Colorectal Cancer In Inflammatory Bowel Disease Patients Research Articles

Occurrence of Colorectal Cancer After a Negative Colonoscopy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Despite the application of colorectal cancer (CRC) surveillance guidelines, the detection of early neoplastic lesions might be difficult in patients with inflammatory bowel disease (IBD). To explore the risk of post-colonoscopy CRC (PCCRC) in patients with IBD we performed a systematic review and meta-analysis. A systematic literature search was performed (PROSPERO; no. CRD42023453049). We included studies reporting the 3-year PCCRC (PCCRC-3y) prevalence, according to World Endoscopy Organization (WEO)-endorsed definition, in IBD and non-IBD patients. As primary outcome we evaluated the PCCRC-3y prevalence, according to WEO definitions, in IBD- and non-IBD patients and calculated the odds ratio (OR). The secondary outcome was to assess risk factors for PCCRC development in IBD patients. Three retrospective observational cohort studies were included. The pooled PCCRC-3y rate in patients with IBD was 30.8% [95% confidence interval (CI)=24.4-37.5%] and in non-IBD patients was 6.8% (95%CI=6.2-7.4%). The PCCRC-3y occurrence in IBD patients was significantly higher than that in non-IBD patients (OR=6.04; 95%CI=4.04-9.4; I2=95%), but a high heterogeneity among studies was noted. Furthermore, patients with ulcerative colitis (UC) had a significantly higher prevalence of PCCRC than patients with Crohn's Disease (CD): 30.9% (95%CI=27.8-34.2%) vs. 22.3% (95%CI=18-27%), respectively (OR=1.6, 95%CI=1.2-2.2; I2=0%). One-third of CRC in IBD patients were PCCRC, and these numbers were significantly higher when compared with those in non-IBD patients. Furthermore, the prevalence of PCCRC in patients with UC was higher compared to those with CD. However, prospective studies are required to better characterize risk factors for PCCRC development in patients with IBD.

Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed.

Risk Factors for Colorectal Cancer in Patients with Inflammatory Bowel Disease and Management During Cancer Treatment: A Systematic Review

Introduction: Inflammatory bowel disease (IBD) is a group of conditions involving inflammation of the gastrointestinal tract. Patients with IBD are at an increased risk of developing colorectal cancer (CRC). Current evidence regarding risk factors for CRC in IBD patients and guidelines for IBD treatment upon cancer diagnosis is inconclusive. A systematic review was conducted to evaluate evidence on risk factors resulting in an increased incidence of CRC among IBD patients and modifications made to IBD management during cancer treatment. Methods: The PubMed database was searched from inception to 2019 with an English-language restriction, and two independent reviewers screened the articles for inclusion according to established criteria. Results: Eight studies (five literature reviews and three retrospective cohort studies) were included. Of the eight articles, six reported several risk factors for CRC in IBD patients such as duration of IBD, extent of IBD, co-existing primary sclerosing cholangitis, family history of CRC, age at IBD onset, vitamin D deficiency, and gender. The other two articles discussed IBD management during cancer treatment in the form of suspending immunosuppressive medications and administering those of an anti-inflammatory nature. Discussion: An individualized, case-by-case approach for IBD patients diagnosed with cancer was recommended. No standardized course of treatment was found. Conclusion: Despite the limitations of this review, numerous potential risk factors for CRC in IBD patients were identified. However, a lack of definitive evidence pertaining to modifications made to IBD management during cancer treatment suggests that additional research is needed to draw material conclusions.

Risk factors for colorectal cancer in IBD patients

A characteristic feature of inflammatory bowel diseases (IBD) is an increased risk of neoplasia and colorectal cancer (CRC). The introduction of screening programs, as well as modern advances in therapy and endoscopic technologies, awareness of the risk factors of IBD-associated CRC will contribute to reducing the frequency of this dangerous complication of IBD. The presented review describes epidemiological data on the incidence of IBD-associated CRC, established risk factors for CRC, as well as modern methods of prevention, screening and early diagnosis. Literature search was conducted in PubMed and Google Scholar systems by keywords: inflammatory bowel diseases, ulcerative colitis, Crohn’s disease, colorectal cancer, risk factors, screening, endoscopy, dysplasia.

Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

ABSTRACT Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn’s disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P < .01) and 3.56 (95% CI 1.4–9.2, P < .01)). In this multicentre observational study, a limited number of taxa were associated with neoplasia and exploratory microbiota clusters co-associated with clinical features, including neoplasia risk in UC. Given the very small number of cancers, the robustness of these findings will require assessment and validation in future studies.

Colitis-Associated Colorectal Cancer in Patients with Inflammatory Bowel Diseases in a Tertiary Referral Center: A Propensity Score Matching Analysis.

Background: Inflammatory bowel disease (IBD) is a risk factor in developing colitis-associated colorectal cancer (CA-CRC). CA-CRC causes the death of about 15% IBD patients and the risk is 1.5–2.4 fold higher among IBD sufferers than in the general population. The dysplasia CA-CRC develops in a different mechanism in comparison to sporadic colorectal cancer (CRC). This study aimed at evaluating the surgical treatment and its outcomes as well as 5-year survival rates in the CA-CRC and sporadic CRC patients. Materials and methods: This single-center, retrospective, propensity score-matched case-control study was conducted with 2204 patients operated on due to primary CRC, who were hospitalized from 2003 to 2019. The CA-CRC group consisted of 49 patients with CRC in the course of IBD. The sporadic CRC group was selected with the propensity score matching technique and comprised 98 patients with sporadic CRC who did not have clinical or histopathological features characteristic for IBD. Results: CA-CRC is characterized by a more aggressive clinical course. Surgical treatment of CA-CRC involves more palliative operations and is related with a higher risk of perioperative and postoperative complications. Further studies of CA-CRC risk factor stratification and the development of molecular markers hold promise in reducing CRC in IBD patients in the future were warranted.

The outcome of patients with inflammatory bowel disease\u2013associated colorectal cancer is not worse than that of patients with sporadic colorectal cancer\u2013a matched-pair analysis of survival

PurposePatients with inflammatory bowel disease (IBD) have an increased risk for colorectal cancer (CRC). In IBD patients, cancer is often diagnosed in advanced stages and conflicting data on survival compared to sporadic CRC have been reported. The aim of this study was to directly compare clinical characteristics and prognosis of patients with IBD-CRC and sporadic CRC.MethodsThe clinical and pathological data of 63 patients with IBD-CRC and 3710 patients with sporadic CRC treated at the University Hospital of Erlangen between 1995 and 2015 were compared. Forty-seven M0 patients with IBD were matched with sporadic CRC patients after curative resection (R0) according to tumor localization, stage, sex, and year of treatment. Overall and disease-free survival were compared.ResultsSixty-three patients presented IBD-CRC. Fifty were affected with ulcerative colitis (UC) and 13 with Crohn’s disease (CD). CRC was diagnosed within 1.45 years since last endoscopic surveillance. Twelve patients (19%) had a diagnosis of primary sclerosing cholangitis. In matched analysis, IBD patients were diagnosed with CRC at younger age compared to sporadic CRC and were more likely to have right-sided CRC (40% versus 23.3%) and rare histological subtypes (19% versus 9.2%). No differences in 5-year overall (78.7 versus 80.9 months) and 5-year disease-free survival (74.5 versus 70.2 months) were noted.ConclusionIBD-CRC patients were younger and more frequently had right-sided carcinomas compared to sporadic CRC. CRC in IBD patients did not show survival difference compared to matched-pair sporadic CRC patients without distant metastases after curative resection. Surveillance might be important for early detection of CRC in IBD patients.

P596 Risk of colorectal cancer and other malignancies in association with the use of thiopurines, tumour necrosis factor antagonists or mesalazine

