Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Prevention Research
Cancer Prevention Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Minireview

Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management

Parambir S. Dulai, William J. Sandborn and Samir Gupta
Parambir S. Dulai
1Division of Gastroenterology, University of California San Diego, La Jolla, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William J. Sandborn
1Division of Gastroenterology, University of California San Diego, La Jolla, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samir Gupta
1Division of Gastroenterology, University of California San Diego, La Jolla, California.
2Veterans Affairs San Diego Healthcare System, San Diego, California.
3Moores Cancer Center, University of California San Diego, La Jolla, California.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: s1gupta@ucsd.edu
DOI: 10.1158/1940-6207.CAPR-16-0124 Published December 2016
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Crohn disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) characterized by recurrent episodes of mucosal inflammation. This chronic mucosal inflammation has several potential consequences, one of which is the occurrence of colitis-associated colorectal cancer. Over the past decade, our understanding of the epidemiology, pathophysiology, and overall approach to diagnosing and managing colitis-associated colorectal cancer has grown considerably. In the current review article, we outline these advancements and highlight areas in need of further research. Cancer Prev Res; 9(12); 887–94. ©2016 AACR.

Epidemiology

The increased risk for colorectal cancer among patients with inflammatory bowel disease (IBD) with colitis is well-established (1, 2). Earlier studies had suggested a substantial excess risk, with an estimated incidence of nearly 1% per year (3). More recently, an updated meta-analysis of population-based cohort studies has quantified the incidence of colorectal cancer among patients with IBD to be 1%, 2%, and 5% after 10, 20, and > 20 years of disease duration (4). Although this would suggest that the burden of this disease is declining, population-based data have been conflicting. A Danish study observed that the overall risk for colorectal cancer in ulcerative colitis was now similar to that of the general Danish population [relative risk (RR), 1.07; 95% confidence interval (CI), 0.95 – 1.21], and although the risk of colorectal cancer among patients with Crohn disease had remained stable over time, the risk of colorectal cancer among patients with ulcerative colitis had declined considerably (1979–1988: RR, 1.34, 95% CI, 1.13–1.58; 1999–2008: RR, 0.57, 95% CI, 0.41–0.80; ref. 5).

In contrast, a US-based study from the Kaiser Permanente Healthcare System observed that the incidence of colorectal cancer among patients with both ulcerative colitis and Crohn disease was 60% higher than the general population, even after accounting for the growth of colorectal cancer screening programs. Furthermore, observed incidence remained stable over time for both ulcerative colitis and Crohn disease (6). These variations in observations help highlight several key issues with prior studies. Dissimilarities in estimates are likely, in large part, due to different study designs, outcome classification and ascertainment, an inability to accurately classify disease onset, insufficient study size, and differences in the threshold for performing colectomy (7). Furthermore, the presence of active inflammation has a substantial impact on the ability to diagnose dysplasia. With advancements in biologic therapies and treatment strategies over time and improvements in disease control and quality of life, a lead time bias from early dysplasia detection in patients with well-controlled IBD without active inflammation may be partially responsible for varying incidence of colorectal cancer overtime and across populations, particularly when considering the advancements being made in endoscopic imaging technology. Taken together, colitis-associated colorectal cancer remains an important consequence of long-standing IBD with an estimated incidence of approximately 5% after 20 years of disease duration, but large-scale high-quality population-based studies are still needed to quantify its true burden.

Clinical risk factors

Although uncertainty remains as to the true estimate of disease burden, high-risk subpopulations and risk factors have consistently been identified, including age of colitis onset, disease extent, duration, and severity, inflammatory complications, primary sclerosing cholangitis (PSC), and family history of colorectal cancer (Table 1; refs. 1–30). For age of disease onset, risk is highest among those diagnosed at a younger age (≤15 years), which is perhaps attributable to longer overall disease duration or a more aggressive phenotype among these individuals. An important marker of disease severity and persistence of inflammation may be the development of colonic strictures. Earlier studies suggested that up to 40% of colonic strictures harbored colorectal cancer (8), but more recent studies note much lower, but still substantial, risk, reporting that 2% to 3.5% of colonic strictures harbor dysplasia or colorectal cancer (9, 10). Furthermore, one of these studies suggested that the only factor associated with an increased risk for dysplasia or colorectal cancer within colonic strictures was the absence of disease activity at the time of surgery (OR, 4.86; 95% CI, 1.11 – 21.27; ref. 9). This is a direct contrast to the majority of other risk factors, which are clearly linked to disease activity and inflammation, and highlights the potential gaps in our knowledge and understanding of the pathogenesis of colitis-associated colorectal cancer. While risk factors have been identified, comparison of the magnitude and significance of risk is a challenge due to variation in study designs, and, in some cases, small sample size. In addition, the true prevalence of risk factors is difficult to ascertain. A recent population-based cohort study demonstrated that the true prevalence of PSC may be much higher than previously estimated (31). This might suggest that PSC as a risk factor for colorectal cancer is only of significance in clinically active PSC. More research on risk factors for colitis-associated cancer utilizing population-based data is needed.

View this table:
  • View inline
  • View popup
Table 1.

Clinical risk factors for colitis-associated colorectal cancer

View this table:
  • View inline
  • View popup
Table 2.

