The human gut microflora, comprising some 100 trillion microbial organisms, is critical in maintaining host health, both in the gastrointestinal tract itself and systemically, through the absorption of metabolites [86]. Recent studies have implicated specific strains of bacteria in the regulation of intestinal homeostasis, by delivering regulatory signals to the epithelium, to the mucosal immune system, and to the neuromuscular activity of the gut [87, 88]. However, some commensal and pathogenic organisms belonging to the human enteric microbiome contribute to the pathogenesis of IBD and CRC. Therefore, the use of probiotic bacteria to manipulate gut bacterial composition and local metabolite production has been explored as a therapeutic intervention to prevent CRC. Probiotics are live microbial food supplements with positive effects on host health. However, the efficacy of probiotics in this setting is unclear, and studies in mice have yielded controversial results [88–90]. To date, there have been no proper evaluations in humans.

Patients with IBD are commonly administered 5-aminosalicylate (5-ASA) as maintenance therapy, which in in vitro studies was shown to have antineoplastic properties by inhibiting the nuclear kappa-B pathway involved in tumor progression [91]. However, the evidence for a potential chemoprophylactic effect of 5-ASA is contradictory. In 2005, Velayos et al. [92] reported a meta-analysis of nine studies examining the effect of 5-ASA in preventing CA-CRC in IBD. The pooled analysis revealed a protective effect of 5-ASA use on the risk of CA-CRC (odds ratio = 0.51; 95 % CI, 0.37–0.69). However, a chemopreventive effect of 5-ASA has not been confirmed in case–control and population-based studies [93–95]. In a recent meta-analysis, Nguyen et al. [96] reported a pooled adjusted odds ratio of 0.95 (95 % CI, 0.66–1.38) for CA-CRC in patients with IBD treated with 5-ASA, nor did 5-ASA seem to have a protective effect in preventing CA-CRC in IBD. However, long-standing mild colitis, which could be maintained by 5-ASA administration alone, without aggressive therapy such as corticosteroids, immunomodulators, or biologics, could increase the risk of CA-CRC [15], by maintaining a state of chronic inflammation without complete remission or mucosal healing.

An increasing number of IBD patients are being treated with the thiopurine drugs azathioprine and 6-mercaptopurine, based on the consideration that aggressive therapy can induce complete remission and may therefore have a preventive effect. However, data on the potential chemopreventive effect of thiopurines in IBD are conflicting. In the CESAME study [58], nearly half of the 19,484 IBD patients had been exposed to thiopurines; among current users, the adjusted hazard ratio (HR) for CA-CRC was 0.57 (95 % CI, 0.24–1.32), thus ruling out a significant protective effect of thiopurine use on CA-CRC risk in the general IBD population. However, in a subanalysis confined to IBD patients with long-standing extensive colitis, current treatment with thiopurines reduced the risk of advanced CRC significantly (HR 0.28; 95 % CI, 0.09–0.89). In a Dutch cohort study, van Schaik et al. [97] estimated the effect of thiopurines on the risk of CA-CRC in an IBD cohort of 2578 IBD patients, of whom 770 had been exposed to thiopurines. They found that thiopurine exposure decreased the risk of advanced CA-CRC significantly (adjusted HR = 0.10; 95 % CI, 0.01–0.75). However, in a Danish, nationwide, population-based study, Pasternak et al. [98] found no effect of thiopurine on the occurrence of CA-CRC among 43,969 IBD patients, of whom 12 % had been exposed to thiopurines (adjusted RR = 1.00; 95 % CI, 0.61–1.63). Similar results were reported in another large population-based study from the United Kingdom [99].

Recent data from models of experimental colitis have demonstrated the tumor-promoting effect of tumor necrosis factor (TNF)-α [100]; but, only a few studies have evaluated the effect of new biological treatments, such as anti-TNF-α, on the risk of CA-CRC, as they have not been used long enough relative to the latency of CA-CRC. In a Dutch nested case–control study, Baars et al. [22] evaluated the risk factors for CA-CRC by comparing 173 CA-CRC patients with 393 non-CRC patients with IBD. They found that the use of anti-TNF-α was a protective factor for the development of CA-CRC (odds ratio = 0.09; 95 % CI, 0.01–0.68). In a Danish nationwide population-based cohort study, the risk of CA-CRC was compared between patients treated or not with anti-TNF-α. There was no correlation between anti-TNF-α and the prevalence of CA-CRC (adjusted RR = 1.06; 95 % CI, 0.33–3.40) [101]. Given that anti-TNF-α may be both tumor promoting and tumor preventing, further studies are needed to confirm its efficacy as a chemopreventive agent.

Surveillance colonoscopy for CA-CRC has been standardized, and its use in patients with long-standing IBD (≥8–10 years) has been widely advocated [7–9, 11, 23, 24]. Dysplasia or cancer found in surveillance is an absolute indication for proctocolectomy in patients with UC. Although it remains unclear whether proctocolectomy can decrease the incidence of CA-CRC in UC and improve the prognosis of these patients, the 5-year survival rate was higher in patients who underwent surveillance (87 %) than in those who did not (55 %) [43]. In Japan, Hata et al. [13] suggested that surveillance would allow the detection of CA-CRC at an earlier stage. In a recent review and meta-analysis of the incidence of CA-CRC, the risk of UC patients developing CRC was found to have decreased steadily over the last six decades [102]. Whether these improvements can be attributed to surveillance colonoscopy and prophylactic proctocolectomy remains to be determined.

In patients at risk of SBC, prophylactic resection of the small intestine is contraindicated by its absolute necessity for nutrient absorption, although total parenteral nutrition therapy can be considered. However, in patients with anorectal CD, prophylactic proctectomy may decrease the incidence of ARC. As discussed in Sect. 3.3, ARC is rarely detected in its early stage owing to the difficulty of proper surveillance and accurate diagnosis. Furthermore, ostomy diversion of anorectal CD increases the risk of ARC [64, 65, 69]. However, in patients with severe perianal disease with stricture, in whom both medical management and local surgical treatment have failed, the first surgical option is a diverting colostomy or ileostomy. If these do not provide sufficient relief, the final option is proctectomy, performed in 10–20 % of patients with perianal CD [103, 104]. Proctectomy generally consists of either a low Hartmann’s procedure or a complete proctectomy with sphincter resection. The disadvantages of Hartmann’s procedure include the risk of ARC in the residual distal rectum. This can cause persisting complaints of Crohn’s disease, and anastomotic breakdown will result in a presacral abscess draining and fistulizing through the perineum [105–108]. Therefore, in our institution, complete proctectomy is preferred when the stricturing anorectal lesion, regardless of the presence of a fistula tract, cannot be improved by any treatment. In our experience, proctectomy for these lesions improves not only the severe symptoms of anorectal lesions but also the incidence of ARC. However, an as yet unresolved problem is that the perineal wound after proctocolectomy heals poorly and there is a high incidence of persistent sinus in patients with CD [109, 110]. Long-term cohort studies, performed after several decades, are still needed to determine the outcomes of these patients.