Crohn’s disease: preserve or resect the mesentery?

Résumé fourni par la source

Crohn’s disease (CD) is an inflammatory bowel disease characterized by chronic, transmural inflammation of the gastrointestinal tract1. The terminal ileum is affected in approximately one-third of patients and up to 50 per cent of patients develop intestinal complications (for example stricturing or fistulation) at 20 years after diagnosis2. Today, therapeutic options aim to enhance mucosal healing to achieve clinical and endoscopic remission, in order to avoid the risks of surgery and improve quality of life (QoL). Tremendous advancements in medical management options have been achieved in recent decades, with the introduction of biological anti-inflammatory agents, including anti-tumour necrosis factor-α (anti-TNF-α) agents. The introduction of anti-TNF-α agents, such as infliximab and adalimumab, has resulted in improved rates of response in patients with CD3,4. Early treatment with anti-TNF-α reduces the risk of developing bowel strictures and the need for intestinal surgery5,6. Mucosal healing is the primary aim of therapy, as this decreases the risk of penetrating complications and surgical intervention, and results in improved QoL2. Many patients still require surgical intervention, due to stenosis or penetrating disease. The Montreal classification (Table 1) is most commonly used for CD and distinguishes ileal strictures, penetrating disease (for example fistulae), and perforating disease (for example abscesses)7. In patients with strictures and subsequent pre-stenotic dilatation or obstructive symptoms, fistulae, or perforation, there is a clear indication for surgical intervention7. The LIR!C trial (RCT, open-labelled) demonstrated that laparoscopic ileocaecal resection is a good therapeutic alternative to infliximab in adults with non-stricturing, limited ileocaecal CD8. The decision for surgical intervention, however, should be weighed against the risk of complications, disease recurrence, and intestinal failure after bowel resection. Various surgical techniques have been described, ranging from strictureplasties to ileocolic resection with mesenterectomy, and include different anastomotic techniques. Unfortunately, disease recurrence occurs frequently and about 25 per cent of patients require further surgery after 5 years9. Interestingly, therapeutic paradigms have shifted over time and long-term outcomes after surgical intervention with close endoscopic surveillance and early treatment of disease recurrence with biological agents are not yet available6. Revised Montreal classification for Crohn’s disease GI, gastro-intestinal. Revised Montreal classification for Crohn’s disease GI, gastro-intestinal. To improve surgical decision-making and technique, a greater understanding of the biological behaviour of CD is needed; is this solely limited to the intestinal barrier and microbiome, or does it extend beyond the intestine, with a more prominent role for the mesentery? Recently, renewed interest has been directed towards the role of the mesentery in CD. The mesentery was disregarded for a long time, until a systematic study revealed functional features of the mesentery and its role in inflammatory diseases10. The mesentery has been proposed as an organ with unique functions, including mediation of local immune response and metabolism10. In addition to adipocytes, the mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts, and abnormalities in any of these structures can be observed and influence pathogenesis and prognosis in CD11. In particular, thickened and stiff mesentery with creeping of fat is a well-known feature, which can be observed on abdominal scans or at intraoperative assessment. It is also postulated that mesenchymal abnormalities can extend from the mesentery into the adjacent intestine12. These morphological and/or functional abnormalities in the mesenteric structures likely contribute to disease progression in CD, and, to a lesser extent, disease initiation. Thus, the mesentery might not just be a bystander of CD, but an active participant, due to the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia, resulting in adipose tissue remodelling. This novel understanding supports the rationale for performing an extended mesenteric resection with division of the vessels close to its origin, to reduce the risk of recurrence. Coffey et al.13 were the first to incorporate this concept into surgical practice. They performed a retrospective study of ileocolic resection for CD, comparing extended mesenteric resection with close bowel resection. A reduced reoperation rate of 2.9 per cent was found after extended mesenteric resection, compared with 40 per cent after close bowel resection13. However, critical concerns were raised, as follow-up time differed between groups. Additionally, clinical guidelines changed during the study interval, to more intensified surveillance and earlier initiation of medical therapy, which could also have influenced outcomes, as more patients undergoing extended mesenteric resection received biological agents before surgery13,14. Conversely, the recently published Remedy study reported no difference in disease recurrence after extended mesenteric resection compared with mesentery-sparing resection for patients with either stricturing or penetrating CD after a median follow-up of 5 years14. In this retrospective study, endoscopic recurrence was 45–47 per cent in both groups and no statistically significant differences were found. Strikingly, adjuvant immunosuppressive therapy significantly reduced the risk of postoperative disease recurrence, resulting in a surgical recurrence rate of only 4 per cent15. Additionally, there is an ongoing debate about the importance of disease-free resection margins regarding the risk of disease recurrence. Haiduc et al.16 compared patients with disease-free resection margins determined by histopathology with patients who did not have disease-free resection margins; however, they did not find sufficient evidence to conclude that a disease-free resection margin is associated with decreased disease recurrence. Although still not fully understood, the pathogenesis of stricturing CD involves an intricate interplay of both inflammatory and non-inflammatory pathways in the development of fibrostenosis17. In patients with stricturing CD, surgical options other than segmental resection should be considered, such as strictureplasty, while preserving the mesentery. This is particularly true if multiple segments of small bowel are involved. Several types of strictureplasties have been described, including Heineke–Mikulicz strictureplasty, Finney strictureplasty, and Michelassi strictureplasty (side-to-side isoperistaltic strictureplasty (SSIS)) (Fig. 1)18–20. Various strictureplasty techniques a Heineke–Mikulicz strictureplasty. b Finney strictureplasty. c Michelassi strictureplasty (side-to-side isoperistaltic strictureplasty). Resection of long segments is avoided with these bowel-sparing techniques and the mesentery is not resected, while significant healing of the intestinal mucosa has been reported21. de Buck van Overstraeten et al.21 observed clinical recurrence in one-third of patients after SSIS, with a median follow-up of 22 months. This contradicts the hypothesis of the mesentery as a driver for CD, as the mesentery is spared during strictureplasty. The optimal reconstruction method for restoration of intestinal continuity is also under debate, as this may influence the risk of recurrence. Although evidence is scarce, it seems that faecal stream and anastomotic diameter are important factors for disease recurrence22. Various anastomotic techniques have been described, and can either be handsewn or stapled. One trial compared both techniques and no statistically significant difference was found, although the endoscopic recurrence rate was lower in the stapled group23,24. Again, lower rates of recurrence were fou

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