Update and latest advances in mechanisms and management of colitis-associated colorectal cancer

Table 1 Summary of guidelines and consensus statements reporting on colonoscopic surveillance in inflammatory bowel disease

Society	Disease type	Initiation	Risk categories	Surveillance intervals	Endoscopic selection of dysplasia detection
ACG, 2019; Guideline[51]	UC	8 yr; concomitant PSC: From diagnosis	No specific recommendation	UC: 1-3 yr; concomitant PSC: 1 yr	Dye spray chromoendoscopy with methylene blue or indigo carmine; white-light endoscopy with narrow-band imaging
ACG, 2018; Guideline[56]	CD	No specific recommendation			Colonoscopy with chromoendoscopy: high risk for colorectal neoplasia1
AGA, 2021; expert consensus[52]	IBD	8-10 yr; after a negative screening colonoscopy: 1-5 yr; concomitant PSC: From diagnosis	No specific recommendation	High risk for developing colorectal dysplasia2, persistent moderate-severe pouchitis, and/or pre-pouch ileitis: At least 1 yr	Dye spray chromoendoscopy; high-definition endoscopy with virtual chromoendoscopy
AOCC and APAG, 2021; expert consensus[57]	IBD	8 yr		UC patients with LGD in flat mucosae: In 3-6 mo	No specific recommendation
BSG, 2019; guideline[58]	IBD	8 yr; concomitant PSC: From diagnosis	Lower risk: Extensive colitis with no active inflammation; colitis affecting < 50% of the colon; intermediate risk: extensive colitis with mildly active inflammation; post-inflammatory polyps; CRC in an FDR older than 50 yr; higher risk: Extensive colitis with moderate-to-severely active inflammation; stricture or dysplasia in last 5 yr; history of PSC (including after orthotopic liver transplantation); CRC in a FDR younger than 50 yr	Lower risk: 5 yr; intermediate risk: 3 yr; higher risk: 1 yr	High-definition colonoscopy with chromoendoscopy
CCA, 2018; Guideline[59]	IBD	8-10 yr	Lower risk: Quiescent disease and no other risk factors; intermediate risk: Quiescent disease without high risk factors; family history of CRC in an FDR; higher risk: Chronic active inflammation; prior colorectal dysplasia; evidence of intestinal damage with foreshortened tubular colon, colonic stricture, or pseudopolyps; PSC; family history of CRC younger than 50 yr	Lower risk: 5 yr; Intermediate risk: 3 yr; higher risk: 1 yr	Colonoscopy with chromoendoscopy
CSG, 2018; Chinese consensus[53]	IBD	8-10 yr	No specific recommendation	UC: 8-10 yr; montreal type E2: 2 yr (15 yr after the onset of the disease); montreal type E3: 2 yr (8-10 yr after the onset of the disease); 1 yr (after 20 yr); concomitant PSC: 1 yr	No specific recommendation
ECCO, 2017; guideline[55]	UC	Over 8 yr	Lower risk: Neither intermediate nor high-risk features; intermediate risk: Extensive colitis with mild or moderate active inflammation; post-inflammatory polyps; CRC in a FDR older than 50 yr; higher risk: Extensive colitis with severe active inflammation; stricture or dysplasia in last 5 yr; PSC	Lower risk: 5 yr; intermediate risk: 2-3 yr; higher risk: 1 yr	High-definition endoscopy; chromoendoscopy with targeted biopsies
ECCO, 2019; guideline[60,61]	IBD	No specific recommendation	Same with BSG Guideline (2019)	Lower risk: 5 yr; intermediate risk: 2-3 yr; higher risk: 1 yr
JSG, 2020; Guideline[62]	IBD	8 yr	No specific recommendation		Targeted biopsies
NCCN, 2022; Guideline[63]	IBD	8 yr	Low risk: No active inflammation; high risk: Extensive colitis with active inflammation; dysplasia; PSC; family history of CRC younger than 50 yr	Low risk: 2-3 yr; high risk: 1 yr; HGD or piecemeal resection: 3-6 mo	High-definition white light endoscopy; colonoscopy with chromoendoscopy
NICE, 2022; guideline[64]	IBD	UC but not proctitis alone or CD involving more than one segment of the colon: 10 yr	Same with BSG guideline (2019)	Low risk: 5 yr; intermediate risk: 3 yr; high risk: 1 yr	Colonoscopy with chromoendoscopy
WGO, 2015; guideline[54]	IBD	8 yr	No specific recommendation		Magnification and chromoendoscopy

¹Personal history of dysplasia, primary sclerosing cholangitis (PSC).

