Management of Inflammatory Bowel Disease and Colorectal Cancer: Comparison
Please note this is a comparison between Version 1 by Yoshihiro Sato and Version 2 by Alfred Zheng.

Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. 

  • colorectal cancer
  • inflammatory bowel diseases
  • surveillance

1. Introduction

Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), have an increased risk of developing colorectal cancer (CRC) [1][2][1,2]. Although the incidence of CRC with IBD (IBD-CRC) is decreasing [3], its prognosis remains poorer than that of sporadic CRCs. Several distinct characteristics of IBD-CRC may contribute to this difference in prognosis, such as younger age at diagnosis, emergency presentation or diagnosis as an emergency, an increased likelihood of right-sided colon involvement [4], and histological features like multifocal tumors, poor/undifferentiated histology, or mucinous carcinomas [5][6][5,6]. Therefore, accurate risk stratification is crucial for effective personalized cancer surveillance by distinguishing between high-risk and low-risk individuals [7]. Advanced technologies during endoscopic surveillance programs provide valuable tools for diagnosing dysplastic and cancerous lesions [8][9][10][8,9,10], while new advanced techniques for endoscopic resection can also improve the prognosis of IBD-CRC [11].

2. Surveillance Strategy and Management

2.1. Surveillance Strategies

Colonoscopy is considered the fundamental tool for CRC surveillance in patients with IBD. The primary objective of this surveillance is to identify endoscopically removable premalignant lesions or early-stage CRC, leading to improved prognosis and treatment outcomes [12][44]. A recent meta-analysis, conducted in 2018, highlighted the importance of appropriate surveillance [13][45]. Bye et al. assessed the effectiveness of endoscopic surveillance in decreasing IBD-CRC-related mortality and found that the cancer detection rate was significantly higher in the non-surveillance group (3.2%) than in the surveillance group (1.8%) (OR, 0.58; 95% CI, 0.42–0.80; p < 0.001). Moreover, CRC-associated death was significantly lower in the surveillance group (8.5%, 15/176) than in the non-surveillance group (22.3%, 79/354) (OR, 0.36; 95% CI, 0.19–0.69; p = 0.002). In addition, the early-stage CRC detection rate was significantly higher in the surveillance group (15.5%) than in the non-surveillance group (7.7%) (OR, 5.4; 95% CI, 1.51–19.3; p = 0.009) [13][45]. Several international guidelines recommend active surveillance of patients with IBD to detect and resect dysplastic lesions before they progress to HGD or CRC [8][9][14][15][16][17][8,9,38,46,47,48]. Most guidelines advocate that all patients with colonic IBD undergo initial colonoscopy screening for dysplasia 8–10 years after the diagnosis of the disease. Continued surveillance colonoscopy is advised even if the disease is well-controlled, as chronic inflammation can lead to a false-positive pathological diagnosis of dysplasia [18][49]. Table 1 shows the recommended surveillance intervals after the initial colonoscopy, which are based on individual risk of CRC [12][14][38,44].
Table 1.
Recommended surveillance strategies based on risk stratification in patients with IBD.

2.2. Recommended Endoscopic Techniques

To maximize the efficacy of endoscopic surveillance, optimized mucosal visualization and improved operator performance are crucial [19][50]. Recently, several new endoscopic techniques have emerged to identify dysplastic or cancerous lesions [8][9][8,9]. According to the SCENIC Consensus, high-definition (HD) white-light endoscopy (WLE) is preferred over standard-definition (SD) WLE for surveillance [17][48]. Several international societies provide guidance on techniques for surveillance colonoscopy (Table 2) [8][14][16][20][21][8,38,47,51,52]. A retrospective analysis compared 160 colonoscopies with SD-WLE and 209 colonoscopies with HD-WLE and showed that the colonoscopies with HD-WLE improved the targeted detection of dysplastic lesions during periodic surveillance [22][53]. Although HD-WLE can allow visualization of most forms of dysplasia, chromoendoscopy (CE) may further facilitate the detection of dysplasia [23][54]. Dye spray CE (DCE) using methylene blue or indigo carmine can help identify the areas of interest and distinguish the borders between the normal mucosa and the suspected lesions. Technical advancements in endoscopic imaging have developed virtual CE (VCE) that can be utilized without spraying dye agents. The American College of Gastroenterology (ACG) clinical guidelines advocate endoscopic surveillance with HD-WLE using narrow-band imaging (NBI) or DCE to identify dysplasia in patients with UC [8].
Table 2.
Recommended techniques for surveillance colonoscopy.

