (x axis) and time from the first dilatation (y axis). Avoidance of surgical intervention was achieved in 77% (61 patients). Only 18 (23%) patients needed surgery at follow-up. Duration to surgery after the index EBD was 2.6 to 71.1 months (median, 12.8 mo). Adverse event rate was low with 4% (3 patients) suffering minor adverse event immediately after EBD. Two of these patients had suffered nonsignificant bleeding from the dilated stricture after EBD. One of them required overnight observation in hospital, but no further intervention or blood transfusion, and the other stopped bleeding spontaneously by the end of the procedure itself. One patient suffered vasovagal syncope during the dilatation and was observed overnight in hospital and later discharged without need for any further intervention. No serious adverse events like bowel perforation or procedure-related death occurred in our series.
DISCUSSION Our audit shows that EBD was successful at improving patients’ symptoms and avoiding surgical intervention in 77% of cases during follow-up. This is the largest U.K. series to date and represents data from the past decade when biologics and other potent immunosuppressants have played a major role in defining the outcome of CD. The 30-day adverse event rate in our series was very low and probably reflects the patient selection process, expert endoscopists skills, and cautious technique of balloon dilatation. All of our cases were discussed at Inflammatory Bowel Disease multidisciplinary meetings between gastrointestinal radiologists, surgeons, and endoscopists to appropriately select patients based on stricture location, severity, angulation, and any evidence of
FIGURE 1. Outcome of EBD.
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associated complications such as fistulation or abscess formation. Furthermore, caution was applied with the balloon dilatation technique, and initially, the smallest sized balloon (8–10 mm) was tried followed by a 3-step increment in size to a maximum of 20mm balloon diameter. The maximum duration of stretch at each increment was variable but mostly around 1 minute. It is worth noting that Gustavsson et al9 reported a much higher complication rate in the largest balloon diameter (25 mm) at 9.3%, as compared with 3.5% for the other smaller sizes (P , 0.01) despite a stepwise increase in balloon diameter. Almost all our procedures were performed under conscious sedation, further reducing the risk of causing adverse events because of direct patient feedback at the time of dilatation procedure. After each dilatation, the area was carefully examined for excessive bleeding or mucosal tears before proceeding to further increment in size of balloon dilatation. If the endoscope passed through the stricture, the dilatation was considered adequate at least for the index procedure. Data on prognostic factors that affect long-term outcomes after EBD are very limited and heterogenous. To date, there has been no prospective controlled trial studying EBD outcome in stricturing CD. Most reported studies are small and retrospective observational studies. Smoking has long been considered to predict poor prognosis in CD. However, in the context of EBD, some studies have shown it to predict poor outcome,10,11 whereas others have shown smoking to have no influence on EBD outcome.12,13 Hoffmann et al14 indicated that the presence of ulcers in strictures to be associated with poorer long-term outcomes, whereas Thienpont et al15 reported that there was no association of long-term outcome with endoscopic activity (as determined by the size and the number of ulcerations). Thienpont et al15 also reported that the increased levels of CRP did not influence long-term outcomes and nor did medical therapy after dilatation. As for the characteristics of strictures, Mueller et al16 suggested the length and the location of strictures affected long-term outcomes. In their report, the patients who required surgery after EBD had longer de novo strictures than those who did not, and all of the surgical patients had de novo strictures in the terminal ileum. Similarly, Endo et al17 found that the anastomotic type stricture to be associated with significantly better surgery-free survival rates. Some studies have reported technical success17–19 as predictors of long-term good outcome, whereas a systemic review by Hassan et al6 found only stricture length ,4 cm to be a good prognostic factor. In our series, longer duration of CD (P ¼ 0.03) and abnormal CRP (P ¼ 0.008) at the time EBD were associated with an increased risk of requiring surgery in the long-term. Interestingly, none of the other patient-, disease-, or procedure-related factors (such as age, sex, current or exsmoking status, stricture length, balloon dilatation diameter, number of dilatations, stricture location, stricture type, and disease activity) were found to predict surgical intervention. It is also important to note that the strictures treated through DBE had similar outcomes to those at colonoscopy. This is in keeping with the limited published data on the efficacy of small bowel Crohn’s stricture dilatations.7,20,21 Patients
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FIGURE 2. The Lexis plot of outcomes after the index EBD leading up to the end of follow-up period or further dilatation or surgical intervention (sample thinned for legibility).
