Keywords

Introduction

It has become well known that patients with longstanding inflammatory bowel disease (IBD) are at a high risk of developing colorectal cancer (CRC) since Crohn and Rosenburg [1, 2] in 1925 and Warren and Sommers [1, 2] in 1948 reported this in association with ulcerative colitis (UC) and Crohn’s disease (CD), respectively. However, the magnitude of this risk is still debatable; older literature [3] reports a rapid increase after 10 years of disease, whereas more recent studies show smaller risks [4, 5]. Overall, after 10 years of disease, cancer risk has been reported in the range of 0.5–1 % per year [3, 6–9]. A recent nationwide, population-based analysis from the Netherlands found that up to 20 % of all UC-related cancers were detected before 8 years of disease [10], and those authors recommended that screening should start earlier than previously recommended.

These variations in risk are poorly understood but may be due to improved control of the disease, implementation of surveillance programs, and early detection of neoplastic lesions complicating IBD [11]. Compared with non–colitis-associated CRC, cancers associated with colitis are more often multiple: two primaries occur in about 20 % of patients and three or more primaries are detected in about 10 % of patients [12]. These tumors tend to have a higher grade and more types of signet rings [13], often arising from flat mucosa instead of following the usual adenoma-cancer sequence. They also occur in younger age groups compared with sporadic cases of CRC [8]. Somewhat unexpectedly, approximately 11 % of colitis-associated tumors are composed of well-differentiated glands with minimal desmoplasia. This has been termed low-grade tubuloglandular adenocarcinoma and has been shown to develop from areas of low-grade dysplasia [14].

Cancers in the setting of IBD are believed to occur by a progression from no dysplasia to indefinite dysplasia through to low-grade dysplasia (LGD) and from high-grade dysplasia (HGD) to carcinoma. However, cancer can arise without going through all of these steps [15, 16]. Some studies have shown the development of node-positive CRC without intervening HGD and after dysplasia-free surveillance examinations less than a year before the appearance of the malignancy [17–19].

Survival of patients with colitis-associated cancer is roughly similar to that of those with sporadic cancer when compared by stage and histologic subtype. Similar to sporadic cancer, the most important prognostic factors of colitis-associated cancer are pathologic stage and grade [20, 21]. A recent study, published in abstract form, showed that in patients with longstanding UC, left LGD is more common and progresses more rapidly to advanced HGD and cancer than right LGD [22].

Risk Factors for the Development of CRC in IBD

Ulcerative Colitis

The two most important risk factors for cancer development are the duration and the extent of disease. It is important to define disease duration from the onset of symptoms and not from the date of establishment of the diagnosis [23, 24]. Eaden and colleagues [3] confirmed that CRC risk seems to increase 8–10 years after the onset of UC-related symptoms and that it subsequently increases in later decades of the disease. In their study, the cumulative incidence of CRC was 2 % at 10 years, 8 % at 20 years, and 18 % at 30 years. However, when reporting their 30-year results of surveillance of patients with UC, Rutter et al. [9] found the risk to be less – 2.5 % at 20 years, 7.6 % at 30 years, and 10.8 % at 40 years – and was constant for up to 40 years of colitis duration, suggesting that there is no need to intensify surveillance after this more limited follow-up.

Overall, the vast majority of studies show that the incidence is low at 10 years of disease and may actually be decreasing [3, 9, 11], so that the commencement of surveillance before 8 years of disease is not justifiable. Patients with extensive colitis have a 19-fold higher risk of cancer compared with the general population, whereas patients with left colitis have a 4-fold risk and those with proctitis alone have no increased risk [25, 26]. The majority of studies show insufficient evidence that backwash ileitis is a risk factor for CRC [27].

Primary sclerosing cholangitis (PSC) is a strong independent risk factor for CRC in patients with UC [28], and up to 25 % of patients with UC and PSC developed dysplasia compared with only 6 % of patients with only UC [29]. Importantly, studies have shown that this increased risk remains high even after liver transplantation for PSC [30]. The association is so high that even patients with PSC but without a known diagnosis of IBD are recommended to undergo a diagnostic colonoscopy with biopsies to determine if they have subclinical evidence of colitis [31].

A positive family history of CRC has been shown to be another risk factor, with a two-fold increase with such a family history, especially if a first-degree relative was diagnosed with CRC before the age of 50 years [32]. Younger age at diagnosis and early age of onset of disease are inconsistently reported risk factors for CRC in IBD. Thus the current recommendation is to perform surveillance in children as frequently as in adults, and this should be based on the duration of illness and not chronological age [3].