Abstract Background Mesalazine, thiopurines and TNF antagonists play an important role in management of inflammatory bowel disease (IBD). It is generally accepted that longstanding ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). In addition to colorectal cancer, there are data that suggest that IBD is also associated with an increased risk of extra-intestinal malignancies but the results are inconclusive. The evidence concerning the effects of mesalazine on the risk of CRC in IBD patients remains conflicting. Methods In this review, cancer-reported outcomes with IBD drugs reported to FAERS (USA) were extracted for adalimumab, infliximab, thiopurines and mesalazine and compared with all other 25’382 drugs in the database. The data were used to calculate reporting odds ratio (ROR) and 95% CI for CRC, lymphoma, Hodgkin’s disease and all cancers outcomes. A sub-analysis was conducted to include patients exposed to mesalazine alone without IBD co-medications. Results The databases contained approximately 17 million reports for all drugs of which 401’084 were for adalimumab, 121 562 for infliximab, 11’985 for mesalazine, and 25’286 for thiopurines. Of these, a total of 259 757 concerned cancer-related AEs associated with the drugs under consideration. All IBD drugs were associated with a positive ROR for CRC with infliximab presenting the highest point estimate 8.01 (CI 95% 7.48–8.59) and adalimumab the lowest 2.52 (CI 95% 2.35–2.69). Considering patients exposed to only mesalazine, this association remained positive at 2.39 (CI 95% 1.58–3.59). For lymphoma, all IBD drugs also showed a positive ROR where thiopurines were associated with the highest 7.25 (CI 95% 6.69–7.84) and mesalazine with the lowest 1.46 (CI 95% 1.14 -2.73) point estimate. With regards to patients only exposed to mesalazine, the association showed protective effect, 0.24 (CI 95% 0.13–0.47). For Hodgkin’s disease again all IBD drugs showed a positive ROR where thiopurines were associated with the highest 34.65 (CI 95% 28.88–41.59) and adalimumab with the lowest 4.98 (CI 95% 4.39 -5.65) point estimate. In patients only exposed to mesalazine, no association 0.66 (CI 95% 0.09–4.66) was observed. Considering all cancers only positive ROR were observed where infliximab was associated with the highest 7.31 (CI 95% 7.17–7.45) and mesalazine with the lowest 1.33 (CI 95% 1.17–1.51) point estimate. In patients only exposed to mesalazine, a protective effect 0.73 (CI 95% 0.61–0.88) was observed. Conclusion FAERS data showed an association between reported occurrence of cancer and the drugs under consideration. Considering patients only exposed to mesalazine the odds ratio was positive only for colorectal cancer but lower than all other IBD drugs.

P198 Colorectal cancer diagnosis in patients with inflammatory bowel disease in Spain: A room for improvement

Abstract Background Ulcerative colitis (UC) and Crohn’s disease (CD) are inflammatory bowel diseases (IBD), characterised by chronic inflammation of the digestive tract. IBD patients have an increased risk of developing colorectal cancer (CRC) compared with the general population. A proper screening in this population is essential to guarantee an early CRC diagnosis and maximise the success of the treatment. The aim of the study was to analyse the usual clinical practice in the diagnosis of CRC in IBD patients in Spain, and possible areas of improvement. Methods This preliminary qualitative study was carried out through the creation of four round tables with gastroenterologists and oncologists from different cities of Spain. The opening and closing tables were composed by 1 representative of the Confederation of Associations of Patients with CD and UC of Spain, an expert patient, a nurse from an IBD Unit, a representative of the Spanish Working Group on CD and UC, a gastroenterologist, an oncologist. The first one was necessary to point out the issues that were considered as the most important ones to be discussed in the round tables. In the closing table, all the debates were analysed in order to formulate conclusions. Results According to health professionals, the average delay time from the suspicion of an IBD flare, until the diagnosis of a CRC, is 3 months. The difficulty and delay in the diagnosis of CRC is generally attributed to the fact that the symptoms of the two pathologies usually overlap. Medical specialists currently suggest performing chromoendoscopy, in order to increase the rate of early detection of CRC. However, even if patients’ management and CRC prevention are described by the ECCO guidelines, we identify a lack of standardisation of the techniques for the diagnosis of CRC, which cannot guarantee an equal follow-up of IBD patients at the national level. Also, it can vary not only depending on the geographical area, but also in the centre. The reasons why the follow-up cannot be done – or is not done properly, are the lack of time, human resources, diagnostic tools and patient collaboration. Conclusion From a quantitative point of view, specialists perceive the early CRC underdiagnosis in IBD patients as a minor problem, since they agree that there may be little escaping to the screenings that are routinely performed to these patients. On the other hand, at a qualitative level they recognise it is a major problem, since a delay in diagnosis or misdiagnosis can lead to patient’s death. Thus, hospital administrations should provide resources that allow an adequate follow-up of all IBD patients. Also, the creation of multidisciplinary units would guarantee better management of these patients.

