The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.

Disclosures: Mark A Peppercorn, MD Nothing to disclose. Robert D Odze, MD, FRCPC Nothing to disclose. Paul Rutgeerts, MD, PhD, FRCP Grant/Research Support: Centocor; Merck; UCB; Abbott (IBD treatment). Consultant: Centocor; Merck; UCB; Abbott; Millennium/Takeda; Genentech/Hoffman LaRoche; Neovacs: Merck/Serono; Bristol Myers Squibb; Robarts; Tillotts; Pfizer; Falk Pharma; Galapagos (IBD treatment). Speaker's Bureau: Centocor; Merck; UCB; Abbott (IBD treatment). Shilpa Grover, MD, MPH Employee of UpToDate, Inc.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2014. | This topic last updated: Jul 22, 2014.

INTRODUCTION — Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer [1-9]. The risk is related to the duration and anatomic extent of the disease. The mortality in patients diagnosed with colorectal cancer in the setting of IBD is higher than for sporadic colorectal cancer [7].

Although no large controlled trials have proven that surveillance reduces mortality, surveillance is recommended by the American Gastroenterological Association (AGA) [9-11], the American College of Gastroenterology (ACG) [12], the American Society for Gastrointestinal Endoscopy (ASGE) [13], and the British Society of Gastroenterology [14,15].

The epidemiology and pathology of colon cancer in IBD and the evidence supporting a role for cancer surveillance will be reviewed here. Newer techniques for cancer surveillance will also be discussed, although there is insufficient evidence to support their widespread use. The definition, risk factors, clinical manifestations, diagnosis, and management of IBD are discussed separately. (See "Definition, epidemiology, and risk factors in inflammatory bowel disease" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults" and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults" and "Overview of the medical management of mild to moderate Crohn disease in adults" and "Management of severe ulcerative colitis" and "Surgical management of ulcerative colitis".)

EPIDEMIOLOGY — The risk of colorectal cancer (CRC) is increased in ulcerative colitis (UC) and Crohn disease (CD). However, much more is known about the risk in UC. A population-based study from Sweden estimated that the overall risk of colorectal cancer in inflammatory bowel disease (IBD) was 95 cases per 100,000 population [16]. The risk of colorectal cancer in patients with UC appears to have decreased over time but it is unclear if this is due to improved medical therapy and dysplasia surveillance [16,17]. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors".)

It is also unclear if there is a gender difference in the risk for colorectal cancer. In a population-based study of more than 7000 patients with IBD, males had a 60 percent higher risk of CRC than females (cumulative incidence 40 years after diagnosis, 8 versus 3 percent, respectively) [18]. The effect of sex was seen only after ten years of follow-up and limited to patients diagnosed before age 45. This gender difference may be explained by differences in the extent of inflammation, or by factors related to patient behaviors leading to differences in medication or surveillance exposure [19].

Ulcerative colitis — The risk of CRC in UC depends upon the duration and extent of disease [1-3,17,20-23]. In an observational study in which 19,486 patients with IBD were followed for a median duration of 35 months, patients with longstanding and extensive colitis (LEC), defined as colitis for >10 years and involving ≥50 percent of the colon, had an increased risk of CRC as compared with the general population (standardized incidence ratio [SIR] 7.0, 95% CI 4.4-10.5). In contrast, the risk of CRC in IBD patients without LEC was not significantly elevated as compared with the general population (SIR 1.1, 95% CI 0.6-1.8). Patients with UC complicating primary sclerosing cholangitis (PSC) may be at increased risk for CRC compared to those without PSC [17].

A case-control study (in which cases and controls were matched for the extent and duration of disease) found that the risk of CRC was reduced with use of anti-inflammatory agents (including aspirin, nonsteroidal anti-inflammatory drugs, and 5-aminosalicylic acid agents) and by surveillance colonoscopy while it was increased in patients with a history of postinflammatory pseudopolyps [24]. While some studies have suggested that thiopurine use may decrease the risk of CRC, there are insufficient data to recommend thiopurines for chemoprevention in patients with IBD [9,23,25,26].

Pancolitis — Patients with disease extending to the hepatic flexure or more proximally have the greatest risk of CRC. Compared to an age-matched population, the risk begins to increase eight to 10 years following the onset of symptoms [27-29]. The approximate cumulative incidence of CRC is 5 to 10 percent after 20 years and 12 to 20 percent after 30 years of disease [4,27,30-32]. Lower rates of CRC have also been found [33,34]. In a population-based study from Copenhagen, the risk of CRC was not different from the general population, a finding that the authors hypothesize may have been due to an active surgical approach in medical treatment failures and long-term use of 5-ASA drugs [34]. The highest cancer risks have been reported by medical centers that predominantly receive referral patients who may have more severe or longstanding disease [20].

In one series, the absolute risk of CRC in patients with pancolitis was 30 percent after 35 years of disease [4]. The risk was increased in those with the onset of symptoms prior to age 15. However, in other reports, the age of onset of colitis did not increase the risk of CRC after adjusting for the longer period of time that young patients were at risk and the extent of the disease [8].

One study suggested that the presence of "backwash ileitis" (in which mucosal inflammation involves the terminal ileum) may be an independent risk factor for CRC [35]. However, other studies have not confirmed this association [36,37]. (See "Endoscopic diagnosis of inflammatory bowel disease", section on 'Backwash ileitis'.)

The severity of inflammation may also be an important marker of risk. A case-control study found a significant correlation between the severity of inflammation as assessed by histology and the risk of colorectal neoplasia (OR 4.7) [36]. A similar degree of risk was found in a later cohort study [38].

Left-sided colitis — Most studies have found that the risk of CRC increases after 15 to 20 years (approximately one decade later than in pancolitis) in patients with colitis confined to the left colon (ie, distal to the splenic flexure) [39]. However, rates of CRC and dysplasia similar to those seen in patients with pancolitis have been described [40].

Proctitis — Patients with ulcerative proctitis and proctosigmoiditis are probably not at increased risk for CRC [41].

Ileal pouch anal anastomosis — The incidence of CRC in patients with IBD who have undergone restorative proctocolectomy with an ileal pouch anal anastomosis (IPAA) is low [42]. In a case-control study that included 1200 patients with IBD (1053 with UC, 46 with Crohn disease, and 101 with indeterminate colitis) and IPAA, the cumulative incidence for pouch carcinoma at 5, 10, 15, and 20 years was 0.6, 1.4, 2.1, and 3.3 percent, respectively. A prior history of colorectal dysplasia and carcinoma were the only risk factors for pouch neoplasia (HR 3.8 and 24.7, respectively).

