Postoperative Crohn's Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques

Abstract

After ileocolic resection with ileocolic anastomosis for Crohn's disease, most patients experience early endoscopic recurrence of which the severity predicts the risk of subsequent clinical and surgical recurrence.1Rutgeerts P. Geboes K. Vantrappen G. et al.Predictability of the postoperative course of Crohn’s disease.Gastroenterology. 1990; 99: 956-963Crossref PubMed Scopus (1351) Google Scholar Although current strategies recommend endoscopic surveillance and use of biologic therapies to reduce postoperative recurrence (POR), the need for a second surgery has not been reduced in the last 30 years.2Kalman T.D. Everhov A.H. Nordenvall C. et al.Decrease in primary but not in secondary abdominal surgery for Crohn’s disease: nationwide cohort study, 1990–2014.Br J Surg. 2020; 107: 1529-1538Crossref PubMed Scopus (12) Google Scholar Furthermore, the introduction of different anastomotic techniques may hamper endoscopic scoring of recurrence and partly explain prevailing difficulties in management of POR. New anastomosis techniques have been developed to reduce postoperative anastomotic complications and POR. Based on the association between Crohn's disease recurrence in the neoterminal ileum and the fecal stream, wide-lumen stapled side-to-side or side-to-end anastomosis preventing fecal stasis and bacterial overgrowth and preserving bowel vascularization have progressively gained popularity over end-to-end anastomosis (Figure 1). Retrospective studies have shown superiority of side-to-side stapled anastomosis over end-to-end hand-sewn configuration in terms of postoperative anastomotic complications and disease recurrence.3Muñoz-Juárez M. Yamamoto T. Wolff B.G. et al.Wide-lumen stapled anastomosis vs. conventional end-to-end anastomosis in the treatment of Crohn’s disease.Dis Colon Rectum. 2021; 44 (discussion 25–26): 20-25Crossref Google Scholar However, results are strongly biased by differences in surgical technique, site of anastomosis, definition of recurrence, and length of follow-up. A randomized controlled trial (RCT) failed to demonstrate a significant difference in endoscopic recurrence at 12 months between side-to-side and end-to-end anastomosis.4McLeod R.S. Wolff B.G. Ross S. et al.Recurrence of Crohn’s disease after ileocolic resection is not affected by anastomotic type: results of a multicenter, randomized, controlled trial.Dis Colon Rectum. 2009; 52: 919-927Crossref PubMed Scopus (180) Google Scholar A possible explanation is that, in a side-to-side anastomosis, the inlet of the anastomosis at the level of the terminal ileum represents the invariable critical diameter of the anastomosis independently of the length of the longitudinal stapler line (Figure 1). The observation that anastomotic recurrence arises on the mesenteric side of the intestine has led to a recent interest in the Kono-S anastomosis (Figure 1).5Yamamoto T. A new anastomotic technique for prevention of postoperative recurrence in Crohn’s disease.J Gastrointest Surg. 2012; 17: 1169Crossref PubMed Scopus (2) Google Scholar This consists of a wide antimesenteric functional end-to-end anastomosis, in which the mesentery is excluded from the anastomotic rhyme. A recent RCT has shown a significant reduction of endoscopic and clinical POR and reduced leak rates in patients who underwent a Kono-S compared with a side-to-side anastomosis.6Luglio G. Rispo A. Imperatore N. et al.Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn’s Disease: the SuPREMe-CD study - a randomized clinical trial.Ann Surg. 2020; 272: 210-217Crossref PubMed Scopus (46) Google Scholar Next to their direct impact on POR, the evolution of surgical techniques has transformed the endoscopic evaluation of POR, by creating new anatomic locations and by modifying the access to the neoterminal ileum. The Rutgeerts score, designed 30 years ago, was constructed based on lesions observed in patients with end-to-end anastomosis.1Rutgeerts P. Geboes K. Vantrappen G. et al.Predictability of the postoperative course of Crohn’s disease.Gastroenterology. 1990; 99: 956-963Crossref PubMed Scopus (1351) Google Scholar Today's leading surgical techniques, the side-to-side and side-to-end anastomosis, design anatomic locations ignored by the Rutgeerts score (ie, the inlet of the neoterminal ileum and the ileal segment [ileal body] facing the colon) (Figure 1). When looking at RCTs evaluating medical therapies for the prevention of POR, a steady increase in endoscopic recurrence rates in the placebo arms is observed in the last 5 years.7Regueiro M. Feagan B.G. Zou B. et al.Infliximab reduces endoscopic, but not clinical, recurrence of Crohn’s disease after ileocolonic resection.Gastroenterology. 2016; 150: 1568-1578Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 8de Bruyn J.R. Bossuyt P. Ferrante M. et al.High-dose vitamin D does not prevent postoperative recurrence of Crohn’s disease in a randomized placebo-controlled trial.Clin Gastroenterol Hepatol. 2021; 19: 1573-1582Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 9Bommelaer G. Laharie D. Nancey S. et al.Oral curcumin no more effective than placebo in preventing recurrence of Crohn’s disease after surgery in a randomized controlled trial.Clin Gastroenterol Hepatol. 