should therefore be considered for referral to centers providing DBE for assessment and dilatation before surgery where possible. Our audit has some limitations. Although the audit has relatively large number of patients, it is retrospective and lacks a control group (patients going direct to surgery). We only included patients who were from the local catchment area of the respective hospitals where they would have being followed-up, but we cannot be absolutely certain if any patient was readmitted elsewhere after the EBD procedure with delayed adverse events. Accurate differentiation between inflamed and fibrotic strictures may influence treatment options; however, such differentiation remains a challenge even with the most sophisticated imaging modalities, like high-resolution transabdominal ultrasound, computed tomography enterography, and magnetic resonance enteroclysis.22,23 However, endoscopy can assess only the mucosal surface but provides no information on transmural inflammation or bowel wall thickening. PreEBD imaging is however imperative in defining the stricture location, severity, angulation, and associated complications. It is therefore mandatory for better patient selection in the view of EBD or surgery as the treatment of choice. Vrabie et al24 suggested the likely success rate of stricture shorter than 5 cm is probably based on the length (5.5 cm) of the commonly used Boston Scientific balloon. Although we agree in theory, it is worth noting that strictures longer than 5 cm can still be dilated successfully using a stepwise technique. Hence, we advocate discussing each case on individual basis as no consensus has yet been made on the optimal stricture length for dilatation. Based on the findings from the largest reported study (178 patients) to date, with the longest median follow-up period of
5.8 years,9 it is reasonable to infer that patients are likely to need more than 1 EBD over 5 years to achieve a durable response in 50% of cases. The authors of this study concluded that the length of symptom-free interval, technical feasibility, and patients’ preference will aid in the clinical choice between surgery and repeated dilatation. Adjunctive endoscopic treatments during the dilatation procedure have also been studied such as corticosteroid25 or anti–tumor necrosis factor agent injection directly into the strictures.26 The true benefit of these types of endoscopic treatments is still unknown, and further data are awaited. Similarly, endoscopic placement of temporary self-expanding metal stents has been attempted in small case series; however, it has been associated with problems like stent migration and impaction.27,28 EBD offers many advantages over surgery, including bowel preservation and reduced adhesion formation. Also surgical stricturoplasty has been noted to have a higher significant complication rate compared with EBD (5 versus 3%) in 1 study.29 The only drawback of EBD is the need for repeat dilatation, but neither EBD nor surgery offers long-term cure to the problem with CD.
CONCLUSIONS Our audit demonstrates that EBD of Crohn’s stricture provides an acceptable long-term avoidance of surgery and low complication rates. We recommend EBD should be considered as a treatment option in selected CD patients with a nonangulated, predominantly fibrotic stricture of the gastrointestinal tract www.ibdjournal.org |
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including the small intestine, which is now amenable to therapy through DBE in expert centers. Surgical strictureplasty or resection should be reserved for lesions that fail to respond to EBD. A large prospective, randomized trial of standardized EBD technique versus surgical intervention will now help to evaluate the key predictors of long-term EBD success.
ACKNOWLEDGMENTS We would like to thank our gastroenterology trainees, E. Hargraves, T. Gledhill, Y. Prasad, and J. Geraghty, who helped collate data for this audit. Author Contributions: Dr. M. Bhalme led the overall audit, collated and analyzed the data, and wrote the draft manuscript. Dr. S. Sarkar, Dr. K. Bodger, Dr. S. Lal, and Dr. R. Willert suggested amendments to the draft manuscript. R. Baker carried out the statistical analysis and suggested amendments. Dr. R. Willert was the senior lead on the audit project.
REFERENCES 1. Cosnes J, Gower-Rousseau C, Seksik P, et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140: 1785–1794. 2. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg. 2000;231:38–45. 3. Farmer RG, Whelan G, Fazio VW. Long-term follow-up of patients with Crohn’s disease. Relationship between the clinical pattern and prognosis. Gastroenterology. 1985;88:1818–1825. 4. Yamamoto T. Factors affecting recurrence after surgery for Crohn’s disease. World J Gastroenterol. 2005;11:3971–3979. 5. Rutgeerts P, Geboes K, Vantrappen G, et al. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99:956–963. 6. Hassan C, Zullo A, De Francesco V, et al. Systematic review: endoscopic dilatation in Crohn’s disease. Aliment Pharmacol Ther. 2007;26:1457–1464. 7. Hirai F, Beppu T, Sou S, et al. Endoscopic balloon dilatation using double-balloon endoscopy is a useful and safe treatment for small intestinal strictures in Crohn’s disease. Dig Endosc. 2010;22:200–204. 8. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010;71:446–454. 9. Gustavsson A, Magnuson A, Blomberg B, et al. Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn’s disease. Aliment Pharmacol Ther. 2012;36:151–158. 10. Cosnes J, Carbonnel F, Beaugerie L, et al. Effects of cigarette smoking on the long-term course of Crohn’s disease. Gastroenterology. 1996;110: 424–431. 11. Sabaté JM, Villarejo J, Bouhnik Y, et al. Hydrostatic balloon dilatation of Crohn’s strictures. Aliment Pharmacol Ther. 2003;18:409–413.