Primary sclerosing cholangitis — An increased risk of CRC has been observed in patients with UC complicated by PSC. Cancer in patients with PSC was more likely to be in the right colon, suggesting a possible role of bile acids in oncogenesis (a hypothesis supported by studies showing a protective effect of ursodeoxycholic acid). (See "Colorectal cancer and primary sclerosing cholangitis".)

Crohn disease — The risk of CRC in longstanding Crohn disease (CD) involving the colon is probably comparable to ulcerative colitis [5-8,43-46]. However, not all studies reached these conclusions and thus the magnitude of risk in patients with CD remains unsettled. Some reports found no increased risk of CRC in patients with CD, but most did not adjust for the duration and extent of the disease [47-50]. The following studies support the need for CRC surveillance in patients with CD:

In a population-based study from Sweden, the relative risk of colon cancer was 2.5 in patients with CD and 5.6 in those with disease restricted to the colon [8]. The relative risk was even greater in patients who were less than 30 at the time of diagnosis (relative risk 21 compared to those diagnosed after age 30). Similar findings have been reported in other studies [5,51,52].

Another report suggested the benefit from regular surveillance in patients with Crohn colitis of at least seven years duration (and affecting at least one-third of the colon) was similar to that of ulcerative colitis [46].

On the other hand, a population-based study from the United States (which did consider disease duration) found a significantly increased risk of small bowel but not colorectal cancer [22].

CRC in CD is observed in a similar time frame as in UC [53,54]. This was illustrated in one series that included 80 patients with CRC complicating UC or CD [53]. The median duration of disease prior to the diagnosis of CRC was comparable for CD and UC (15 and 18 years, respectively). The median age at diagnosis of CRC was 55 in CD and 43 in UC. One series found that CD patients undergoing surgery for cancer had more advanced CRC than patients with UC [55].

Despite the increased risk, the absolute number of patients at risk is relatively small. Many patients with extensive colitis undergo colectomy early in the course of disease to relieve persistent symptoms [54]. Furthermore, sporadic CRC is far more common than CRC arising in the setting of IBD. As a result, CD accounts for a small proportion of CRC for the overall population (figure 1).

PATHOGENESIS — The pathogenesis of colon cancer in inflammatory bowel disease (IBD) is poorly understood. However, several lines of evidence suggest that the pathobiology is different than for sporadic colorectal cancer (CRC). (See "Molecular genetics of colorectal cancer".)

The mean age of developing CRC in the setting of IBD is lower than for sporadic CRC (40 to 50 versus 60 years).

Dysplasia in ulcerative colitis (UC) is preceded by a long history of chronic inflammation and can be found at distant sites from the cancer. In contrast, dysplasia in sporadic colon cancer is usually associated with a discrete polyp without inflammation.

Mutations in the ras protooncogene are present in 40 to 60 percent of sporadic colon cancers and are probably an early event; in contrast, these mutations are less frequently observed in cancer associated with UC, and are probably a late event [56-58].

Loss of heterozygosity for the p53 gene and src activation occur earlier in cancers associated with IBD than in sporadic CRC [56,58-60]. Src activity in UC correlates with the degree of dysplasia [58].

Abnormalities of the p53 locus are absent in nondysplastic mucosa of patients with sporadic colon cancer [61]. In contrast, nondysplastic mucosa in UC frequently has aneuploid DNA content and may show clones of cells with loss of heterozygosity of the p53 gene [61].

PATHOLOGY — Colorectal cancer (CRC) complicating inflammatory bowel disease may appear polypoid, nodular, ulcerated, or plaque-like [62]. As in sporadic colorectal cancer, most lesions in the colon are adenocarcinomas [63]. However, poorly differentiated, anaplastic, and mucinous carcinomas are more common in colitis-associated CRC than in sporadic CRC [7,58,64,65]. (See "Pathology and prognostic determinants of colorectal cancer".)

Location — CRC associated with ulcerative colitis (UC) is most common in the rectum and sigmoid colon (image 1) [53]. In contrast, CRC associated with CD is evenly distributed between the right colon and rectosigmoid. Cancer always occurs in areas involved in chronic inflammation [53]. Synchronous tumors are much more common in inflammatory bowel disease (IBD) than in sporadic CRC (12 versus 3 to 5 percent) [58]. This can include the colon, rectum, anus, and internal or external fistulous tracts [63].

Dysplasia — It is generally accepted that CRC in IBD is preceded by dysplasia. Thus, dysplastic epithelium may be a marker for coexisting malignancy, and provides the rationale for surveillance.

A uniform terminology for dysplasia in IBD has been proposed [66]. The classification categorizes histology as:

Negative

Indefinite

Positive (with subgroups of low grade and high grade dysplasia)

Dysplastic areas are often difficult to recognize on endoscopy. They may appear as flat or only slightly elevated above the level of the mucosa. Dysplasia may also occur within or near raised plaque-like lesions, nodules, polyps, or masses (referred to as dysplasia-associated lesion or mass [DALM]) (see 'Dysplasia associated lesion or mass' below).

Dysplasia may be difficult to distinguish from epithelial regeneration due to inflammation on histologic sections [67]. As a result, the presence of dysplasia should be confirmed by an experienced GI pathologist. The criteria for dysplasia stress the uniform clonal nature of dysplastic changes, which affects all parts of the crypt and surface epithelium. In contrast, regenerative changes are usually most prominent at the bases of the crypts and show evidence of surface maturation [66]. One study found that immunostaining for alpha-methylacyl-Coa-racemase (AMACR), a mitochondrial and peroxisomal enzyme overexpressed in many types of cancers, was highly specific for detecting dysplasia and distinguishing regenerating epithelium from true dysplasia [68].

Other architectural and cytological abnormalities seen in dysplastic epithelium include [66,69-71]:

Increased mitoses (typical and atypical)

Back to back gland pattern

Increased nuclear size

Variation in the size and shape of nuclei (pleomorphism)

Increased nuclear/cytoplasmic ratio

Altered nuclear polarity

Hyperchromaticity

Lack of surface maturation

Stratification of nuclei

Dysplasia associated lesion or mass — Patients with ulcerative colitis have the same risk for sporadic adenomas as the general population. However, some patients with UC who are found to have dysplasia associated with a non-adenoma-like lesion or mass (DALM) may have an underlying invasive carcinoma, which may not be detectable by endoscopic biopsy and warrants colectomy. The risk of cancer associated with DALM was illustrated in a series that included 12 patients with DALM who underwent resection [72]. The endoscopic appearance of the lesions was:

Single polypoid mass (five patients)

Plaque-like lesion (two patients)

Multiple polyps (five patients)

Invasive carcinoma was found on resection specimens in seven patients (60 percent), including all five who had a single polypoid mass. Malignancy was not detected in any of the patients prior to resection despite multiple biopsies.

