Risk Of Colonic Neoplasia Research Articles

Serum ferritin and risk of colonic neoplasia: Implications for the workup and treatment of iron deficiency.

Iron deficiency is the most common extraintestinal sign of colonic neoplasia, including colorectal cancer (CRC) and other lower gastrointestinal pathology. Both upper endoscopy and colonoscopy is usually recommended in the work-up of patients with unexplained iron deficiency, particularly in men and postmenopausal women. As the incidence of early-onset CRC (age <50 years) rises in the United States, there is an increasing need to identify risk predictors to aid in the early detection of CRC. It remains unknown if serum ferritin (SF), and what specific threshold, can be used as a marker to stratify those at risk for CRC and other lower gastrointestinal pathology. In this current review of the literature, we aimed to review guidelines for diagnostic workup of colonic neoplasia in the setting of iron deficiency and examine the association and specific thresholds of SF and risk of CRC by age. Some of the published findings are conflicting, and conclusions specific to younger patients are limited. Though further investigation is warranted, the cumulative findings suggest that SF, in addition to considering the clinical context and screening guidelines, may have potential utility in the assessment of colonic neoplasia.

S2505 Holy Cow! When Cecal “Polypectomy” Specimen Shows Cow’s Liver

Introduction: Patients with history of colon tubular adenomas need surveillance colonoscopies to decrease the risk of colon neoplasia. Sometimes, contamination of polypectomy specimen with ingested food can create confusion while interpreting the results. We present an interesting case of a cecal "polypectomy" specimen that showed liver tissue, that on further investigation was attributed to a cow's liver that the patient ingested the day before his procedure. Case Description/Methods: A 72-year-old White male with past medical history of colon tubular adenomas, chronic constipation, hypertension, obstructive sleep apnea and class III obesity was referred for surveillance colonoscopy. His constipation was well-controlled with linaclotide 72 mcg daily. He did not report any hematochezia or weight loss. His physical examination including vital signs and abdominal examination was unremarkable. Colonoscopy was performed after a 4-liter polyethylene glycol bowel preparation which revealed 3 polyps. These included a 5 mm Paris 0-1s polyp which was removed via cold snare polypectomy (Figure A), and 2 2 mm sessile polyps in the ascending and descending colon (removed via biopsy forceps). The ascending and descending colon polyps were tubular adenomas on histological examination. We were notified by the reading pathologist that the cecal "polyp" showed liver tissue (Figure B, C) with the concern for iatrogenic perforation of the colon during colonoscopy and accidental biopsy of patient's liver. The patient denied any symptoms suggestive of colonic perforation. Upon further discussion, he informed us that he ate fried cow's liver the day before the procedure which was inadvertently suctioned in the trap after cold snare polypectomy of his cecal polyp. Discussion: Identification of liver tissue in colonoscopy polypectomy specimens should raise possibility of catastrophic complication such as a perforation or simply a possibility of contamination of specimen with ingested food. Following-up with the patient to clarify the situation is important. A careful review of patient’s dietary intake before the colonoscopy procedure can help correctly interpret the unexpected pathology results.Figure 1.: 1A: Paris 0-1s 5 mm cecal polyp during surveillance colonoscopy. Figure 1B: At low power the section shows an eosinophilic homogenous tissue without surface epithelium. Figure 1C: At higher power: sheets of polygonal cells with round, centrally located nuclei, and abundant eosinophilic cytoplasm compatible with hepatocytes. The hepatocytes arranged in plates extend from central vein to portal triad.

