Risk Of Colorectal Neoplasia Research Articles

Association of Antibody Responses to Helicobacter pylori Proteins with Colorectal Adenoma and Colorectal Cancer.

Helicobacter pylori (H. pylori) has been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology. Immunoglobulin (Ig) A and G antibody responses to thirteen proteins of H. pylori were measured by a Luminex-based multiplex assay in plasma from patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85) and controls (n = 100). Multivariable logistic regression was used to assess the association of bacterial seropositivity with colorectal neoplasia. The threshold for overall seropositivity required subjects to be positive for at least 4 out of the 13 tested antigens. In a cohort subset with matched data (n = 34), H. pylori seropositivity was correlated with bacterial abundance in both neoplastic and matched normal tissue. While no association was found between H. pylori seropositivity and the presence of CRC, IgA seropositivity to CagA was associated with a decreased risk of advanced adenoma (odds ratio, OR = 0.48, 95% confidence intervals, CIs: 0.24-0.96). Regarding IgG, higher antibody responses to HpaA was associated with advanced adenoma occurrence (OR = 2.46, 95% CI: 1.00-6.01), while responses to HP0395, CagA and Catalase were associated with polyp development (OR = 2.65, 95%, CI: 1.31-5.36, OR = 1.83, 95% CI: 1.01-3.32, and OR = 2.16, CI: 1.09-4.29, respectively). Positive correlations were found between H. pylori abundance in the normal mucosa and levels of both the IgA and IgG antibody response to Catalase and VacA antigens (r = 0.48, p < 0.01; r = 0.37, p = 0.04; r = 0.51, p < 0.01; and r = 0.71, p = 0.04, respectively). Conversely, H. pylori abundance was negatively correlated with levels of IgA antibody response to HpaA and with IgG antibody response to HP0231 in the diseased tissue (r = -0.34, p = 0.04 and r = -0.41, p = 0.01, respectively). The association between levels of H. pylori antigens and colorectal neoplasia risk gradually decreased with the adenoma progression, implicating the early activation of the immune response at the polyp stage. Thus, the evaluation of antibody response to certain bacterial antigens may indicate the presence of early-stage colorectal neoplasia. Further studies are needed to clarify the role H. pylori or the immune response to its antigens may have in colorectal carcinogenesis stages.

Association between Diverticulosis and Colorectal Neoplasia: Analysis from a Large Austrian Database.

Background: Colorectal neoplasia and diverticulosis are common findings on colonoscopies. While adenomas are precursors to colorectal cancer, diverticulosis is usually asymptomatic but can lead to diverticulitis. Despite their prevalence and coexistence, the relationship between these conditions remains unclear. This study investigates whether diverticulosis is associated with adenomas, considering shared risk factors and potential inflammation-driven mechanisms. Methods: We examined 6154 asymptomatic individuals undergoing colorectal cancer screening in Austria. Diverticulosis and colorectal neoplasia were documented during screenings based on macroscopic definitions. Advanced neoplasia was defined as polyps >1 cm or high-grade dysplasia. Associations between diverticulosis and neoplastic findings were assessed using univariate and multivariable logistic regression models. Results: Although the overall incidence of any polypoid lesion was higher in the diverticulosis group (37% vs. 30%), statistical analysis revealed a comparable rate of advanced neoplasms in both groups. Importantly, no significant link between diverticulosis and advanced neoplasms was found (OR 1.125; 95% CI: 0.933 to 1.357, p = 0.218) even after adjusting for confounding factors. In a univariate analysis, a statistically significant association between diverticulosis and the presence of any colorectal polyps was identified (OR 1.388; 95% CI: 1.244-1.549, p < 0.0001). However, after adjusting for confounding factors in model 2 (OR 1.065, 95% CI: 0.942 to 1.204, p = 0.314) and model 3 (OR 1.071, 95% CI: 0.925 to 1.239, p = 0.360), this effect was also not statistically significant. Conclusions: Patients with diverticulosis share demographic and clinical features with those at risk of colorectal neoplasia, such as older age, male gender, and higher cardiometabolic risk. However, diverticulosis does not independently increase the risk of advanced colorectal neoplasia or unspecified polypoid lesions.

Family History of Colorectal Cancer and the Risk of Colorectal Neoplasia: A Systematic Review and Meta-Analysis.