Surveillance intervals and strategies

Pathogenesis

Given the microenvironment within which colitis-associated dysplasia and colorectal cancer are arising, it is not unexpected that host immune and inflammatory responses play a key role in the pathogenesis. The mechanism through which chronic inflammation results in colorectal cancer is felt to be through the induction of cytokines and chemokines, with ensuing alterations in epithelial cell proliferation, survival, and migration (32–42; Fig. 1). In contrast to sporadic colorectal cancer, which is postulated to develop from 1 or 2 foci of dysplasia, colitis-associated colorectal cancer is hypothesized to develop from multifocal dysplasia where the inflamed colonic mucosa undergoes a field change of cancer-associated molecular alterations before there is any histologic evidence of dysplasia (2, 24, 43–45). Broadly, 2 of the most common somatic genetic abnormalities identified in colorectal cancer are chromosomal instability (CIN) and microsatellite instability (MSI). These occur with the same frequency in colitis-associated colorectal cancer as they do with sporadic colorectal cancer, but there are differences with respect to the timing and frequency of some alterations in the colitis associated dysplasia–carcinoma sequence (2, 24, 46–52). For example, p53 mutations (common to both sporadic and colitis-associated colorectal cancer) appear to occur earlier in carcinogenesis in colitis-associated colorectal cancer, as these mutations are more commonly observed in colitis-associated dysplasia than among sporadic polyps (47, 51). Mutations in APC and K-ras, which are known to occur much earlier within the adenoma–carcinoma sequence of sporadic colorectal cancer, are seen less frequently in colitis-associated colorectal cancer and are thought to arise much later in the dysplasia–carcinoma sequence where they promote NF-κB–mediated cytokine secretion, neovascularization, and maintenance of tumor growth (24, 51, 53).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Key alterations within the colitis-associated colorectal cancer dysplasia–carcinoma sequence. COX-2, cyclooxygenase-2; ECM, extra-cellular matrix; LPS, lipopolysaccharide; MMR, mismatch repair mutation; TNF, tumor necrosis factor; VEGF, vascular endolethial growth factor.

Recently, whole-exome analyses of tumor specimens from patients with colitis-associated colorectal cancer were compared with exome analyses from tumor specimens from patients with sporadic colorectal cancer included in The Cancer Genome Atlas (TCGA). The comparisons suggested that colitis-associated colorectal cancers have a distinct profile and are enriched with mutations associated with cell communication, cell-to-cell signaling, and cell adhesion, all of which may be linked with the dysregulated cytokines and inflammatory mediators associated with IBD (51, 54). Limitations of this prior work include a paucity of clinical data on the patients who contributed colorectal cancer samples and small sample size (n < 30). Nonetheless, recognition that colitis-associated colorectal cancer may have a unique genetic profile could offer novel opportunities for chemoprevention and for the development of biomarkers for colitis surveillance. Extension of genetic profiling work to include precancerous dysplasia and expansion to include additional assessments such as DNA methylation and mucosal microbiome profiles has great potential to expand our understanding of colitis-associated colorectal cancer pathogenesis and opportunities for surveillance, intervention, and prevention.

Chemoprevention

No primary randomized controlled trials of chemoprevention for colitis-associated colorectal cancer have been conducted. In observational studies, the 2 most widely studied anti-inflammatory drugs are 5-aminosalicylic acid (5-ASA) and immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine). Although both of these drug categories inhibit NF-κB activation, and to some extent, reduce the overall burden of cytokine production (55–59), clinical data supporting their use as chemoprevention agents have been conflicting. Indeed, the majority of population-based studies suggesting no therapeutic benefit exists for this indication (60–65). Similarly, pooled meta-analyses of observational studies for other nonspecific anti-inflammatory agents, such as aspirin and non-aspirin nonsteroid anti-inflammatory drugs, have also suggested no chemoprevention benefit exists for these agents, despite their demonstrated efficacy as chemoprevention agents for sporadic colorectal cancer colorectal cancer (66). Among a high-risk population of patients suffering from PSC, early data suggested a substantial chemoprevention benefit with ursodexycholic acid (67). However, more recent meta-analyses of population-based studies have suggested that a chemoprevention benefit may not exist for all patients, particularly when considering the dose of UCDA used (68, 69). This lack of benefit with prior chemoprevention studies may be, in part, due to variability in disease activity, extent, and presence of established risk factors, or the nonspecific mechanism through which these agents inhibit inflammation and modulate cancer risk.

Given the known importance of TNF and interleukins within the pathogenesis of colitis-associated colorectal cancer, more targeted inhibition of these pathways may offer an opportunity to prevent colitis-associated colorectal cancer, particularly among high-risk individuals who have developed early dysplastic lesions where these cytokines serve to stabilize the cancer microenvironment. In non–colorectal cancer malignancy, such as ovarian and renal cell cancers, the use of TNF antagonists in early-phase clinical trials has been shown to stabilize disease and prevent further progression among those with advanced cancer (70). Within colitis-associated colorectal cancer, although animal models have suggested that TNF antagonists may prevent the development or progression of dysplasia and cancer (71), and some population-based data within IBD have demonstrated a lower frequency of colorectal cancer among those treated with infliximab (72, 73), non-IBD data have suggested a potential increased frequency of colorectal cancer with infliximab treatment (74). This has created uncertainty as to whether TNF antagonist and biologics are effective chemoprevention agents for colitis-associated colorectal cancer (75).

Overall, chemoprevention against colitis-associated colorectal cancer is understudied. Well-designed randomized controlled trials for candidate agents are needed, and large population-based registries or healthcare databases may help guide the identification of these candidate agents. An example of this can be seen within the Boston healthcare network where statin use was observed to be inversely associated with colorectal cancer risk and thus may be a potential candidate chemoprevention agent worthy of future research (76). As alluded to above, expanding understandings of the genetic and molecular profiles of colitis-associated dysplasia and colorectal cancer offers potential to engage in a new era of chemoprevention research in IBD. For example, mutations in Rac GTP may be more common in IBD-associated neoplasia, and Rac1 inhibition has been shown in animals to prevent colorectal cancer carcinogenesis (51). The potential impact of such genetic observations is highlighted by a recent successful pilot trial against adenomas in patients with familial adenomatous polyps (FAP), where observations of EGFR upregulation in FAP-associated polyps led to a successful placebo controlled proof-of-concept human trial of erlotinib that markedly reduced adenoma burden and progression (77).