²Prior colorectal cancer or dysplasia, PSC.

ACG: American College of Gastroenterology; AGA: American Gastroenterological Association; AOCC: Asian Organization for Crohn’s and Colitis; APAG: Asia Pacific Association of Gastroenterology; BSG: British Society of Gastroenterology; CCA: Cancer Council Australia; CD: Crohn’s disease; CRC: Colorectal cancer; CSG: Chinese Society of Gastroenterology; ECCO: European Crohn’s and Colitis Organization; FDR: First-degree relative; HGD: High-grade dysplasia; IBD: Inflammatory bowel disease; LGD: Low-grade dysplasia; JSG: Japanese Society of Gastroenterology; NCCN: National Comprehensive Cancer Network; NICE: National Institute for Health and Care Excellence; PSC: Primary sclerosing cholangitis; UC: Ulcerative colitis; WGO: World Gastroenterology Organization.

Table 2 Summary of guidelines and consensus statements reporting on surgical management in inflammatory bowel disease

Society	Disease type	Absolute indication (surgery is recommended)	Relative indication (surgery can be considered)
ACG, 2019; guideline[51]	UC	Dysplasia in UC is not resectable or is multifocal	Moderately to severely active UC who are refractory or intolerant to medical therapy
ACG, 2018; guideline[56]	CD	No statements are provided	Intra-abdominal abscess
AGA, 2021; expert consensus[52]	IBD	Unresectable visible dysplasia or invisible multifocal or high-grade dysplasia on histology	No statements are provided
AOCC and APAG, 2021; expert consensus[57]	IBD	No statements are provided
BSG, 2019; guideline[58]	UC	Patients with acute severe UC who have not responded within 7 d of rescue therapy with infliximab or ciclosporin, or those with deterioration or complications before that time (including toxic megacolon, severe hemorrhage or perforation): Subtotal colectomy and ileostomy, with preservation of the rectum; patients who have chronic active symptoms despite optimal medical therapy: Surgical resection of the colon and rectum
	CD	Localized ileocaecal CD for those failing or relapsing after initial medical therapy, or in those preferring surgery to the continuation of drug therapy: Lparoscopic resection; patients with small bowel CD strictures shorter than 10 cm: Strictureplasty/resection; patients with severe perianal CD refractory to medical therapy: Fecal stream diversion
ASCRS, 2020[71]; guideline	CD	Patients with severe acute colitis who do not adequately respond to medical therapy or who have signs or symptoms of impending or actual perforation; patients with a free perforation: surgical resection of the perforated segment	Patients who demonstrate an inadequate response to, develop complications from or are nonadherent with medical therapy; patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy and/or endoscopic dilation; patients with strictures of the colon that cannot be adequately surveyed endoscopically: Resection; patients with penetrating Crohn’s disease with abscess formation; patients with enteric fistulas that persist despite appropriate medical therapy
CSG 2018; Chinese consensus[53]	UC	Massive hemorrhage, perforation, malignancy, and high suspicion of malignant pathology	Severe UC that is refractory to active medical treatment, and toxic megacolon refractory to medical treatment should; undergo surgical intervention early; poor efficacy of medical treatment and/or adverse drug reactions that have seriously affected patients’ quality of life
	CD	CD complications1, ineffective medical treatment2	No statements are provided
ECCO, 2019; guideline[70]	UC	No statements are provided	Refractory and corticosteroid-dependent patients; patients with UC and a minimally affected rectum
ECCO, 2020; guideline[72]	CD	Patients with refractory pancolonic Crohn’s disease without a history of perianal disease: Restorative proctocolectomy with IPAA; patients with a single involved colonic segment in CD: Segmental colectomy; patients with limited, nonstructuring, ileocaecal CD (diseased terminal ileum < 40 cm): Laparoscopic resection; Small-bowel strictures related to CD: Strictureplasty; patients with short (< 5 cm) strictures of the terminal ileum in CD: Endoscopic balloon dilatation or surgery; patients with CD and complex perianal fistulae: Ligation of the intersphincteric fistula tract
JSG, 2020; guideline[62]	IBD	In severe cases of IBD and those with cancer or dysplasia; patients with symptoms caused by the primary disease that do not improve with medical treatment, side effects of medication, and extraintestinal complications (especially pyoderma gangrenosum)
WGO, 2015; guideline[54]	UC	Medical treatment is not completely successful or in the presence of dysplasia
	CD	Surgery should be considered as an alternative to medical treatment early in the disease course for short-segment CD limited to the distal ileum