Although there is enough pooled evidence supporting the positive association between family history of colorectal cancer (CRC) in first-degree relatives (FDRs) and the risk of CRC, synthesized data on its association with the risk of other colorectal neoplasia are lacking. Therefore, we aimed to systematically assess this issue. We searched PubMed, Web of Science, and Embase from database inception through May 9, 2024, to identify observational studies investigating the association between family history of CRC in FDRs and the risk of colorectal neoplasia (excepting CRC). Adenoma, nonadvanced adenoma (NAA), advanced adenoma (AA), and advanced neoplasia (AN) were further chosen as main outcomes because of data availability. Random-effects model was used for data synthesis. Subgroup meta-analyses were performed to evaluate the robustness of results. Of 5,172 initial records screened, 75 studies (with 931,515 participants) were identified for analysis. Family history of CRC in FDRs was associated with increased risk of adenoma (pooled odds ratio [OR] 1.67, 95% confidence interval [CI] 1.46-1.91), NAA (pooled OR 1.35, 95% CI 1.21-1.51), AA (pooled OR 1.66, 95% CI 1.46-1.88), and AN (pooled OR 1.58, 95% CI 1.44-1.73). The positive associations persisted in all examined subgroups. The risk of adenoma (pooled OR 4.18, 95% CI 1.76-9.91), AA (pooled OR 2.42, 95% CI 1.72-3.40), and AN (pooled OR 2.00, 95% CI 1.68-2.38) was more evident among individuals with 2 or more affected FDRs. Family history of CRC is associated with increased risk of adenoma, NAA, AA, and AN totally, and in all available subgroups. The findings further strengthen the necessity and importance of an intensified screening strategy for individuals with a positive family history of CRC, which is very useful for related health resource allocation and policymaking.

S556 Quality Indicators of Endoscopists for Baseline and Surveillance Colonoscopy are Associated With Risk of Metachronous Colorectal Neoplasia

S556 Quality Indicators of Endoscopists for Baseline and Surveillance Colonoscopy are Associated With Risk of Metachronous Colorectal Neoplasia

Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use

BackgroundSurveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals...

Incidence of rectal cancer after colectomy for inflammatory bowel disease: nationwide study.

Inflammatory bowel disease increases the risk of colorectal neoplasia. A particular problem arises in patients who have undergone subtotal colectomy leaving a rectal remnant. The risk of future rectal cancer must be accurately estimated and weighed against the risks of further surgery or surveillance. The aim of this study was to estimate the 10-year cumulative incidence of rectal cancer in such patients. A nationwide study using England's hospital administrative data was performed. A cohort of patients undergoing subtotal colectomy between April 2002 and March 2014 was identified. A competing risks survival analysis was performed to calculate the cumulative incidence of rectal cancer. The effect of the COVID-19 pandemic on endoscopic surveillance was investigated using time-trend analysis. A total of 8120 patients were included and 61 patients (0.8%) were diagnosed with cancer. The cumulative incidence of rectal cancer was 0.26% (95% c.i. 0.17% to 0.39%), 0.49% (95% c.i. 0.36% to 0.68%), and 0.77% (95% c.i. 0.57% to 1.02%) at 5, 10, and 15 years respectively. A previous diagnosis of colonic dysplasia (HR 3.34, 95% c.i. 1.01 to 10.97; P = 0.047), primary sclerosing cholangitis (HR 5.42, 95% c.i. 1.34 to 21.85; P = 0.018), and elective colectomy (HR 1.83, 95% c.i. 1.11 to 3.02; P = 0.018) was associated with an increased incidence of rectal cancer. Regarding endoscopic surveillance, there was a 43% decline in endoscopic procedures performed in 2020 (333 procedures) compared with 2019 (585 procedures). The incidence of rectal cancer after subtotal colectomy is low. Asymptomatic patients without evidence of rectal dysplasia should be carefully counselled on the possible benefits and risks of prophylactic proctectomy.

Metachronous Colorectal Neoplasia in Young Adults With Advanced Neoplasia Undergoing Colonoscopy: A Comparison of Risk by Age

The risk of metachronous advanced colorectal neoplasia (mACRN) in young adults with advanced lesions at baseline colonoscopy is not well defined. To examine the risk for (mACRN) in adults <50 years old who had advanced neoplasia (AN) at baseline colonoscopy and determine factors associated with mACRN in these patients. Patients 18 to 49 years of age with ≥1 AN [tubular adenoma (TA) ≥10mm or with villous features or high-grade dysplasia (HGD), sessile serrated lesion (SSL) ≥10mm or with dysplasia, traditional serrated adenoma (TSA)] on baseline colonoscopy between 2011 and 2021 who had surveillance colonoscopy >6 months after their baseline examination were included. Outcomes were assessed based on age at baseline colonoscopy, <45 years versus 45 to 49 years, and by follow-up colonoscopy findings: (1) normal, (2) nonadvanced neoplasia (NAN), and (3) AN. Three hundred sixty-six patients with AN underwent ≥1 surveillance colonoscopy: 310 (84.7%) <45 years versus 56 (15.3%) 45 to 49 years. The mean follow-up time was longer for the <45-year-olds versus the 45 to 49-year-olds (43±26.4 vs. 28.4±12.8mo respectively, P<0.001). The absolute risk of mACRN was 13.5% in the <45 age group versus 16.1% in the 45 to 49 age group, P=0.28. The 3-year cumulative incidence rates of mACRN were comparable for patients <45 and 45 to 49 years old: 10% (95% CI: 10% to 42%) versus 20% (95% CI: 7% to 15%), P=0.065. BMI was the only risk factor associated with mACRN OR 1.045 [95% CI (1.001 to 1.09)]. In our cohort of patients <50 years old with AN at baseline, mACRN occurred at a similar rate to that reported by guidelines in 50 years and older, suggesting that current recommended post polypectomy surveillance is appropriate for this age group. BMI was independently associated with mACRN. Future studies should examine how weight management in patients with high BMI mitigates the recurrence of advanced neoplasia.

Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia.

The significance of serrated epithelial change (SEC), defined as endoscopically invisible hyperplastic polyp (HP)-like mucosal change identified in patients with inflammatory bowel disease (IBD), remains unclear. Although some studies reported an increased risk of synchronous and/or metachronous colorectal neoplasia in patients with SEC, including advanced neoplasia (high-grade dysplasia or colorectal cancer), the development of SEC is not significantly associated with increased colonic inflammation. This contrasts with the reported positive correlation between increased colonic inflammation and the risk of colorectal neoplasia in ulcerative colitis, arguing against the notion that SEC may represent a form of dysplasia. As such, this study aimed to characterize the features of synchronous and metachronous dysplasia detected in patients with SEC to identify factors contributing to the increased risk of colorectal neoplasia, including advanced neoplasia, observed in a subset of these patients. Clinicopathologic features of 46 IBD patients with SEC (n=109) and synchronous and/or metachronous dysplasia (n=153) were analyzed. All dysplastic lesions were subtyped as either conventional or nonconventional dysplasia. As controls, 45 IBD patients with endoscopically visible or polypoid HP (n=75) and synchronous and/or metachronous dysplasia (n=87) were analyzed. The SEC group included 28 (61%) men and 18 (39%) women with a mean age of 58 years and a long history of IBD (mean duration: 23 years). The majority of patients (n=34; 74%) had ulcerative colitis, and 12 (26%) had Crohn's disease. Thirty-nine (85%) patients had a history of pancolitis, and 2 (4%) had concomitant primary sclerosing cholangitis. Twenty-seven (59%) patients had multifocal SEC. SEC was predominantly found in the left colon (n=52; 48%) and rectum (n=34; 31%). Dysplasia in the SEC group was often endoscopically invisible or flat (n=42; 27%) and demonstrated nonconventional dysplastic features (n=49; 32%). Six nonconventional subtypes were identified in the SEC group, including 17 (11%) dysplasia with increased Paneth cell differentiation, 12 (8%) hypermucinous dysplasia, 8 (5%) crypt cell dysplasia, 7 (5%) goblet cell deficient dysplasia, 3 (2%) sessile serrated lesion-like dysplasia, and 2 (1%) traditional serrated adenoma-like dysplasia. Advanced neoplasia was detected in 11 (24%) patients. The SEC group was more likely to have nonconventional dysplasia (32%, P <0.001), invisible/flat dysplasia (27%, P <0.001), and advanced neoplasia (24%, P <0.001) than the control group (7%, 2%, and 0%, respectively). High-risk nonconventional subtypes (ie, hypermucinous, crypt cell, and goblet cell deficient dysplasias) accounted for 18% of all dysplastic lesions in the SEC group, which were not seen in the control group ( P <0.001). The SEC group (n=35; 76%) also had a higher rate of concordance between the location of SEC and the area of synchronous/metachronous dysplasia than the control group (n=22; 49%) ( P =0.007). In conclusion, dysplasia detected in patients with SEC is often endoscopically invisible/flat (27%), nonconventional (32%, including the high-risk subtypes), and found in the same colonic segment as SEC (76%), which may in part explain why some patients with SEC are associated with an increased risk of colorectal neoplasia, including advanced neoplasia. The finding of SEC may warrant a careful follow-up colonoscopy with increased random biopsy sampling, especially in the segment of colon with SEC.

Risk prediction of advanced colorectal neoplasia varies by race and neighbourhood socioeconomic status

ObjectiveNeighbourhood deprivation increases the risk of colorectal neoplasia and contributes to racial disparities observed in this disease. Developing race-specific advanced colorectal neoplasia (ACN) prediction models that include neighbourhood socioeconomic status...

Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

Although the increased risk of colorectal neoplasia in patients with both primary sclerosing cholangitis (PSC) and ulcerative colitis (UC; termed PSC-UC) is well documented, the mechanism through which concomitant PSC increases the risk of colorectal neoplasia remains unclear. Given that the risk of colorectal neoplasia in UC is positively correlated with increased histologic inflammation, this study sought to investigate whether increased histologic inflammation could be used to stratify the risk of dysplasia development in patients with PSC-UC. Twenty patients with PSC-UC and dysplasia were compared with 30 control patients with PSC-UC who had no history of neoplasia. For each patient, all surveillance biopsies were scored using a 4-point scoring system: (1) no epithelial neutrophils = 0, (2) cryptitis only = 1, (3) cryptitis plus crypt abscess in <50% of crypts = 2, and (4) crypt abscess in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration = 3. A score was designated for each biopsy, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores derived from all colonoscopies for each patient were used to determine the patient's overall mean, maximum, and inflammation burden scores. In both the dysplasia and control groups, the 3 summative inflammation scores were calculated independently for the entire colon, right colon, and left colon. The dysplasia group consisted of 14 (70%) men and 6 (30%) women, with a mean age of 27 years at UC diagnosis and a long history of pancolitis (mean duration: 17y). A total of 49 dysplastic lesions were detected in the dysplasia group, and 8 (40%) of the 20 patients had multifocal dysplasia. The majority of dysplastic lesions belonged to nonconventional subtypes (n = 28; 57%) and were located in the right colon (n = 37; 76%). Irrespective of the colon segment, there was no significant difference in the 3 summative inflammation scores between the dysplasia and control groups ( P > 0.05). However, in each group, the 3 summative inflammation scores were significantly higher in the right colon than in the left colon ( P < 0.05). In conclusion, patients with PSC-UC exhibit increased histologic inflammation in the right colon compared with the left colon, regardless of the presence of dysplasia. Although this may provide an explanation for the predominance of right-sided colorectal neoplasia in patients with PSC-UC, increased histologic inflammation does not reliably predict an elevated risk of dysplasia in patients with PSC-UC. These findings reinforce the current recommendation for annual endoscopic surveillance for all patients with PSC-UC, irrespective of the extent and severity of inflammation.

Predictive Score for Advanced Colorectal Neoplasia Based on Cardiovascular and Colorectal Cancer Risk Factors.

Background and Aims: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. Materials and Methods: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients, respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE, and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). Results: CRN were found in 379 subjects from the derivation cohort (36%), including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS) showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p < 0.001). In the validation cohort, the AUC of CRNAS for advanced CRN was 0.67 (95% CI: 0.57-0.76). Conclusions: The newly validated CRNAS has a better discriminatory capacity to predict advanced CRN than cardiovascular scores. It may be useful for selecting candidates for screening colonoscopy, especially in those with cardiovascular risk factors.

Management of colorectal neoplasia in IBD patients: current practice and future perspectives.

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal neoplasia (CRN). In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard (cold snare) polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity (size, delineation, morphology, surface architecture, submucosal fibrosis/invasion) to maximize the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. While (sub)total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualization with shortened intervals for at least 5 years after treatment of CRN.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. 477 patients with serrated polyps were eligible (mean age 61years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.

The Development of Serrated Epithelial Change in Ulcerative Colitis is not Significantly Associated With Increased Histologic Inflammation.

Serrated epithelial change (SEC) in inflammatory bowel disease is most often defined as hyperplastic polyp-like mucosal change detected on random biopsies. Although SEC has been reported to be associated with an increased risk of synchronous and/or metachronous colorectal neoplasia, it remains unknown if SEC represents a form of dysplastic lesion despite the lack of morphologic evidence of dysplasia. Since the risk of colorectal neoplasia in ulcerative colitis (UC) is positively correlated with increased histologic inflammation, this study investigated if increased colonic inflammation is an independent risk factor for SEC. A cohort of 28 UC patients with SEC was analyzed and compared with 51 control UC patients without SEC. None of these patients had a history of colorectal neoplasia. For each patient with SEC, all biopsies conducted before and at the time of SEC diagnosis (versus all biopsies for each control patient) were scored by using a 4-point scoring system: no activity (no epithelial infiltration by neutrophils=0); mild activity (cryptitis only=1); moderate activity (cryptitis plus crypt abscess formation in <50% of crypts=2); and severe activity (crypt abscess formation in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration=3). Each biopsy was designated a score, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores of all colonoscopies for each patient were used to assign the patient's overall mean, maximum, and inflammation burden scores. The SEC cohort included 12 (43%) men and 16 (57%) women with a mean age of 47 years at the time of the first SEC diagnosis and a long history of UC (mean: 13y). The majority of patients (n=21; 75%) had pancolitis, and only 1 (4%) patient had primary sclerosing cholangitis. A total of 37 SEC were identified in the 28 patients, 4 (14%) of whom had multifocal SEC. SEC was predominantly found in the left colon (n=32; 86%). In the multivariate analysis, none of the 3 summative inflammation scores, including overall mean (odds ratio [OR] 1.9, P =0.489), maximum (OR 0.4, P =0.259), and inflammation burden scores (OR 1.2, P =0.223), were significantly associated with the development of SEC. