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

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


Background

Colorectal cancer (CRC) is one of the most serious complications of chronic colitis in patients with inflammatory bowel disease (IBD).[1]

Current strategies for risk reduction and management of colitis-associated CRC are chemoprophylaxis, colonoscopic surveillance of at-risk individuals, endoscopic removal of dysplastic lesions, and proctocolectomyA surgical procedure to remove the colon and rectum., which is a potentially curative treatment for those with precancerous dysplasia or early cancer.

Maintaining mucosal healing may reduce colorectal carcinogenesis. Chemoprophylaxis using mesalazine, thiopurines and ursodeoxycholic acid has also been proposed in the management of IBD with and without primary sclerosing cholangitis (PSC).

Observational data suggest colonoscopy is associated with a reduced risk of CRC and mortality in patients with IBD.[2] Guidelines based on case series suggest that IBD 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 proctocolectomyA surgical procedure to remove the colon and rectum..[4]
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Epidemiology

Since IBD was first recognised in 1925,[5] substantial variation in the incidence of CRC in patients with IBD 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 CRC.

Initial data suggested a difference in risk of CRC between those with ulcerative colitis (UC) 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 CRC in any patient with UC 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 CRC among patients with UC for the first, second and third decades were 1% (95% confidence intervalA measure that quantifies the uncertainty in measurement. When reported as 95% CI, it is the range of values within which we can be 95% sure that the true value for the whole population lies. [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 CRC in IBD patients in low-prevalence countries might be similar to that of Western countries. The incidence of CRC in patients with IBD may continue to fall with regular surveillance colonoscopy, improvements in imaging and adenoma detection and aggressive use of maintenance therapies to achieve mucosal healing.

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Pathological characteristics

Intraepithelial dysplasia (superficial to the lamina propria) is the premalignant lesion in IBD-associated CRC, and is classified as low grade or high grade according to histopathological features. The differentiation of low-grade dysplasia (LGD) from high-grade dysplasia (HGD) 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 CRC. For the most part, IBD-associated CRC is histologically similar to sporadic CRC, although it exhibits several different pathobiological features.

Colorectal cancer in IBD, like its sporadic counterpart, is most commonly adenocarcinomaA type of cancerous tumour that forms from glandular structures in epithelial tissue.. Dysplasia in IBD 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 CRC is lower for IBD patients than for sporadic CRC patients, and synchronous tumours have been historically reported more commonly in IBD, 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.

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Colorectal cancer and dysplasia risk

Modern IBD 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 ratioA comparison of the odds (probability) of something happening in one group with the odds of it happening in another. (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 IBD increases CRC risk.[7][11][12] The risk of CRC 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 CRC[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 IBD was associated with an increased risk of gastrointestinal cancers (hazard ratioA measure of how often a particular event happens in one group compared to how often it happens in another group, over time. 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 CRC risk seen in those with extensive colitis or pancolitis.[17] An Australian UC cohort study identified CRC 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 CRC in patients with IBD.

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

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

For patients with UC treated with proctocolectomyA surgical procedure to remove the colon and rectum. and ileal pouch-anal anastomosis, the risk of pouch cancer is very rare, questioning the need for selective surveillance.[28]
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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 (WLE) 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 proctocolectomyA surgical procedure to remove the colon and rectum., due to the high likelihood of missed synchronous invasive CRC 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 WLE.[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, PSC or foreshortened tubular colon).[32]

Ultimately, the primary goal of IBD management should be prevention of IBD 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]
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References

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