High Risk For Colorectal Neoplasia Research Articles

Abstract 770: The innate immune system response to malignancy- under the radar

Abstract It has become clear that many cancers evade detection by, for example, silencing of immune checkpoints. Re-activation of the immune armamentarium by checkpoint inhibitors has improved survival in many types of cancer. However, we still are unable to gauge the response of the innate immune system (InImS) to incipient malignancy. The InImS is likely both a sentient early warning system and an immediately deployed cancer combatant. We describe a potential marker that quantifies the innate immune system response to multiple deadly tumors. Methods: We obtained a database of patients at high risk of colorectal neoplasia and prospectively noted those who contracted cancer on follow up. We contrasted the historic, premorbid biomarker response from the time of enrolment, primarily using the FERAD ratio. This was obtained by dividing the ferritin blood concentration by the denominator of fecal shedding of a Paneth cell marker, p87. We also compared the FERAD response to the absolute neutrophil:lymphocyte ratio (NLR), a known prognostic biomarker, and also the available, known PDL-1 response for each group of cancers. Results: We found that certain groups of cancers historically had very low FERAD ratios while others were high. Using FERAD ratios for lung, gastric, non-Hodgkin’s lymphoma, melanoma, thyroid, renal, and head and neck cancers, there is a significant inverse correlation between survival and FERAD (r=-0.8;p<0.025) which is similar to that of NLR (r=-0.7;p<0.035). For prostate cancer, breast, colorectal cancer (CRC), leukemia/MDS, there is a direct correlation between survival and FERAD (r=0.99;p<0.002). There is also an inverse relationship between NLR and PDL-1 response rates (r=-0.8;p<0.04). An observed mild positive trend for FERAD PDL-1 response rates may bode well for melanoma, lung, head and neck and renal cancers. Conclusions: Since p87 could be manipulated by dietary means to affect the FERAD ratio favorably, this could be incorporated into more effective chemotherapy regimens and result in better cancer treatment outcomes. Hepatocellular cancer (HCC) and CRC-liver metastasis appear to be immunological outliers. This will need an additional unique approach such as TIGIT intervention therapy (Zheng et al.. Immune checkpoint targeting TIGIT in HCC. Am J Transl Res. 2020). This may allow modulation of the immune response based on FERAD, NLR ratios, and other considerations of mutational burden and genetic mutations, in patients with selected cancers. Citation Format: Martin Tobi, Harvinder Talwar, Benita McVicker. The innate immune system response to malignancy- under the radar [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 770.

Designing a Predictive Model for Colorectal Neoplasia Diagnosis Based on Clinical and Laboratory Findings in Colonoscopy Candidate Patients.

Health authorities have expanded two strategies to diminish CRC-related influence: CR screening and improve diagnostic process in symptomatic patients. The aim of the current study is to design a predictive model to identify the most important risk factors that can efficiently predict patients who have high risk of colorectal neoplasia. A cross-sectional study was constructed to include all patients who had positive test for FIT or had one or more risk factors for colorectal cancer based on the guidelines of detecting high-risk groups for colorectal cancer in Iran. Multivariable binary logistic regression model was constructed for prediction of colorectal neoplasia. We used sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio to check the accuracy. The Hosmer-Lemeshow test, chi-square test, and p value were used to determine the precision of model. Following an AIC stepwise selection model, only nine potential variables, namely gender, watery diarrhea, IBD, abdominal pain, melena, body mass index, depression drug, anti-inflammatory drug, and age, were found to be a predictor of colorectal neoplasia. The best cut-point probability in the final model was 0.27 and results of sensitivity and specificity, based on maximizing these two criteria, were 66% and 62%, respectively. Overall, our model prediction was comparable with other risk prediction models for colorectal cancer. It had a modest discriminatory power to distinguish an individual's neoplasia colorectal risk.