A164 PATTERNS IN MEDICAL THERAPY AND CLINICAL OUTCOMES IN PATIENTS WITH CONCOMITANT INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS: A SINGLE CENTRE RETROSPECTIVE ANALYSIS

Abstract Background Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) is characterized by pancolitis with rectal sparing and is associated with an increased risk of colorectal and biliary malignancies. Currently, pharmacologic management of IBD in the setting of PSC is the same as in IBD alone. Aims To assess patterns in medical therapy, and incidence of adverse outcomes in patients with concomitant IBD and PSC. Methods A retrospective review was conducted on all PSC-IBD patients followed between January 2010 and June 2018. The Endoscopic Mayo Score was used to grade IBD severity in PSC-ulcerative colitis (UC). Results 69 patients were identified, 44 (63.8%) were male. The mean ages of IBD and PSC diagnosis were 28.6 (SD 14.9) and 37.0 (SD 18.9) years, respectively. The median length of follow up was 12 (range 2–49) years. 52 (75.4%) patients had UC, and 17 (24.6%) had Crohn’s disease (CD). 28 (87.5%) PSC-UC patients had pancolitis, and 4 (12.5 %) had proctitis. Among those with pancolitis, 8 (28.6%) had relative rectal sparing. 4 (14.3%) patients had more severe inflammation proximally, whereas only 1 (3.6%) had more severe distal inflammation. 23 (82.1%) patients had the same degree of inflammation throughout. 14 (93.3%) PSC-CD patients had colitis/ileocolitis and 1 (6.7%) had ileitis. Among those with PSC-UC, 16 (50.0%), 12 (37.5%), and 4 (12.5%) patients had grade 1, 2, and 3 disease, respectively. 62 (89.9%) PSC-IBD patients were treated with aminosalicylates, and 26 (37.7%) with biologics at some point in their IBD course. 26 (37.7%) were treated with aminosalicylates alone. 4 (5.8%) did not require any IBD therapy. Cholangiocarcinoma, colorectal cancer, and gallbladder cancer developed in 8 (11.6%), 1 (1.4%), and 1 (1.4%) PSC-IBD patients, respectively. 16 (23.2%) patients required partial or total colectomy. Indication for surgery was inflammation or stenosis, dysplasia, and neoplasia in 13 (81.3%), 2 (12.5%), and 1 (6.3%) patients, respectively. Conclusions The majority of this cohort had UC with mild disease activity. Pancolitis was common, with frequent rectal sparing and more severe right-sided inflammation. Despite the predominance of low-grade colitis, a large portion of patients required treatment with biologics. The incidence of adverse outcomes underscores the need for strict adherence to recommended surveillance practices. Low grade endoscopic activity, typical of the quiescent IBD course in PSC-IBD, may mask low grade histologic inflammation, which in turn may contribute to the increased risk of colonic neoplasia. Further studies are needed to determine the best management strategy for IBD in patients with PSC. Funding Agencies None

Chronic Hepatitis C as a Risk Factor for Colonic Neoplasia in a Community Setting

An estimated 3.5 million people have Chronic Hepatitis C (CHC) in the United States [1]. With the current opioid epidemic, the number of people who are injecting drugs in the US. Has substantially increased the incidence of CHC virus [2]. With an apparent second wave of CHC, it will be important to manage the sequelae of these chronically infected patients and recognize associated comorbidities. CHC has been shown to increase the risk of hepatocellular carcinoma and has been linked to such malignancies as Non-Hodgkin lymphoma, cholangiocarcinoma, breast, pancreatic, renal, skin/oral, thyroid, and colon cancer [3-6]. Colon cancer is the second leading cause of cancer-related death in men in developed countries and the third most prevalent cause of death from cancer for women [7]. Colorectal Cancer (CRC) screening has been shown to reduce the risk for the development of CRC and prevent the development of more advanced disease [8,9]. The risks for developing colorectal cancer are associated with increasing age, family history, history of adenomas or Inflammatory Bowel Diseases (IBD) and ethnicity. Other possible risk factors include a high fat, low-fiber diet, obesity, smoking, and excessive alcohol use. A possible link between colon cancer and CHC has not been extensively studied. However, previous studies have suggested that patients with CHC have a higher risk of colonic adenomas and more advanced lesions. Thus, the goal of this study was to determine if patients with CHC undergoing screening or surveillance colonoscopies in a community setting have an increased risk of colonic neoplasia.