Screening and surveillance

Although a great deal of research has been conducted to understand the pathogenesis of colitis-associated colorectal cancer, and attempts have been made to off-set the natural course of this disease through chemoprevention, the timing of these dysplastic transitions can vary, and tumor progression can skip one or more of these steps (78). This creates a great deal of uncertainty with regards to screening and surveillance. Efforts have therefore now focused on the early detection of dysplastic changes through endoscopic surveillance with the intent of reducing the risk of progression through early colectomy when colitis-associated dysplasia is found. This approach has been associated with a reduction in colorectal cancer–related mortality (79–84) and is now considered standard of care by several gastrointestinal societies. The optimal approach and timing to surveillance, however, continues to be debated.

Surveillance intervals

When considering endoscopic surveillance intervals, societies vary in the manner in which they stratify patients and the intervals they recommend. Broadly, surveillance can be classified as risk-stratified or nonstratified intervals (Table 2; refs. 78, 85–89). European societies have suggested a more stratified approach to surveillance, after taking into account the number of risk factors and strength of each risk factor, whereas U.S. societies have suggested a more aggressive and nonstratified approach to surveillance, assuming an equal degree of risk across subpopulations. A recent cost-effectiveness analysis suggested that the European-based risk profiling approach may be more cost-effective as compared with the nonstratified U.S. approach, but this cost-effectiveness was largely driven by the cost of colonoscopy, and it is unclear whether the different strategies are equal in their ability to improve colorectal cancer–related morbidity and mortality (90). Furthermore, the overall utilization of surveillance colonoscopy programs at the population level has been demonstrated to be low, with only a quarter of patients undergoing surveillance at recommended intervals (91, 92). Even among high-risk individuals (PSC), adherence to guidelines is reported to be less than 40% (91–94). Thus, irrespective of the interval or strategy followed, adherence to any surveillance program would be considered an optimization of current practices.

View this table:
  • View inline
  • View popup
Table 3.

Unanswered questions and future research

Surveillance techniques and management of dysplasia

Uncertainty and variability surround surveillance techniques and the optimal management of dysplastic lesions. Providers have traditionally failed to comply with biopsy protocols, with some reports documenting adherence to be less than 5% (92, 93, 95, 96). It is unclear whether this variation in practice and adherence to surveillance techniques is due to patient preferences, provider practice preferences, or technical challenges (i.e., time required to submit multiple biopsies in multiple sample jars; ref. 97), but it may help explain why the rate of early/missed colorectal cancer after colonoscopy is reported to be nearly 15% among patients with IBD as compared with only 5% in non-IBD patients (98). In an effort to address this gap, a group of experts recently came together and prepared the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients Internal Consensus Recommendations (SCENIC Recommendations; ref. 99; Fig. 2). Within these recommendations, a key point to note is that not all dysplastic lesions require colectomy, and certain patients with focal low-grade dysplasia (LGD) or visible lesions can be monitored endoscopically or undergo focal endoscopic resection.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Clinical approach to endoscopic dysplasia surveillance and management based on the SCENIC consensus, ref. 99.

When performing surveillance, the SCENIC recommendations place a great deal of emphasis on the use of chromoendoscopy to optimize surveillance techniques. However, it should be noted that this recommendation is a conditional recommendation when using newer high definition colonoscopy equipment, as it is based largely upon on a single observational study and no randomized trials currently exist in this arena. Given the increased effort and time required to perform chromoendoscopy, with an unclear added benefit, several authors have brought into question the optimal use of chromoendoscopy and whether it is truly required in all patients (100, 101). Furthermore, if chromoendoscopy is to be used, it is unclear whether random biopsies are still needed beyond targeted biopsies. Nonetheless, although several of the recommendations are conditional and/or have low quality of evidence supporting them, this consensus recommendation statement helps highlight the need for a unified approach to diagnosing, characterizing, and treating these lesions in routine practice and represents a step toward a more integrated approach to dealing with colitis-associated dysplasia and colorectal cancer (102).

Emerging surveillance techniques

Recently, the use of stool-based surveillance has been considered and the detection of CpG island methylation in human DNA isolated from stool has been proposed for noninvasive screening (103). Kisiel and colleagues (104) demonstrated that methylated gene markers BMP3, vimentin, EYA4, and NDRG4 showed a high discrimination between neoplastic and nonneoplastic tissue (ROC curve of 0.91, 0.91, 0.85, and 0.84 for total IBD neoplasia and 0.97, 0.97, 0.95, and 0.85 for cancer). Azuara and colleagues (105) found that SLIT2 gene methylation was more frequently seen in patients at high risk of dysplasia or cancer as compared with those at low risk (25% vs. 0%, P < 0.01), suggesting this may also be a potential stool-based surveillance biomarker. Several other studies have since been conducted to evaluate the potential of stool-based testing for colitis-associated colorectal cancer surveillance, but to date, no well-validated panels are available for routine clinical use in IBD, and further studies are needed to understand the optimized use of these stool-based biomarkers, and the comparative effectiveness of this approach as compared with currently accepted standards—high-definition colonoscopy with chromoendoscopy (103).

Summary

Significant advances have been made in our understanding and approach to managing colitis-associated colorectal cancer. Despite this, several important gaps remain which will need to be addressed (Table 3). Quantifying the true burden of disease, impact of changing treatment paradigms on disease risk, and identifying subpopulations at greatest risk is of utmost importance as we transition to personalized risk profiling and surveillance. New insights into the pathogenesis of colitis-associated colorectal cancer, and rigorous, comprehensive analyses of genetic and molecular profiles associated with colitis-associated dysplasia and colorectal cancer, could pave the way for targeted chemoprevention and surveillance strategies. Although a great deal of work has been done to optimize the surveillance and management of dysplasia and colorectal cancer, questions remain regarding the optimal integration of novel optical technology, endoscopic therapeutics, and changing risk profiles over time. Well-designed population-level comparative effectiveness studies are needed to optimize the value and utility of colorectal cancer surveillance and screening in IBD.

