Multidisciplinary Approach to Stricturing Crohn’s Disease: Medical Versus Endoscopic Versus Surgical Therapy

Introduction

Crohn's disease (CD) is characterized by segmental, transmural inflammation of the gut wall, which can affect any part of the gastrointestinal (GI) tract. CD has been categorized into inflammatory (B1), fibrostenotic (B2), and penetrating (B3) phenotypes, based on the Montreal Classification. The majority of patients would have B1 at presentation and as time goes by, B2 and B3 become predominant phenotypes. In fact, one-third of CD patients develop strictures within 10 years after diagnosis. According to the Montreal Classification, strictures are defined as ‘constant luminal narrowing on endoscopy, imaging, or surgery’ with prestenotic dilation or obstructive signs without penetrating disease. This definition may fail to include all patients with true stricture. In fact, stricture with prestenotic lumen dilation can be present. A number of clinical and genetic factors have been associated with the development of strictures in CD patients including ileocolonic disease location, long disease duration, severe disease, and NOD2/CARD15 mutations. There are ongoing studies in the biomarkers for intestinal fibrosis, with one of the goals being the prediction of inflammatory bowel disease (IBD)–related strictures. The candidate markers include NOD2/CARD15 gene variants, microRNAs, extracellular matrix proteins (e.g., collagen and fibronectin), enzymes (e.g., tissue inhibitor of matrix metalloproteinase-1), growth factors (e.g., basic fibroblast growth factor, YKL-40), anti- Saccharomyces cerevisiae , and circulating fibrocytes.

Crohn's stricture can occur anywhere along the GI tract, predominantly at the terminal ileum, surgical anastomotic site, or colon. The pathogenetic pathways of stricture formation involve tissue healing and remodeling process to chronic inflammation in the intestinal walls with fibrosis and hypertrophy of muscularity propria and muscularis mucosae. Patients with strictures may or may not have the symptoms. Symptoms associated with strictures range from postprandial abdominal bloating, nausea, and distension to frank intestinal obstruction. CD strictures have been treated with medications, endoscopy (endoscopic balloon dilation [EBD] and endoscopic stricturotomy [ES]), and surgery (bowel resection and strictureplasty [STX]). Medical therapy is routinely used for the treatment of B1 and B3 CD. However, medical therapy has a limited role in treating stricturing CD, especially in those with fibrosis being predominant.

Approximately 80% of the CD patients would eventually require at least one bowel resection surgery surgical resection within 10 years after diagnosis. Bowel resection or STX is not a curative surgery, and postoperative disease recurrence is common. It was reported that disease recurrence at the neoterminal ileum developed in 70% of the patients within a year of surgery, and 40% of these patients would need additional surgery within 4 years. Therefore conservative surgical approaches like STX have gained popularity. Nonetheless, surgical treatment is more effective and definitive in treating stricture than medical approach. Endoscopic therapy plays a growing role in the management of CD strictures, bridging medical and surgical therapy.

Medical Therapy

The last 2 decades have witnessed availability and a wide spread of various biological agents for the treatment of CD as well as ulcerative colitis (UC). Despite mucosal or tissue healing, there is concern that the rapid healing may predispose to strictures or aggravate existing strictures, leading to obstructive symptoms.