The prevalence of small-bowel polyps on video capsule endoscopy in patients with sporadic duodenal or ampullary adenomas

Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30mm (range, 10-80mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P=.002)). Advanced colonic adenoma (high-grade dysplasia, >10mm, villous histology) were found in 18% of the DA group and 5% of the control group (P=.018). Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.).

Efficacy of various endoscopic modalities in detecting dysplasia in ulcerative colitis: A systematic review and network meta-analysis

BACKGROUNDLongstanding ulcerative colitis (UC) is associated with an increased risk of colonic neoplasia. Various endoscopic modalities, such as chromoendoscopy (CE), narrow band imaging (NBI) and random biopsy have been introduced for surveillance, however, there exists a paucity of direct comparisons between them. We aimed to conduct a network meta-analysis of randomized controlled trials (RCTs) performed for surveillance of neoplasia in UC.AIMTo provide a comparative evaluation of the efficacy of the above-mentioned various modalities.METHODSWe searched MEDLINE/PubMed, Web of Science, Embase, Google Scholar and Cochrane Central Registry through May 2016 for RCTs evaluating the efficacy of endoscopic modalities for surveillance of neoplasia in UC. The primary outcomes of interest were dysplasia (low- or high-grade) detection rates per biopsy and per patient, and dysplasia numbers per patient. Studies were simultaneously analyzed using a random-effects network meta-analysis under the Bayesian framework to identify the modality with the highest dysplasia detection rate. The best ranking probability for the dysplasia detection rate was analyzed by surface under the cumulative ranking (SUCRA) technique.RESULTSSix prospective RCTs of a total 1038 patients were identified. We identified 4 different modalities; white light (WL) high definition (HD) or standard definition (SD), CE HD, and NBI HD. For dysplasia per biopsy, direct meta-analysis showed superiority of NBI HD over WL HD and CE HD over WL SD. Network meta-analysis demonstrated the rank order of best modality as NBI HD, CE HD, WL HD and WL SD with close SUCRA scores of the first two. For dysplasia per patient, direct meta-analyses showed equivocal results between each modality. Network meta-analysis demonstrated the rank order of best modality as WL HD, NBI HD, CE HD and WL SD with small differences of the SUCRA score among the first two. For dysplasia numbers per patient, direct meta-analysis showed superiority of CE HD over WL SD. Network meta-analysis demonstrated the rank order of best modality as WL HD, NBI HD, CE HD, and WL SD with small differences of the SUCRA score among the first three.CONCLUSIONWe demonstrated that there were small differences among WL HD, NBI HD, and CE HD, while WL SD was inferior, in detecting dysplasia in UC.

Nancy Index Scores of Chronic Inflammatory Bowel Disease Activity Associate With Development of Colorectal Neoplasia

The degree of histologic and endoscopic disease activity has been associated with an increased risk of colorectal neoplasia (CRN) in patients with inflammatory bowel diseases (IBDs), but no histologic scoring systems have been validated for determining risk of CRN. We investigated the association between histologic and endoscopic disease activity and risk of first CRN in patients with IBD who had negative findings from a surveillance colonoscopy. We performed a retrospective analysis of consecutive patients who underwent at least 2 colonoscopies at Saint Antoine Hospital in France from January 1, 1996, through March 1, 2015, and whose first procedure was a surveillance colonoscopy. Histologic IBD activity was assessed by the Nancy histologic index. Patients were followed up for a mean 5.7 ± 3.3 years. Logistic regression and generalized estimating equations were used to identify clinical, endoscopic, and histologic factors associated with detection of neoplasia in the inflamed colon mucosa. Among 398 patients who underwent 1277 colonoscopies, we identified 45 patients with CRN. Factors associated with CRN were primary sclerosing cholangitis (odds ratio [OR], 2.65; 95% CI, 1.06-6.61; P= .04), age (OR per 1-year increase, 1.04; 95% CI, 1.01-1.07; P= .003), and mean Nancy histologic index during follow-up evaluation (per 1-unit increase, OR, 1.69; 95% CI, 1.29-2.21; P < .001). After adjustment for established factors, chronic disease activity defined as detection of ulcerations at more than 50% of colonoscopies was not associated with an increased risk of CRN (OR, 1.24; 95% CI, 0.53-2.91; P= .62). In addition to established risk factors, we associated Nancy histologic index scores with development of CRN. Histologic findings based on the Nancy histologic index therefore should be included in determining the risk of colonic neoplasia in patients with IBD.

Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis Frequently Have Subclinical Inflammation in the Proximal Colon

Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have a high risk of colonic neoplasia. Neoplasia frequently develops in the proximal colon in patients with PSC. Histologic inflammation is an independent risk factor for the development of neoplasia; we investigated whether patients with UC and PSC have more subclinical disease activity than patients with UC alone. We performed a retrospective analysis of data from 143 patients (205 examinations) with ulcerative pancolitis who were in clinical remission and treated at a tertiary medical center from May 2011 through May 2016. Endoscopic and histologic activity were compared between patients with PSC (from 36 examinations) and without PSC (from 169 examinations). Disease activity was scored per colonic segment using a modified Mayo endoscopic subscore and histologic assessment. In each colonic segment, differences in disease activity and the degree of discordance between endoscopic and histologic inflammation among UC patients with and without PSC were compared. Patients with UC-PSC had significantly more subclinical endoscopic (odds ratio [OR], 4.21; 95% CI, 1.67-10.63) and histologic activity (OR, 5.13; 95% CI, 2.25-11.68) in the right colon, as well as greater degree of histologic than endoscopic inflammation in the proximal colon (OR, 3.14, 95% CI, 1.24-7.97), compared with patients without PSC. Patients with UC-PSC had significantly less histologic activity in the rectum on multivariate analysis (OR, 0.24; 95% CI, 0.08-0.72). Patients with UC and PSC who are in clinical remission are significantly more likely to have endoscopic and histologic inflammation in the right colon than patients with UC without PSC. Our findings provide insight into cause of colorectal cancer in UC patients with PSC.

Sa1466 - A National Study of Cancer Diagnoses in Irish Liver Transplant Recipients with Primary Sclerosing Cholangitis

Background Primary sclerosing cholangitis (PSC) is associated with an increased risk of cholangiocarcinoma, colorectal and gallbladder cancers. Orthotopic liver transplantation (OLT) patients are at risk of developing de novo malignancies, however limited/conflicting data exists regarding cancer risk post OLT for PSC. Aim To examine all recorded malignancies over 2 decades in OLT-PSC patients; to compare these to non-transplanted PSC cohort; to analyse for any associated factors. Method We studied PSC patients attending SVUH (1/1/1994–30/9/2016). We integrated this database with National Cancer Registry Ireland, to enable accurate determination of number of malignancies. Results 173 PSC pts (75.7% male) have attended SVUH since 1994. 107 (61.8%) have undergone 124 OLT. 27/107 were transplanted for cholangiocarcinoma. 12 de novo cancers (excluding non-melananomatous skin) were found during 737.8 person years of follow-up. Median time to cancer diagnosis post OLT was 5 years. As expected, cholangiocarcinoma as OLT indication (p=0.005) and older age at transplant (p=0.05) were associated with higher mortality. Post-transplant lymphoproliferative disease (PTLD) remains a major complication. 5 pts developed lymphoma post OLT (4.7% of cohort). Two patients developed CRC post OLT; 4 developed colonic dysplasia. 3/4 underwent colectomy. All who developed colonic dysplasia/CRC post OLT had IBD. All 5 colectomies for dysplasia/CRC showed significant co-existing inflammation. Conclusions This represents national cancer figures for PSC-OLT. The rates of PTLD are slightly higher than previously reported. We could not find any association between the development of PTLD and immunosuppressive regimes for IBD post OLT. This study highlights that IBD/PSC patients remain at significant risk of colonic neoplasia after OLT and require intensive surveillance.