The severity of inflammation in patients with IBD (apart from PSC) has been demonstrated to impose an increased risk of dysplasia and CRC [33]. Histologic involvement, rather than the endoscopic (macroscopic) appearance of disease, is a better determinant of extent of disease with regard to evaluating cancer risk [27]. Macroscopic features of previous and ongoing inflammation (polyps, scarring, and strictures after inflammation) indicate increased risk, whereas a macroscopically normal colon carries a risk no higher than that of the general population [34]. The presence of pseudopolyps, which can be considered a marker of severe inflammation, has been associated with double the risk of CRC [33]. Strictures also are considered a risk factor for CRC in patients with IBD. Several studies have shown a higher than expected frequency of malignancy in patients with UC and strictures [35, 36] and has been reported in the range of 24–40 % of cases [37]. A study by Gumaste et al. [35] has shown that strictures that develop after 20 years of UC and that are located proximal to the splenic flexure and cause symptomatic large-bowel obstructions are associated with a higher risk of cancer They also showed that malignancy associated with these strictures seems to be more advanced.

Crohn’s Disease

Since Warren and Barwick [38] reported the first case of CRC in CD in 1983, significant evidence has shown that CD carries an increased risk of both small- and large-bowel carcinomas, and there is a cumulative risk of CRC of 2.9 % at 10 years [39]. The extent of colitis also is an important factor; patients who have extensive CD are at greatest risk [40]. Ribeiro et al. [41] found that approximately 87 % of CRC in patients with CD occurred after 20 years’ duration. Despite the limited data, it seems that the risk of malignancy in colonic CD only becomes significant after 8–10 years, similar to that observed with UC [23]. Gillen et al. [39] have shown that the frequency of CRC in patients with CD and UC are nearly identical – 8 and 7 %, respectively – after 20 years. They also showed (similar to other studies) an 18-fold increase in the risk of development of CRC in patients with extensive Crohn’s colitis compared with a 19-fold increase in risk in those with extensive ulcerative colitis [42].

Some studies have shown that the relative risk of CRC in patients with CD was even greater in those who were younger than 30 years of age at the time of diagnosis [43]. Furthermore there is evidence that the presence of colonic Crohn’s strictures increases the risk of CRC development [44, 45], so a biopsy is essential for its exclusion. There also have been reports of cancer arising in an excluded strictured segment in CD, although these types of bypass operations are now rarely performed [46].

Dysplasia

Definition and Classification

Dysplasia is a histological diagnosis and is defined as an unequivocal neoplastic change that is intraepithelial and within the confines of the glandular basement membrane [47]. Dysplasia is considered to be a precursor of and a marker for coexisting CRC in patients with IBD [17]. It is present in more than 90 % of UC cases with carcinoma and occurs in any part of the colon, often near the cancer [15]. Dysplasia adjacent to colorectal carcinoma has been reported in between 83 and 100 % of patients with CD; in contrast, only 2 % of colectomy specimens from patients with CD without carcinoma contained mild dysplasia [18, 38]. In a landmark 1983 article, Riddell et al. [47] established a standardized classification for dysplasia (Table 19.1), dividing it into HGD, LGD, and indefinite for dysplasia (IND) on the basis of the histological appearance of the epithelial cells and their nuclei (Fig. 19.1).

Table 19.1 Classification of dysplasia [47]
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Fig. 19.1
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(a) Low grade dysplasia with uniform, elongated, crowded, basally located nuclei and a few mucin vacuoles. (b) High-grade dysplasia with marked nuclear stratification, loss of cellular polarity, and abundant mitoses. (c, d) Low-grade tubuloglandular adenocarcinoma with well-differentiated adenocarcinoma (d) arising from low-grade dysplasia (c). The invasive glands show minimal atypia with little or no desmoplasia

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  1. 1.

    LGD (see Fig. 19.1a) is a lesion characterized by crowded glands that vary slightly in size, similar to colonic tubular adenomas. These glands are populated by dysplastic cells with large, spindle-shaped, basally orientated hyperchromatic nuclei. There is little or no inflammation.

  2. 2.

