Colonoscopic surveillance and management of dysplasia in inflammatory bowel disease (IBD): Introduction

From Cancer Guidelines Wiki
Clinical Practice Guidelines for Surveillance Colonoscopy > Colonoscopic surveillance and management of dysplasia in inflammatory bowel disease (IBD): Introduction


Background

ColorectalReferring to the large bowel, comprising the colon and rectum. cancer (CRCColorectal cancer) is one of the most serious complications of chronic colitis in patients with inflammatory bowel disease (IBDInflammatory bowel disease).[1]

Current strategies for risk reduction and management of colitis-associated CRCColorectal cancer are chemoprophylaxis, colonoscopic surveillance of at-risk individuals, endoscopic removal of dysplastic lesions, and proctocolectomy, which is a potentially curative treatment for those with precancerous dysplasia or early cancer.

Maintaining mucosal healing may reduce colorectal carcinogenesis. ChemoprophylaxisAdministration of a medication or drug to prevent disease. using mesalazine, thiopurines and ursodeoxycholic acid has also been proposed in the management of IBDInflammatory bowel disease with and without primary sclerosing cholangitis (PSCPrimary sclerosing cholangitis).

Observational data suggest colonoscopy is associated with a reduced risk of CRCColorectal cancer and mortality in patients with IBDInflammatory bowel disease.[2] Guidelines based on case series suggest that IBDInflammatory bowel disease surveillance may permit earlier detection of cancers and improve prognosis.[3] In Australia, there is increasing acceptance that improved endoscopic technologies have resulted in improved identification of dysplasia and have permitted resection of dysplastic lesions before resorting to proctocolectomy.[4]Back to top

Epidemiology

Since IBDInflammatory bowel disease was first recognised in 1925,[5] substantial variation in the incidence of CRCColorectal cancer in patients with IBDInflammatory bowel disease has been reported in the literature. This variation is thought to be due to referral centre bias, heterogeneity in study design and possibly also to environmental or geographical factors.[6] Furthermore, changes in the surveillance and management of dysplasia, including improved endoscopic technologies that enable earlier identification of pre-cancerous dysplasia, have undoubtedly affected both the reported rates and outcomes of dysplasia and CRCColorectal cancer.

Initial data suggested a difference in risk of CRCColorectal cancer between those with ulcerative colitis (UCUlcerative colitis) and Crohn’s disease, but it is now generally accepted that the risks are approximately equivalent, when patients are stratified according to the extent of colonic involvement.[7][8][9][10] A meta-analysis of 116 studies including 54,478 patients, reported the overall prevalence of CRCColorectal cancer in any patient with UCUlcerative colitis to be 3.7%, and an overall incidence of 3 cases per 1,000 person-years duration (PYD).[11] When stratified for disease duration, the incidence increased from 2 per 1000 PYD (cumulative probability 2%) for the first decade, to 7 per 1000 PYD (cumulative probability 8%) for the second decade, and 12 per 1000 PYD (cumulative probability 18%) for the third decade.

Another study from Australia reported that the cumulative incidences of CRCColorectal cancer among patients with UCUlcerative colitis for the first, second and third decades were 1% (95% confidence interval [CI]: 0–2), 3% (95% CI: 1–5) and 7% (95% CI: 4–10), respectively.[12] Similar findings have recently been described in a large Korean multicentre study[13] indicating that the cumulative incidence of CRCColorectal cancer in IBDInflammatory bowel disease patients in low-prevalence countries might be similar to that of Western countries. The incidence of CRCColorectal cancer in patients with IBDInflammatory bowel disease may continue to fall with regular surveillance colonoscopy, improvements in imaging and adenoma detection and aggressive use of maintenance therapies to achieve mucosal healing.

Back to top

Pathological characteristics

Intraepithelial dysplasia (superficial to the lamina propria) is the premalignant lesion in IBDInflammatory bowel disease-associated CRCColorectal cancer, and is classified as low grade or high grade according to histopathological features. The differentiation of low-grade dysplasia (LGDLow grade dysplasia) from high-grade dysplasia (HGDHigh grade dysplasia) is based on the degree and extent of nuclear stratification, haphazardness and loss of nuclear polarity, nuclear atypia, nucleolar size, nuclear clumping and presence of atypical mitotic figures.

Low-grade dysplasia needs to be differentiated from reactive changes due to inflammation. The presence of neoplastic invasion is diagnostic of CRCColorectal cancer. For the most part, IBDInflammatory bowel disease-associated CRCColorectal cancer is histologically similar to sporadic CRCColorectal cancer, although it exhibits several different pathobiological features.