Chronic Hepatitis C as a Risk Factor for Colonic Neoplasia in a Community Setting

Introduction: Evidence indicates that patients with chronic hepatitis C (CHC) have an increased risk of neoplasia. Data from tertiary referral centers suggests that HCV may be an independent risk factor for colonic neoplasia. However, the link between colon cancer and CHC in a community setting has not been extensively studied. The goal of this study was to determine if patients with CHC undergoing colonoscopies have an increased risk of colonic neoplasia. Methods: Colonoscopy data were retrospectively collected and compared for patients with CHC and controls who underwent screening (N=370) and surveillance (N=126) between 1993 and 2016. Patients were matched for age, sex, and race. Data based on polyp size and histology was collected. Regression analysis was applied. Results: The screening data consists of 185 patients with CHC and 185 non-hepatitis controls. The surveillance data consists of 67 CHC and 59 controls. Screening data analysis indicated that patients with CHC had a greater number of adenomas in comparison to controls (70% vs 45%; pntrols (31% vs 19%; p< 0.05, respectively). CHC and male sex were found to be independent risk factors for colonic neoplasia on regression analysis. The odds of having polyps in CHC patients was 255% higher than in controls (odds ratio 3.55, 95% confidence interval [CI]: 2.16, 5.94). In the surveillance data, the total number of patients with polyps was higher in the CHC group than in controls (70% vs 47%, p < 0.05). The CHC group also had a higher proportion of patients with tubular adenomas (61% vs 46%, p=0.12). The CHC group had a trend of having polyps larger than 0.75 cm in comparison to controls (25% vs 19%, p=NS). Surveillance data regression analysis revealed CHC as an independent risk factor for the development of colonic neoplasia. The odds of having polyps for CHC patients were 227% higher than in controls (odds ratio 3.27, 95% CI: 1.37, 8.25). Conclusion: This study concludes an association between HCV infections, increased numbers of polyps and more advanced neoplasia in patients undergoing screening colonoscopy. CHC patients undergoing surveillance had greater odds of polyp formation than controls. Further research should decide if this high risk population should undergo screening earlier and/or at decreased intervals.

Colon neoplasia in patients with type 2 diabetes on metformin: A meta-analysis

BackgroundA growing body of evidence has suggested that metformin potentially reduces the risk of cancer. ObjectiveWe performed a meta-analysis of available studies to better define the effect of metformin on colon neoplasia (cancer and polyps) in patients with type 2 diabetes. MethodsMedical literature searches for human studies were performed through December 2015, using suitable keywords. Pooled estimates were obtained using fixed or random-effects models. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger's regression test. In addition subgroup and sensitivity analyses were performed. ResultsA total number of 709,980 patients, with type 2 diabetes, were included in 17 studies eligible for meta-analysis [1 RCT and 16 observational studies (13 cohort and 3 case–controls)]. The risk of colon neoplasia was significantly lower among metformin users than controls (non-metformin users) [pooled RRs (95% CI)=0.75 (0.65–0.87), test for overall effect Z=−3.95, p<0.001]. This observation applied separately for colon cancer [0.79 (0.69–0.91), Z=−3.34, p<0.001] and for colon polyps [0.58 (0.42–0.80), Z=−3.30, p<0.001]. ConclusionThis meta-analysis shows that the use of metformin in patients with type 2 diabetes is associated with significantly lower risk of colon neoplasia.

PTH-031 Knife Assisted Resection for Dysplasia Associated Lesion or Mass: A Video Abstract