Whereas non-adenoma-like DALMs is an indication for colectomy, sporadic adenomas may be removed endoscopically even if they occur in an area histologically involved with colitis. As a result, non-adenoma-like DALMs and sporadic adenomas need to be distinguished to prevent unnecessary colectomy.

A number of clinical, histologic, and molecular features have been studied to help make this distinction:

Patients with non-adenoma-like DALM are more likely to be younger and have a longer duration of disease, more extensive disease, and larger lesions (1.8 versus 0.5 cm in one study [73]).

Lesions that appear endoscopically as adenomas (pedunculated or sessile) rather than having other characteristics (such as flat, ulcerated, or plaque-like appearance) even if within an area of histologic colitis have a favorable prognosis with endoscopic removal and close follow-up [74-77].

Beta catenin and P53 are molecular markers that have been proposed to distinguish DALM from sporadic adenomas [78,79]. Beta catenin is a cell membrane protein that accumulates more frequently in nuclei of cells within sporadic colon cancer compared to DALM. In comparison, mutations with P53 (a tumor suppressor gene) occur more frequently in DALM than sporadic adenomas. In one study, for example, these markers were compared in 17 adenoma-like DALM specimens and 21 sporadic adenomas in patients with UC [80]. Positive staining for P53 was more common in DALM (29 versus 5 percent), whereas positive staining for beta catenin was more common in sporadic adenomas (40 versus 8 percent).

Long-term follow-up suggests that polypectomy with complete excision and continued surveillance provides adequate treatment of patients with an adenoma-like DALM [75,81,82]. In a meta-analysis of 10 studies that included 376 patients with ulcerative colitis who underwent resection of polypoid dysplasia with a total follow-up of 1704 years, the pooled incidence of cancer and dysplasia were 5.3 and 65 per 1000 patient-years, respectively [82].

Our approach to patients with ulcerative colitis who are found to have a polyp is discussed below (see 'Summary and recommendations' below).

Inflammatory pseudopolyps — Inflammatory pseudopolyps are irregularly shaped islands of residual intact colonic mucosa that are the result of the mucosal ulceration and regeneration that occurs in inflammatory bowel disease (IBD). These polyps are typically multiple and scattered throughout the colitic region of the colon (picture 1). They are not dysplastic and are not a risk factor for colon cancer. However, their presence can complicate the recognition of true adenomas and DALM. Inflammatory pseudopolyps can be recognized by their histologic features; thus a biopsy can help make the distinction in unclear cases.

PREDICTIVE VALUE OF DYSPLASIA

Ulcerative colitis — The predictive value of dysplasia has been best studied in ulcerative colitis (UC). There is general agreement that the finding of high-grade dysplasia warrants prompt colectomy because of the high rate of synchronous colorectal cancer (eg, 42 percent [10 of 24] in one study) [83].

More controversial is the proper course of action in patients found to have low-grade dysplasia who are at lower risk [83-90]. The following highly variable rates of progression to high-grade dysplasia or colorectal cancer (CRC) were noted in patients with low-grade dysplasia in different studies with different durations of follow-up:

19 percent (3 of 16) had CRC at immediate colectomy [83]

34 percent (26 of 77) had CRC at colectomy at 12 months [89]

50 percent (9 of 18) progressed to a more advanced lesion (eg, high-grade dysplasia or CRC) at a median of 32 months [84]

15 percent (7 of 46) progressed to CRC at five years [90]

10 percent (3 of 29) progressed to high-grade dysplasia or CRC at 10 years [85]

Although dysplasia is a marker for future or concurrent malignancy, it can also regress or remain stable for long periods [69,91]. There is currently no reliable way to predict which of these outcomes is most likely. Furthermore, most patients with dysplasia do not have cancer [32,92,93], and dysplasia is absent in the colonic regions distant from the malignancy in 25 to 30 percent of patients [88,94,95].

To further complicate matters, the diagnosis of dysplasia is not straightforward, even when using specific criteria for diagnosis. Interpretation of biopsy samples may be confounded by interobserver variation in the recognition and grading of dysplasia [88,96,97]. As a result, it is important that difficult cases be reviewed by a pathologist who is experienced in this area.

Crohn disease — The association between dysplasia and CRC in CD appears to be similar to that in UC. Dysplasia is present in 83 to 100 percent of patients diagnosed with CRC [7,64,65], and dysplasia distant from the cancer has been found in 23 to 70 percent [64,65,98,99]. In contrast, dysplasia is much less common in colectomy specimens of patients with CD without CRC, occurring in only 2 percent of specimens in one series [100].

SURVEILLANCE — The relatively young age at which colorectal cancer (CRC) develops in patients with inflammatory bowel disease (IBD) has led to attempts to stratify patients at greatest risk. The goal of most surveillance programs has been the detection of dysplasia, which is associated with a high risk of CRC [40,53,101,102]. There are conflicting data as to whether patients with CRC associated with IBD have a worse or similar prognosis compared to patients with sporadic CRC [103-107].

The optimal surveillance strategy in patients with IBD remains controversial. The debate revolves around the sensitivity of the detection system, the predictive value of dysplasia for assessing the risk of CRC, and the cost [28,29,83,84,91,108,109]. Detection of dysplasia is important because concurrent CRC is common. In a review of 10 prospective studies with a total of 1225 patients, high- or low-grade dysplasia was associated with CRC at immediate colectomy in 13 of 40 patients (33 percent) [83]. (See 'Predictive value of dysplasia' above.)

It is also unclear if surveillance improves patient survival. Outcomes after the diagnosis of CRC were evaluated in a study of 149 patients with IBD-associated CRC: 23 had undergone colonoscopic surveillance prior to the discovery of CRC, while 126 patients had not [110]. Five-year survival was significantly higher in the prior surveillance group (100 versus 74 percent). In contrast, in a pooled analysis of three observational studies (published before the above report), death from CRC was nonsignificantly lower with surveillance [111]. The somewhat conflicting findings may be explained by the low rate at which dysplasia was detected.

Other issues are that advanced CRC can occur despite surveillance [21,91,112] and the effectiveness of surveillance programs has been limited by both patient compliance [28,29] and unwillingness to undergo prophylactic colectomy when dysplasia is identified [113].

In summary, the data supporting the effectiveness of surveillance in patients with IBD are not uniform but suggest a reduction in mortality from CRC in patients undergoing surveillance who are willing to undergo prophylactic colectomy. As a result, the current balance of evidence provides some support for routine colonoscopic surveillance for dysplasia.

Surveillance in patients with dysplasia — In patients with unifocal, flat, low-grade dysplasia on initial surveillance colonoscopy, a decision-analysis estimated the cost-effectiveness of enhanced surveillance (colonoscopy at three, six, and 12 months, then annually) versus immediate colectomy in a simulated cohort of patients [114]. Immediate colectomy was associated with higher quality-adjusted life years and lower costs. Enhanced surveillance was cost-effective only when considering health utilities of living with a proctocolectomy that were generally lower than what was considered to be likely.