    HGD (see Fig. 19.1b) is associated with major architectural abnormalities of the glands, which are lined by large vesicular stratified nuclei, prominent nucleoli with or without loss of orientation, and abnormal mitoses. There is little or no inflammation.

The original classification of dysplasia created by Riddell et al. remains essentially unchanged. In 2000, a group of gastrointestinal pathologists from Europe, Japan, and North America gathered in Vienna, Austria, to propose a new classification to bridge the gap between the terminologies used by these various groups (Table 19.2) [49, 50]. However, there are no important differences between the original classification and that created in 2000 with regard to patient management, and we recommend using both systems when needed.

Table 19.2 The Vienna classification of gastrointestinal neoplasia [48]
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When IND is detected during initial colonoscopy, progression to advanced neoplasia occurs in approximately 13–26 % of cases [9, 17]. In a study from Mount Sinai Hospital in New York, the 5-year rate of progression to either HGD or CRC was 1.1, 9, and 45 %, respectively, in patients who initially had no dysplasia, a status of IND, and a status of LGD [51]. A review of ten prospective studies reported that when LGD was found during initial surveillance colonoscopy, HGD or CRC developed in up to 29 % of patients [17].

Interobserver Variation in the Interpretation of Dysplasia

There is a significant degree of inter- and intraobserver variability in the histological diagnosis of dysplasia. Collins et al. [52] found that agreement is best when identifying HGD but is less accurate for IND and LGD. This is, in part, due to variation in the understanding of the term indefinite for dysplasia, a label usually given to specimens that are inadequate in size or orientation or when there is severe inflammation and secondary reactive change [24]. In this regard, less experienced pathologists tend to use IND more than experienced pathologists. Nevertheless, even amongst experts, variation occurs and overall agreement is less than optimal [53]. This has led to the recommendation that two pathologists, one of whom is an experienced gastrointestinal pathologist, should report these cases of dysplasia by consensus [54].

Recently, the positive presence of alpha-methylacyl-­coenzyme A racemase, a peptide expressed in a high proportion of prostatic intraepithelial neoplasia and prostatic carcinomas, has not been expressed in any UC foci that are considered negative for dysplasia, but it has been shown to be significantly increased in foci of LGD (96 %), HGD (80 %), and adenocarcinoma (71 %) [55]. This immunostain has been used as an adjunct in difficult cases.

Number of Biopsies Required to Detect Dysplasia

A second controversial point is the number of biopsies required for an accurate diagnosis or exclusion of dysplasia. Itzkowitz and Harpaz [15] commented that a typical biopsy samples less that 0.05 % of the total colonic surface area. It is, therefore, universally accepted that a considerable number of biopsies should be taken, but there is wide variation in current practice. Rubin et al. [56] showed that at least 33 biopsies are required to detect dysplasia with 90 % accuracy and that 64 biopsies would be required to increase this accuracy to 95 %. The Crohn’s and Colitis Foundation of America [23], the American College of Gastroenterology [57], and the British Society of Gastroenterology [58] all differ in their recommendations of the exact number of biopsies needed for accurate detection of dysplasia and the technique required to obtain this. However, in practice, the number of biopsies taken is often less than that indicated in any of the recommended guidelines [59, 60]. The practical recommendation is to take four random biopsies every 10 cm along the colon, and extra biopsies should be obtained from any strictured or abnormal areas. In patients with UC, it is recommended that four-quadrant biopsies be taken every 5 cm in the distal sigmoid colon and the rectum [23, 58]. Full colonoscopy is necessary because approximately one third of UC-associated CRC develops in the proximal colon [27, 61].

New Endoscopic Techniques in the Detection of Dysplasia

Improving the detection of dysplastic lesions in patients with IBD should reduce sampling errors during colonoscopy, thereby improving overall efficiency. This can be enhanced by targeted rather than random colonic biopsies [27]. Two such developments are spraying dye in the mucosa (chromoendoscopy) and the use of a high-resolution colonoscope. Chromoendoscopy detects a significantly higher number of neoplastic lesions [62, 63] but does not significantly increase examination performance time. The new guidelines of the British Society of Gastroenterology [61] recommend that pancolonic dye spraying be adopted by endoscopists as the technique of choice. If chromoendoscopy is not used, the strategy outlined in the 2002 guidelines should be followed (namely, two to four random biopsies from every 10 cm along the colon) [58, 61]. The use of chromoendoscopy by appropriately trained endoscopists was formally endorsed by the American Gastroenterological Association [27]. With chromoendoscopy, the crypt architecture can be categorized by evaluation of the pit pattern, which facilitates differentiation between neoplastic and nonneoplastic changes and enables the performance of targeted biopsies [27]. Moreover, chromoendoscopy has been shown to provide a more accurate evaluation of the extent of disease and the degree of inflammatory activity [63].