Interval Colorectal Cancer in Inflammatory Bowel Disease: The Role of Guideline Adherence.

Factors associated with interval colorectal cancer (CRC) development in the inflammatory bowel disease (IBD) population remain unclear. Among a cohort of patients with interval CRC, we aimed to evaluate IBD characteristics, colonoscopy quality indicators, and surveillance guideline adherence. We performed a retrospective review of IBD- and non-IBD-associated interval CRCs diagnosed between January 2007 and December 2014 within a large US healthcare system. We evaluated risk factors for CRC among patients with IBD. We assessed adherence to surveillance guidelines according to the American Society for Gastrointestinal Endoscopy (IBD surveillance) and the US Multi-Society Task Force on Colorectal Cancer (polyp surveillance). We compared colonoscopy quality measures between patients with and without IBD. Among 5345 cases of colonic adenocarcinoma, we detected 15 IBD-associated cases of interval CRC and 230 non-IBD-associated cases of interval CRC. Compared to patients without IBD, IBD patients were younger (54.5 vs. 70.4years; p < 0.0001) and experienced a shorter interval between index colonoscopy and CRC diagnosis (20.7 vs. 35.1months; p = 0.0009). Fifty three percent (8/15) of interval CRCs in IBD patients were detected within surveillance guidelines. All IBD patients with interval CRC detected after guideline surveillance interval had high-risk features, including active inflammation, previous low-grade or indefinite dysplasia, multiple pseudopolyps on index colonoscopy, or a first-degree relative with CRC. There were no differences in colonoscopy quality measures between patients with and without IBD. This study stresses the importance of strict short-interval surveillance for IBD patients with high-risk features, including active inflammation on index colonoscopy.

Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.

Screening and surveillance methods for dysplasia in inflammatory bowel disease patients: Where do we stand?

Patients with long-standing ulcerative colitis (UC) and extensive Crohn’s colitis (CC) are at increased risk for dysplasia and colorectal cancer (CRC). Several studies have shown that UC extending proximal to the rectum, CC involving at least 1/3 of the colon, co-existence of primary sclerosing cholangitis, undetermined or unclassified colitis, family history of CRC and young age at diagnosis appear to be independent risk factors for inflammatory bowel disease (IBD) - related CRC. Therefore, screening and surveillance for CRC in IBD patients is highly recommended by international and national guidelines, whilst colonoscopy remains the unequivocal tool in order to detect potentially resectable dysplastic lesions or CRC at an early stage. Although the importance of screening and surveillance is widely proven, there is a controversy regarding the time of the first colonoscopy and the criteria of who should undergo surveillance. In addition, there are different recommendations among scientific societies concerning which endoscopic method is more efficient to detect dysplasia early, as well as the terminology for reporting visible lesions and the management of those lesions. This article concisely presents the main endoscopic methods and techniques performed for detecting dysplasia and CRC surveillance in patients with IBD focusing on their evidence-based accuracy and efficiency, as well as their cost-effectiveness. Finally, newer methods are mentioned, highlighting their applicability in daily endoscopic practice.

P058 INCREASES IN HEMOGLOBIN ARE ASSOCIATED WITH A DECREASED RISK FOR COLORECTAL CANCER IN VETERAN’S AFFAIRS INFLAMMATORY BOWEL DISEASE PATIENTS