Surveillance techniques

Colonoscopy with biopsy — Multiple biopsies are required to adequately sample the colon. In one report, it was estimated that 33 biopsy specimens from a single colonoscopy would be required to detect dysplasia with 90 percent confidence [115]. In addition, areas of mucosal irregularity should be biopsied [116]. Guidelines for biopsies have been proposed in the society guidelines summarized below. (See 'Recommendations of major societies' below.)

A study comparing eight paired biopsy specimens from the rectosigmoid obtained by either jumbo or standard large-capacity forceps concluded that the jumbo forceps were superior for obtaining diagnostically adequate surveillance biopsy specimens [117]. Thus, use of jumbo forceps has the potential to improve the dysplasia detection rate.

Chromoendoscopy — Chromoendoscopy involves the topical application of stains or pigments to improve tissue localization, characterization, or diagnosis during endoscopy. (See "Chromoendoscopy".)

A least one controlled trial suggested that staining with methylene blue enhanced the ability to detect the extent of inflammatory changes and identify intraepithelial neoplasia in patients with ulcerative colitis undergoing surveillance [118]. Other studies have suggested that staining with indigo carmine permitted better detection of dysplasia [119,120]. The clinical implications and generalizability of these findings require further clarification. Other staining techniques designed to augment visualization of dysplastic changes have also been described.

Narrow band imaging — Narrow band imaging (NBI) is a high-resolution endoscopic technique that enhances the fine structure of the mucosal surface without the use of dyes. NBI is not recommended for surveillance in patients with IBD as it has not demonstrated a benefit in the detection of dysplasia as compared with white light endoscopy or chromoendoscopy [121-123]. In one study that compared the performance of NBI with chromoendoscopy, 44 patients with colitis of eight years or greater disease duration underwent screening colonoscopy with NBI, followed by chromoendoscopy [124]. NBI detected significantly fewer lesions as compared with chromoendoscopy (102 versus 131); however, most missed lesions were not dysplastic. NBI also detected fewer dysplastic lesions as compared with chromoendoscopy (20 versus 23), although the difference was not statistically significant in this small study.

New markers — Because of the limitations of surveillance strategies based upon the detection of dysplasia, newer techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated [61,125]. As examples:

Sialosyl-Tn is a mucin-associated carbohydrate antigen that may presage the development of dysplasia and CRC by several years [58,126].

Allelic deletions and point mutations of tumor suppressor genes, such as p53, Rb, mcc and APC have been found in dysplastic and cancerous ulcerative colitis (UC) [58,61,127].

It is likely that changes in nuclear DNA content are detectable earlier than histologic signs of premalignancy. As a result, detection of DNA aneuploidy by flow cytometry of mucosal specimens in UC patients may be more objective and less sensitive to assessment error than dysplasia [125]. DNA aneuploidy detected by these techniques has been correlated with dysplasia and carcinoma [96,128,129]. However, as with dysplasia, the predictive value of aneuploidy is uncertain. Neoplasms can arise without preexisting aneuploidy, and conversely, aneuploidy may exist for many years without progression to malignancy [58].

These newer techniques have been insufficiently standardized and validated in the clinical setting to be recommended for general use. Until further data are available, endoscopic evaluation for dysplasia remains the standard for cancer surveillance programs in IBD.

RECOMMENDATIONS OF MAJOR SOCIETIES — Optimal surveillance strategies for CRC in patients with inflammatory bowel disease (IBD) have not been established. The following recommendations have been issued by the major national societies in the United States and the British Society of Gastroenterology. Our approach to surveillance is summarized below. (See 'Summary and recommendations' below.)

Ulcerative colitis

American Gastroenterological Association — Guidelines issued by the American Gastroenterological Association (AGA) recommend the following [9-11]:

Colonoscopic surveillance should begin after eight years in patients with pancolitis, and 15 years in patients with colitis involving the left colon

Colonoscopy should be repeated every one to two years

American College of Gastroenterology — Guidelines issued by the American College of Gastroenterology (ACG) recommend the following [12]:

Annual surveillance colonoscopy beginning after 8 to 10 years of disease in patients who are surgical candidates

Multiple biopsies should be obtained at regular intervals

The finding of definite dysplasia (of any grade) should be confirmed by an expert pathologist and is an indication for colectomy

Patients whose biopsies are indefinite for dysplasia after review by an expert pathologist should undergo repeat surveillance colonoscopy at a shorter interval

The ACG recommendations do not specify whether surveillance can begin later in patients with disease limited to the left colon

American Society for Gastrointestinal Endoscopy — The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend the following [13]:

Patients with ulcerative colitis who have pancolitis should begin surveillance colonoscopy after eight years of disease.

Four biopsies should be obtained every 10 cm from the cecum to the rectum. In addition, any suspicious lesions or masses should be biopsied.

Colonoscopy should be repeated every one to three years.

The finding of carcinoma or high-grade dysplasia is an indication for colectomy. Colectomy is also indicated for any degree of dysplasia associated with a lesion or mass. The finding of dysplasia should be confirmed by an expert pathologist.

The finding of low-grade dysplasia should be confirmed by an expert pathologist. The ASGE acknowledges that most experts recommend colectomy. However, in patients in whom colectomy is not feasible or is unacceptable, frequent surveillance (eg, every three to six months) is considered an acceptable alternative.

Patients with left-sided colitis surveillance should begin surveillance after 15 years of disease. Surveillance is not indicated in ulcerative proctitis. The ASGE also recommends that prophylactic colectomy should be considered in patients with longstanding colitis. The definition of longstanding was not specified.

British Society of Gastroenterology — Guidelines issued by the British Society of Gastroenterology in 2002 and updated in 2010 recommend the following [14,15]:

Surveillance colonoscopies should be performed when the disease is in remission, if possible. However, a surveillance procedure should not be unduly delayed if remission cannot be achieved.

All patients should have a surveillance colonoscopy 10 years after the onset of symptoms to assess disease extent and other endoscopic risk factors.

The interval for surveillance colonoscopy depends upon the duration and extent of disease and the presence of additional risk factors (eg, family history of colon cancer or primary sclerosing cholangitis).

Surveillance should be performed every five years for patients at lower risk (extensive colitis with no active endoscopic or histologic inflammation, left-sided colitis, or Crohn colitis involving less than 50 percent of the colon).

Surveillance should be performed every three years for patients at intermediate risk (extensive colitis with mildly active endoscopic or histologic inflammation, post-inflammatory polyps, or a family history of colorectal cancer in a first-degree relative who was at least 50 years of age).