2.3. Management of Dysplasia

During surveillance colonoscopy, precancerous lesions have been identified as adenomatous polyps, dysplasia-associated lesions or masses, and flat dysplasia [25][59]. In 2015, the SCENIC international consensus described the term “lesions” based on the standard Paris classification [17][48]. The AGA Expert Review classified the lesions into polypoid (≥2.5 mm tall), non-polypoid (<2.5 mm), or invisible (detected on non-targeted biopsy) [14][38]. In patients with well-controlled inflammation, endoscopic resection of dysplastic lesions should be considered. Patients must provide informed consent, understanding the risks, complications, and possibility of surgery if incomplete endoscopic resection occurs [24][37]. Endoscopic mucosal resection and endoscopic submucosal dissection (ESD) are used for endoscopic resection. ESD allows en bloc resection of larger lesions with distinct margins. Nevertheless, ESD in patients with IBD can be challenging due to the presence of fibrosis and chronic inflammation [26][60]. Manta et al. analyzed 53 patients with UC who underwent ESD for visible dysplastic lesions, showing en bloc and R0 resection rates of 100% and 96.2%, respectively, with the detection of two metachronous lesions. Another systematic review, including six other studies, revealed that the en bloc resection rate was 88.4% for lesions and 91.8% for 208 patients, while the R0 resection rate was 78.2% for lesions and 81.3% for patients. Thus, this study suggested that ESD is a feasible treatment option for resecting non-invasive dysplastic lesions in patients with UC [27][61]. However, when invisible dysplasia is detected through random biopsies, the appropriate strategies to discuss include intense surveillance, reassessment by IBD experts, or surgical resection based on patient factors (such as age, family history, and concomitant PSC) and disease factors (such as severity of dysplasia, inflammation in the background mucosa, and uni- or multi-focality of the dysplasia) [12][14][24][37,38,44].

2.4. Chemoprevention of IBD-CRC

Various therapeutic agents have been employed in clinical practice to prevent carcinogenesis in patients with IBD [28][29][36,62]. Qiu et al. reported in their systematic review with meta-analysis that 5-aminosalicylic acid (5-ASA) demonstrated a chemopreventive effect on dysplasia/CRC in clinical-based studies. However, the effect was limited to patients with UC, not in those with CD [30][63]. According to the recent consensus guidelines, the BSG, the European Crohn’s and Colitis Organization (ECCO), and the Japanese Society of Gastroenterology (JSGE) have recommended the use of 5-ASA for chemoprevention [16][31][32][47,64,65]. The BSG also suggested the use of thiopurines with a weak recommendation [16][47], but the benefit must be weighed against the potential risk of thiopurines for secondary development of lymphoproliferative malignancies [29][62]. In contrast, protective roles of statins and ursodeoxycholic against CRC have been controversial. Folic acids might have a protective effect, although sufficient evidence has been still lacking. Biologic agents such as tumor necrosis factor-α (TNF-α), nonsteroidal anti-inflammatory drugs (NSAIDs), or acetylsalicyclic acid have failed to demonstrate protective effects [29][62]. Overall, mesalamine has solely been accepted as an effective chemopreventive agent, supported with strong recommendations by the current guidelines worldwide.

2.5. Surgical Management of IBD-CRC

Surgery is indicated for endoscopically unresectable dysplasia due to submucosal invasion, invisible dysplasia detected in random biopsy, or “high-risk” colons, such as those with HGD with PSC [17][33][48,66]. Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard procedure for cases of HGD or CRC [25][34][59,67]. Stapled anastomosis is technically simple and superior to hand-sewn in terms of fewer anastomotic complications, better bowel function, and improved quality of life [35][68]. However, stapled anastomosis may carry the risk of neoplasia arising from a “cuff” of residual rectal mucosa. A systematic review that focused on pouch-related cancer showed that rectal mucosectomy did not eliminate subsequent dysplasia or cancer, but the incidence of cancer increased by eight times (OR, 8; 95% CI, 1.3–48.7) when mucosectomy was not indicated [36][69]. While total proctocolectomy is generally recommended, subtotal or partial colectomy are optional for patients with significant comorbidities, endoscopically unresectable unifocal neoplasia without other high-risk histological factors, and colonic CD without rectal involvement [24][37]. Dysplasia or cancer may arise from a diverted rectum or rectal stump left in situ [37][70]. Derikx et al. evaluated the risk of cancer after colectomy in their systematic review and meta-analysis, including 13 studies involving rectal stump surgery, 35 studies involving ileorectal anastomosis (IRA), and 33 studies of IPAA. The incidence of cancer was significantly increased in the rectal stump (2.1%) and IRA groups (2.4%) compared with that in the IPAA group (0.5%), and the OR was 6.4 (95% CI, 4.3–9.5, p < 0.001) [38][71]. Another recent systematic review involving 23 studies reported a pooled incidence of residual rectal carcinoma of 1.3%, with an incidence of 0.7% in patients with rectal stump surgery and 3.2% in those with IRA [39][72]. Bogach et al. evaluated the relationship between the surgical extent and prognosis in their population-based study. The 5-year survival rates were 63.7% in patients with UC and 57.5% in those with CD, and the multivariate analysis revealed that the survival outcome was inferior in patients who underwent total colectomy than in those who underwent segmental resection (HR, 1.70; 95% CI, 1.31–2.21; p < 0.001). No significant difference was observed between patients who underwent segmental resection and those who underwent proctocolectomy (HR, 0.99; 95% CI, 0.78–1.27) [40][73]. Adequate assessment of patients’ risk factors and reasonable decisions regarding surgical procedures are important for improving surgical outcomes in patients with IBD. Ramsay et al. reported a short-term outcome after CRC surgery between patients with IBD and those without IBD. Patients with IBD had increased postoperative complications (adjusted OR [AOR], 1.26; 95% CI, 1.06–1.50) including postoperative infection and deep vein thrombosis. Moreover, patients with IBD had a longer hospital stay (adjusted coefficient, 0.86 days; 95% CI, 0.42–1.30), received more blood transfusions (AOR, 1.59; 95% CI, 1.30–1.94), and experienced more readmissions within 30 days (AOR, 1.44; 95% CI, 1.01–2.04) than those without IBD. Therefore, the authors concluded that IBD could adversely affect outcomes after CRC surgery [41][74].
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