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12. Morini S, Hassan C, Lorenzetti R, et al. Long-term outcome of endoscopic pneumatic dilatation in Crohn’s disease. Dig Liver Dis. 2003;35:893–897. 13. Thomas-Gibson S, Brooker JC, Hayward CM, et al. Colonoscopic balloon dilation of Crohn’s strictures: a review of long-term outcomes. Eur J Gastroenterol Hepatol. 2003;15:485–488. 14. Hoffmann JC, Heller F, Faiss S, et al. Through the endoscope balloon dilation of ileocolonic strictures: prognostic factors, complications, and effectiveness. Int J Colorectal Dis. 2008;23:689–696. 15. Thienpont C, D’Hoore A, Vermeire S, 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;59:320–324. 16. Mueller T, Rieder B, Bechtner G, et al. The response of Crohn’s strictures to endoscopic balloon dilation. Aliment Pharmacol Ther. 2010;31: 634–639. 17. Endo K, Takahashi S, Shiga H, et al. Short and long-term outcomes of endoscopic balloon dilatation for Crohn’s disease strictures. World J Gastroenterol. 2013;19:86–91. 18. Scimeca D, Mocciaro F, Cottone M, et al. Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn’s disease strictures. Dig Liver Dis. 2011;43:121–125. 19. Couckuyt H, Gevers AM, Coremans G, et al. Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn’s strictures: a prospective longterm analysis. Gut. 1995;36:577–580. 20. Despott EJ, Fraser C. Small bowel endoscopy in inflammatory bowel disease. Best Pract Res Clin Gastroenterol. 2012;26:279–291. 21. Despott EJ, Gupta A, Burling D, et al. Effective dilation of small-bowel strictures by double-balloon enteroscopy in patients with symptomatic Crohn’s disease (with video). Gastrointest Endosc. 2009;70:1030–1036. 22. Lenze F, Wessling J, Bremer J, et al. Detection and differentiation of inflammatory versus fibromatous Crohn’s disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis. 2012;18:2252–2260. 23. Adler J, Punglia DR, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn’s disease. Inflamm Bowel Dis. 2012;18:849–856. 24. Vrabie R, Irwin GL, Friedel D. Endoscopic management of inflammatory bowel disease strictures. World J Gastrointest Endosc. 2012;4:500–505. 25. Brooker JC, Beckett CG, Saunders BP, et al. Long-acting steroid injection after endoscopic dilation of anastomotic Crohn’s strictures may improve the outcome: a retrospective case series. Endoscopy. 2003;35:333–337. 26. Swaminath A, Lichtiger S. Dilation of colonic strictures by intralesional injection of infliximab in patients with Crohn’s colitis. Inflamm Bowel Dis. 2008;14:213–216. 27. Attar A, Maunoury V, Vahedi K, et al. 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– 1854. 28. Loras C, Pérez-Roldan F, Gornals JB, et al. Endoscopic treatment with self expanding metal stents for Crohn’s disease strictures. Aliment Pharmacol Ther. 2012;36:833–839. 29. Wibmer AG, Kroesen AJ, Gröne J, et al. Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn’s disease—review of the literature. Int J Colorectal Dis. 2010;25:1149–1157.
Endoscopic Balloon Dilatation of Crohn’s Disease Strictures: Results from a Large United Kingdom Series Mahesh Bhalme, MRCP,* Sanchoy Sarkar, FRCP, PhD,† Simon Lal, FRCP, PhD,‡ Keith Bodger, FRCP, MD,§,k Rose Baker, PhD, FRSS, FIMA, CStat, CMath,¶ and Robert P. Willert, FRCP, PhD**
Introduction: Stricturing is a common complication of Crohn’s disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. Methods: A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn’s strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Results: Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1–11; median 2) were carried out on 93 strictures (range, 1–5; median 1) over a median duration of 12 months (range, 1–84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn’s disease duration (P ¼ 0.03) and high C-reactive protein (P ¼ 0.008) were associated with an increased need for subsequent surgery.