Surveillance should be performed every year for patients at higher risk (extensive colitis with moderately active endoscopic or histologic inflammation, a stricture in the preceding five years, dysplasia in the previous five years that was not treated surgically, primary sclerosing cholangitis, or a family history of colorectal cancer in a first-degree relative younger than 50 years of age).

Pancolonic dye spraying with targeted biopsies of abnormal areas. If chromoendoscopy is not used, two to four random biopsy specimens every 10 cm from the entire colon should be taken with additional samples of suspicious areas.

If a dysplastic polyp is detected within an area of inflammation and can be removed in its entirety, it is not necessary to recommend colectomy.

Postcolectomy surveillance with yearly flexible sigmoidoscopy of pouch/rectal mucosa should be considered for patients at high risk (previous rectal dysplasia or dysplasia or colorectal cancer at the time of pouch surgery or primary sclerosing cholangitis or type C mucosa [mucosa exhibiting permanent persistent atrophy and severe inflammation] in the pouch). In patients with none of the risk factors above, five-yearly flexible sigmoidoscopy of pouch/rectal mucosa should be considered.

Crohn disease

American Gastroenterological Association — The AGA concluded that the risk of colorectal cancer associated with ulcerative colitis (UC) and Crohn colitis is similar for comparable extent, duration, and age of onset of inflammatory disease [9-11]. As a result, the surveillance strategy discussed above for UC also applies for Crohn colitis.

American College of Gastroenterology — The ACG recognizes the expanding evidence of the carcinogenic potential of longstanding Crohn disease but found insufficient evidence to provide guidelines for surveillance [130].

American Society for Gastrointestinal Endoscopy — The ASGE also recognizes that the risk of colorectal cancer is increased in Crohn colitis [13]. Surveillance colonoscopy and biopsy for dysplasia should be offered to patients with longstanding Crohn colitis. However, the ASGE finds that the data guiding the selection of intervals and proper performance of biopsies are limited.

British Society of Gastroenterology — Recommendations for ulcerative colitis also apply to Crohn colitis in a guideline issued by the British Society of Gastroenterology (see 'British Society of Gastroenterology' above) [14,15].

CHEMOPROPHYLAXIS — There is presently no drug that is generally considered to be effective in the primary prevention of colorectal cancer in patients with inflammatory bowel disease (IBD). Thus, chemoprophylaxis is not recommended. Several drugs have been studied in the non-IBD population (particularly nonsteroidal antiinflammatory drugs and calcium) and some have also been evaluated in IBD and in the aggregate have not been found to be effective. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors" and "NSAIDs (including aspirin): Role in prevention of cancer".)

The latter include folic acid, fatty acids, and ursodeoxycholic acid [131-135]. (See "Colorectal cancer and primary sclerosing cholangitis".)

Several lines of evidence also suggest that the risk may be reduced with aminosalicylates, but studies have been mixed and magnitude of benefit is unclear. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease".) In contrast, 6-mercaptopurine or azathioprine does not appear to influence the rate of neoplastic transformation [136].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient information: Colon and rectal cancer screening (The Basics)" and "Patient information: Ulcerative colitis in adults (The Basics)" and "Patient information: Crohn disease in adults (The Basics)" and "Patient information: Colonoscopy (The Basics)")

Beyond the Basics topics (see "Patient information: Colon and rectal cancer screening (Beyond the Basics)" and "Patient information: Ulcerative colitis (Beyond the Basics)" and "Patient information: Crohn disease (Beyond the Basics)" and "Patient information: Colonoscopy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS — There is consensus that patients with ulcerative colitis (UC) should undergo surveillance colonoscopy, although the interval in which this should be done and the optimal number and location that biopsies should be obtained are uncertain. Furthermore, a reduction in mortality due to surveillance has not been clearly established. Patients with Crohn colitis probably have the same risk of colorectal cancer as those with UC, and should also undergo surveillance. Our current approach is as follows:

In patients with ulcerative colitis extending proximal to the splenic flexure or Crohn colitis, we suggest initiating surveillance colonoscopy after eight years of disease followed by annual examinations (Grade 2B). Those with Crohn colitis may require use of a thin caliber colonoscope to adequately sample the colon including strictured areas [44]. We offer surgical resection to patients with Crohn colitis who have an impassable stricture since they cannot be surveyed adequately; we suggest a barium enema in those who decline resection.

In patients with left-sided UC, we suggest beginning with colonoscopy after 12 years of disease; examinations are then performed every year thereafter (Grade 2C).

In patients who have undergone a subtotal colectomy with an ileostomy and have rectum left in place and tied off (ie, a Hartmann's pouch), we suggest surveillance of the remaining rectum every year (Grade 2B).

We suggest not performing surveillance for patients with ulcerative colitis limited to the rectum (Grade 2B).

In patients with a pouch, we suggest flexible sigmoidoscopy every three to five years in the absence of inflammation and atrophy. However, in the presence of severe inflammation or atrophy we increase the surveillance interval to yearly (Grade 2C).

Multiple biopsies are required to adequately sample the colon. We typically obtain four biopsies every 10 cm from the cecum to the rectum. In addition, areas of mucosal irregularity should be biopsied.

We recommend colectomy for patients who are found to have high-grade dysplasia (Grade 1B). Although opinions continue to vary, we also suggest colectomy for those with low-grade dysplasia (Grade 2B).

In some cases a spontaneous adenoma cannot be distinguished from a non-adenoma-like dysplasia associated lesion or mass (DALM), by either endoscopy or pathology. Lesions can definitely be considered sporadic adenomas if they occur proximal to known areas of colitis (eg, right-sided polyp in a patient with left-sided colitis).

For lesions that appear endoscopically and histologically similar to a sporadic adenoma, we suggest performing extensive biopsies in the surrounding area, and in the rest of the colon (Grade 2C).

Patients considered to have a sporadic adenoma who did not have adequate surveillance biopsies obtained throughout the colon at the time of polypectomy should undergo a repeat colonoscopy with surveillance biopsies throughout the colon (and extra attention to the area of the polypectomy); standard surveillance can be resumed if there is no evidence of flat dysplasia.

For polyps that appear endoscopically and histologically to be adenomas (ie, adenoma-like DALM) regardless of whether they occurred in an area of the colon involved with colitis and are not associated with dysplastic changes in flat mucosa elsewhere in the colon, we suggest that rather than performing a colectomy, the adenomatous polyp be removed endoscopically with close follow-up (Grade 2B).

In the absence of dysplasia in the flat mucosa in the surrounding area or elsewhere in the colon, or invasive carcinoma in the polyp, the clinical aspects of the tumor and the patient's overall clinical status should be considered for recommending further surveillance or colectomy (table 1 and algorithm 1). However, most, if not all, adenoma-like lesions can be treated safely by polypectomy and continuous surveillance. Standard surveillance intervals can be continued in patients with low-risk lesions (although shortening the interval between examinations is also reasonable).