Another promising area is the use of confocal laser endomicroscopy, which permits in vivo histology during endoscopy and, when combined with chromoendoscopy, significantly decreases the number of biopsies required for cancer surveillance in patients with UC, providing a fourfold higher diagnostic yield compared with white-light ­endoscopy used for random biopsies [64].

Molecular Pathology of CRC in IBD

A number of differences exist between the molecular pathology of sporadic and colitis-associated CRC. Loss of function of the adenomatous polyposis coli gene is a common and early event in sporadic CRC, but it is much less frequent in UC and usually occurs late in the dysplasia-carcinoma sequence of colitis-related CRC [15]. In contrast, p53 mutations arise late in sporadic CRC, whereas in IBD they occur early and seem to play an important role. In this respect, Burmer et al. [64] found that p53 loss of heterozygosity correlates with malignant transformation and occurs in 9 % of biopsy specimens of those cases labeled as IND, 33 % with LGD, 63 % with HGD, and 85 % with CRC [65]. Mutations of the DPC4 and K-ras genes are common events in sporadic CRC but are infrequent in patients with IBD and cancer [66, 67]. Finally, Schulmann et al. [68] found that the frequency and profiles of high-level microsatellite mutations differ significantly between sporadic and colitic CRC. It is anticipated that these molecular biologic characteristics will provide new profiles for risk categorization in IBD-related CRC and will ­continue to be a principal area of future research [69].

Management of Dysplasia

The management of patients with dysplasia (Fig. 19.2) has been the subject of a controversial debate for many years. Dysplasia is grossly divided into flat (endoscopically undetectable) or raised (endoscopically detectable). For patients who test negative for dysplasia, regular follow-up and endoscopic surveillance should continue per national guidelines. In cases of IND due to inflammation, patients should undergo treatment for colitis, allowing the inflammation to subside before biopsy is repeated. If there is still a nuclear abnormality, then changing the diagnosis to flat LGD is warranted. If the grade remains classified as IND, then closer follow-up and repeat biopsies should be performed.

Fig. 19.2
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The management of dysplasia in patients with irritable bowel disease (IBD). LGD low-grade dysplasia, HGD high-grade dysplasia, DALM dysplasia-associated lesion or mass. (Modified from reference [24])

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Flat Dysplasia

The management of flat LGD is controversial. A number of studies have reported a 50 % rate of progression from LGD to HGD or CRC over 5 years [19, 53, 70]. In patients who have undergone urgent colectomy for LGD, coexisting CRC has been found in 16–34 % of specimens [17, 70]. In this regard, Ullman and colleagues [70] found the rate of progression to be independent of focality because unifocal and multifocal flat LGD progressed at similar rates. This group also reported that the presence of flat LGD was a “powerful predictor of advanced neoplasia” and that continued surveillance as opposed to immediate colectomy was “at best a risky strategy.” The 30-year experience of St. Mark’s Hospital, London, also found similar results: coexisting CRC was found in 20 % of patients with LGD who were undergoing colectomy, and 39.1 % of patients with LGD progressed to HGD or CRC during follow-up [9].

However, there are other schools of thought concerning this issue. Lim et al. [71] showed that only 10 % of patients with LGD developed HGD or CRC compared with 4 % of patients with UC without dysplasia after 10 years of follow-up. They concluded that the diagnosis of LGD is insufficient to justify colectomy. Similar findings have been reported by Befrits and colleagues [72]. We approach these cases through discussion during multidisciplinary team meetings involving gastroenterologists, pathologists, and colorectal surgeons; a combined decision should be made and patients should be informed about the possibility or probability of negative colectomy and the potential morbidity and complications associated with surgical treatment versus a wait-and-see ­policy. If colectomy is not performed, then close endoscopic and clinical follow-up should be continued [24].