Conclusions: EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn’s disease phenotype, and the role of concomitant medication to identify those best suited to EBD. (Inflamm Bowel Dis 2014;20:265–270) Key Words: stricture, Crohn’s disease, endoscopic balloon dilatation, surgery
C
rohn’s disease (CD) is a chronic inflammatory granulomatous disorder that can affect any part of the intestinal tract. Unfortunately, one-third of patients may develop structuring disease within 10 years of initial diagnosis,1 and up to 80% of patients eventually require at least 1 surgical resection within 10 years of diagnosis.2,3 Furthermore, up to 48% will require reoperation within
Received for publication October 7, 2013; Accepted November 14, 2013. From the *Royal Bolton Hospital, Bolton, United Kingdom; †Department of Gastroenterology and Hepatology, Royal Liverpool University Hospitals, Liverpool, United Kingdom; ‡Intestinal Failure Unit, Salford Royal Foundation Trust, Salford, United Kingdom; §Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; kDigestive Diseases Centre, Clinical Sciences Centre, Aintree University Hospital, Liverpool, United Kingdom; ¶School of Business, Salford University, Salford, United Kingdom; and **Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester, United Kingdom. Presented as part of CERT-N (Collaboration of Endoscopy Research and Training in Northwest England). The authors have no conflicts of interest to disclose. Reprints: Robert P. Willert, FRCP, PhD, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Trust, Manchester M13 9WL, United Kingdom (e-mail: [email protected]). Copyright © 2013 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/01.MIB.0000439067.76964.53 Published online 26 December 2013.
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5 to 8 years, most often at the anastomosis, irrespective of whether the surgery was a stricturoplasty or a resection.4 Both de novo and postsurgical stricturing are often responsible for patients’ symptoms, repeated hospitalization, and surgeries. Inflammatory strictures may respond well to medical therapies, including immunomodulators and anti–tumor necrosis factor agents. However, predominantly fibrotic strictures are less amenable to medical therapy and are more likely to require surgical resection. Surgery, although effective in such circumstances, is not a permanent cure. Multiple surgical interventions carry the risk of causing short bowel syndrome and the risk of perioperative adverse events. Over 70% of patients who underwent operation will have new endoscopic lesions in the neoterminal ileum within a year and, 40% of patients will become symptomatic within 4 years after surgery.5 Therefore, bowel-preserving strategies, such as surgical stricturoplasty and endoscopic balloon dilatation (EBD) have been investigated as alternatives to resection. A number of uncontrolled observational studies indicate that EBD is a safe and efficacious alternative to bowel resection in selected patients with de novo and anastamotic strictures at colonoscopy6 and more recently using double-balloon enteroscopy (DBE) in the small intestine.7 However, there is paucity and heterogeneity of data on factors that may influence the safety and efficacy of this technique. Furthermore, the Global Rating www.ibdjournal.org |
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Scale framework that supports the accreditation of endoscopy services in the United Kingdom recommends that all units undertake quality assurance audit for low-volume therapeutic procedures. Our aim was to perform a retrospective multicenter audit to evaluate the outcomes and efficacy of EBD in symptomatic patients with CD strictures and identify factors that may predict EBD success.
MATERIALS AND METHODS Audit Design We undertook a multicenter retrospective case series analysis of CD patients with strictures treated with EBD. Patients presenting between 1998 and 2011 were identified from endoscopy databases across 4 large National Health Service Teaching Hospitals (Central Manchester University Hospital, Salford Royal Foundation Trust, Royal Liverpool and Broadgreen University Hospital, and Aintree University Hospital) in the Northwest of England as part of the CERT-N (Collaboration of Endoscopy Research and Training in Northwest England). Patient information was anonymized and exchanged through a secure National Health Service server for final analysis and interpretation. We had approval from clinical audit department across all of the participating hospitals.
Data Collection Data were collected using a standard proforma, which recorded information acquired from medical case notes, hospital electronic endoscopy databases, and patients electronic records. Details included patient demographics, disease characteristics, smoking status, medications, C-reactive protein (CRP), endoscopic findings, EBD technical details including adverse events, and subsequent surgery at follow-up. Radiological assessment (computed tomography, magnetic resonance imaging, and/or barium study) was used to define stricture length, location, degree of stenosis, any angulation, and associated complications (e.g., fistulation). Only patients with a minimum of 3-month follow-up, data after EBD were included in the audit. Success of EBD was defined as symptomatic improvement without need for surgery at follow-up.