Non-adenoma-like polyps or other masses occurring in an area of colon that has been histologically involved with colitis, with or without surrounding dysplasia, should be considered as potentially containing invasive carcinoma.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. Rosenqvist H, Ohrling H, Lagercrantz R, Edling N. Ulcerative colitis and carcinoma coli. Lancet 1959; 1:906.
  2. Course and prognosis of ulcerative colitis: Part IV Carcinoma of the colon. Gut 1964; 5:15.
  3. MacDougall IP. The cancer risk in ulcerative colitis. Lancet 1964; 2:655.
  4. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990; 323:1228.
  5. Weedon DD, Shorter RG, Ilstrup DM, et al. Crohn's disease and cancer. N Engl J Med 1973; 289:1099.
  6. Softley A, Clamp SE, Watkinson G, et al. The natural history of inflammatory bowel disease: has there been a change in the last 20 years? Scand J Gastroenterol Suppl 1988; 144:20.
  7. Richards ME, Rickert RR, Nance FC. Crohn's disease-associated carcinoma. A poorly recognized complication of inflammatory bowel disease. Ann Surg 1989; 209:764.
  8. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 1990; 336:357.
  9. Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:746.
  10. Farraye FA, Odze RD, Eaden J, et al. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:738.
  11. Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 2003; 124:544.
  12. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 1997; 92:204.
  13. Leighton JA, Shen B, Baron TH, et al. ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease. Gastrointest Endosc 2006; 63:558.
  14. Eaden JA, Mayberry JF, British Society for Gastroenterology, Association of Coloproctology for Great Britain and Ireland. Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Gut 2002; 51 Suppl 5:V10.
  15. Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut 2010; 59:666.
  16. Söderlund S, Brandt L, Lapidus A, et al. Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease. Gastroenterology 2009; 136:1561.
  17. Jess T, Simonsen J, Jørgensen KT, et al. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012; 143:375.
  18. Söderlund S, Granath F, Broström O, et al. Inflammatory bowel disease confers a lower risk of colorectal cancer to females than to males. Gastroenterology 2010; 138:1697.
  19. Ullman TA. Inflammatory bowel disease-associated cancers: does gender change incidence? Gastroenterology 2010; 138:1658.
  20. Devroede GJ, Taylor WF, Sauer WG, et al. Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 1971; 285:17.
  21. Rutter MD, Saunders BP, Wilkinson KH, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006; 130:1030.
  22. Jess T, Loftus EV Jr, Velayos FS, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology 2006; 130:1039.
  23. Beaugerie L, Svrcek M, Seksik P, et al. Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. Gastroenterology 2013; 145:166.
  24. Velayos FS, Loftus EV Jr, Jess T, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology 2006; 130:1941.
  25. Velayos FS, Ullman TA. Looking forward to understanding and reducing colorectal cancer risk in inflammatory bowel disease. Gastroenterology 2013; 145:47.
  26. Rubin DT, Huo D, Kinnucan JA, et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol 2013; 11:1601.
  27. Gyde SN, Prior P, Allan RN, et al. Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut 1988; 29:206.
  28. Lennard-Jones JE. Cancer risk in ulcerative colitis: surveillance or surgery. Br J Surg 1985; 72 Suppl:S84.
  29. Collins RH Jr, Feldman M, Fordtran JS. Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. N Engl J Med 1987; 316:1654.
  30. Katzka I, Brody RS, Morris E, Katz S. Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice. Gastroenterology 1983; 85:22.
  31. Mir-Madjlessi SH, Farmer RG, Easley KA, Beck GJ. Colorectal and extracolonic malignancy in ulcerative colitis. Cancer 1986; 58:1569.
  32. Lennard-Jones JE, Melville DM, Morson BC, et al. Precancer and cancer in extensive ulcerative colitis: findings among 401 patients over 22 years. Gut 1990; 31:800.
  33. Langholz E, Munkholm P, Davidsen M, Binder V. Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 1992; 103:1444.
  34. Winther KV, Jess T, Langholz E, et al. Long-term risk of cancer in ulcerative colitis: a population-based cohort study from Copenhagen County. Clin Gastroenterol Hepatol 2004; 2:1088.
  35. Heuschen UA, Hinz U, Allemeyer EH, et al. Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis. Gastroenterology 2001; 120:841.
  36. Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004; 126:451.
  37. Haskell H, Andrews CW Jr, Reddy SI, et al. Pathologic features and clinical significance of "backwash" ileitis in ulcerative colitis. Am J Surg Pathol 2005; 29:1472.
  38. Gupta RB, Harpaz N, Itzkowitz S, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007; 133:1099.
  39. Greenstein AJ, Sachar DB, Smith H, et al. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979; 77:290.
  40. Nugent FW, Haggitt RC, Gilpin PA. Cancer surveillance in ulcerative colitis. Gastroenterology 1991; 100:1241.
  41. Levin B. Inflammatory bowel disease and colon cancer. Cancer 1992; 70:1313.
  42. Derikx LA, Kievit W, Drenth JP, et al. Prior colorectal neoplasia is associated with increased risk of ileoanal pouch neoplasia in patients with inflammatory bowel disease. Gastroenterology 2014; 146:119.
  43. Rubio CA, Befrits R. Colorectal adenocarcinoma in Crohn's disease: a retrospective histologic study. Dis Colon Rectum 1997; 40:1072.
  44. Friedman S, Rubin PH, Bodian C, et al. Screening and surveillance colonoscopy in chronic Crohn's colitis. Gastroenterology 2001; 120:820.
  45. Maykel JA, Hagerman G, Mellgren AF, et al. Crohn's colitis: the incidence of dysplasia and adenocarcinoma in surgical patients. Dis Colon Rectum 2006; 49:950.
  46. Moreels TG, Pelckmans PA. Double-balloon endoscope for failed conventional colonoscopy. Clin Gastroenterol Hepatol 2008; 6:259; author reply 259.
  47. Binder V, Hendriksen C, Kreiner S. Prognosis in Crohn's disease--based on results from a regional patient group from the county of Copenhagen. Gut 1985; 26:146.
  48. Kvist N, Jacobsen O, Nørgaard P, et al. Malignancy in Crohn's disease. Scand J Gastroenterol 1986; 21:82.
  49. Gollop JH, Phillips SF, Melton LJ 3rd, Zinsmeister AR. Epidemiologic aspects of Crohn's disease: a population based study in Olmsted County, Minnesota, 1943-1982. Gut 1988; 29:49.
