Although the risk of bowel resection has decreased in people with Crohn's disease (CD), about 25% of patients still require surgery within 10 years of diagnosis. Surgery relieves symptoms and induces remission, but it is not curative, and postoperative recurrence is common. Postoperative colonoscopy is the gold standard for diagnosing postoperative recurrence (POR) and is usually assessed using either the Rutgeerts score (RS) or the modified Rutgeerts score (mRS). Postoperative recurrence (ePOR) on endoscopy is defined as RS ≥ i2 or mRS ≥ i2a. The onset of ePOR precedes the recurrence of clinical symptoms. European and US guidelines recommend postoperative prophylaxis in high-risk patients to prevent ePOR.
This systematic review assessed the available evidence linking microbiological, surgical, and histopathological risk factors associated with CD with ePOR.
MethodsThe protocol for this review was registered with PROSPERO (CRD42022351074).
Inclusion criteria included: (1) studies including patients with Crohn's disease aged ≥16 years who had undergone ileocolectomy (re)resection (ICR), (2) endoscopic evaluation of ileocolic anastomosis and neoterminal ileum within 18 months of ICR using mRS, (3) reporting of associations of patient-related, microbiological, surgical, and/or histopathological factors with ePOR (i.e., RS≥i2 or mRS≥i2a at the time of first postoperative colonoscopy), and (4) published in 2000 or later. Studies not included included: studies containing patients with permanent ileostomy, (conference) abstracts, case reports, case series, reviews, animal studies, and non-English studies.
The investigators took into account that guidelines published in 2017 or later recommended that the first colonoscopy be performed within 12 months after surgery, and this study has relaxed the cut-off point to <18 months to include studies prior to the publication of these guidelines. First postoperative colonoscopy is used to evaluate ePOR, as ePOR at first postoperative colonoscopy is known to be associated with a higher risk of subsequent clinical and surgical recurrence.
ResultsThe study included 47 studies with a total of 6006 patients (Figure 1).
Figure 1. Flowchart of study selection
Source: References [1]
Active smoking has been found in eight studies to be a risk factor for ePOR. In these studies, active smoking was defined as smoking at the time of surgery, with no clear daily limit for cigarette smoking. In addition, active smoking at the time of surgery was associated with severe ePOR (≥i3) (OR: 2.75; 95% CI: 1.20-6.31)。
Most studies did not find a consistent association between lesion location and ePOR. Boschetti et al. found that the ePOR was significantly higher in patients with ileal involvement than in patients with ileal involvement. Rectal involvement is considered an independent risk factor for ePOR. Most of the available studies reported no association between disease manifestations (including perforation and perianal disease) and ePOR. ePOR was more common in patients undergoing surgery for fistula/abscess (P = 0.02).
Gender and ethnicity In four studies, male sex was identified as a risk factor for ePOR. Two studies reported European ancestry (OR: 5.78; 95% CI: 1.28 to 26.21) associated with ePOR.
History of enterectomy and age: Six studies found that previous enterectomy for CD was independently associated with ePOR. In patients without postoperative prophylaxis, age at diagnosis of CD >40 years was a risk factor for ePOR (OR: 3.05; 95% CI: 1.07-8.69)。
Body composition: Most studies have found that body mass index is not associated with ePOR.
Microbial factors were studied in seven studies as potential risk factors for ePOR in resected specimens or in the neo-ileum (table 1). Individual bacterial taxa have been found to be associated with ePOR, but there are differences between studies. Three studies evaluated the role of microbial factors in stool (table 1).
Table 1. Association of microbial factors with ePOR
Source: References [1]
Surgical factorsCD-related resection is recommended for a variety of reasons (eg, reduced pain, reduced postoperative adhesions, aesthetics). However, it is not known whether the surgical method will affect the results of postoperative endoscopy. In Thin et al.'s study, emergency surgery was found to be significantly associated with ePOR (mRS ≥ i2b) (OR: 3.14; 95% CI: 1.26-7.86). However, patients undergoing emergency surgery are also more likely to have other risk factors for ePOR (e.g., smoking, perforation). Carvello et al reported a significantly higher rate of ePOR in patients with postoperative complications.
Histopathological factors In the study by Poredska et al., patients with granulomas in the excised specimen had a significantly higher incidence of ePOR (P = 0.003). Lemmens et al reported that patients with submucosal lymphocytic clusteritis with proximal resection margins were more likely to develop ePOR (p = 0.02). Patients with active inflammation at the proximal resection margin are at higher risk of developing ePOR. In a recent prospective study, univariate analysis found that submucosal fibrosis (OR: 1.80; 95% CI: 1.01-3.21) and submucosal lymphoplasmacytic infiltration (OR: 1.89; 95% CI: 1.01-3.51) were associated with ePOR.
In conclusion, the researchers found that the risk factors for ePOR in international guidelines are not consistently reported as risk factors in the current literature, with the exception of active smoking and previous bowel resection. In order to develop an evidence-based, personalized strategy, it is necessary to conduct large prospective studies to identify risk factors for ePOR.
Thanks
Third Xiangya Hospital, Central South University, Ruan Xixian, Wang Sidan, Fu Tian
Sun Yuhao, School of Medicine, Zhejiang University
Chen Jie, Zhejiang University
Contribute to the interpretation of this article
bibliography
1. Bak MTJ, Demers K, Hammoudi N, et al. Systematic review: Patient-related, microbial, surgical, and histopathological risk factors for endoscopic post-operative recurrence in patients with Crohn's disease. Aliment Pharmacol Ther. Published online June 17, 2024. doi:10.1111/apt.18040
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