Dilatation Procedure All EBD procedures were carried out in a dedicated endoscopy unit by experienced endoscopists. When possible conscious sedation was preferred using a combination of midazolam and opiate (e.g., pethidine or fentanyl). The use of gastroscope, colonoscopy, or DBE was determined by stricture accessibility. A single experienced endoscopist performed all DBE procedures. Fluoroscopy was not used routinely. A mixture of de novo and anastomotic strictures was dilated using a throughthe-scope CRE wire-guided balloon catheter device developed by Boston Scientific (Boston Scientific Corporation, One Boston Scientific Place, Natick, MA). The balloon was positioned across the stricture and filled with sterile water under direct vision until the desired diameter was achieved. The desired diameter (limited
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to a maximum of 20 mm) was achieved in a 3-step increment of size. The maximum duration of stretch at each increment was variable but mostly around 1 minute with apposition of the clear transparent balloon to the tip of the endoscope allowing direct visualization of the dilatation process. If patients complained of any significant abdominal pain during the dilatation, then a further increment in diameter was avoided. At the end of each balloon dilatation, an attempt was made to pass the endoscope through the dilated stricture to define the technical success of the dilatation. Patients were observed in endoscopy recovery for at least 2 hours after EBD. If there were any concerns, patients were admitted to hospital for observation and further tests as necessary.
End Points Four end points were evaluated:
1. Technical success at index EBD (defined as passage of scope through the dilated stricture), 2. Clinical success at index EBD (defined as symptomatic improvement with no need for further EBD or surgery at follow-up), 3. Avoidance of surgical intervention for stricture-related problems at follow-up (after the first and subsequent EBDs), and 4. Severe adverse events8 (e.g., bowel perforation, significant bleeding needing blood transfusion, and procedure-related death).
Statistical Analysis The relationships between potential prognostic factors (such as age, sex, duration of CD, current or past smoking, stricture length, maximum balloon dilatation diameter, number of dilatations, CRP, stricture location, stricture type, and disease activity) and end points 2 and 3 described above were assessed using Cox regression (the proportional hazards model). Here, the hazard of an event is the “baseline” hazard, multiplied by the exponential of a regression term linear in the predictor variables. Thus, the logarithm of the hazard is linear in the predictor variables. The hazard of the next event occurring (another EBD or surgery) timed from the first EBD was modeled using each covariate (such as duration of CD) separately. The censoring event was the time of data collection.
RESULTS Patient and Disease Characteristics Data from 79 patients were available for analysis. Of these, 75 patients had their index EBD from year 2005 onwards and the remaining 4 underwent index EBD between 1998 and 2004. The median duration of follow-up (time from the first dilatation to the end of follow-up or to surgery) was 26.8 months (interquartile ratio, 12–62). Baseline patient demographics and disease characteristics are summarized in Table 1. The median number of strictures per patient was 1 (range, 1–5). The stricture characteristics are
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TABLE 1. Patient with EBD Demographics, CD Characteristics, and Immunomodulation Details N Patients Female, N (%) Age, median (range), yr Positive smoking history, N (%) Duration of CD, median (range), yr Disease location, N (%) Ileal (L1) Colonic (L2) Ileocolonic (L3) Upper GI (L4) Panenteric (L1–4) L3 + L4 Previous surgery, N (%) Concomitant medications in combinations, N Corticosteroids Azathioprine/6-MP/Methotrexate/Tacrolimus Biologics (infliximab or adalimumab) 5-ASA None Duration of follow-up, median (IQR), mo
47 48 33 17
79 (60) (17–85) (42) (0–64)
21 8 45 1 3 1 64
(27) (10) (57) (1) (4) (1) (81)
10 41 23 22 14 26.8 (12–62)
TABLE 2. The Characteristics of CD Stricture and the Details of Balloon Dilatation Procedure P*
0.832 0.532 0.620 0.036 0.574
NA 0.358
NA
*Significances are based on Wald tests (N ¼ number of patients; P-values are for Cox regressions, modeling the hazard of the next intervention, i.e., another dilatation or surgery). NA, not applicable; 6-MP, mercaptopurine; 5-ASA, aminosalicylic acid; IQR, interquartile ratio.
summarized in Table 2. For those patients undergoing repeat dilatations (n ¼ 45), we used the duration between these dilatations to find median time to the next dilatation. Based on the 112 durations between these dilatations, the median time to the next dilatation was 36.5 weeks (interquartile ratio, 12.6–97). Just over 5% repeat dilatations were within 4 weeks of the previous dilatation and 0.9% were within 2 weeks. The regression coefficients are not shown, and most were not statistically significant, but abnormal CRP at the time of dilatation and the duration of CD was significant (P ¼ 0.036) with longer duration giving a higher hazard of further interventions.