Postgastrectomy gastric cancer patients are at high risk for colorectal neoplasia: a case control study

Background/AimsSeveral studies have shown that colorectal neoplasms (CRN) including colorectal cancer (CRC) may be prevalent in patients with gastric cancer. However, in most of these studies, colonoscopy to investigate the prevalence of CRN was performed prior to surgery. We aimed to investigate whether CRN was more prevalent in postgastrectomy gastric cancer patients than in healthy individuals.MethodsWe reviewed the medical records of those patients within a cohort of gastric cancer patients with gastrectomy who underwent colonoscopy between 2016 and 2017. Controls age- and sex-matched with gastric cancer patients at a 2:1 ratio were identified among those who underwent colonoscopy at a health-promotion center. The frequencies of CRN, advanced CRN (ACRN), and CRC among patients with gastrectomy were compared with those in the control subjects. A total of 744 individuals (gastric cancer, 248; control, 496) were included.ResultsThe rates of CRN and ACRN in the gastric cancer group were higher than those in the healthy individuals (CRN, 47.6% vs. 34.7%, P<0.001; ACRN, 16.9% vs. 10.9%, P=0.020). The rate of CRC was comparable between the 2 groups (2.0% vs. 0.6%, P=0.125). Multivariate analysis identified previous gastrectomy for gastric cancer and male sex as significant risk factors for (A)CRN.ConclusionsCRN and ACRN were more prevalent in patients who underwent surgery for gastric cancer than in the control group. Regular surveillance colonoscopy at appropriate intervals is indicated after gastrectomy.

Oncomir MicroRNA-346 Is Upregulated in Colons of Patients With Primary Sclerosing Cholangitis

INTRODUCTION:Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder that is frequently associated with ulcerative colitis (UC). Patients with PSC and UC (PSC-UC) have a higher risk of colorectal neoplasia compared with patients with UC. The oncogenic properties of microRNA-346 (miR-346) have been recently reported. We investigated the expression of miR-346 and its 2 target genes, the receptor of vitamin D (VDR), and the tumor necrosis factor-α (TNF-α), which are known to modulate carcinogenesis.METHODS:Ascending and sigmoid colon biopsies were obtained from patients with PSC, PSC and UC (PSC-UC), UC, and healthy controls (n = 10 in each group). Expressions of VDR, TNF-α, 18S RNA, p27Kip1, miR-346, and reference microRNA, miR-191, were evaluated by real-time PCR using human TaqMan Gene Expression and TaqMan MicroRNA Assays. Functional studies with miR-346 mimic and inhibitor were conducted in HepG2 and Caco-2 cells. The effect of ursodeoxycholic acid on miR-346 expression was examined in Caco-2 cells.RESULTS:An increased expression of miR-346 in the ascending colon of PSC-UC was observed (P < 0.001 vs all groups). In patients with UC, an exceptionally low colonic expression of miRNA-346 was accompanied by the extensive upregulation of VDR and TNF-α genes. A functional in vitro analysis demonstrated that inhibition of miR-346 resulted in the upregulation of VDR and TNF-α, whereas the induction of miR-346 activity suppressed VDR, TNF-α, and p27Kip1.DISCUSSION:The upregulation of miRNA-346 in the colon of patients with PSC may be responsible for the disturbance of VDR and TNF-α signaling pathway, which could result in an inadequate suppression of neoplasia.

296 Antibiotic Use and Risk of Colorectal Neoplasia: A Systematic Review and Meta-Analysis

INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent cancer and the third leading cause of cancer death for women and men in the United States. There is emerging evidence that the gut microbiome plays a role in CRC development, and antibiotics are one of the most common exposures that can alter the gut microbiome. We performed a systematic review and meta-analysis to characterize the association between antibiotic use and colorectal neoplasia risk. METHODS: We searched Pubmed, EMBASE, and Web of Science for articles describing the relationship between antibiotic exposure and colorectal neoplasia (cancer or adenoma) through October 2018. A total of 5342 citations were identified, which were reviewed independently by two investigators. After screening, we evaluated 15 articles and included 5 in the final analysis. We assessed the association between any antibiotic use as well as intensity of antibiotic use (defined as number of courses or duration of therapy) and colorectal neoplasia risk. Random effects meta-analysis was performed. RESULTS: Four studies provided five estimates for the association between any antibiotic use and risk of colorectal neoplasia. There was a 4% increased risk of neoplasia among individuals exposed to antibiotics (RR 1.04, 95% CI 1.02–1.07, Figure 1), with no evidence of heterogeneity (P = 0.96, I2 = 0%). Five studies provided 13 estimates of the association between antibiotic intensity and colorectal neoplasia. Individuals with the highest intensity of antibiotic exposure had a 13% higher risk of colorectal neoplasia than those with lowest exposure (RR 1.13, 95% CI 1.06–1.21, Figure 2). However, significant heterogeneity was observed (P = 0.04, I2 = 45%). Given the small number of studies, sub-group analyses on antibiotic class could not be performed. CONCLUSION: Antibiotic exposure is associated with a subsequent increased risk of colorectal neoplasia. Furthermore, this relationship appears to be dose-dependent. Given the widespread use of antibiotics in childhood and early adulthood, additional research to further characterize this relationship is needed.