2020; 18: 1553-1560Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar This could be related to the fact that these trials, using the original Rutgeerts score for assessment of endoscopic recurrence, observed a shift from i2a (lesions confined to the anastomosis) in the older studies using end-to-end anastomosis to i2b in a side-to-side anastomosis where the inlet of the neoterminal ileum rather than the wide longitudinal stapler line shows ulcerations (Figure 1). This could also explain the conflicting results obtained for the i2a and i2b modified Rutgeerts score categories in predicting clinical recurrence. Indeed, a retrospective study found no difference between the 2 categories in terms of clinical recurrence risk,10Rivière P. Vermeire S. Irles-Depe M. et al.No change in determining Crohn’s disease recurrence or need for endoscopic or surgical intervention with modification of the Rutgeerts scoring system.Clin Gastroenterol Hepatol. 2019; 17: 1643-1645Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar whereas the REMIND group found that lesions confined to the anastomosis had a better prognosis than neoterminal ileum lesions.11Hammoudi N. Auzolle C. Tran Minh M. et al.Postoperative endoscopic recurrence on the neoterminal ileum but not on the anastomosis is mainly driving long-term outcomes in Crohn’s disease.Am J Gastroenterol. 2020; 115: 1084-1093Crossref PubMed Scopus (11) Google Scholar As we describe previously, especially the i2a and i2b categories are influenced by the type of anastomosis. Notably, the REMIND study group found more ileal lesions and less anastomotic lesions in patients with a side-to-side anastomosis than in patients with an end-to-end or end-to-side anastomosis.11Hammoudi N. Auzolle C. Tran Minh M. et al.Postoperative endoscopic recurrence on the neoterminal ileum but not on the anastomosis is mainly driving long-term outcomes in Crohn’s disease.Am J Gastroenterol. 2020; 115: 1084-1093Crossref PubMed Scopus (11) Google Scholar This underpins the theory that the inlet of the neoterminal ileum, corresponding to the critical diameter of the anastomosis, is the location with the higher risk of recurrence related to fecal stream stasis. Depending on the type of anastomosis, the endoscopist scores those lesions as i2a or i2b or even i3 or i4 blurring the predictive value of the modified Rutgeerts score. Next to the inlet of the neoterminal ileum, the ileal segment facing the colon (the ileal body) is not included in the original description of the Rutgeerts score because this structure is not present in an end-to-end anastomosis. This may participate in the current suboptimal reproducibility of the score.12Marteau P. Laharie D. Colombel J.F. et al.Interobserver variation study of the Rutgeerts score to assess endoscopic recurrence after surgery for Crohn’s disease.J Crohns Colitis. 2016; 10: 1001-1005Crossref PubMed Scopus (35) Google Scholar Finally, the new surgical techniques may hamper the visualization and access to the neoterminal ileum. Notably, a 180° retroversion of the endoscope is often required to enter the neoterminal ileum in case of an antiperistaltic side-to-side anastomosis (Figure 1). We therefore suggest a new terminology as a basis for an updated postoperative endoscopic recurrence score taking into account 6 anatomic locations created by side-to-side or side-to-end anastomosis (Figure 1). The term “anastomotic line” should be restricted to the stapled or hand-sewn junction of the ileum and the colon created by the surgeon, including 1 cm above and below. In case of side-to-end and side-to-side anastomosis, the entry of the neoterminal ileum represents the critical diameter of the anastomosis and a site of high interest for POR. We propose to call this structure the “ileal inlet” including 1 cm above and below. The ileum between the anastomotic line and the ileal inlet could be called “ileal body” and, for side-to-end and isoperistaltic side-to-side anastomosis, the ileal segment opposite to the inlet on the other side of the anastomosis could be called “ileal blind loop.” Similarly, a “colonic blind loop” can be identified in end-to-side and side-to-side anastomosis. A new POR score taking into account these anatomic locations should be developed to differentiate: (1) lesions distal from the ileal inlet in side-to-side anastomosis, including the ileal blind loop, ileal body, and anastomotic line; (2) lesions in the neoterminal ileum proximal to the ileal inlet; and (3) lesions confined to the ileal inlet. Unfortunately, we cannot describe the relative frequencies of isolated lesions in each of these structures. In the coming years, data will be needed about the distribution of the lesions and their implications for clinical and surgical recurrence risk. One hypothesis is that lesions of the ileal inlet will be more prone to evolve rapidly toward a stricture. However, this reflects our opinion and actual data from real-life studies and RCT are needed to confirm or not the relevance of the classification we propose. This new terminology should be evaluated first by testing intraobserver and interobserver variability of new anastomotic locations identification and scoring. Next, a prospective study should assess the predictive value of this new score compared with the original Rutgeerts score. As a transition before an updated score is validated, we recommend using a more stringent definition for