  50. Fireman Z, Grossman A, Lilos P, et al. Intestinal cancer in patients with Crohn's disease. A population study in central Israel. Scand J Gastroenterol 1989; 24:346.
  51. Greenstein AJ, Sachar DB, Smith H, et al. A comparison of cancer risk in Crohn's disease and ulcerative colitis. Cancer 1981; 48:2742.
  52. Gyde SN, Prior P, Macartney JC, et al. Malignancy in Crohn's disease. Gut 1980; 21:1024.
  53. Choi PM, Zelig MP. Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 1994; 35:950.
  54. Gillen CD, Walmsley RS, Prior P, et al. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 1994; 35:1590.
  55. Kiran RP, Khoury W, Church JM, et al. Colorectal cancer complicating inflammatory bowel disease: similarities and differences between Crohn's and ulcerative colitis based on three decades of experience. Ann Surg 2010; 252:330.
  56. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319:525.
  57. Burmer GC, Levine DS, Kulander BG, et al. c-Ki-ras mutations in chronic ulcerative colitis and sporadic colon carcinoma. Gastroenterology 1990; 99:416.
  58. Itzkowitz SH. Inflammatory bowel disease and cancer. Gastroenterol Clin North Am 1997; 26:129.
  59. Baker SJ, Preisinger AC, Jessup JM, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 1990; 50:7717.
  60. Hussain SP, Amstad P, Raja K, et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 2000; 60:3333.
  61. Burmer GC, Rabinovitch PS, Haggitt RC, et al. Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 1992; 103:1602.
  62. Butt JH, Konishi F, Morson BC, et al. Macroscopic lesions in dysplasia and carcinoma complicating ulcerative colitis. Dig Dis Sci 1983; 28:18.
  63. Connell WR, Sheffield JP, Kamm MA, et al. Lower gastrointestinal malignancy in Crohn's disease. Gut 1994; 35:347.
  64. Hamilton SR. Colorectal carcinoma in patients with Crohn's disease. Gastroenterology 1985; 89:398.
  65. Petras RE, Mir-Madjlessi SH, Farmer RG. Crohn's disease and intestinal carcinoma. A report of 11 cases with emphasis on associated epithelial dysplasia. Gastroenterology 1987; 93:1307.
  66. Riddell RH, Goldman H, Ransohoff DF, et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol 1983; 14:931.
  67. Odze RD. Pathology of dysplasia and cancer in inflammatory bowel disease. Gastroenterol Clin North Am 2006; 35:533.
  68. Dorer R, Odze RD. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease. Am J Surg Pathol 2006; 30:871.
  69. Albert MB, Nochomovitz LE. Dysplasia and cancer surveillance in inflammatory bowel disease. Gastroenterol Clin North Am 1989; 18:83.
  70. Allen DC, Hamilton PW, Watt PC, Biggart JD. Morphometrical analysis in ulcerative colitis with dysplasia and carcinoma. Histopathology 1987; 11:913.
  71. Allen DC, Hamilton PW, Watt PC, Biggart JD. Architectural morphometry in ulcerative colitis with dysplasia. Histopathology 1988; 12:611.
  72. Blackstone MO, Riddell RH, Rogers BH, Levin B. Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology 1981; 80:366.
  73. Suzuki K, Muto T, Shinozaki M, et al. Differential diagnosis of dysplasia-associated lesion or mass and coincidental adenoma in ulcerative colitis. Dis Colon Rectum 1998; 41:322.
  74. Odze RD. Adenomas and adenoma-like DALMs in chronic ulcerative colitis: a clinical, pathological, and molecular review. Am J Gastroenterol 1999; 94:1746.
  75. Engelsgjerd M, Farraye FA, Odze RD. Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis. Gastroenterology 1999; 117:1288.
  76. Rubin PH, Friedman S, Harpaz N, et al. Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps. Gastroenterology 1999; 117:1295.
  77. Odze RD, Brown CA, Hartmann CJ, et al. Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas. Am J Surg Pathol 2000; 24:1209.
  78. Morin PJ, Sparks AB, Korinek V, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 1997; 275:1787.
  79. Munemitsu S, Albert I, Souza B, et al. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci U S A 1995; 92:3046.
  80. Walsh SV, Loda M, Torres CM, et al. P53 and beta catenin expression in chronic ulcerative colitis--associated polypoid dysplasia and sporadic adenomas: an immunohistochemical study. Am J Surg Pathol 1999; 23:963.
  81. Odze RD, Farraye FA, Hecht JL, Hornick JL. Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis. Clin Gastroenterol Hepatol 2004; 2:534.
  82. Wanders LK, Dekker E, Pullens B, et al. Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: a meta-analysis. Clin Gastroenterol Hepatol 2014; 12:756.
  83. Bernstein CN, Shanahan F, Weinstein WM. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 1994; 343:71.
  84. Ullman TA, Loftus EV Jr, Kakar S, et al. The fate of low grade dysplasia in ulcerative colitis. Am J Gastroenterol 2002; 97:922.
  85. Lim CH, Dixon MF, Vail A, et al. Ten year follow up of ulcerative colitis patients with and without low grade dysplasia. Gut 2003; 52:1127.
  86. Befrits R, Ljung T, Jaramillo E, Rubio C. Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a follow-up study. Dis Colon Rectum 2002; 45:615.
  87. Jess T, Loftus EV Jr, Velayos FS, et al. Incidence and prognosis of colorectal dysplasia in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Inflamm Bowel Dis 2006; 12:669.
  88. Connell WR, Lennard-Jones JE, Williams CB, et al. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 1994; 107:934.
  89. Gorfine SR, Bauer JJ, Harris MT, Kreel I. Dysplasia complicating chronic ulcerative colitis: is immediate colectomy warranted? Dis Colon Rectum 2000; 43:1575.
  90. Ullman T, Croog V, Harpaz N, et al. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 2003; 125:1311.
  91. Axon AT. Cancer surveillance in ulcerative colitis--a time for reappraisal. Gut 1994; 35:587.
  92. Broström O, Löfberg R, Ost A, Reichard H. Cancer surveillance of patients with longstanding ulcerative colitis: a clinical, endoscopical, and histological study. Gut 1986; 27:1408.
  93. Manning AP, Bulgim OR, Dixon MF, Axon AT. Screening by colonoscopy for colonic epithelial dysplasia in inflammatory bowel disease. Gut 1987; 28:1489.
  94. Ransohoff DF, Riddell RH, Levin B. Ulcerative colitis and colonic cancer. Problems in assessing the diagnostic usefulness of mucosal dysplasia. Dis Colon Rectum 1985; 28:383.
  95. Taylor BA, Pemberton JH, Carpenter HA, et al. Dysplasia in chronic ulcerative colitis: implications for colonoscopic surveillance. Dis Colon Rectum 1992; 35:950.