Introduction The risk of colonic neoplasia is increased in inflammatory bowel disease. Dysplasia-associated lesion or mass (DALM) can be difficult to detect and challenging to resect endoscopically. Conventional endoscopic mucosal resection (EMR) has been used but as these lesions are often flat morphologically, the snare slips off. Endoscopic submucosal dissection (ESD) has been shown to be able to resect flat lesions, however, they carry a high perforation rate outside the rectum. Knife assisted snare resection (KAR) is a novel technique that combines the principles of EMR and ESD. We aim to evaluate the safety and efficacy of this technique in resecting DALMS as well as demonstrate the technique in the accompanying video abstract. Methods Data of all KARs undertaken by a single endoscopist in our institution from 2012 to 2014 were prospectively compiled in a pre-designed database. 2 independent researchers interrogated the database. Endoscopic follow-up was performed to identify recurrence. Results 9 patients underwent KAR during this period. 8 patients had ulcerative colitis and 1 had Crohn’s colitis. The mean polyp size was 29 mm (10–60 mm). Scarring was noted in 89% of resections despite no previous resection attempts. En-bloc resection was achieved in 7 patients (78%). Endoscopic curative resection was achieved in 7 patients and 1 patient is awaiting endoscopic follow-up. 1 patient experienced a delayed perforation, which was managed surgically. Histological assessment of the resected polyps revealed 8 adenomas with low grade dysplasia and 1 cancer. Conclusion DALMs are difficult to detect and challenging to resect endoscopically using conventional methods. We have demonstrated that KAR as a novel technique is safe and effective in resecting DALMs. As the learning curve of KAR is not as steep as ESD, we believe that is a viable endoscopic resection technique of DALMs in inflammatory bowel disease. Disclosure of Interest None Declared

Recent advances in inflammatory bowel disease.

Recent advances in inflammatory bowel disease.

Colonic carriage of Streptococcus bovis and colorectal neoplasia: a prospective 17-year longitudinal case-control study.

Patients with Streptococcus bovis infective endocarditis have an increased prevalence of advanced colonic neoplasia; however, an association with fecal carriage of the organism is unclear. S. bovis has been shown to promote colonic neoplasia in preclinical studies. The aim of this study was to examine the effect of S. bovis fecal carriage on the long-term risk of colonic neoplasia. Patients were prospectively recruited before colonoscopy. S. bovis was detected by culture in stool, colonic fluid aspirates, and biopsies. Patients continued colonoscopic surveillance at intervals according to accepted guidelines. The National Cancer Registry was checked for diagnoses of colorectal cancer on 31 December 2014. A total of 118 patients were recruited [75 (72.8%) men, aged 64.5±9.3 years] including 15 with S. bovis. The mean duration of follow-up was 190.7±123.5 months. Colonic neoplasia was detected at colonoscopy in six (40.0%) and 49 (47%) patients with and without S. bovis, respectively (P=0.78). At the end of follow-up, colorectal cancer had developed in one (6.7%) S. bovis-positive and six (5.8%) S. bovis-negative patients (P=1.00). Fecal carriage of S. bovis at baseline is not associated with an increased long-term risk of developing colonic neoplasia in this longitudinal study.

Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions between the intestinal microbiota, colonic epithelial barrier, and host immune system, are also discussed.

Primary sclerosing cholangitis and the risk of colon neoplasia in patients with Crohn's colitis.

Background and aim: Crohn’s colitis (CC) is associated with primary sclerosing cholangitis (PSC). However the risk of colon cancer or dysplasia in CC and PSC is unclear. Our aim was to study the risk of colon neoplasia in CC in patients with and without PSC.Methods: This is a nested, case-control cohort study of all patients diagnosed with concurrent CC and PSC, seen at the Cleveland Clinic between 1985 and 2012. Forty-three patients with both CC and PSC were compared with a random sample of 159 CC controls without PSC during the same period.Results: Seven (16.3%) of 43 CC patients with PSC developed colon cancer or dysplasia, compared with 22 (13.8%) of 159 controls (P = 0.98). Of seven colon neoplasia cases in the PSC group, 100% occurred proximal to the splenic flexure, compared with 50% (11/22) cases of colon neoplasia in controls occurring in the proximal colon (P = 0.001). Based on Cox regression analysis, male gender independently increased the risk of neoplasia [hazard ratio (HR) = 2.68; 95% confidence interval (CI) 1.30–5.54; P = 0.008], as did age at CC diagnosis (HR = 1.29; 95% CI 1.14–1.47; P < 0.001), while the use of azathioprine/6-mercaptopurine was protective (HR = 0.30; 95% CI 0.13–0.70; P = 0.005). The presence of PSC did not increase the risk for colon neoplasia (HR = 0.45; 95% CI 0.18–1.13; P = 0.09).Conclusions: CC patients with PSC appear not to be at increased risk of developing colon neoplasia. Among patients in our cohort with colon neoplasia and concurrent PSC, the neoplasia occurred in the proximal colon in all cases.