Colorectal cancer (CRC) has long been associated with inflammatory bowel disease (IBD), thought to be due to chronic mucosal inflammation. With newer IBD treatments, the incidence of CRC is decreasing, possibly due to improved therapies or improved treatment endpoints. Our primary aim was to assess for risk factors for CRC in IBD patients compared to IBD patients with adenomas to identify those at higher risk for CRC to target preventive measures. We performed a retrospective case-control study at a Veteran’s Affairs (VA) medical center. Data collection included IBD history, presence of active inflammation, history of prior adenomas, family history of CRC, labs, endoscopy and pathology results at the time of CRC or adenoma diagnosis (Table 1). The cases of CRC were then compared to a cohort of IBD patients with adenomas matched for age, IBD diagnosis, and gender. A matched-pair (1 case: 2 controls) conditional logistic regression model used backward, forward, and stepwise procedures for variable selection. Only 17 IBD patients with CRC (8 UC, 9 CD) met criteria and were disease- and age-matched with 34 IBD patients with adenomas (16 UC, 18 CD) (Table 2). In the IBD cases, a higher hemoglobin was found to have an estimated odds ratio of 0.343 (95% CI 0.137 – 0885). This indicates that with one unit increase in hemoglobin, the odds of developing colon cancer is decreased by 65%. No other variables were significant. In this single-center, case-control, retrospective analysis, higher hemoglobin levels were associated with a lower risk of having CRC. This finding is likely due to mucosal healing or due to occult blood loss in those with CRC. Though larger studies are still needed, our results suggest no difference between IBD patients with CRC versus adenomas and stress the importance of regular CRC surveillance in IBD patients, particularly those with anemia.

P282 Despite surveillance and increased use of biologics and immunosuppressives colorectal cancer detection in IBD patients remains unchanged over the past ten years

Inflammatory bowel disease (IBD) is considered a risk factor for colorectal cancer (CRC). Patients with IBD are at higher risk of CRC compared with normal population and therefore undergo surveillance colonoscopy according to national guidelines which have changed over the past 10 years. Globally, the cumulative risk has generally reduced over the years and it is likely due to better management of IBD and robust surveillance practices. We aimed to study impact and outcomes of surveillance in our IBD patients with changing surveillance guidelines. We reviewed all patients with IBD undergoing surveillance during a 10-year period from 2007 to 2017 in our tertiary care centre. Patients with histological reports confirming any grade of dysplasia (low grade, high grade) or CRC were included. Lesions indefinite for neoplasia were excluded. All electronic clinical records were reviewed and relevant data compiled using the endoscopy, histology, and radiology databases. Patients were also analysed as a sub-group if found to have CRC. Eighty-three patients (M = 58) were diagnosed with dysplasia or cancer (median age 65 years range 34–87 years) between 2007–2017. Eighty (97%) patients had ulcerative colitis (UC) and 40 (48%) had pancolitis. Seventy-five patients had identifiable lesions at endoscopy (polypoid = 35; non-polypoid = 11; other findings including pseudopolyps = 29). 76.2 % of lesions were in the left colon and rectum. Fifty-two patients underwent surgery based on surveillance findings, the majority having a panproctocolectomy. Of 28 patients (M = 20) diagnosed to have CRC in this cohort, 20 adenocarcinomas were diagnosed on histology of biopsies at colonoscopy. Of 28 CRC, 26 were associated with UC, 2 with Crohn’s disease, and 5 had primary sclerosing cholangitis. 70% of the CRC were in left colon and rectum. Only 32% of patients had surveillance within 5 years of cancer detection and majority had white light endoscopy (WLE) with random biopsies; 4 CRC patients had previous surveillance within 1 year. 29% had active disease on endoscopy. Over the 10-year period there was no change in the detection rate of dysplasia or CRC. In our cohort of patients, male gender and UC were associated with higher risk of CRC. Our data show high interval cancer risk highlighting that WLE with random biopsies are likely to miss early dysplastic lesions. There was no change in detection rate of CRC in IBD patients over 10-year period. Unless surveillance techniques and protocols are rigorously optimised, the risk of interval CRC should be kept in mind when implementing guidelines regarding surveillance frequency.

Inflammatory Bowel Disease Adversely Impacts Colorectal Cancer Surgery Short-term Outcomes and Health-Care Resource Utilization.