There is little controversy surrounding flat HGD because there is concurrent CRC in 42–45.5 % of colectomy specimens from these patients [9, 17, 73]. Therefore, there is a general agreement that the presence of HGD warrants prompt colectomy. LGD in a mass lesion [74] that does not resemble a typical sporadic adenoma and cannot be resected endoscopically, or a stricture that is symptomatic or is not passable during colonoscopy [35, 36, 75], especially in longstanding disease, often is indicative of coexistent colon cancer, necessitating a colectomy.

A recent publication in the pathology literature identified low-grade tubuloglandular adenocarcinoma (see Fig. 19.1c, d) as a finding responsible for 11 % of IBD-associated adenocarcinomas, and superficial LGD was associated with underlying invasive adenocarcinoma [14]. This finding has reinforced the recommendation of colectomy for patients with LGD. A study by Rodriguez et al. [73] showed that 60 % of gastroenterologists in the US did not recommend immediate colectomy for a confirmed finding of LGD but rather favored continued and closer surveillance [27]. Interestingly, recent work by Siegel and colleagues [76] has shown that almost all patients who responded to questionnaires in the study recognized that UC raises their chance of getting colon cancer. In this study, 60 % of patients would refuse a physician’s recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20 % risk of having cancer at the time. On average, these patients would agree to colectomy only if their risk of colon cancer at that time were at least 73 %.

Epithelial regeneration and repair, especially in the setting of active inflammation, may result in atypia, which can be difficult to distinguish from true dysplasia. These cases are classified as IND [77]. Patients whose biopsy specimens are IND are a poorly studied group of patients with IBD. In a 1991 report by Nugent et al. [78], 20 patients with biopsies considered “indefinite” were followed for an unspecified length of time. Three subjects developed HGD, one of whom was discovered to have an adenocarcinoma at the time of colectomy.

Raised Dysplasia

Any raised lesion within an area affected by colitis is referred to as a dysplasia-associated lesion or mass (DALM); this first was described in 1981 by Blackstone et al. [74]. In their original report, a high incidence of CRC in these lesions was found. Other studies showed the rates of CRC in the presence of DALMs to be between 31 and 65 % [9, 17, 52]. As a result, initially the presence of a DALM posed a high risk for either concurrent CRC or progression to CRC, and colectomy was strongly recommended. In recent years, studies have demonstrated that not all polypoid lesions in patients with IBD necessitate radical treatment in the form of colectomy. Separation of DALM from sporadic adenoma posed another problem because the former required colectomy whereas the latter can be managed adequately with polypectomy and subsequent surveillance [79].

Studies have evaluated the value of immunohistochemistry in separating DALM from sporadic adenoma. Neither histological appearance nor immunohistochemistry has been shown to be useful in clinical practice. These differences are now of no clinical value in the treatment of patients harboring these lesions. Recent evidence shows that dysplastic masses detected outside of an area of colitis may be reliably diagnosed as sporadic adenomas and treated as such [80, 81].

Recent studies have shown that DALM can be classified grossly into those that endoscopically resemble sporadic adenomas – and hence are called adenoma-like DALMs (ALMs) – and those that do not look like adenoma and hence are labeled non-adenoma-like DALMs (NALDs) [82–84]. ALM endoscopically appears as a well-circumscribed, smooth or papillary, nonnecrotic, sessile or pedunculated polyp [82, 85], whereas NALD lesions appear as velvety patches, plaques, irregular bumps or nodules, or stricturing lesions that are not amenable to endoscopic resection [86]. Recent reports [82, 83] have shown that ALM lesions can be treated safely with endoscopic excision, provided that they are completely excised and that multiple biopsies are taken from the base of the stalk and the adjacent flat mucosa after excision, each of which must show no evidence of dysplasia. If such endoscopic excision is performed, close follow-up surveillance should be carried out in case further dysplastic lesions develop. This is supported by the fact that there were no significant differences in the incidence of polyp formation during follow-up after the initial resection between patients with UC and an ALM (62.5 %) and patients with UC and a known sporadic adenoma (50 %) or between either of these two UC patient subgroups and a control group of patients with no UC sporadic adenoma (49 %) [84].