Prospective assessment of the risk for colorectal neoplasia in a Mexican population according to risk categories.

e15158 Background: General population screening can reduce colorectal cancer (CRC) mortality. International guidelines recommend CRC screening for asymptomatic people over 50 years. There is no established national screening program in Mexico. Even in countries with low incidence of CRC such as Mexico, targeted screening of subjects at high risk could decrease resource utilization and cost. Our aim was to describe the distribution among an average-risk population based on risk for colorectal neoplasia (CRN). Methods: We performed a prospective assessment of the risk for CRN among asymptomatic people over 50 years at Instituto Nacional de Ciencias Médicas y Nutrición between 2017-2018. The inclusion was competitive consistent with our age-sex pyramid. We included workers, non-family attendants and patients (internal medicine consultation). Each subject answered a standardized questionnaire, which included information on their age, gender, family history of CRC, diabetes, body mass index (BMI), smoking status and drinking habits. In order to stratify the population according to their risk for CRN, we used the Asia-Pacific Colorectal Screening (APCS) score. Results: We included 256 subjects. Median age was 59 y/o (50-93), 52% were female. 5% had a first-degree relative with CRC. 44% were current or ex-smoker and 9% reported alcohol consumption. 21% had diabetes. The median BMI was 27.3 (17-51). According to the APCS score, 60% were assigned as average risk (AR) and 40% as high risk (HR) for CRN. We observed a higher proportion of HR compared to our previous retrospective data (Table). Conclusions: We prospectively confirmed that using basic clinical information (age, gender, smoking status, family history of CRC, BMI and diabetes), it is possible to identify a subset of asymptomatic subjects at high risk for CRN in whom screening strategies should be prioritized. In developing countries with limited resources, a focus on high risk groups could improve cost effectiveness of screening colonoscopy. Risk stratification based on APCS score. [Table: see text]

Association Between Cotinine-verified Smoking Status and Risk of Colorectal Neoplasia.

We evaluated the association of urinary cotinine-verified smoking status with the risk of colorectal neoplasia (CRN). Many studies have reported the association between the risk of CRN and smoking status, based on self-reported questionnaires. Although self-reported smoking status may be inaccurate, to our knowledge, no study has yet assessed the association between objective biomarkers of tobacco exposure and the risk of CRN. A cross-sectional study was conducted on 96,806 asymptomatic examinees who underwent colonoscopy and urinary cotinine measurements as part of a health check-up. Cotinine-verified current smokers were participants having a urinary cotinine level ≥50 ng/mL. The mean participant age was 38.4 years, and the proportion of cotinine-verified current smokers was 23.0%. Cotinine-verified current smoking was an independent risk factor for CRN [adjusted odds ratio (AOR), 1.49; 95% confidence interval (CI), 1.42-1.56] and advanced CRN (ACRN) (AOR, 1.79; 95% CI, 1.57-2.05). Moreover, the risk of CRN and ACRN increased with increasing cotinine levels. Among self-reported never smokers, cotinine-verified current smokers had a higher risk of CRN (AOR, 1.77; 95% CI, 1.57-2.00) and ACRN (AOR, 1.94; 95% CI, 1.37-2.74) than cotinine-verified never smokers did, whereas among self-reported current smokers, cotinine-verified never smokers had a lower risk of CRN (AOR, 0.78; 95% CI, 0.70-0.87) and ACRN (AOR, 0.71; 95% CI, 0.52-0.98) than cotinine-verified current smokers did. Cotinine-captured smoking status and metabolic variation exhibit associations with CRN more accurately and objectively than self-reporting does, providing clearer evidence for the role of tobacco in the development of CRN.