N No. of dilatations, N (median, range) 191 (2, 1–11) Type of stricture, N Anastomotic 48 De novo 31 Duration of dilatations, median 12 (1–84) (range), mo No. of strictures, N (median, range) 93 (1, 1–5) Location of strictures Anastomotic 48 Oesophageal 1 Duodenum 9 Jejunum 15 Terminal ileum 9 Colon 11 Length of stricture, median (range), cm 2 (0.5–7) Disease activity at anastomotic strictures i0 (no lesions) 15 i1 (,5 aphthous lesions) 11 i2 (.5 aphthous lesions with normal 15 intervening) i3 (diffuse aphthous ileitis with 2 diffusely inflamed mucosa) i4 (diffuse inflammation with large 3 ulcers, nodules, and/or narrowing) Unknown 2 Disease activity at de novo strictures Mild 7 Moderate 11 Severe 8 Unknown 5 Maximum diameter of balloon dilatation, median (range), mm Index dilatation 15 (10–20) Subsequent dilatations 18 (10–20) Time to the next dilatation, median 36.5 (12.6–97) (IQR), wk CRP (median, range) Index dilatation 5 (1–188) Subsequent dilatations 22.5 (3–382)
P* NA 0.521
NA NA NA
0.990 0.343
0.225
0.422 NA NA 0.008
Procedure The balloon dilatation procedure details are summarized in Table 2. Sixty-six patients had EBD performed at colonoscopy, 11 were performed at DBE (9 antegrade and 2 retrograde), and 2 at gastroscopy. Only 2 patients had EBD done under general anesthetic, and both these patients had distal jejunal small bowel strictures requiring an antegrade DBE procedure. The remaining patients had their procedures done using a combination of midazolam (median, 3.5 mg; range, 1–20 mg) and fentanyl (median, 100 mg; range, 25–200 mg) or pethidine (median, 50 mg; range, 25–50 mg), respectively.
*Significances are based on Wald tests (N ¼ number of patients; P-values are for Cox regressions, modeling the hazard of the next intervention, i.e., another dilatation or surgery). NA, not applicable; IQR, interquartile ratio.
Outcomes Technical success at index EBD was 95% (75 patients). Of the 4 cases where index EBD was technically unsuccessful, 3 had subsequent success after further attempts at EBD and avoided www.ibdjournal.org |
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surgery, whereas 1 required surgical resection after another EBD attempt with technical success. Clinical success at index EBD was 34% (27 patients), whereas another 43% (34 patients) achieved long-term symptomatic relief from further episodes of EBDs and avoided surgery at follow-up (Fig. 1). The Lexis diagram (Fig. 2) plots the medical interventions by calendar time (x axis) and time from the first dilatation (y axis). Avoidance of surgical intervention was achieved in 77% (61 patients). Only 18 (23%) patients needed surgery at follow-up. Duration to surgery after the index EBD was 2.6 to 71.1 months (median, 12.8 mo). Adverse event rate was low with 4% (3 patients) suffering minor adverse event immediately after EBD. Two of these patients had suffered nonsignificant bleeding from the dilated stricture after EBD. One of them required overnight observation in hospital, but no further intervention or blood transfusion, and the other stopped bleeding spontaneously by the end of the procedure itself. One patient suffered vasovagal syncope during the dilatation and was observed overnight in hospital and later discharged without need for any further intervention. No serious adverse events like bowel perforation or procedure-related death occurred in our series.
DISCUSSION Our audit shows that EBD was successful at improving patients’ symptoms and avoiding surgical intervention in 77% of cases during follow-up. This is the largest U.K. series to date and represents data from the past decade when biologics and other potent immunosuppressants have played a major role in defining the outcome of CD. The 30-day adverse event rate in our series was very low and probably reflects the patient selection process, expert endoscopists skills, and cautious technique of balloon dilatation. All of our cases were discussed at Inflammatory Bowel Disease multidisciplinary meetings between gastrointestinal radiologists, surgeons, and endoscopists to appropriately select patients based on stricture location, severity, angulation, and any evidence of
FIGURE 1. Outcome of EBD.