ColorectalReferring to the large bowel, comprising the colon and rectum. cancer in IBDInflammatory bowel disease, like its sporadic counterpart, is most commonly adenocarcinoma. Dysplasia in IBDInflammatory bowel disease is typically multifocal, and variously described as flat, indistinct, ulcerated, plaque-like, nodular, velvety, stricturing or mass-like, whereas sporadic dysplasia is more classically unifocal and associated with discrete polyp formation.[10]

Lesions arise from currently or previously inflamed areas of the colon, but may occur in areas of microscopic inflammation rather than macroscopic involvement.[14] Being associated with chronic inflammation, colitis-associated dysplasia is most commonly located in the distal colon. The mean age at diagnosis of CRCColorectal cancer is lower for IBDInflammatory bowel disease patients than for sporadic CRCColorectal cancer patients, and synchronous tumours have been historically reported more commonly in IBDInflammatory bowel disease, occurring in up to 12%.[15] This finding might be explained by the subtlety of dysplastic lesions, but might also be partly accounted for by the failure of inferior, older generation colonoscopes to identify lesions.

Back to top

ColorectalReferring to the large bowel, comprising the colon and rectum. cancer and dysplasia risk

Modern IBDInflammatory bowel disease surveillance strategy is underpinned by risk stratification. Compared with healed mucosal inflammation, the presence of objective mucosal inflammation (endoscopic or histologic) is associated with a greater risk of subsequent colorectal dysplasia. A meta-analysis reported that the odds ratio (OR) for colorectal dysplasia was 3.5 (95% CI: 2.6–4.8) in those with any endoscopic mucosal inflammation and 2.6 (95% CI: 1.5–4.5) in those with histologic inflammation.[16]

Increased duration of IBDInflammatory bowel disease increases CRCColorectal cancer risk.[7][11][12] The risk of CRCColorectal cancer increases markedly after 10 years of disease duration in patients with extensive colitis, and somewhat later in those with limited left-sided colitis.

The age of onset might be an independent predictor for the development of CRCColorectal cancer[8], but this effect appears to be attenuated after adjusting for disease duration.[17] The commencement of surveillance is therefore calculated based upon disease duration, not patient age. Nevertheless, a nationwide cohort study showed that childhood-onset IBDInflammatory bowel disease was associated with an increased risk of gastrointestinal cancers (hazard ratio 18.0; 95% CI: 14.4–22.7).[18]

Greater extent of disease also equates to an increase in cumulative inflammatory insults, reflected in the corresponding increase in CRCColorectal cancer risk seen in those with extensive colitis or pancolitis.[17] An Australian UCUlcerative colitis cohort study identified CRCColorectal cancer in 24 patients, of whom 1 (1.6%) had proctitis, 8 (3.8%) had left-sided colitis, 12 (6.1%) had extensive colitis and 3 (8.8%) had an unknown extent of colitis at study entry.[12]

Evidence of chronic intestinal damage is also associated with the risk of developing colorectal neoplasia. Colonic strictures,[19][20][21] a foreshortened colon,[19] and pseudopolyps[19][22] represent healing of severe inflammation. These endoscopic features have been shown to be associated with a higher rate of CRCColorectal cancer in patients with IBDInflammatory bowel disease.

The risk of developing colitis-associated CRCColorectal cancer is increased in the presence of PSCPrimary sclerosing cholangitis. A meta-analysis of studies that compared the risk of CRCColorectal cancer in patients with UCUlcerative colitis with and without PSCPrimary sclerosing cholangitis[23] confirmed the CRCColorectal cancer risk to be 4.8-fold higher in patients with PSCPrimary sclerosing cholangitis. Australian data demonstrated a trend towards increased CRCColorectal cancer risk in the presence of PSCPrimary sclerosing cholangitis with IBDInflammatory bowel disease (6%), compared with PSCPrimary sclerosing cholangitis without IBDInflammatory bowel disease (0%, P=0.08).[24] Interestingly cancers associated with PSCPrimary sclerosing cholangitis and IBDInflammatory bowel disease tend to be located predominantly in the proximal colon (as distinct from UCUlcerative colitis patients without PSCPrimary sclerosing cholangitis).[25]The risk of CRCColorectal cancer remains elevated following orthotopic liver transplant and ongoing yearly surveillance is recommended.[23]