Patients with breast cancer may be at higher risk of colorectal neoplasia.

BackgroundThe risk of colorectal neoplasia in breast cancer survivors is unclear. This study aimed to determine the colonic adenoma detection rate (ADR) in patients with breast cancer.MethodsWe conducted a retrospective study of patients with breast cancer who underwent a colonoscopy between 2000 and 2017. A control group (n=3295), comprising cancer-free patients undergoing their first screening colonoscopy, was used for comparison.ResultsOf 62,820 breast cancer patients, 3304 met the inclusion criteria. The mean age at the time of first colonoscopy was 59 years. ADR was 55%; 1803 patients had adenomas. High-grade dysplasia was evident in 28% of polyps and invasive adenocarcinoma was detected in 172 patients (5%). The median time from breast cancer diagnosis to adenoma detection was 3 years. The ADR was 21% in patients aged <40 years (n=63) and 39% in patients aged 40-50 years (n=314). The ADR was 26% in patients <50 years with a body mass index (BMI) lower than 30 kg/m2 or no family history of colorectal cancer. Multivariate logistic regression analysis revealed that the following independent factors were associated with a greater risk of colon adenoma: older age, higher BMI, family history of colorectal cancer, and personal history of breast cancer.ConclusionsIn patients with breast cancer, the ADR was higher than the reported rates for the general population. Screening colonoscopy should be considered soon after breast cancer diagnosis in patients <50 years of age. Further prospective studies investigating our findings are warranted.

The risk of colorectal neoplasia can be different according to the types of family members affected by colorectal cancer.

A family history of colorectal cancer (CRC) is an important risk factor for CRC, but more detailed data are needed to prepare effective screening guidelines. We aimed to evaluate the risk of colorectal neoplasia (CRN) among individuals with different relatives affected by CRC (the first-degree relatives [FDRs] or the second-degree relatives or the first cousins) and to assess the effects of family histories according to age groups (30-39, 40-49, and ≥50years). A cross-sectional study was performed on 98562 asymptomatic examinees aged ≥30years who underwent colonoscopy as part of a health checkup. Mean age of the study population was 41.4years, and the prevalence of CRN was 15.7%. Participants with ≥1 FDRs and ≥2 FDRs affected by CRC had a higher risk of CRN than those with no family history of CRC, while those with ≥1 second-degree relatives or first cousins affected did not. In the 30-39 and 40-49years age groups, a family history of CRC in parents was a risk factor for CRN and advanced CRN, but not in siblings. By contrast, in the ≥50 age group, participants with affected siblings (reference group) had a significantly higher risk for advanced CRN than those with affected parents (adjusted odds ratio; 95% confidence interval: 0.39; 0.16-0.94 in father and 0.43; 0.18-0.995 in mother). The risk of CRN can be different according to the types of family members affected, and the impact of such family histories can be different according to age.

Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis.

The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association. A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies. Eleven cohort and 16 case-control studies involving 95397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis. This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].

Performance of quantitative immunochemical test for fecal hemoglobin for surveillance of colorectal neoplasia after polypectomy in clinical practice

SummaryAimsWe examined the yield of immunochemical test for fecal hemoglobin (FIT) for the post‐polypectomy individuals in a colorectal cancer screening program.MethodsWe enrolled 50‐75 years average‐risk individuals who attended a biennial FIT‐based colorectal cancer screening program from March 2010 to December 2011 (index round) and from January 2012 to December 2013 (repeated round). Colonoscopy was recommended to the participants with an FIT ≧ 30 μg Hb/g feces.Participants identified with adenomas and removed by polypectomy in the index round were defined as surveillance group (Sur‐G). Participants with an FIT &lt; 30 μg Hb/g feces in the index round or identified as non‐neoplastic findings of the indexed colonoscopy were defined as repeated screening group (Rsc‐G). We compared key quality indicators for FIT and colonoscopy between Sur‐G and Rsc‐G according to the findings of the repeated round. A p &lt; 0.05 determined by chi‐square test was defined as significant.ResultsThere were 222 post‐polypectomy surveillance (Sur‐G) and 7311 repeated screening individuals (Rsc‐G) enrolled for analysis. The FIT positivity rate, colonoscopy compliance rate and colorectal neoplasia (CRN) detection rate were 504 of 7311 (6.9%) vs. 46 of 222 (20.7%) (p &lt; 0.001); 381 of 504 (75.6%) vs. 44 of 46 (95.7%) (p &lt; 0.001) and 207 of 504 (41.1%) vs. 32 of 46 (69.6%) (p &lt; 0.001) for Rsc‐G and Sur‐G respectively. The FIT positivity rate, colonoscopy compliance rate and CRN detection rate were significantly higher in the Sur‐G.ConclusionsOur results suggest individuals after polypectomy still had high risk of CRN. Biennial FIT may play a role for post‐polypectomy surveillance. Subsequent prospective study is necessary to evaluate the effectiveness of FIT for post‐polypectomy surveillance.Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

Development of a Novel Scoring System for Predicting the Risk of Colorectal Neoplasia: A Retrospective Study.

ObjectiveThe purpose of this study was to develop a novel scoring system to screen subjects who have a high risk for colorectal neoplasia.Study Design and SettingWe retrospectively analyzed 1061 subjects undergoing total colonoscopy (TCS) for the first time at Gihoku Kosei Hospital. The characteristics and habits of the subjects were analyzed using a multivariate logistic regression analysis. The risk score was established according to each odds ratio of the individual risk factors, and the correlations between the sum of the risk scores and the prevalence of colorectal neoplasia for each individual were evaluated.ResultsAge 45–59 (risk score: 2 points) and ≥60 (3 points), male gender (1 point), and habitual alcohol consumption ≥21g daily (1 point) were extracted as the significant risk factors for colorectal neoplasia. When the risk groups were determined by summing up these risk scores, the prevalence rates of colorectal neoplasia were 8.8% for the low risk group (0–2 points), 30.5% for the low-moderate risk group (3 points), 39.1% for the high-moderate risk group (4 points), and 57.6% for the high risk group (5 points). In comparison with the low risk group, the odds ratio of the low-moderate risk, the high-moderate risk, and the high risk groups were 4.6, 6.7, and 14.1 folds, respectively.ConclusionOur scoring system, which linearly correlates with the prevalence rate of colorectal neoplasia, may be an effective tool for screening the subjects who have a high risk for colorectal neoplasia. These subjects, therefore, should be recommended to undergo TCS.

Male pattern baldness and risk of colorectal neoplasia.

Background:Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia.Methods:From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs.Results:Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03–1.62) and 1.31 (95% CI, 1.01–1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06–1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98–1.33).Conclusions:Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.

Mo1953 “SCORE” for Cardiovascular Risk: A Tool for Screening to Detect High Risk of Colorectal Neoplasia

Mo1953 “SCORE” for Cardiovascular Risk: A Tool for Screening to Detect High Risk of Colorectal Neoplasia

Sporadic Duodenal Adenoma and Association with Colorectal Neoplasia: A Case–Control Study

Sporadic duodenal adenomas are uncommon. Prior studies show that patients with sporadic duodenal adenoma have increased risk of colorectal neoplasia and should undergo colorectal screening. However, the nature of the risk, location, and type of colorectal neoplasia are not well studied. We aimed to identify the risk of colorectal neoplasia in patients who have duodenal adenomas. A retrospective case-control study was conducted to identify sporadic duodenal adenoma patients using the databases at one academic center. Colonoscopic findings including histology and location of colorectal cancer neoplasia in sporadic duodenal adenoma patients were compared with a control group of patients without duodenal adenomas who underwent both gastroduodenoscopy and colonoscopy. Hundred and two patients with sporadic duodenal adenomas or adenocarcinomas were identified. Colonoscopy was performed in 47 patients (46%), and colorectal neoplasia was present in 22 (46%). There was a significantly higher rate of colorectal neoplasia in patients with sporadic duodenal adenoma (43%) compared to the control group (24%) odds ratio 4.8, 95% confidence interval (1.7-7.4), but not for advanced colorectal adenoma (9 vs. 26%, p = 0.17). Case patients had significantly more right-sided lesions than matched controls (p = 0.02). Single-center, retrospective study. Individuals with sporadic duodenal adenomas have a significantly higher risk of colorectal neoplasia and proximal location of neoplasia. Therefore, these patients should undergo colonoscopy with particular attention to the right colon.