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associated complications such as fistulation or abscess formation. Furthermore, caution was applied with the balloon dilatation technique, and initially, the smallest sized balloon (8–10 mm) was tried followed by a 3-step increment in size to a maximum of 20mm balloon diameter. The maximum duration of stretch at each increment was variable but mostly around 1 minute. It is worth noting that Gustavsson et al9 reported a much higher complication rate in the largest balloon diameter (25 mm) at 9.3%, as compared with 3.5% for the other smaller sizes (P , 0.01) despite a stepwise increase in balloon diameter. Almost all our procedures were performed under conscious sedation, further reducing the risk of causing adverse events because of direct patient feedback at the time of dilatation procedure. After each dilatation, the area was carefully examined for excessive bleeding or mucosal tears before proceeding to further increment in size of balloon dilatation. If the endoscope passed through the stricture, the dilatation was considered adequate at least for the index procedure. Data on prognostic factors that affect long-term outcomes after EBD are very limited and heterogenous. To date, there has been no prospective controlled trial studying EBD outcome in stricturing CD. Most reported studies are small and retrospective observational studies. Smoking has long been considered to predict poor prognosis in CD. However, in the context of EBD, some studies have shown it to predict poor outcome,10,11 whereas others have shown smoking to have no influence on EBD outcome.12,13 Hoffmann et al14 indicated that the presence of ulcers in strictures to be associated with poorer long-term outcomes, whereas Thienpont et al15 reported that there was no association of long-term outcome with endoscopic activity (as determined by the size and the number of ulcerations). Thienpont et al15 also reported that the increased levels of CRP did not influence long-term outcomes and nor did medical therapy after dilatation. As for the characteristics of strictures, Mueller et al16 suggested the length and the location of strictures affected long-term outcomes. In their report, the patients who required surgery after EBD had longer de novo strictures than those who did not, and all of the surgical patients had de novo strictures in the terminal ileum. Similarly, Endo et al17 found that the anastomotic type stricture to be associated with significantly better surgery-free survival rates. Some studies have reported technical success17–19 as predictors of long-term good outcome, whereas a systemic review by Hassan et al6 found only stricture length ,4 cm to be a good prognostic factor. In our series, longer duration of CD (P ¼ 0.03) and abnormal CRP (P ¼ 0.008) at the time EBD were associated with an increased risk of requiring surgery in the long-term. Interestingly, none of the other patient-, disease-, or procedure-related factors (such as age, sex, current or exsmoking status, stricture length, balloon dilatation diameter, number of dilatations, stricture location, stricture type, and disease activity) were found to predict surgical intervention. It is also important to note that the strictures treated through DBE had similar outcomes to those at colonoscopy. This is in keeping with the limited published data on the efficacy of small bowel Crohn’s stricture dilatations.7,20,21 Patients
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FIGURE 2. The Lexis plot of outcomes after the index EBD leading up to the end of follow-up period or further dilatation or surgical intervention (sample thinned for legibility).
should therefore be considered for referral to centers providing DBE for assessment and dilatation before surgery where possible. Our audit has some limitations. Although the audit has relatively large number of patients, it is retrospective and lacks a control group (patients going direct to surgery). We only included patients who were from the local catchment area of the respective hospitals where they would have being followed-up, but we cannot be absolutely certain if any patient was readmitted elsewhere after the EBD procedure with delayed adverse events. Accurate differentiation between inflamed and fibrotic strictures may influence treatment options; however, such differentiation remains a challenge even with the most sophisticated imaging modalities, like high-resolution transabdominal ultrasound, computed tomography enterography, and magnetic resonance enteroclysis.22,23 However, endoscopy can assess only the mucosal surface but provides no information on transmural inflammation or bowel wall thickening. PreEBD imaging is however imperative in defining the stricture location, severity, angulation, and associated complications. It is therefore mandatory for better patient selection in the view of EBD or surgery as the treatment of choice. Vrabie et al24 suggested the likely success rate of stricture shorter than 5 cm is probably based on the length (5.5 cm) of the commonly used Boston Scientific balloon. Although we agree in theory, it is worth noting that strictures longer than 5 cm can still be dilated successfully using a stepwise technique. Hence, we advocate discussing each case on individual basis as no consensus has yet been made on the optimal stricture length for dilatation. Based on the findings from the largest reported study (178 patients) to date, with the longest median follow-up period of
5.8 years,9 it is reasonable to infer that patients are likely to need more than 1 EBD over 5 years to achieve a durable response in 50% of cases. The authors of this study concluded that the length of symptom-free interval, technical feasibility, and patients’ preference will aid in the clinical choice between surgery and repeated dilatation. Adjunctive endoscopic treatments during the dilatation procedure have also been studied such as corticosteroid25 or anti–tumor necrosis factor agent injection directly into the strictures.26 The true benefit of these types of endoscopic treatments is still unknown, and further data are awaited. Similarly, endoscopic placement of temporary self-expanding metal stents has been attempted in small case series; however, it has been associated with problems like stent migration and impaction.27,28 EBD offers many advantages over surgery, including bowel preservation and reduced adhesion formation. Also surgical stricturoplasty has been noted to have a higher significant complication rate compared with EBD (5 versus 3%) in 1 study.29 The only drawback of EBD is the need for repeat dilatation, but neither EBD nor surgery offers long-term cure to the problem with CD.