¹Intestinal obstruction, abdominal abscess, fistula formation, acute perforation, major bleeding, carcinogenesis.

²Severe Crohn’s disease refractory to steroid therapy; patients with poor efficacy of medical treatment and/or adverse drug reactions that have seriously affected the quality of life.

IPAA: Ileal pouch-anal anastomosis; UC: Ulcerative colitis; IBD: Inflammatory bowel disease; CD: Crohn’s disease; ACG: American College of Gastroenterology; AGA: American Gastroenterological Association; AOCC: Asian Organization for Crohn’s and Colitis; BSG: British Society of Gastroenterology; CSG: Chinese Society of Gastroenterology; ECCO: European Crohn’s and Colitis Organization; JSG: Japanese Society of Gastroenterology; WGO: World Gastroenterology Organization.

Table 3 Summary of chemoprevention in colitis-associated colorectal cancer

Population	Agent	Efficacy of candidate chemopreventive drugs	Type of study
CAC[77]	5-ASA	Protective factors	Meta-analysis
CAC[78]	5-ASA	Protective factors	Meta-analysis
CAC[76]	Mesalamine; Sulfasalazine	Protective factors; No statistical effect	Meta-analysis
CAC[80]	5-ASA	No statistical effect	Meta-analysis
CAC[81]	Mesalamine	Protective factors	Case-control study
CAC[84]	5-ASA	Protective factors	Case-control study
GI cancer in IBD[91]	5-ASA	Protective factors	Cohort study
CAC[79]	5-ASA	Protective factors	Nested case-control study
CAC[87]	5-ASA	No statistical effect	A population-based study
CAC[85]	Thiopurines	Protective factors	Meta-analysis
CAC[83]	Thiopurines	No statistical effect	Meta-analysis
CAC[84]	Thiopurines	No statistical effect	Case-control study
Advanced neoplasia in IBD1[82]	Thiopurines	Protective factors	Cohort study
CRC[88]	Immunomodulators Anti-TNF-α agents	No statistical effect No statistical effect	Nested case-control study
CRC[92]	Folic acid	No statistical effect	Meta-analysis
CRC[93]	Folic acid	No statistical effect	Meta-analysis
CAC[94]	Non-aspirin NSAIDs	No statistical effect	Meta-analysis
CRC[95]	Vitamin D	No statistical effect	Meta-analysis
Colorectal adenomas[96]	Calcium intake as a food and dairy product	Significantly decrease	Meta-analysis
CRC[93]	Calcium	No statistical effect	Meta-analysis
CAC[97]	Statin	No statistical effect	Cohort study

¹Advanced neoplasia: including high-grade dysplasia and colorectal cancer.

ASA: Aminosalicylates; NSAIDs: Nonsteroidal anti-inflammatory drugs; CAC: Colitis-associated colorectal cancer; CRC: Colorectal cancer; IBD: Inflammatory bowel disease.