7Precancerous lesions in inflammatory bowel disease
Introduction
The development of colorectal cancer (CRC) poses the most serious long-term health risk faced by patients with chronic inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and colonic Crohn's disease (CD) [1], [2], [3]. Although CRC in the setting of IBD accounts for less than 0.5% of the total burden of CRC in the general population, its high relative incidence, especially among younger patients and those with longstanding extensive colitis, make its prevention one of the primary clinical goals in the long-term medical management of these patients.
The pathogenesis of CRC in IBD is a prototype of the ‘inflammation-dysplasia-cancer sequence’, a series of molecular alterations within the intestinal epithelium that is initiated and partially sustained by chronic inflammation, becomes expressed histopathologically as dysplasia, and culminates in invasive cancer [2], [4]. As the immediate precursor of CRC in IBD, dysplasia plays a central role both in our clinical efforts to reduce mortality from cancer and in our scientific understanding of its pathogenesis. These two aspects of dysplasia provide the broad themes of this review.
Section snippets
CRC risk in IBD
The magnitude of the risks of CRC incurred by patients with IBD has not been firmly established because of methodological variations among published studies. As a rule, risk estimates based on population-based studies have been more conservative than those based on referral populations and other groups. For example, a widely cited meta-analysis based on data pooled from studies of diverse design estimated the cumulative risk among patient with UC to be 2%, 8% and 18% at 10, 20 and 30 years from
Pathological features of dysplasia
Colorectal dysplasia, a term synonymous with intraepithelial neoplasia in the World Health Organization and Vienna nomenclature systems, is defined as an unequivocal neoplastic alteration of the intestinal epithelium that remains confined within the basement membrane in which it originated. As the earliest histologically recognizable precursor of CRC, a diagnosis of dysplasia serves both as the first clinical alert that neoplasia of the intestinal epithelium has been initiated and the most
Natural history of dysplasia and management implications
Successful surveillance requires an understanding of the natural history of dysplasia and of the uncertainties inherent in the relevant published data. Table 1 summarizes the classification of dysplasia, the likelihood that patients diagnosed with dysplasia will develop CRC based on published data, and the corresponding clinical implications. The broad variations within these data are related to procedural and analytical factors, discussed below, and to biological factors that are not
How should surveillance colonoscopy be performed?
The efficacy of endoscopic surveillance depends on a host of procedural and analytical factors including the frequency of colonoscopy, the techniques used for visualization and biopsy sampling, the number, distribution, quality and size of biopsy samples, the expertise and conscientiousness of the endoscopist and pathologist, and patient compliance [25]. The most appropriate protocol for performing surveillance colonoscopy has never been subjected to a randomized clinical trial, thus, different
Advances in the endoscopic detection of dysplasia
The success of endoscopy-based techniques for the detection of dysplasia in IBD is predicated on the direct, visual recognition of suspicious lesions by the gastroenterologist with subsequent biopsy for histologic confirmation. Recent advances in imaging techniques during colonoscopy have questioned the efficacy of current protocols that rely on random biopsies throughout the diseased colon and instead may allow for surveillance with improved efficacy based entirely on targeted biopsies.
The
Molecular pathogenesis of dysplasia in IBD
The role of sustained inflammation in the pathogenesis of neoplasia is a universal theme in human carcinogenesis and is especially relevant to the gastrointestinal tract [50], [51], [52], [53]. Clinically, compelling evidence for an association between colorectal neoplasia and inflammation in IBD comes from the heightened risks conferred by increased disease duration, increased colonic extent and severity of inflammation, as well as evidence that anti-inflammatory chemoprophylaxis may reduce
What is known
Subsets of patients with UC and CD, particularly those with extensive, longstanding disease or primary sclerosing cholangitis, incur substantially increased risks of developing CRC. CRC in this setting is the culmination of progressive molecular and morphological alterations encapsulated by the term inflammation-dysplasia-cancer sequence. The pathologic diagnosis of dysplasia in a patient with IBD provides the earliest clinical alert that this sequence is under way and is the most reliable
Conflict of interest statement
The authors declare that they have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) the content of this article.
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