CONCLUSIONS Our audit demonstrates that EBD of Crohn’s stricture provides an acceptable long-term avoidance of surgery and low complication rates. We recommend EBD should be considered as a treatment option in selected CD patients with a nonangulated, predominantly fibrotic stricture of the gastrointestinal tract www.ibdjournal.org |
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including the small intestine, which is now amenable to therapy through DBE in expert centers. Surgical strictureplasty or resection should be reserved for lesions that fail to respond to EBD. A large prospective, randomized trial of standardized EBD technique versus surgical intervention will now help to evaluate the key predictors of long-term EBD success.
ACKNOWLEDGMENTS We would like to thank our gastroenterology trainees, E. Hargraves, T. Gledhill, Y. Prasad, and J. Geraghty, who helped collate data for this audit. Author Contributions: Dr. M. Bhalme led the overall audit, collated and analyzed the data, and wrote the draft manuscript. Dr. S. Sarkar, Dr. K. Bodger, Dr. S. Lal, and Dr. R. Willert suggested amendments to the draft manuscript. R. Baker carried out the statistical analysis and suggested amendments. Dr. R. Willert was the senior lead on the audit project.
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12. Morini S, Hassan C, Lorenzetti R, et al. Long-term outcome of endoscopic pneumatic dilatation in Crohn’s disease. Dig Liver Dis. 2003;35:893–897. 13. Thomas-Gibson S, Brooker JC, Hayward CM, et al. Colonoscopic balloon dilation of Crohn’s strictures: a review of long-term outcomes. Eur J Gastroenterol Hepatol. 2003;15:485–488. 14. Hoffmann JC, Heller F, Faiss S, et al. Through the endoscope balloon dilation of ileocolonic strictures: prognostic factors, complications, and effectiveness. Int J Colorectal Dis. 2008;23:689–696. 15. Thienpont C, D’Hoore A, Vermeire S, 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;59:320–324. 16. Mueller T, Rieder B, Bechtner G, et al. The response of Crohn’s strictures to endoscopic balloon dilation. Aliment Pharmacol Ther. 2010;31: 634–639. 17. Endo K, Takahashi S, Shiga H, et al. Short and long-term outcomes of endoscopic balloon dilatation for Crohn’s disease strictures. World J Gastroenterol. 2013;19:86–91. 18. Scimeca D, Mocciaro F, Cottone M, et al. Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn’s disease strictures. Dig Liver Dis. 2011;43:121–125. 19. Couckuyt H, Gevers AM, Coremans G, et al. Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn’s strictures: a prospective longterm analysis. Gut. 1995;36:577–580. 20. Despott EJ, Fraser C. Small bowel endoscopy in inflammatory bowel disease. Best Pract Res Clin Gastroenterol. 2012;26:279–291. 21. Despott EJ, Gupta A, Burling D, et al. Effective dilation of small-bowel strictures by double-balloon enteroscopy in patients with symptomatic Crohn’s disease (with video). Gastrointest Endosc. 2009;70:1030–1036. 22. Lenze F, Wessling J, Bremer J, et al. Detection and differentiation of inflammatory versus fibromatous Crohn’s disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis. 2012;18:2252–2260. 23. Adler J, Punglia DR, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn’s disease. Inflamm Bowel Dis. 2012;18:849–856. 24. Vrabie R, Irwin GL, Friedel D. Endoscopic management of inflammatory bowel disease strictures. World J Gastrointest Endosc. 2012;4:500–505. 25. Brooker JC, Beckett CG, Saunders BP, et al. Long-acting steroid injection after endoscopic dilation of anastomotic Crohn’s strictures may improve the outcome: a retrospective case series. Endoscopy. 2003;35:333–337. 26. Swaminath A, Lichtiger S. Dilation of colonic strictures by intralesional injection of infliximab in patients with Crohn’s colitis. Inflamm Bowel Dis. 2008;14:213–216. 27. Attar A, Maunoury V, Vahedi K, et al. 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– 1854. 28. Loras C, Pérez-Roldan F, Gornals JB, et al. Endoscopic treatment with self expanding metal stents for Crohn’s disease strictures. Aliment Pharmacol Ther. 2012;36:833–839. 29. Wibmer AG, Kroesen AJ, Gröne J, et al. Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn’s disease—review of the literature. Int J Colorectal Dis. 2010;25:1149–1157.