Disclosure of Potential Conflicts of Interest

W.J. Sandborn reports receiving Commercial Research Grant from Exact Sciences. No potential conflicts of interest were disclosed by the other authors.

  • Received May 11, 2016.
  • Revision received August 25, 2016.
  • Accepted August 30, 2016.
  • ©2016 American Association for Cancer Research.

References

  1. 1.↵
    1. Ekbom A,
    2. Helmick C,
    3. Zack M,
    4. Adami HO
    . Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990;323:1228–33.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Beaugerie L,
    2. Itzkowitz SH
    . Cancers complicating inflammatory bowel disease. N Engl J Med 2015;372:1441–52.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Eaden JA,
    2. Abrams KR,
    3. Mayberry JF
    . The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001;48:526–35.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Lutgens MW,
    2. van Oijen MG,
    3. van der Heijden GJ,
    4. Vleggaar FP,
    5. Siersema PD,
    6. Oldenburg B
    . Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis 2013;19:789–99.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Jess T,
    2. Simonsen J,
    3. Jorgensen KT,
    4. Pedersen BV,
    5. Nielsen NM,
    6. Frisch M
    . Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012;143:375–81.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Herrinton LJ,
    2. Liu L,
    3. Levin TR,
    4. Allison JE,
    5. Lewis JD,
    6. Velayos F
    . Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 2012;143:382–9.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Adami HO,
    2. Bretthauer M,
    3. Emilsson L,
    4. Hernan MA,
    5. Kalager M,
    6. Ludvigsson JF,
    7. et al.
    The continuing uncertainty about cancer risk in inflammatory bowel disease. Gut 2016;65:889–93.
    OpenUrlFREE Full Text
  8. 8.↵
    1. Lashner BA,
    2. Turner BC,
    3. Bostwick DG,
    4. Frank PH,
    5. Hanauer SB
    . Dysplasia and cancer complicating strictures in ulcerative colitis. Dig Dis Sci 1990;35:349–52.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Fumery M,
    2. Pineton de Chambrun G,
    3. Stefanescu C,
    4. Buisson A,
    5. Bressenot A,
    6. Beaugerie L,
    7. et al.
    Detection of dysplasia or cancer in 3.5% of patients with inflammatory bowel disease and colonic strictures. Clin Gastroenterol Hepatol 2015;13:1770–5.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Sonnenberg A,
    2. Genta RM
    . Epithelial dysplasia and cancer in IBD strictures. J Crohn's Colitis 2015;9:769–75.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Peyrin-Biroulet L,
    2. Phelip JM,
    3. Roblin X
    . Is ulcerative colitis proctitis associated with an increased risk of colorectal cancer? Gastroenterology 2009;137:1857–8
    OpenUrl
  12. 12.↵
    1. Soderlund S,
    2. Brandt L,
    3. Lapidus A,
    4. Karlen P,
    5. Brostrom O,
    6. Lofberg R,
    7. et al.
    Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease. Gastroenterology 2009;136:1561–7
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Heuschen UA,
    2. Hinz U,
    3. Allemeyer EH,
    4. Stern J,
    5. Lucas M,
    6. Autschbach F,
    7. et al.
    Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis. Gastroenterology 2001;120:841–7.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Biancone L,
    2. Michetti P,
    3. Travis S,
    4. Escher JC,
    5. Moser G,
    6. Forbes A,
    7. et al.
    European evidence-based Consensus on the management of ulcerative colitis: Special situations. J Crohn's Colitis 2008;2:63–92.
    OpenUrlFREE Full Text
  15. 15.↵
    1. Itzkowitz SH,
    2. Present DH
    . Consensus conference: colorectal cancer screening and surveillance in inflammatory bowel disease. Inflamm Bowel Dis 2005;11:314–21.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Beaugerie L,
    2. Svrcek M,
    3. Seksik P,
    4. Bouvier AM,
    5. Simon T,
    6. Allez M,
    7. et al.
    Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. Gastroenterology 2013;145:166–75
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Nuako KW,
    2. Ahlquist DA,
    3. Mahoney DW,
    4. Schaid DJ,
    5. Siems DM,
    6. Lindor NM
    . Familial predisposition for colorectal cancer in chronic ulcerative colitis: a case-control study. Gastroenterology 1998;115:1079–83.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Askling J,
    2. Dickman PW,
    3. Karlen P,
    4. Brostrom O,
    5. Lapidus A,
    6. Lofberg R,
    7. et al.
    Family history as a risk factor for colorectal cancer in inflammatory bowel disease. Gastroenterology 2001;120:1356–62.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Soetikno RM,
    2. Lin OS,
    3. Heidenreich PA,
    4. Young HS,
    5. Blackstone MO
    . Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002;56:48–54.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Broome U,
    2. Lofberg R,
    3. Veress B,
    4. Eriksson LS
    . Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology 1995;22:1404–8.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Devroede GJ,
    2. Taylor WF,
    3. Sauer WG,
    4. Jackman RJ,
    5. Stickler GB
    . Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 1971;285:17–21.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Ekbom A,
    2. Helmick C,