endoscopic POR in ongoing studies corresponding to i2b lesions in the neoterminal ileum including the ileal inlet and ileal body but excluding lesions of the anastomotic line and ileal blind loop (Table 1). The i2a category should refer only to lesions confined to the anastomotic line. Lesions restricted to the ileal inlet cannot be called i2a because these lesions can hardly be attributed to potential consequences of the surgical procedure. Lesions restricted to the ileal inlet or the ileal body should be classified i1, i2b, i3, or i4 depending on their severity. Lesions from the ileal blind loop could be related to the consequences of the surgical procedure but are not located at a critical place. Therefore, they should not be accounted for to calculate the updated Rutgeerts score (Table 1).Table 1Updated Rutgeerts Score Taking into Account the Anatomic Locations Created by New Surgical TechniquesCurrent version of the Rutgeerts score (modified Rutgeerts score)aFrom Gecse K, Lowenberg M, Bossuyt P, et al. Sa1198 agreement among experts in the endoscopic evaluation of postoperative recurrence in Crohn’s disease using the Rutgeerts score. Gastroenterology 2014;146:S-227. i0No lesions in the distal ileum i1Less than 5 aphthous lesions in the distal ileum i2aLesions confined to the ileocolonic anastomosis with or without less than 5 aphthous ulcers in the ileum i2bMore than 5 aphthous ulcers in the ileum with normal mucosa in between, with or without anastomotic lesions i3More than 5 aphthous lesions with diffusely inflamed mucosa in between i4Large ulcers with diffuse mucosal inflammation in between or nodules or stenosis in the distal ileumUpdated Rutgeerts scorebAnastomotic line refers to the surgical connection between the ileum and the colon and the centimeter above and below. Ileal blind loop refers to the ileal pouch created by the surgeon for a side-to-side or side-to-end anastomosis. Lesions in the blind loop are NOT used to score the updated Rutgeerts score (eg, isolated lesions of ileal blind loop are scored i0). Ileal body refers to the ileum between the anastomotic line and the ileal inlet in case of a side-to-side or side-to-end anastomosis. Lesions in the ileal body are considered like neoterminal ileum lesions to score the updated Rutgeerts score (eg, isolated lesions of ileal body are scored i1-i2b-i3-i4 depending on their severity). Ileal inlet refers to the most distal narrowing of the neoterminal ileum and the centimeter above and below, distinct from the anastomotic line in case of a side-to-side or side-to-end anastomosis. Lesions confined to the inlet are considered like neoterminal ileum lesions to score the updated Rutgeerts score (eg, isolated lesions of ileal inlet are scored i1-i2b-i3-i4 depending on their severity). Neoterminal ileum refers to the ileum proximal to the ileal inlet in case of a side-to-side or side-to-end anastomosis, and proximal to the anastomotic line in case of an end-to-end or end-to-side anastomosis. i0No lesions in the neoterminal ileum, anastomotic line, ileal inlet, or ileal body i1Less than 5 aphthous lesions in the neoterminal ileum, ileal inlet, or ileal body with normal mucosa in between i2aLesions confined to the ileocolic anastomotic line with or without less than 5 aphthous lesions in the neoterminal ileum, ileal inlet, or ileal body with normal mucosa in between i2b5 or more aphthous lesions or skip areas of larger ulcers in the neoterminal ileum, ileal inlet, or ileal body with normal mucosa in between, with or without anastomotic line lesions i3Aphthous lesions (regardless their number) with diffusely inflamed mucosa in between in the neoterminal ileum, ileal inlet, or ileal body i4Large ulcers with diffuse mucosal inflammation in between or nodules or nonpassable stenosis in the neoterminal ileum, ileal inlet, or ileal bodya From Gecse K, Lowenberg M, Bossuyt P, et al. Sa1198 agreement among experts in the endoscopic evaluation of postoperative recurrence in Crohn’s disease using the Rutgeerts score. Gastroenterology 2014;146:S-227.b Anastomotic line refers to the surgical connection between the ileum and the colon and the centimeter above and below. Ileal blind loop refers to the ileal pouch created by the surgeon for a side-to-side or side-to-end anastomosis. Lesions in the blind loop are NOT used to score the updated Rutgeerts score (eg, isolated lesions of ileal blind loop are scored i0). Ileal body refers to the ileum between the anastomotic line and the ileal inlet in case of a side-to-side or side-to-end anastomosis. Lesions in the ileal body are considered like neoterminal ileum lesions to score the updated Rutgeerts score (eg, isolated lesions of ileal body are scored i1-i2b-i3-i4 depending on their severity). Ileal inlet refers to the most distal narrowing of the neoterminal ileum and the centimeter above and below, distinct from the anastomotic line in case of a side-to-side or side-to-end anastomosis. Lesions confined to the inlet are considered like neoterminal ileum lesions to score the updated Rutgeerts score (eg, isolated lesions of ileal inlet are scored i1-i2b-i3-i4 depending on their severity). Neoterminal ileum refers to the ileum proximal to the ileal inlet in case of a side-to-side or side-to-end anastomosis, and proximal to the anastomotic line in case of an end-to-end or end-to-side anastomosis. Open table in a new tab