  96. Melville DM, Jass JR, Shepherd NA, et al. Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis. Observer variation and correlations. Gastroenterology 1988; 95:668.
  97. Dixon MF, Brown LJ, Gilmour HM, et al. Observer variation in the assessment of dysplasia in ulcerative colitis. Histopathology 1988; 13:385.
  98. Fresko D, Lazarus SS, Dotan J, Reingold M. Early presentation of carcinoma of the small bowel in Crohn's disease ("Crohn's carcinoma"). Case reports and review of the literature. Gastroenterology 1982; 82:783.
  99. Korelitz BI, Lauwers GY, Sommers SC. Rectal mucosal dysplasia in Crohn's disease. Gut 1990; 31:1382.
  100. Warren R, Barwick KW. Crohn's colitis with carcinoma and dysplasia. Report of a case and review of 100 small and large bowel resections for Crohn's disease to detect incidence of dysplasia. Am J Surg Pathol 1983; 7:151.
  101. Lennard-Jones JE, Morson BC, Ritchie JK, et al. Cancer in colitis: assessment of the individual risk by clinical and histological criteria. Gastroenterology 1977; 73:1280.
  102. Rozen P, Baratz M, Fefer F, Gilat T. Low incidence of significant dysplasia in a successful endoscopic surveillance program of patients with ulcerative colitis. Gastroenterology 1995; 108:1361.
  103. Jensen AB, Larsen M, Gislum M, et al. Survival after colorectal cancer in patients with ulcerative colitis: a nationwide population-based Danish study. Am J Gastroenterol 2006; 101:1283.
  104. Delaunoit T, Limburg PJ, Goldberg RM, et al. Colorectal cancer prognosis among patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2006; 4:335.
  105. Aarnio M, Mustonen H, Mecklin JP, Järvinen HJ. Prognosis of colorectal cancer varies in different high-risk conditions. Ann Med 1998; 30:75.
  106. Sugita A, Greenstein AJ, Ribeiro MB, et al. Survival with colorectal cancer in ulcerative colitis. A study of 102 cases. Ann Surg 1993; 218:189.
  107. Ali RA, Dooley C, Comber H, et al. Clinical features, treatment, and survival of patients with colorectal cancer with or without inflammatory bowel disease. Clin Gastroenterol Hepatol 2011; 9:584.
  108. Provenzale D, Wong JB, Onken JE, Lipscomb J. Performing a cost-effectiveness analysis: surveillance of patients with ulcerative colitis. Am J Gastroenterol 1998; 93:872.
  109. Vemulapalli R, Lance P. Cancer surveillance in ulcerative colitis: more of the same or progress? Gastroenterology 1994; 107:1196.
  110. Lutgens MW, Oldenburg B, Siersema PD, et al. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease. Br J Cancer 2009; 101:1671.
  111. Collins PD, Mpofu C, Watson AJ, Rhodes JM. Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease. Cochrane Database Syst Rev 2006; :CD000279.
  112. Lashner BA, Kane SV, Hanauer SB. Colon cancer surveillance in chronic ulcerative colitis: historical cohort study. Am J Gastroenterol 1990; 85:1083.
  113. Choi PM, Nugent FW, Schoetz DJ Jr, et al. Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology 1993; 105:418.
  114. Nguyen GC, Frick KD, Dassopoulos T. Medical decision analysis for the management of unifocal, flat, low-grade dysplasia in ulcerative colitis. Gastrointest Endosc 2009; 69:1299.
  115. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 1992; 103:1611.
  116. Rutter MD, Saunders BP, Wilkinson KH, et al. Most dysplasia in ulcerative colitis is visible at colonoscopy. Gastrointest Endosc 2004; 60:334.
  117. Elmunzer BJ, Higgins PD, Kwon YM, et al. Jumbo forceps are superior to standard large-capacity forceps in obtaining diagnostically adequate inflammatory bowel disease surveillance biopsy specimens. Gastrointest Endosc 2008; 68:273.
  118. Kiesslich R, Fritsch J, Holtmann M, et al. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 2003; 124:880.
  119. Rutter MD, Saunders BP, Schofield G, et al. Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis. Gut 2004; 53:256.
  120. Matsumoto T, Nakamura S, Jo Y, et al. Chromoscopy might improve diagnostic accuracy in cancer surveillance for ulcerative colitis. Am J Gastroenterol 2003; 98:1827.
  121. Dekker E, van den Broek FJ, Reitsma JB, et al. Narrow-band imaging compared with conventional colonoscopy for the detection of dysplasia in patients with longstanding ulcerative colitis. Endoscopy 2007; 39:216.
  122. Pellisé M, López-Cerón M, Rodríguez de Miguel C, et al. Narrow-band imaging as an alternative to chromoendoscopy for the detection of dysplasia in long-standing inflammatory bowel disease: a prospective, randomized, crossover study. Gastrointest Endosc 2011; 74:840.
  123. Ignjatovic A, East JE, Subramanian V, et al. Narrow band imaging for detection of dysplasia in colitis: a randomized controlled trial. Am J Gastroenterol 2012; 107:885.
  124. Efthymiou M, Allen PB, Taylor AC, et al. Chromoendoscopy versus narrow band imaging for colonic surveillance in inflammatory bowel disease. Inflamm Bowel Dis 2013; 19:2132.
  125. Löfberg R, Broström O, Karlén P, et al. DNA aneuploidy in ulcerative colitis: reproducibility, topographic distribution, and relation to dysplasia. Gastroenterology 1992; 102:1149.
  126. Itzkowitz SH, Young E, Dubois D, et al. Sialosyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective case-control study. Gastroenterology 1996; 110:694.
  127. Greenwald BD, Harpaz N, Yin J, et al. Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis. Cancer Res 1992; 52:741.
  128. Löfberg R, Broström O, Karlén P, et al. Colonoscopic surveillance in long-standing total ulcerative colitis--a 15-year follow-up study. Gastroenterology 1990; 99:1021.
  129. Löfberg R, Broström O, Karlén P, et al. Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study. Gut 1991; 32:900.
  130. Hanauer SB, Meyers S. Management of Crohn's disease in adults. Am J Gastroenterol 1997; 92:559.
  131. Tung BY, Emond MJ, Haggitt RC, et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med 2001; 134:89.
  132. Hontecillas R, Wannemeulher MJ, Zimmerman DR, et al. Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. J Nutr 2002; 132:2019.
  133. Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993; 119:549.
  134. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. Gastroenterology 1989; 97:255.
  135. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997; 112:29.
  136. Matula S, Croog V, Itzkowitz S, et al. Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine. Clin Gastroenterol Hepatol 2005; 3:1015.
Topic 4079 Version 13.0

Topic Outline

GRAPHICS

RELATED TOPICS

All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.