    3. Zack M,
    4. Adami HO
    . Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet 1990;336:357–9.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Rutter M,
    2. Saunders B,
    3. Wilkinson K,
    4. Rumbles S,
    5. Schofield G,
    6. Kamm M,
    7. et al.
    Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004;126:451–9.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Ullman TA,
    2. Itzkowitz SH
    . Intestinal inflammation and cancer. Gastroenterology 2011;140:1807–16.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Gupta RB,
    2. Harpaz N,
    3. Itzkowitz S,
    4. Hossain S,
    5. Matula S,
    6. Kornbluth A,
    7. et al.
    Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007;133:1099–105
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Rubin DT,
    2. Huo D,
    3. Kinnucan JA,
    4. Sedrak MS,
    5. McCullom NE,
    6. Bunnag AP,
    7. et al.
    Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol 2013;11:1601–8
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Jess T,
    2. Rungoe C,
    3. Peyrin-Biroulet L
    . Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012;10:639–45.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Greenstein AJ,
    2. Sachar DB,
    3. Smith H,
    4. Pucillo A,
    5. Papatestas AE,
    6. Kreel I,
    7. et al.
    Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979;77:290–4.
    OpenUrlPubMed
  29. 29.↵
    1. Gilat T,
    2. Fireman Z,
    3. Grossman A,
    4. Hacohen D,
    5. Kadish U,
    6. Ron E,
    7. et al.
    Colorectal cancer in patients with ulcerative colitis. A population study in central Israel. Gastroenterology 1988;94:870–7.
    OpenUrlPubMed
  30. 30.↵
    1. Torres J,
    2. Pineton de Chambrun G,
    3. Itzkowitz S,
    4. Sachar DB,
    5. Colombel JF
    . Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease. Aliment Pharmacol Ther 2011;34:497–508.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Lunder AK,
    2. Hov JR,
    3. Borthne A,
    4. Gleditsch J,
    5. Johannesen G,
    6. Tveit K,
    7. et al.
    Prevalence of sclerosing cholangitis, detected by magnetic resonance cholangiography, in patients with long-term inflammatory bowel disease. Gastroenterology 2016;151:660–9.
    OpenUrl
  32. 32.↵
    1. Popivanova BK,
    2. Kitamura K,
    3. Wu Y,
    4. Kondo T,
    5. Kagaya T,
    6. Kaneko S,
    7. et al.
    Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest 2008;118:560–70.
    OpenUrlPubMed
  33. 33.↵
    1. Kim S,
    2. Keku TO,
    3. Martin C,
    4. Galanko J,
    5. Woosley JT,
    6. Schroeder JC,
    7. et al.
    Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 2008;68:323–8.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Chan IH,
    2. Jain R,
    3. Tessmer MS,
    4. Gorman D,
    5. Mangadu R,
    6. Sathe M,
    7. et al.
    Interleukin-23 is sufficient to induce rapid de novo gut tumorigenesis, independent of carcinogens, through activation of innate lymphoid cells. Mucosal Immunol 2014;7:842–56.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Tong Z,
    2. Yang XO,
    3. Yan H,
    4. Liu W,
    5. Niu X,
    6. Shi Y,
    7. et al.
    A protective role by interleukin-17F in colon tumorigenesis. PLoS One 2012;7:e34959.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Grivennikov S,
    2. Karin E,
    3. Terzic J,
    4. Mucida D,
    5. Yu GY,
    6. Vallabhapurapu S,
    7. et al.
    IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009;15:103–13.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Brighenti E,
    2. Calabrese C,
    3. Liguori G,
    4. Giannone FA,
    5. Trere D,
    6. Montanaro L,
    7. et al.
    Interleukin 6 downregulates p53 expression and activity by stimulating ribosome biogenesis: a new pathway connecting inflammation to cancer. Oncogene 2014;33:4396–406.
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. Wang S,
    2. Liu Z,
    3. Wang L,
    4. Zhang X
    . NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol 2009;6:327–34.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Agoff SN,
    2. Brentnall TA,
    3. Crispin DA,
    4. Taylor SL,
    5. Raaka S,
    6. Haggitt RC,
    7. et al.
    The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. Am J Pathol 2000;157:737–45.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. De Simone V,
    2. Franze E,
    3. Ronchetti G,
    4. Colantoni A,
    5. Fantini MC,
    6. Di Fusco D,
    7. et al.
    Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene 2015;34:3493–503.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Liu S,
    2. Sun X,
    3. Wang M,
    4. Hou Y,
    5. Zhan Y,
    6. Jiang Y,
    7. et al.
    A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFkappaB and STAT3 in colorectal cancer cells. Gastroenterology 2014;147:847–59
    OpenUrl
  42. 42.↵
    1. Shi C,
    2. Yang Y,
    3. Xia Y,
    4. Okugawa Y,
    5. Yang J,
    6. Liang Y,
    7. et al.
    Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer. Gut 2015;65:1470–81.
    OpenUrl
  43. 43.↵
    1. Triantafillidis JK,
    2. Nasioulas G,
    3. Kosmidis PA
    . Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res 2009;29:2727–37.
    OpenUrlAbstract/FREE Full Text
  44. 44.↵
    1. Willenbucher RF,
    2. Zelman SJ,
    3. Ferrell LD,
    4. Moore DH 2nd.,