Colorectal neoplasia in long‐standing ulcerative colitis – a prospective study from a low‐prevalence area

Despite increasing recognition of ulcerative colitis (UC) in Asia in recent decades, reports on the occurrence of colorectal neoplasia (CRN) in UC are scarce and surveillance for this complication is not routinely practised in this region. We aimed to assess the outcome of a newly initiated pilot screening programme for screening CRN among UC patients in India. In this prospective study from an academic hospital setting, patients with UC at high risk of CRN were offered screening by magnifying chromocolonoscopy and the frequency of neoplastic lesions was assessed. Twenty-nine (70.7%) of 41 eligible patients [a median age of 46 (interquartile range 36-54.5) years; 17 (58.6%) men] enrolled for surveillance; 41 colonoscopies were undertaken over 42 months. The median disease duration was 10 (interquartile range 7.5-14.5) years. Sixteen (55.1%) had extensive colitis. On initial screening, low-grade dysplasia (LGD) was seen in five (17.2%) and high-grade dysplasia (HGD) in three (10.3%). Of these three, one accepted proctocolectomy immediately, one underwent surgery for adenocarcinoma and one refused surgery. Twelve follow-up colonoscopies in nine patients revealed three new LGD. High-grade dysplasia and subsequent adenocarcinoma can be detected with careful follow-up in Indian patients with long-standing UC but acceptance of surveillance and subsequent therapy are suboptimal. We found evidence that screening and surveillance programmes are useful for detecting neoplasias in UC, and need to be customized for this region.

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study

Objective. Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. Material and methods. In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. Results. Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0–50) years at the time of Ltx and follow-up after Ltx was 5 (0–20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3–2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. Conclusion. The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.

Sa1841 Targeted Biopsies Using Chromoendoscopy Can Replace Random Biopsies in Patients With IBD at High Risk for Colorectal Neoplasia

try using image processing software. Results To date, 25 subjects have been enrolled, 12 control and 13 cirrhotic patients with documented PHT. Average vessel diameter (AVD) was measured in 249 regions of interest from control vs. 301 regions from subjects with PHT. AVD in controls was 11.4μm (95% CI: 10.5−12.3μm) vs. 17.4μm (95% CI: 15.9−18.9μm) in PHT, p=3.9x10-7. In addition, regression analysis revealed a correlation of r=0.77 (95% CI: 0.54−0.89, p=6.4x10-6) between AVD and the severity of portal gastropathy (none, mild, moderate, severe), and revealed a correlation of r=0.79 (95% CI: 0.58−0.9, p=2.4x10-6) between AVD and variceal grade (0-3). The average columnar cell height (ACCH) within the villus epithelial stripe was measured in 219 control vs. 197 PHT regions. ACCH was 39.4μm (95% CI: 33.9−44.9μm) in controls and 52.8μm (95% CI: 48.6−57μm) in PHT, p=3.5x10-4. ACCH correlated with the severity of portal gastropathy with r=0.66 (95% CI: 0.35−0.84, p=3.6x10-4), and variceal grade with r=0.5 (95% CI: 0.14−0.75, p=0.01). Conclusion: In the duodenal mucosa, PHT appears to be associated with (1) endoscopicallyinapparent microvascular dilatation and (2) altered epithelial cell volume/morphology revealed In Vivo by pCLE. While PHE has been described endoscopically by congestive vascular features, changes in epithelial morphology (swelling) have not been reported quantitatively to our knowledge. Additional studies will define the correlation between microscopic PHE, vascular patterns, epithelial cell volume, and the hepatic venous pressure gradient. Quantitative pCLE may reveal subclinical PHT and serve as a novel and early biomarker of chronic liver disease and its complications.

Chemoprevention of Intestinal Polyps in ApcMin/+ Mice Fed with Western or Balanced Diets by Drinking Annurca Apple Polyphenol Extract

The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 μmol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.

Investigation of the Birt–Hogg–Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer

BackgroundBirt–Hogg–Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially...