The management of ulcerative colitis (UC) and Crohn’s disease (CD), the two major forms of inflammatory bowel diseases (IBD), has dramatically changed over the last decade. Progress has been supported by the increasing evidence from therapeutic strategies, the introduction of biologics providing more alternative options in patients with severe diseases, and new concepts as to how and when treatments should be used [1, 2]. Immunomodulators and biologics are classically used following a step-up approach in patients with refractory disease, who are unresponsive to conventional therapies or are steroid-dependent. Beyond their high efficacy in induction and maintenance of remission, it has been demonstrated that anti-tumor necrosis factor (TNF) therapies can close fistulae and heal mucosal lesions, and reduce rates of hospitalization and surgery [3]. Several recent studies suggest that early intervention with combination therapy may modify the long-term course of CD [4–6]. Meanwhile studies performed with regard to prediction of the disease activity have mainly focused on clinical and biological parameters, and endoscopy has been rarely investigated as a predictor of the clinical course of IBD. However, there is now growing evidence that morphological examination, including endoscopy, may help to identify among IBD patients those who should be treated with more intensive treatments. Furthermore, as demonstrated in a recent study assessing early intervention with combination of infliximab and azathioprine in CD, endoscopy may help to select patients who will obtain the best results with early intervention [4].

Endoscopic assessment of mucosal healing is usually assessed by colonoscopy in patients with UC. In fact, there are several indices proposed to measure endoscopic severity in UC (see Chap. 16); however, they have not been fully validated, and are subject to inter-observer variation. Recently, the development of a validated ulcerative colitis index of severity (UCEIS) has been established, and the American Gastroenterological Association is going to provide a forum for discussing the possibility of design and interpretation of future clinical trials in UC using UCEIS (see also Chap. 16). Meanwhile, the assessment of mucosal healing of CD has been performed by ileocolonoscopy, and recently balloon-assisted small-bowel enteroscopy and video-capsule endoscopy have also contributed to the evaluation of disease activity of small-bowel CD (see Chap. 17). Furthermore, CT-guided colonoscopy (virtual colonoscopy) and MR enterocolonoscopy also have contributed to diagnosis, monitoring, and therapy against IBD. In this chapter, the overview of important aspects of bowel involvement in IBD is discussed.

Carbonnel et al. [2] demonstrated that total colonoscopy is feasible in 86% of cases of severe UC (73/85). In this study, endoscopy accurately identified severe endoscopic lesions (extensive deep ulcerations). Eighty-five consecutive patients with attacks of UC were reviewed. Extensive deep colonic ulcerations were diagnosed in 46 of them. No complication related to colonoscopy occurred except for one colonic dilatation. Forty-three of the 46 patients with severe endoscopic colitis underwent surgery. Extensive ulcerations reaching at least the circular muscle layer were found on pathological examination, and were confirmed in 42/43 of cases [7]. Because of potential risks of complications, some rules have to be applied when performing colonoscopy in patients presenting severe attacks of UC, including pre-radiological examination to exclude megacolon and minimal insufflations; and when severe lesions are detected, the examination can be stopped as further examination has no additional prognostic value.

To date, there is no consensus on the definition of mucosal healing in UC [1]. The International Organization of IBD proposed the following definition: absence of friability, blood, erosions, and ulcers in all visualized segments of the gut mucosa. According to this definition, disappearance of the normal vascular pattern is compatible with mucosal healing [1, 3]. It has been shown that mucosal healing can be obtained with 5-aminosalicylates (5-ASA), steroids, azathioprine or methotrexate, and infliximab. Mucosal healing has been assessed in recent trials with different formulations of 5-ASA. In the ASCEND studies, evaluating different dosages of a delayed-released oral mesalazine in patients with mild or moderate UC, complete remission (including endoscopic remission) ranged between 18% and 25% at week 6 [4, 10]. Truelove et al. [5] demonstrated in 1954 that mucosal healing can be obtained with a high-dose of oral steroids in 30% of patients at week 6, compared with 10% in patients who received placebo (P = 0.02). In a recent review, it was considered that corticosteroids induce mucosal healing in 12–41% of patients with UC, depending on the method of administration and the medication [1]. Some data suggest that mucosal healing may also be obtained with azathioprine or methotrexate [6, 13]. Anti-TNF agents probably induce mucosal healing more rapidly. In ACT 1 and ACT 2, patients with refractory moderate-to-severe UC received placebo or infliximab intravenously [14]. Induction therapy with infliximab resulted in mucosal healing at week 8 in 61% of patients (148/242) compared with 32% (79/244) in the placebo groups (P < 0.001) [14]. At week 54 (ACT 1), scheduled maintenance therapy with infliximab resulted in mucosal healing in 45.5% (55/121) of patients compared with 18.2% (22/121) in the placebo group (P < 0.001). Data from several studies suggest that mucosal healing may be associated with a better outcome in UC, more specifically a decreased risk of relapse. Reduced relapse rates have been demonstrated in UC patients who achieved mucosal healing with steroids. In a study published in 1966, Wright et al. [7] found that 40% of patients who achieved mucosal healing with oral and rectal steroids did not relapse during 1 year of follow-up, as compared to 18% of those who still had lesions. In the ACT1 and ACT2 studies on infliximab maintenance in patients with moderately to severely active UC, 48.3% of the patients who achieved mucosal healing at week 8 were in remission at week 30, as compared to only 9.5% of those who did not achieve mucosal healing [13]. Mucosal healing may also be associated with reduced risk of surgery in UC. In the IBSEN population-based study, UC patients who achieved mucosal healing at 1 year (whatever the treatment) had a decreased risk of colectomy at 5 years (2% vs 7%, P = 0.02) [16]. A study performed in the Leuven cohort of UC patients treated with infliximab showed that colectomy was more frequent in patients who did not achieve mucosal healing at week 4 or 10 (Mayo endoscopic subscore greater than 1) [17]. In ACT1 and ACT2, it was shown that patients treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo [18]. However, data on the relationship between mucosal healing and risk of colectomy are not available in these studies. Finally, there is a clear relationship between the grade and chronicity of inflammation in the colon and the risk of colorectal cancer. Better control of inflammation, as demonstrated with mucosal healing, may be associated with decreased risk of colorectal cancer.

Among patients hospitalized for a severe attack of UC, the presence of extensive and deep ulcerations at colonoscopy is associated with an increased risk of colectomy on that admission [7]. In their study performed in the prebiologic era, Carbonnel et al. [2] showed that colectomy was performed in 43 of the 46 patients who presented severe endoscopic lesions (93%), as compared to 10/39 (26%) of those without such lesions (OR 41). In another study performed in severe UC patients, severe endoscopic lesions at colonoscopy were significantly more frequent in non-responders to medical treatment (91%) compared with responders (34%) (OR >20) [19]. The colonoscopies performed during severe attacks of UC also have an impact on the long-term outcome, with an increased rate of surgery in the long term in patients who exhibit extensive and deep ulcerations at index colonoscopy [20]. Namely, although intravenous cyclosporine treatment could exert high initial efficacy for severe attacks of UC, 50% of patients who had relapse required a colectomy. Specifically, mucosal healing evaluated by a novel endoscopic activity index [8] at day 14 after cyclosporine injection was associated with the 1-year colectomy rate [21].

Severity of colonic lesions in CD relies on the extent in depth and in surface of the mucosal damage. A previous interobserver variation study targeted on evaluation of ileocolonoscopic lesions in CD [9] has shown that deep ulcerations and estimation of ulcerated surface were among the most reproducible endoscopic items. Such lesions were also selected by multivariate analysis for the construction of the CDEIS [22]. Nahon et al. [10] demonstrated that colonoscopy accurately predicts the anatomical severity of colonic CD attacks. In this retrospective study of 78 patients operated for colonic CD resistant to medical treatment, criteria of severity in colectomy specimens were defined as either deep ulcerations eroding the muscle layer, or mucosal detachments, or ulcerations limited to the submucosa but extending to more than one third of one defined colonic segment (right, transverse, left colon). Three endoscopic criteria of severity were defined: (a) deep ulcerations eroding the muscle layer, (b) deep ulcerations not eroding the muscle layer but involving more than one third of the mucosal area, and (c) mucosal detachment at the edge of ulcerations. Evaluation of endoscopic severity correlated well with findings on colectomy specimens. At least one of these criteria was found in 95% of patients with severe anatomic lesions on colectomy specimens. The extent of ulcerations at colonoscopy was correlated to the results of colectomy specimen examination (P < 0.001). This study further demonstrates that colonoscopy can accurately assess anatomical severity of colonic CD.

Endoscopic severity may have an impact on the long-term course of the disease. Allez et al. [11] showed in a retrospective study that patients with CD exhibiting deep and extensive ulcerations at colonoscopy have a more aggressive clinical course with an increased rate of penetrating complications and surgery. Among the 102 patients included, 53 had severe endoscopic lesions at index colonoscopy, defined as extensive and deep ulcerations covering more than 10% of the mucosal area of at least one segment of the colon. During the follow-up (median 52 months), 37 patients underwent colonic resection. Furthermore, patients with severe endoscopic lesions needed significantly more colonic resections than patients without severe lesions [23]. These data suggest that a subset of CD patients have a more aggressive disease, characterized by severe endoscopic lesions in the ileocolon during symptomatic phases, and a higher risk of surgery [23].