P468. Appendectomy is associated with an increased risk of colonic neoplasia in Ulcerative Colitis

P468. Appendectomy is associated with an increased risk of colonic neoplasia in Ulcerative Colitis

Comparison of outcomes for patients with primary sclerosing cholangitis associated with ulcerative colitis and Crohn's disease.

Background: The comparative outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) in patients with primary sclerosing cholangitis (PSC) are unclear; the aim of our study was to make an objective comparison.Methods: A total of 273 patients with PSC and inflammatory bowel disease (223 with UC and 50 with CD) were included. Clinical and demographic variables were obtained.Results: The PSC risk score was similar for both groups. The median follow-up period in patients with PSC-UC was 12 years (range 0–38) and that for PSC-CD was 14 years (range 1–36). The median number of disease flares per year was higher in PSC-UC patients than in the PSC-CD group [1vs.0 (ranges 0–20 and 0–9, respectively); P < 0.001]. More patients with UC developed colon neoplasia than CD (35.9% vs.18%; P = 0.009). On proportional hazards analysis for the risk of colectomy, UC patients had a 12% higher risk for colectomy [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.51–1.51; P = 0.64]. Liver transplantation for PSC was associated with decreased risk (HR = 0.57; 95% CI 0.37–0.89; P = 0.013), while colon neoplasia increased the risk (HR = 3.83; 95% CI 2.63–5.58; P < 0.001) for colectomy. On proportional hazards analysis for the risk of colon neoplasia, UC patients had 56% higher risk of developing colon neoplasia than CD (HR = 0.44; 95% CI 0.16–1.25; P = 0.12).Conclusions: PSC patients with CD appear to be associated with a lower risk of colon neoplasia and colectomy than PSC patients with UC.

Endoscopic Appearances in Predicting Colon Neoplasia in Patients With Ulcerative Colitis on Surveillance Colonoscopy

Introduction: Patients with ulcerative colitis (UC) are at an increased risk for colon cancer. Identification of endoscopic features which increase cancer risk may help stratify patient’s risk for cancer. Objective: To investigate whether endoscopic features predict cancer risk in patients with UC on colonoscopic surveillance. Methods: In this retrospective case-control study, patients who underwent surveillance colonoscopies for underlying UC from 1998-2011 were included. The main outcome measurements were the correlation of endoscopic features with the risk of colon neoplasia. Results: One hundred eleven patients with colon neoplasia were compared to 356 patients without colon neoplasia. The median number of colonoscopies in patients with colon neoplasia was 5 (interquartile range: 3-8) compared to 4 (interquartile range: 3-6) in patients without colon neoplasia (p=0.03). On univariate analysis, male gender (odds ratio [OR] 2.58; 95% confidence interval [CI] 1.71, 3.89) and smoking history (OR 1.62; 95% CI 1.1, 2.39) were associated with detection of colon neoplasia in patients with UC, while endoscopic features including tubular colon, featureless colon, scarring, segment of severe inflammation, post-inflammatory polyps were not associated. On multivariate analysis, only male gender (OR 2.68; 95% CI 1.77, 4.08) remained significant in predicting the development of neoplasia. Conclusion: Endoscopic features of prior inflammation appear not to be clinically relevant in predicting colon neoplasia in UC patients. Surveillance colonoscopy needs to be performed carefully in UC patients irrespective of the presence or absence of endoscopic features of prior inflammation.Table 1: Multivariate Analysis of the Cohort