Objectives:Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC) compared to patients without IBD. There is a lack of population-based data evaluating the in-patient surgical outcomes of CRC in IBD patients. We sought to compare the hospital outcomes of CRC surgery between patients with and without IBD.Methods:We used the National Inpatient Sample (2008–2012) and Nationwide Readmissions Database (NRD, 2013) and selected all adult patients (age ≥18 years) with ulcerative colitis (UC) or Crohn’s disease (CD) who underwent CRC surgery. Multivariate analysis for in-patient outcomes of postoperative complications, health-care resource utilization, readmission rate, and mortality were performed.Results:A total of 397,847 patients underwent CRC surgery from 2008 to 2012, of which 0.8% (3,242) had IBD. Compared to CRC in non-IBD patients, CRC in IBD patients had longer length of stay (adjusted coefficient (AC) 0.86 days, 95% confidence interval (CI): 0.42, 1.30), more likely developed postoperative complications (adjusted odds ratio (AOR) 1.26, 95% CI: 1.06, 1.50), including postoperative infection (AOR 1.69, 95% CI: 1.20, 2.38) and deep vein thrombosis (AOR 2.42, 95% CI: 1.36, 4.28), and more frequently required blood transfusion (AOR 1.59, 95% CI: 1.30, 1.94). CRC in IBD patients was more likely to be readmitted within 30 days (AOR 1.44, 95% CI: 1.01, 2.04).Conclusion:At a population level, IBD adversely impacts outcomes at the time of CRC surgery.

Associations between single-nucleotide polymorphisms and inflammatory bowel disease-associated colorectal cancers in inflammatory bowel disease patients: a meta-analysis.

To assess the correlation between single-nucleotide polymorphisms (SNPs) and inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in IBD patients. A systematic search of PubMed, EmBase, and Cochrane databases was performed. Five genetic models (allelic, dominant, recessive, heterozygous and homozygous models) were used to analyze the associations, and trial sequential analysis was used to analyze the robustness of the results. We collected and analyzed the results of seven trials including a total of 2287 patients in our meta-analysis. A total of 8 SNPs were tested in IBD patients. For rs1800629 of TNF-α, the allelic model showed that polymorphism at this locus significantly increased the risk of IBD-associated CRC in IBD patients (OR 4.45, 95% CI 3.18-6.21, P<0.001). The results also showed a significant association between rs1800629 and an IBD-associated CRC population (heterozygous model: OR 4.335, 95% CI 2.329-8.069, P<0.001; homozygous model: OR 11.5, 95% CI 2.498-52.592, P=0.002; dominant model: OR 4.986, 95% CI 2.754-9.026, P<0.001; recessive model: OR 7.208, 95% CI 1.588-32.72, P=0.01). Other studies have found that mutation of rs1143627 of IL1B (allelic model: OR 2.97; 95% CI 1.74-5.05, P<0.001) and rs1050152 of OCTN1 (allelic model: OR 1.637, 95% CI 1.078-2.485, P=0.021) increased the proportion of IBD-associated CRC in the population. Moreover, there were significant associations between IBD-associated CRC and ITLN rs2274910, gene desert rs1551398 and rs4871611, FCGR2A rs1801274, and S100-Z rs7712957 in the allelic model. Associations between SNPs and the proportion of IBD-associated CRC in IBD patients were examined, and further investigation of additional SNPs and their association with the risk of morbidity is needed.

DOP069 Natural history of dysplasia and colorectal cancer in IBD patients in Belgium tertiary care centers

Background: Inflammatory bowel disease (IBD) patients are at increased risk of developing dysplasia and colorectal cancer, namely colitis-associated colorectal cancer (CAC). Ulcerative colitis (UC) and Crohn's disease (CD) patients are recommended to undergo screening and surveillance colonoscopy. However, large study populations are needed to understand the natural history of dysplasia and CAC and improve their management in IBD patients. Methods: This is a national long-term follow-up retrospective study to evaluate the natural history of low-grade dysplasia (LGD), high-grade dysplasia (HGD) and CAC in IBD patients in Belgium tertiary referral regional and academic centers within the Belgian Inflammatory Bowel Disease Research and Development group. Clinical, endoscopic and pathological data were retrieved through retrospective electronic chart review. All biopsies and surgical specimen were reviewed by a second independent expert IBD pathologist. Results: 195 IBD patients (105 CD, 83 UC, and 7 unclassified IBD) with in total 466 lesions (dysplasia/CAC) were identified. From these 466 lesions, 391 were LGD (346 raised, 45 flat), 40 were HGD (35 raised, 5 flat), and 35 were CAC. Median age at IBD diagnosis was 42 years (IQR 29–57). From the 195 affected patients, 161 (83%) had only dysplasia, while 34 (17%) had CAC (26 CD, 8 UC; 20 men, 14 women). Median disease duration was significantly longer in patients with CAC compared to those with dysplasia (13 (IQR 4–27) vs 7 (IQR 1–16) years; p=0.03). Overall 11 (7.6%) out of 146 patients with firstly diagnosed LGD have progressed to more advanced neoplasia (6 HGD, 5 CAC) after median follow-up of 43 months (IQR 16–79). 27/34 (79%) IBD patients with CAC were diagnosed with CAC without evidence of prior dysplasia, while 7/34 (21%) developed CAC secondarily. Among them, 4 (57%) had early stage CAC, and 3 (43%) had advanced stage (stages II-IV) at diagnosis, while in patients without prior history of dysplasia, 10 (37%) had early stage at diagnosis. CAC was diagnosed during colonoscopy in 26 patients, and at surgery (performed for pre-existing dysplasia (n=2), or for IBD therapeutic management (n=6)) in 8 patients. Table 1 Conclusions: This is one of the largest cohorts of IBD patients with dysplasia and CAC never described so far. The rate of progression of LGD to advanced neoplasia remains low with the limitation of a retrospective study. CAC diagnosis is mostly done during colonoscopy with no prior history of dysplasia. CAC was found incidentally at surgery for indications of dysplasia and refractory disease.