As with sporadic CRCColorectal cancer, a family history of CRCColorectal cancer is associated with a greater risk of developing dysplasia in patients with IBDInflammatory bowel disease. For patients with IBDInflammatory bowel disease and a first-degree relative with CRCColorectal cancer, the risk is at least two times baseline.[26][27]

For patients with UCUlcerative colitis treated with proctocolectomy and ileal pouch-anal anastomosis, the risk of pouch cancer is very rare, questioning the need for selective surveillance.[28]Back to top

Characterisation of lesions and implications for management

New consensus in the nomenclature used to describe dysplasia in IBDs has been developed. Modern descriptors classify lesions based on (i) the Paris classification of endoscopically-detected lesions and (ii) whether they are endoscopically resectable[29]

The use of high-definition white-light endoscopy (WLEWhite light endoscopy) and chromoendoscopy (see Advances in technique) has resulted in greater appreciation of flat and indistinct dysplastic lesions that were previously missed on standard-definition colonoscopy. The inability to visually identify subtle lesions in previous decades led to the approach of random biopsies every 10 cm in the colon in an attempt to identify dysplasia. The finding of dysplasia through random biopsies was often a late event signifying the presence of widespread multifocal dysplasia. As such, many of these patients were treated by proctocolectomy, due to the high likelihood of missed synchronous invasive CRCColorectal cancer or the risk of developing metachronous cancer.

The modern surveillance paradigm is to manage endoscopically-identified lesions by endoscopic removal where possible. High-quality colonoscopy and the use of high-definition colonoscopes are pre-requisites for identifying dysplasia, which is often subtle. When confirmed as dysplasia without invasion, such lesions can be dealt with by endoscopic resection or polypectomy withclose follow-up colonoscopic surveillance. ProctocolectomyA surgical procedure to remove the colon and rectum. is advised if there is evidence of invasion, if dysplastic lesions cannot be removed endoscopically, or if dysplasia is multifocal.

Individualisation of treatment is also important. The new surveillance paradigm accepts the move away from taking random biopsies towards targeted biopsies based on high-definition colonoscopy with other image-enhancement technologies. The most established image enhancement technology remains dye-spray chromoendoscopy, for which there is high-level evidence for superiority of yield of dysplasia compared with standard WLEWhite light endoscopy.[30]

Random biopsies typically have a low yield of dysplasia identification,[31] but are still advocated in those with a high risk of invisible dysplasia (those with prior dysplasia, PSCPrimary sclerosing cholangitis or foreshortened tubular colon).[32]

Ultimately, the primary goal of IBDInflammatory bowel disease management should be prevention of IBDInflammatory bowel disease dysplasia through improved medical management and achievement of mucosal healing. Achieving histological remission might be an emerging treatment paradigm in the prevention of dysplasia development.[33]Back to top