    5. Waldman FM
    . Chromosomal alterations in ulcerative colitis-related neoplastic progression. Gastroenterology 1997;113:791–801.
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Befrits R,
    2. Hammarberg C,
    3. Rubio C,
    4. Jaramillo E,
    5. Tribukait B
    . DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis. A 10-year follow-up study. Dis Colon Rectum 1994;37:313–9
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Kim ER,
    2. Chang DK
    . Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis. World J Gastroenterol 2014;20:9872–81.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Burmer GC,
    2. Rabinovitch PS,
    3. Haggitt RC,
    4. Crispin DA,
    5. Brentnall TA,
    6. Kolli VR,
    7. et al.
    Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 1992;103:1602–10.
    OpenUrlPubMed
  48. 48.↵
    1. Itzkowitz S
    . Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. J Clin Gastroenterol 2003;36:S70–4
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Issa JP,
    2. Ahuja N,
    3. Toyota M,
    4. Bronner MP,
    5. Brentnall TA
    . Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 2001;61:3573–7.
    OpenUrlAbstract/FREE Full Text
  50. 50.↵
    1. Fleisher AS,
    2. Esteller M,
    3. Harpaz N,
    4. Leytin A,
    5. Rashid A,
    6. Xu Y,
    7. et al.
    Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res 2000;60:4864–8.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Robles AI,
    2. Traverso G,
    3. Zhang M,
    4. Roberts NJ,
    5. Khan MA,
    6. Joseph C,
    7. et al.
    Whole-exome sequencing analyses of inflammatory bowel disease-associated colorectal cancers. Gastroenterology 2016;150:931–43.
    OpenUrl
  52. 52.↵
    1. Svrcek M,
    2. El-Bchiri J,
    3. Chalastanis A,
    4. Capel E,
    5. Dumont S,
    6. Buhard O,
    7. et al.
    Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability. J Clin Oncol 2007;25:4231–8.
    OpenUrlAbstract/FREE Full Text
  53. 53.↵
    1. Klampfer L
    . Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011;11:451–64.
    OpenUrlCrossRefPubMed
  54. 54.↵
    1. Yaeger R,
    2. Shah MA,
    3. Miller VA,
    4. Kelsen JR,
    5. Wang K,
    6. Heins ZJ,
    7. et al.
    Genomic alterations observed in colitis-associated cancers are distinct from those found in sporadic colorectal cancers and vary by type of inflammatory bowel disease. Gastroenterology 2016;151:278–87.
    OpenUrl
  55. 55.↵
    1. Weber CK,
    2. Liptay S,
    3. Wirth T,
    4. Adler G,
    5. Schmid RM
    . Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 2000;119:1209–18.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Majumdar S,
    2. Aggarwal BB
    . Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J Immunol 2001;167:2911–20.
    OpenUrlAbstract/FREE Full Text
  57. 57.↵
    1. Minghetti PP,
    2. Blackburn WD Jr.
    . Effects of sulfasalazine and its metabolites on steady state messenger RNA concentrations for inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinase in rheumatoid synovial fibroblasts. J Rheumatol 2000;27:653–60.
    OpenUrlPubMed
  58. 58.↵
    1. Gerards AH,
    2. de Lathouder S,
    3. de Groot ER,
    4. Dijkmans BA,
    5. Aarden LA
    . Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology 2003;42:1189–96.
    OpenUrlAbstract/FREE Full Text
  59. 59.↵
    1. Hildner K,
    2. Marker-Hermann E,
    3. Schlaak JF,
    4. Becker C,
    5. Germann T,
    6. Schmitt E,
    7. et al.
    Azathioprine, mycophenolate mofetil, and methotrexate specifically modulate cytokine production by T cells. Ann N Y Acad Sci 1998;859:204–7.
    OpenUrlCrossRefPubMed
  60. 60.↵
    1. Velayos FS,
    2. Terdiman JP,
    3. Walsh JM
    . Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2005;100:1345–53.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Zhao LN,
    2. Li JY,
    3. Yu T,
    4. Chen GC,
    5. Yuan YH,
    6. Chen QK
    . 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis. PLoS One 2014;9:e94208.
    OpenUrlCrossRefPubMed
  62. 62.↵
    1. Bernstein CN,
    2. Nugent Z,
    3. Blanchard JF
    . 5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. Am J Gastroenterol 2011;106:731–6.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Terdiman JP
    . The prevention of colitis-related cancer by 5-aminosalicylates: an appealing hypothesis that remains unproven. Am J Gastroenterol 2011;106:737–40.
    OpenUrlPubMed
  64. 64.↵
    1. Velayos FS,
    2. Loftus EV Jr.,
    3. Jess T,
    4. Harmsen WS,
    5. Bida J,
    6. Zinsmeister AR,
    7. et al.
    Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology 2006;130:1941–9.
    OpenUrlCrossRefPubMed
  65. 65.↵
    1. Matula S,
    2. Croog V,
    3. Itzkowitz S,
    4. Harpaz N,
    5. Bodian C,
    6. Hossain S,
    7. et al.
    Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine. Clin Gastroenterol Hepatol 2005;3:1015–21.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Burr NE,
    2. Hull MA,
    3. Subramanian V
    . Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease? World J Gastroenterol 2016;22:3679–86.
    OpenUrl
  67. 67.↵
    1. Pardi DS,
    2. Loftus EV Jr.,
    3. Kremers WK,
    4. Keach J,
    5. Lindor KD
    . Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003;124:889–93.
    OpenUrlCrossRefPubMed
  68. 68.↵
    1. Hansen JD,
    2. Kumar S,
    3. Lo WK,
    4. Poulsen DM,
    5. Halai UA,
    6. Tater KC
    . Ursodiol and colorectal cancer or dysplasia risk in primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis. Dig Dis Sci 2013;58:3079–87.
    OpenUrl
  69. 69.↵
    1. Singh S,
    2. Khanna S,
    3. Pardi DS,
    4. Loftus EV Jr.,
    5. Talwalkar JA
    . Effect of ursodeoxycholic acid use on the risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2013;19:1631–8.
    OpenUrlCrossRefPubMed
  70. 70.↵
    1. Balkwill F
    . Tumour necrosis factor and cancer. Nat Rev Cancer 2009;9:361–71.
    OpenUrlCrossRefPubMed
  71. 71.↵
    1. Kim YJ,
    2. Hong KS,
    3. Chung JW,
    4. Kim JH,
    5. Hahm KB
    . Prevention of colitis-associated carcinogenesis with infliximab. Cancer Prev Res 2010;3:1314–33.
    OpenUrlAbstract/FREE Full Text
  72. 72.↵
    1. Fidder H,
    2. Schnitzler F,
    3. Ferrante M,
    4. Noman M,
    5. Katsanos K,
    6. Segaert S,
    7. et al.
    Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut 2009;58:501–8.
    OpenUrlAbstract/FREE Full Text
  73. 73.↵
    1. Biancone L,
    2. Orlando A,
    3. Kohn A,
    4. Colombo E,
    5. Sostegni R,
    6. Angelucci E,
    7. et al.
    Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study. Gut 2006;55:228–33.
    OpenUrlAbstract/FREE Full Text
  74. 74.↵
    1. Bongartz T,
    2. Sutton AJ,
    3. Sweeting MJ,
    4. Buchan I,
    5. Matteson EL,
    6. Montori V
    . Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006;295:2275–85.
    OpenUrlCrossRefPubMed
  75. 75.↵
    1. Biancone L,
    2. Petruzziello C,
    3. Calabrese E,
    4. Zorzi F,
    5. Naccarato P,
    6. Onali S,
    7. et al.
    Long-term safety of Infliximab for the treatment of inflammatory bowel disease: does blocking TNFalpha reduce colitis-associated colorectal carcinogenesis? Gut 2009;58:1703.
    OpenUrlFREE Full Text
  76. 76.↵
    1. Ananthakrishnan AN,
    2. Cagan A,
    3. Cai T,
    4. Gainer VS,
    5. Shaw SY,
    6. Churchill S,
    7. et al.
    Statin use is associated with reduced risk of colorectal cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2016;14:973–9.
    OpenUrl
  77. 77.↵
    1. Samadder NJ,
    2. Neklason DW,
    3. Boucher KM,
    4. Byrne KR,
    5. Kanth P,
    6. Samowitz W,
    7. et al.
    Effect of sulindac and erlotinib vs placebo on duodenal neoplasia in familial adenomatous polyposis: a randomized clinical trial. JAMA 2016;315:1266–75.
    OpenUrlCrossRefPubMed
  78. 78.↵
    1. Farraye FA,
    2. Odze RD,
    3. Eaden J,
    4. Itzkowitz SH
    . AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010;138:746–74
    OpenUrlCrossRefPubMed
  79. 79.↵
    1. Nugent FW,
    2. Haggitt RC,
    3. Gilpin PA
    . Cancer surveillance in ulcerative colitis. Gastroenterology 1991;100:1241–8.
    OpenUrlPubMed
  80. 80.↵
    1. Eaden J,
    2. Abrams K,
    3. Ekbom A,
    4. Jackson E,
    5. Mayberry J
    . Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 2000;14:145–53.
    OpenUrlPubMed
  81. 81.↵
    1. Karlen P,
    2. Kornfeld D,
    3. Brostrom O,
    4. Lofberg R,
    5. Persson PG,
    6. Ekbom A
    . Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study. Gut 1998;42:711–4.
    OpenUrlAbstract/FREE Full Text
  82. 82.↵
    1. Lofberg R,
    2. Brostrom O,
    3. Karlen P,
    4. Tribukait B,
    5. Ost A
    . Colonoscopic surveillance in long-standing total ulcerative colitis–a 15-year follow-up study. Gastroenterology 1990;99:1021–31.
    OpenUrlCrossRefPubMed
  83. 83.↵
    1. Ananthakrishnan AN,
    2. Cagan A,
    3. Cai T,
    4. Gainer VS,
    5. Shaw SY,
    6. Churchill S,
    7. et al.
    Colonoscopy is associated with a reduced risk for colon cancer and mortality in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2015;13:322–9
    OpenUrlCrossRefPubMed
  84. 84.↵
    1. Choi CH,
    2. Rutter MD,
    3. Askari A,
    4. Lee GH,
    5. Warusavitarne J,
    6. Moorghen M,
    7. et al.
    Forty-year analysis of colonoscopic surveillance program for neoplasia in ulcerative colitis: an updated overview. Am J Gastroenterol 2015;110:1022–34.
    OpenUrlCrossRefPubMed
  85. 85.↵
    Centre for Clinical Practice at NICE (UK). Colonoscopic surveillance for prevention of colorectal cancer in people with ulcerative colitis, Crohn's disease or adenomas. London, England: National Institute for Health and Clinical Excellence (UK); 2011 (NICE Clinical Guidelines, No. 118). Available from: http://www.ncbi.nlm.nih.gov/books/NBK82209/.
  86. 86.↵
    1. Annese V,
    2. Daperno M,
    3. Rutter MD,
    4. Amiot A,
    5. Bossuyt P,
    6. East J,
    7. et al.
    European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohn's Colitis 2013;7:982–1018.
    OpenUrlFREE Full Text
  87. 87.↵
    1. Cairns SR,
    2. Scholefield JH,
    3. Steele RJ,
    4. Dunlop MG,
    5. Thomas HJ,
    6. Evans GD,
    7. et al.
    Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut 2010;59:666–89.
    OpenUrlAbstract/FREE Full Text
  88. 88.↵
    1. Sengupta N,
    2. Yee E,
    3. Feuerstein JD
    . Colorectal cancer screening in inflammatory bowel disease. Dig Dis Sci 2016;61:980–9.
    OpenUrl
  89. 89.↵
    1. Kornbluth A,
    2. Sachar DB
    . Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010;105:501–23
    OpenUrlCrossRefPubMed
  90. 90.↵
    1. Lutgens M,
    2. van Oijen M,
    3. Mooiweer E,
    4. van der Valk M,
    5. Vleggaar F,
    6. Siersema P,
    7. et al.
    A risk-profiling approach for surveillance of inflammatory bowel disease-colorectal carcinoma is more cost-effective: a comparative cost-effectiveness analysis between international guidelines. Gastrointest Endosc 2014;80:842–8.
    OpenUrl
  91. 91.↵
    1. Velayos FS,
    2. Liu L,
    3. Lewis JD,
    4. Allison JE,
    5. Flowers N,
    6. Hutfless S,
    7. et al.
    Prevalence of colorectal cancer surveillance for ulcerative colitis in an integrated health care delivery system. Gastroenterology 2010;139:1511–8.
    OpenUrlCrossRefPubMed
  92. 92.↵
    1. van Rijn AF,
    2. Fockens P,
    3. Siersema PD,
    4. Oldenburg B
    . Adherence to surveillance guidelines for dysplasia and colorectal carcinoma in ulcerative and Crohn's colitis patients in the Netherlands. World J Gastroenterol 2009;15:226–30.
    OpenUrlCrossRefPubMed
  93. 93.↵
    1. Eaden JA,
    2. Ward BA,
    3. Mayberry JF
    . How gastroenterologists screen for colonic cancer in ulcerative colitis: an analysis of performance. Gastrointest Endosc 2000;51:123–8.
    OpenUrlCrossRefPubMed
  94. 94.↵
    1. Kaplan GG,
    2. Heitman SJ,
    3. Hilsden RJ,
    4. Urbanski S,
    5. Myers RP,
    6. Lee SS,
    7. et al.
    Population-based analysis of practices and costs of surveillance for colonic dysplasia in patients with primary sclerosing cholangitis and colitis. Inflamm Bowel Dis 2007;13:1401–7.
    OpenUrlPubMed
  95. 95.↵
    1. Rodriguez SA,
    2. Collins JM,
    3. Knigge KL,
    4. Eisen GM
    . Surveillance and management of dysplasia in ulcerative colitis. Gastrointest Endosc 2007;65:432–9.
    OpenUrlPubMed
  96. 96.↵
    1. Gearry RB,
    2. Wakeman CJ,
    3. Barclay ML,
    4. Chapman BA,
    5. Collett JA,
    6. Burt MJ,
    7. et al.
    Surveillance for dysplasia in patients with inflammatory bowel disease: a national survey of colonoscopic practice in New Zealand. Dis Colon Rectum 2004;47:314–22.
    OpenUrlPubMed
  97. 97.↵
    1. Marion JF,
    2. Sands BE
    . The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution. Gastroenterology 2015;148:462–7.
    OpenUrlCrossRefPubMed
  98. 98.↵
    1. Wang YR,
    2. Cangemi JR,
    3. Loftus EV Jr.,
    4. Picco MF
    . Rate of early/missed colorectal cancers after colonoscopy in older patients with or without inflammatory bowel disease in the United States. Am J Gastroenterol 2013;108:444–9.
    OpenUrlCrossRefPubMed
  99. 99.↵
    1. Laine L,
    2. Kaltenbach T,
    3. Barkun A,
    4. McQuaid KR,
    5. Subramanian V,
    6. Soetikno R
    . SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastrointest Endosc 2015;81:489–501.
    OpenUrlPubMed
  100. 100.↵
    1. Vaziri H,
    2. Anderson JC
    . White light endoscopy versus chromoendoscopy for the detection of dysplasia during inflammatory bowel disease surveillance with colonoscopy. Gastroenterology 2015;149:1630–2.
    OpenUrl
  101. 101.↵
    1. Mooiweer E,
    2. Oldenburg B
    . Reply: To PMID 25823770. Gastroenterology 2015;149:1632.
    OpenUrl
  102. 102.↵
    1. Soetikno R,
    2. Kaltenbach T,
    3. McQuaid KR,
    4. Subramanian V,
    5. Laine L,
    6. Kumar R,
    7. et al.
    A paradigm shift in the surveillance and management of dysplasia in inflammatory bowel disease. Dig Endosc 2016;28:266–73.
    OpenUrl
  103. 103.↵
    1. Ahlquist DA
    . Molecular detection of colorectal neoplasia. Gastroenterology 2010;138:2127–39.
    OpenUrlCrossRefPubMed
  104. 104.↵
    1. Kisiel JB,
    2. Yab TC,
    3. Nazer Hussain FT,
    4. Taylor WR,
    5. Garrity-Park MM,
    6. Sandborn WJ,
    7. et al.
    Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013;37:546–54.
    OpenUrlCrossRefPubMed
  105. 105.↵
    1. Azuara D,
    2. Rodriguez-Moranta F,
    3. de Oca J,
    4. Sanjuan X,
    5. Guardiola J,
    6. Lobaton T,
    7. et al.
    Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn's colitis patients. Inflamm Bowel Dis 2013;19:165–73.
    OpenUrlCrossRefPubMed
PreviousNext
Back to top
Cancer Prevention Research: 9 (12)
December 2016
Volume 9, Issue 12
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Prevention Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management
(Your Name) has forwarded a page to you from Cancer Prevention Research
(Your Name) thought you would be interested in this article in Cancer Prevention Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management
Parambir S. Dulai, William J. Sandborn and Samir Gupta
Cancer Prev Res December 1 2016 (9) (12) 887-894; DOI: 10.1158/1940-6207.CAPR-16-0124

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management
Parambir S. Dulai, William J. Sandborn and Samir Gupta
Cancer Prev Res December 1 2016 (9) (12) 887-894; DOI: 10.1158/1940-6207.CAPR-16-0124
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Epidemiology
    • Disclosure of Potential Conflicts of Interest
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • E-Cigarettes and Cancer
  • Scented Candles as Risk Factor for Bladder Cancer
  • The Human Microbiome and Cancer
Show more Minireview
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Prevention Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

Advertisement