How I Approach the Management of Stricturing Crohn's DiseaseINTRODUCTION
Despite major advances in biologic anti-inflammatory therapies for Crohn's disease (CD), more than 50% of patients with CD will develop clinically apparent stricturing disease throughout their lifetime (1). There are no current medications that reverse established fibrosis in CD. CD strictures comprise both fibrosis and inflammation. We present our approach to this frequent but challenging clinical situation.
STEP 1: DIAGNOSIS
According to the European Crohn's and Colitis Organization CD guidelines (2) and stricturing CD consensus (3,4), strictures are defined as a “persistent narrowing, whose functional effects may be judged from pre-stenotic dilatation.” Strictures may have clinically apparent symptoms related to intestinal obstruction or may be clinically silent.
Fibrostenosis is detected using both ileocolonoscopy and cross-sectional imaging (MRI, computed tomography, and/or transabdominal intestinal ultrasound) (5). Although strictures are part of validated endoscopic scores, such as the Simple Endoscopic Score-CD and the CD-Endoscopic Index of Severity, these measures, however, are not reliable (6). Computed tomography enterography, MRI enterography, and ultrasound have a high accuracy for diagnosis of stenosis with sensitivities and specificities around 90% and should be performed in cases where a stricture is suspected (Table 1). They characterize stricture morphology, location, and surrounding complications such as abscesses, phlegmon, or malignancy. However, at this time, there is no diagnostic imaging modality that is validated to differentiate between fibrosis and inflammation.
STEP 2: MANAGEMENT
Patients with CD and complete mechanical obstruction due to fibrostenosis should be hospitalized, have electrolytes assessed, hydrated, and advised to be nil per os with possible placement of a nasogastric tube for bowel decompression in those with active emesis. Diagnostic imaging is necessary to rule out CD complications and to delineate elements of fibrosis and inflammation in the stricture. In case of inflammation, administering intravenous corticosteroids may reduce intestinal edema and open the obstruction, but anecdotal evidence suggests intestinal decompression alone may have a comparable effect. Patients who remain obstructed for 48–72 hours will require optimization of current biologic therapies, endoscopic balloon dilation (EBD), surgery for strictureplasty, resection, or a combination of these therapies. The choice of therapy is dependent on quantity of inflammation, location, stricture length, concomitant complications, and patient preference (Figure 1).
Inflammation is considered a requirement for establishing fibrosis, but is less significant in its progression. Hence, only a small decrease in the incidence of strictures over time has been noted despite abundant use of biologic therapies (7). Reducing inflammation with antitumor necrosis factor medications in symptomatic CD strictures had a successful response, defined as no addition of corticosteroids after 8 weeks of initiation, no addition of other antitumor necrosis factors, and absence of EBD or bowel resection. This was achieved in two-thirds of patients at week 24 and in almost half the number of patients at 4 years (8). Data on newer biologic agents including vedolizumab (anti-αβ7 integrin) and ustekinumab (anti-interleukin 12/23) for treatment of strictures is lacking. In addition, in case of already present bowel damage, medical therapy is considered unlikely to ultimately resolve the obstruction long-term without endoscopic or surgical intervention.
If control of inflammation does not lead to symptom relief, the symptom-free interval is short, or contraindication to medical therapy exists, endoscopic or surgical interventions may be beneficial. Stricture location matches the distribution of CD with most strictures occurring in the ileum or ileocolon (9,10). All strictures require diagnostic imaging to identify the number and length of strictures, and subsequent meticulous biopsies to rule out malignancy before dilation, particularly in the colon. Colonic CD strictures should have low threshold to undergo resection if there is dysplasia, ongoing active inflammation despite medical therapy, or failed EBD.
For strictures less than 5 cm in length, EBD is a first-line therapeutic approach if accessible by endoscopy. EBD has low rates of complication with high rates of short-term technical and clinical efficacy (11). Serial EBD are frequently performed with unchanged outcomes and complication rates compared with the first EBD. Despite having one successful EBD, a large proportion of patients will require a second EBD or future surgical procedure (11). Stricture length greater than 5 cm carries a higher risk for subsequent surgery, and the presence of fistulas, malignancy, or dysplasia should prompt surgical resection over EBD. Balloon dilation may be performed in a retrograde or anterograde manner (Figure 2). Intralesional corticosteroid injection after EBD, and experimental techniques such as stent placement or needle knife are not recommended, because convincing evidence of decreased time to re-dilation in adults is missing or complication rates are high (12). Major complications from dilation include bowel perforation, bleeding, and infection at a rate of approximately 3% (11). Short-term and long-term outcome in naive compared with anastomotic strictures is comparable. Stricture location particularly in the upper gastrointestinal tract portends a shorter time to surgery when compared with jejunal, ileal, or colonic strictures (11). However, EBD of upper tract strictures may allow nutritional optimization before surgery. Regarding anastomotic strictures, concurrent escalation of medical therapy with EBD decreases time to re-dilation and surgery (13).
Surgical management includes bowel-preserving strictureplasty or resection. If strictures are outside the reach of endoscopy, too long to use EBD, in case of previously extensive bowel resections or multiple strictures strictureplasties are an option. If concomitant features are present, such as fistula, phlegmon, or malignancy, the stricture involves or is adjacent to the ileocecal valve, or if EBD or strictureplasty cannot be performed, resection is indicated.
Conventional strictureplasties include Heineke-Mikulicz (5–10 cm stricture) and Finney procedures (10–25 cm stricture), whereas nonconventional techniques include the Michelassi isoperistaltic strictureplasty (>25 cm strictures) (Figure 3). Resection may be preferred over strictureplasty in cases of multiple strictures over a relatively short segment of bowel or if the length of intervening bowel between strictures is less than 5 cm. To derive a decision, collaboration with a surgeon is invaluable to weigh factors such as total length of affected and unaffected bowel, patient age and comorbidities, and risk of stricture recurrence. Upper gastrointestinal tract stricture management also includes bypass procedures (gastrojejunostomy, duodenojejunostomy). Of interest, regression of fibrosis has been observed in patients who have undergone strictureplasty. Most patients with CD require a bowel resection within 10 years of disease onset. Nutrition status should be optimized if possible before surgical intervention. Minimally invasive approaches to resection are recommended. Patients often describe high satisfaction following their CD bowel surgery (14). Intestinal resection has also been reported to be durable in the long-term and to improve short-term and long-term health-related quality of life (14).
In summary, small bowel CD strictures with evidence of active inflammation on imaging and without immediate surgical indications should receive best medical therapy. Once inflammation treatment has been optimized, EBD is an important adjunct approach. Strictureplasties and surgical resection are often required despite optimal endoscopic and medical management. After surgery, the decision to continue or switch biologic agents is dependent on when the medication was initiated. Treatment may have been too late in already established fibrosis, which would not allow conclusions about its anti-inflammatory potency in the setting of prevention of postoperative recurrence.
The management of strictures will continue to evolve over time as we incorporate knowledge from novel definitions, hopefully leading to testing of specific anti-fibrotic therapies in stricturing CD (3).
CONFLICTS OF INTEREST
Guarantor of the article: Cathy Lu, MD, MSc.
Specific author contributions: C.L. and F.R.: planned, conducted the study, and drafted the manuscript. All authors have contributed to drafting the manuscript and approved the final version of the manuscript.
Financial support: This work was supported by grants from the National Institutes of Health [T32DK083251, P30DK097948 Pilot, K08DK110415] to F.R.
Potential competing interests: C.L. is on the advisory board or consultant for AbbVie, Ferring, Janssen, and Takeda. F.R. is on the advisory board or consultant for AbbVie, Celgene, Receptos, Thetis, UCB, Samsung, Pliant, Boehringer-Ingelheim, Helmsley, RedX, Thetis, Gossamer, Pfizer, Gilead, Takeda, and Roche.
REFERENCES
1. Thia KT, Sandborn WJ, Harmsen WS, et al. Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort. Gastroenterology 2010;139:1147–55.
2. Gomollón F, Dignass A, Annese V, et al. 3rd European evidence-based consensus on the diagnosis and Management of Crohn's disease 2016: Part 1: Diagnosis and medical management. J Crohns Colitis 2017;11:3–25.
3. Rieder F, Bettenworth D, Ma C, et al. An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease. Aliment Pharmacol Ther 2018;48:347–57.
4. Rieder F, Latella G, Magro F, et al. European Crohn's and Colitis Organisation Topical Review on prediction, diagnosis and management of fibrostenosing Crohn's disease. J Crohns Colitis 2016;10:873–85.
5. Panés J, Bouzas R, Chaparro M, et al. Systematic review: The use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn's disease. Aliment Pharmacol Ther 2011;34:125–45.
6. Khanna R, Zou G, Stitt L, et al. Responsiveness of endoscopic Indices of disease activity for Crohn's disease. Am J Gastroenterol 2017;112:1584–92.
7. Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: A systematic review and meta-analysis of population-based studies. Gastroenterology 2013;145:996–1006.
8. Bouhnik Y, Carbonnel F, Laharie D, et al. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: A multicentre, prospective, observational cohort (CREOLE) study. Gut 2018;67:53–60.
9. Saunders BP, Brown GJ, Lemann M, et al. Balloon dilation of ileocolonic strictures in Crohn's disease. Endoscopy 2004;36:1001–7.
10. Peyrin-Biroulet L, Harmsen WS, Tremaine WJ, et al. Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970–2004). Am J Gastroenterol 2012;107:1693–701.
11. Bettenworth D, Gustavsson A, Atreja A, et al. A Pooled analysis of efficacy, safety, and long-term outcome of endoscopic balloon dilation therapy for patients with stricturing Crohn's disease. Inflamm Bowel Dis 2017;23:133–42.
12. East JE, Brooker JC, Rutter MD, et al. A pilot study of intrastricture steroid versus placebo injection after balloon dilatation of Crohn's strictures. Clin Gastroenterol Hepatol 2007;5:1065–9.
13. Ding NS, Yip WM, Choi CH, et al. Endoscopic dilatation of Crohn's anastomotic strictures is effective in the long term, and escalation of medical therapy improves outcomes in the biologic era. J Crohns Colitis 2016;10:1172–8.
14. Ha FJ, Thong L, Khalil H. Quality of life after intestinal resection in patients with Crohn disease: A systematic review. Dig Surg 2017;34:355–63.
15. Rieder F, Zimmermann EM, Remzi FH, et al. Crohn's disease complicated by strictures: A systematic review. Gut 2013;62:1072–84.
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Πέμπτη 5 Σεπτεμβρίου 2019
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