References

  1. Leong RW, Koo JH. Colorectal cancer in inflammatory bowel disease. J Gastroenterol Hepatol 2009 Apr;24(4):503-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19368629.
  2. Ananthakrishnan ANAdvanced neoplasia (advanced adenoma or colorectal cancer), Cagan A, Cai T, Gainer VS, Shaw SY, Churchill S, et al. Colonoscopy is associated with a reduced risk for colon cancer and mortality in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2015 Feb;13(2):322-329.e1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25041865.
  3. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017 Jun 1;11(6):649-670 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28158501.
  4. Leong RW, Perry J, Campbell B, Koo J, Turner IB, Corte C, et al. Knowledge and predictors of dysplasia surveillance performance in inflammatory bowel diseases in Australia. Gastrointest Endosc 2015 Oct;82(4):708-714.e4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26007222.
  5. Crohn B, Rosenberg H. The sigmoidoscopic picture of chronic ulcerative colitis (non- specific). Am J Med Sci 1925;170:220–8.
  6. Zisman TL, Rubin DT. Colorectal cancer and dysplasia in inflammatory bowel disease. World J Gastroenterol 2008 May 7;14(17):2662-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18461651.
  7. 7.07.1 Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology 2006 Apr;130(4):1039-46 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16618397.
  8. 8.08.1 Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 1990 Aug 11;336(8711):357-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1975343.
  9. Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 1994 Nov;35(11):1590-2 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7828978.
  10. 10.010.1 Choi PM, Zelig MPMalignant polyp. Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 1994 Jul;35(7):950-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8063223.
  11. 11.011.1 Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001 Apr;48(4):526-35 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11247898.
  12. 12.012.112.2 Selinger CP, Andrews JM, Titman A, Norton I, Jones DB, McDonald C, et al. Long-term follow-up reveals low incidence of colorectal cancer, but frequent need for resection, among Australian patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2014 Apr;12(4):644-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23707778.
  13. Kim BJ, Yang SK, Kim JS, Jeen YT, Choi H, Han DS, et al. Trends of ulcerative colitis-associated colorectal cancer in Korea: A KASID study. J Gastroenterol Hepatol 2009 Apr;24(4):667-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19378391.
  14. Mathy C, Schneider K, Chen YY, Varma M, Terdiman JP, Mahadevan U. Gross versus microscopic pancolitis and the occurrence of neoplasia in ulcerative colitis. Inflamm Bowel Dis 2003 Nov;9(6):351-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14671483.
  15. Itzkowitz SH. Inflammatory bowel disease and cancer. Gastroenterol Clin North Am 1997 Mar;26(1):129-39 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9119437.
  16. Flores BM, OʼConnor A, Moss AC. Impact of Mucosal Inflammation on Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: A Systematic Review and Meta-Analysis. Gastrointest Endosc 2017 Jul 24 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28750838.
  17. 17.017.1 Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990 Nov 1;323(18):1228-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2215606.
  18. Olén O, Askling J, Sachs MC, Frumento P, Neovius M, Smedby KE, et al. Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014. BMJ 2017 Sep 20;358:j3951 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28931512.
  19. 19.019.119.2 Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MAMetachronous adenoma, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut 2004 Dec;53(12):1813-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15542520.
  20. Reiser JR, Waye JD, Janowitz HD, Harpaz N. Adenocarcinoma in strictures of ulcerative colitis without antecedent dysplasia by colonoscopy. Am J Gastroenterol 1994 Jan;89(1):119-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8273779.
  21. Rutter M, Bernstein C, Matsumoto T, Kiesslich R, Neurath M. Endoscopic appearance of dysplasia in ulcerative colitis and the role of staining. Endoscopy 2004 Dec;36(12):1109-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15578305.
  22. Velayos FS, Loftus EV Jr, Jess T, Harmsen WS, Bida J, Zinsmeister AR, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology 2006 Jun;130(7):1941-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16762617.
  23. 23.023.1 Soetikno RM, Lin OS, Heidenreich PA, Young HS, Blackstone MO. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002 Jul;56(1):48-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12085034.
  24. Liu K, Wang R, Kariyawasam V, Wells M, Strasser SI, McCaughan G, et al. Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort. Liver Int 2017 Mar;37(3):442-448 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27891750.
  25. Claessen MM, Lutgens MW, van Buuren HR, Oldenburg B, Stokkers PC, van der Woude CJ, et al. More right-sided IBD-associated colorectal cancer in patients with primary sclerosing cholangitis. Inflamm Bowel Dis 2009 Sep;15(9):1331-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19229982.
  26. Nuako KW, Ahlquist DA, Mahoney DW, Schaid DJ, Siems DM, Lindor NM. Familial predisposition for colorectal cancer in chronic ulcerative colitis: a case-control study. Gastroenterology 1998 Nov;115(5):1079-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9797361.
  27. Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R, et al. Colorectal cancer rates among first-degree relatives of patients with inflammatory bowel disease: a population-based cohort study. Lancet 2001 Jan 27;357(9252):262-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11214128.
  28. Mark-Christensen A, Erichsen R, Brandsborg S, Rosenberg J, Qvist N, Thorlacius-Ussing O, et al. Long-term Risk of Cancer Following Ileal Pouch-anal Anastomosis for Ulcerative Colitis. J Crohns Colitis 2018 Jan 5;12(1):57-62 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28981638.
  29. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc 2003 Dec;58(6 Suppl):S3-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14652541.
  30. Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian V, Soetikno R, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology 2015 Mar;148(3):639-651.e28 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25702852.
  31. Leong RW, Ooi M, Corte C, Yau Y, Kermeen M, Katelaris PH, et al. Full-Spectrum Endoscopy Improves Surveillance for Dysplasia in Patients With Inflammatory Bowel Diseases. Gastroenterology 2017 May;152(6):1337-1344.e3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28126349.
  32. Moussata D, Allez M, Cazals-Hatem D, Treton X, Laharie D, Reimund JM, et al. Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy? Gut 2017 Jan 23 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28115492.
  33. Bryant RV, Winer S, Travis SPSerrated polyp, Riddell RH. Systematic review: histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative. J Crohns Colitis 2014 Dec;8(12):1582-97 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25267173.

Back to top