It is important to realize, however, that the differentiation of ALM, NALD, and inflammatory polyps should be done endoscopically, and this can be a challenging task. A recent article from Farraye et al. [87] showed conclusively that even expert gastroenterologists have difficulty differentiating these polyps. It is also worth noting that Rutter et al. [33], while looking retrospectively at the cases from St. Mark’s Hospital, found that most dysplasia was raised and fell into the ALM category. In this regard, this same group evaluated 56 patients with UC who developed dysplasia (either flat or raised) in the course of a 14-year surveillance program conducted at St Mark’s Hospital in London [86]. Here, a total of 110 neoplastic areas were detected in the 56 patients, of which 77.3 % were visible during colonoscopy. More specifically, 74 of the visible lesions (87 %) were “polypoid” (adenoma-like), four were described as having an “irregular” outline, and one was described as a “plaque.” In addition, six were described as macroscopic cancers. There is high association of cancer, ranging from 38 to 83 %, with NALDs that are considered to be endoscopically unresectable. For this reason, it is recommended that patients with UC and an endoscopically unresectable NALD should undergo a colectomy, regardless of the grade of dysplasia detected on biopsy analysis [88]. These recommendations apply to patients with UC regardless of their age or duration and the extent of their colitis [82, 88]. Although a scar may be detectable after colonoscopic resection, it is advisable to tattoo the mucosa adjacent to any suspicious lesion that is resected endoscopically for ease of future identification. From a practical ­perspective, the important issue is to determine whether the lesion is completely resectable endoscopically without adjacent dysplasia and whether the rest of the colon is also free of dysplasia.

Surveillance in Patients With IBD

Because cancer develops through a chronic inflammation-dysplasia-cancer pathway in IBD, patients begin a surveillance program to detect dysplasia before the development of cancer [31]. The practice of surveillance, however, varies widely. In a recent questionnaire-based study by Rodriguez et al. [73], nearly 80 % of the responding physicians stated that they begin surveillance colonoscopy at 8–10 years of disease duration for patients with pancolitis and 54 % reported sending at least 31 biopsies. However, in a study from the Netherlands, surveillance was started correctly in patients with pancolitis by 53 % of respondents and in cases of left-sided colitis by 44 % of the gastroenterologists, and fewer than 30 biopsies per colonoscopy were taken by 73 % of the respondents [89]. Patient compliance with the surveillance program is also a problematic clinical issue and a confounding variable. Patients must be counseled about the risk of developing CRC and about the risk of developing cancer if they drop out of the surveillance program. They also should be informed that cancer may develop without previous ­detection of dysplasia [15].

Evidence for Surveillance in Ulcerative Colitis

Morson and Pang reported the coexistence of cancer in colectomy specimens in five of nine patients with UC who already had received diagnoses of HGD from previous preoperative rectal biopsies [90]. This led to the development of surveillance programs using multiple biopsies to detect dysplasia. St. Mark’s Hospital was the first in the world to instigate such a colonoscopic surveillance program in patients with UC [91]. Since then, the practice of surveillance has become widely adopted, although the evidence of its benefits is still somewhat limited. Rutter et al. [9] reported a 30-year experience involving 600 patients with longstanding, extensive UC, and they concluded that their study “shows that colitis surveillance can be effective.” At present, no randomized studies have documented a reduction in the risk of developing, or dying from, CRC through the systematic use of surveillance colonoscopy. Limited evidence is available from studies examining the effectiveness of surveillance versus no surveillance, largely because of ethical issues given the available interpretable data.

In a Cochrane analysis of three studies [92–94], 8 of 110 patients in the surveillance group died of CRC ­compared with 13 of 117 patients in the nonsurveillance group [95]. The Cochrane analysis concluded the following: There is evidence that cancers tend to be detected at an earlier stage in patients who are undergoing surveillance and these patients have a correspondingly better prognosis, … There is indirect evidence that surveillance is likely to be effective in reducing the risk of death from IBD-associated cancer.” A fourth recent study by Lutgens et al. [96] showed a significant difference in 5-year cancer-related mortality rates in people undergoing surveillance compared with a no surveillance policy.

Evidence for Surveillance in Crohn’s Disease

There are few data about the effectiveness of surveillance in Crohn’s colitis. One study that followed 259 patients with extensive Crohn’s colitis (affecting at least one third of the colon) found that 7 % of patients had dysplasia or cancer upon screening colonoscopy, and an additional 14 % had dysplasia or cancer found during surveillance examinations [97]. In another study by Friedman and colleagues [98], the cumulative probability of detecting dysplasia or cancer in patients with Crohn’s colitis after a negative initial screening colonoscopy was 22 % by the time of the third follow-up colonoscopy. Despite the lack of data, surveillance colonoscopy is currently considered the standard of care, and patients with Crohn’s colitis should undergo a surveillance schedule similar to patients with UC. The new guidelines from the American Gastroenterology Association and the British Society of Gastroenterology states that, “Despite the lack of randomized controlled trials, surveillance colonoscopy is recommended in patients with IBD at increased risk for developing CRC.” Patients with extensive UC and CD of the colon are most likely to benefit from such a surveillance ­program [27, 61].

Evidence for Surveillance in Patients With an Ileal Anal Pouch

Restorative proctocolectomy was first described in 1978 [99]. Since then, ileal pouch anal anastomosis has become the procedure of choice for patients with UC who require surgery. Dysplasia in this context is rare but can develop in either the pouch ileal mucosa or in any retained anorectal mucosa [61]. In two large series involving 2,415 patients [100, 101], neoplastic change within the pouch was not reported. Although rare, it has become apparent that neoplastic transformation does occur, and there seem to be several risk factors that include dysplasia or colorectal cancer at the time of pouch surgery and associated primary ­sclerosing cholangitis [102, 103]. Practically all cases of dysplasia occur in areas of persistent atrophy with severe inflammation of the ileal mucosa (so-called type C mucosa) [104]. The recent British Society of Gastroenterology guidelines [61] state that, “There is no clear evidence that pouch surveillance is beneficial and thus it cannot be strongly recommended. However, if a clinician wishes to offer surveillance, a policy of annual pouch surveillance by flexible sigmoidoscopy, taking four proximal and four distal pouch biopsies, would seem reasonable.” The occurrence of neoplasia is extremely rare if there is no colorectal cancer at the time of the proctocolectomy and if no other risk factors are present [105]. No data currently exist about whether to survey such patients, but it may be reasonable to perform surveillance by flexible sigmoidoscopy every 5 years.

Conclusion: How Should Surveillance Colonoscopy Be Conducted?

In 2010, both the American Gastroenterology Association and the British Society of Gastroenterology [27, 61] published their new guidelines regarding surveillance of patients with IBD. Stratification of these patients by risk factors is becoming increasingly important, and the recent surveillance guidelines adopt this approach. Both guidelines state that patients with proctitis are not at increased risk for IBD-related CRC and thus may be managed on the basis of average-risk recommendations. All other patients should undergo a screening colonoscopy 8–10 years after the onset of symptoms, with multiple biopsies throughout the colon to assess the true microscopic extent of disease. When performing surveillance colonoscopy, the most proximal extent of disease detected histologically at any point in time should define the true extent of the patient’s disease. Ideally, biopsies of each anatomic segment should be submitted in a separate specimen container to avoid confusion regarding the location of a dysplastic area that might need to be monitored. Both guidelines recommend that surveillance be performed when the patient is in clinical remission; however, if remission cannot be obtained, surveillance should not be delayed.

The American Gastroenterology Association recommends that patients with extensive or left colitis and a negative screening colonoscopy should begin regular surveillance colonoscopy within 1–2 years. With a negative surveillance colonoscopy, subsequent surveillance examinations should be performed every 1–2 years. With two negative examinations, the next surveillance examination may be performed in 1–3 years until UC has been present for 20 years, then subsequent examinations should be performed every 1–2 years. Both guidelines state that patients with PSC should begin surveillance colonoscopy at the time of their initial diagnosis and then yearly thereafter. The use of chromoendoscopy by appropriately trained endoscopists was endorsed by the new British Society of Gastroenterology guidelines. Patients with CD and major colonic involvement (with a minimum of one third of the colon involved) who have experienced at least 8–10 years of disease from the onset of symptoms should undergo screening colonoscopy followed by the same protocol as that used for patients with UC.

The new British Society of Gastroenterology guidelines implement changes to the surveillance intervals that account for patient risk factors, and these are summarized in Fig. 19.3. Pancolonic dye spraying with targeted biopsy of abnormal areas is recommended, and when this is not feasible, random biopsies (two to four biopsies every 10 cm along the colon) should be performed. In the new guidelines, extensive colitis is defined as UC extending proximal to the splenic flexure or Crohn’s colitis affecting at least 50 % of the surface area of the colon according to the Montreal classification [106].

Fig. 19.3
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Surveillance guidelines in patients with irritable bowel disease (IBD). UC ulcerative colitis, CD Crohn’s disease, CRC colorectal cancer, PSC primary sclerosing cholangitis. (Modified from reference [61])

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