The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC). The risk factors of CRC in IBD patients include long disease duration, extensive colitis, severe histological inflammation, and coexistence with primary sclerosing cholangitis (PSC). Several molecular pathways that contribute to sporadic CRC are also involved in the pathogenesis of colitis-associated CRC. It is well established that long-standing chronic inflammation is a key predisposing factor of CRC in IBD. Proinflammatory pathways, including nuclear factor kappa B (NF-κB), IL-6/STAT3, cyclooxygenase-2 (COX-2)/PGE2, and IL-23/Th17, promote tumorigenesis by inducing the production of inflammatory mediators, upregulating the expression of antiapoptotic genes, and stimulating cell proliferation as well as angiogenesis. Better understanding of the underlying mechanisms may provide some promising targets for prevention and therapy. This review aims to elucidate the role of these signaling pathways in the pathogenesis of colitis-associated CRC using evidence-based approaches.

Patients' knowledge and fear of colorectal cancer risk in inflammatory bowel disease.

To investigate knowledge and fear of colorectal cancer (CRC) risk in inflammatory bowel disease (IBD) patients. A 12-item self-administered questionnaire, developed after a careful literature review, was administered to all consecutive IBD patients treated with infliximab who were followed up at Nancy University Hospital (Vandoeuvre-lès-Nancy, France) between February and May 2012. Altogether 100 patients including 72 with Crohn's disease (CD) were included. Only 7.0% of patients spontaneously mentioned CRC risk as a main feature of IBD and 37.0% as a potential IBD complication. CRC was the most feared complication by 26 patients [ulcerative colitis (UC) 46.4% vs CD 18.1%, P < 0.01]. Two-thirds of patients knew that IBD increases CRC risk (UC 81.9% vs CD 57.1%, P = 0.02). Their main source of information was their gastroenterologist (52.0%). On the best screening method for CRC, 86.0% of the respondents mentioned colonoscopy. Only 32.0% of patients knew that it has to be performed 10 years after diagnosis. In case of dysplasia, 51.0% of the patients would not undergo colectomy (CD 59.7% vs UC 28.6%, P < 0.01), mainly due to the fear of having ostomy bags. Only one-quarter of UC patients were aware of the chemopreventive effect of 5-aminosalicylates on CRC risk. Two-thirds of IBD patients are aware of the risk of CRC. UC patients have a better knowledge of this risk and are more afraid of this complication. Our results underscore the need for therapeutic education about CRC in IBD patients.

Hyperhomocysteinemia as a potential contributor of colorectal cancer development in inflammatory bowel diseases: a review.

Homocysteine is an amino acid generated metabolically by the S-adenosylmethionine-dependent transmethylation pathway. In addition to being a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Patients suffering from inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are at increased risk of developing colorectal cancer in comparison to healthy individuals. Furthermore, the risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. In the present article, we review the mechanisms in which hyperhomocysteinemia may contribute to increased risk of colorectal cancer in IBD patients.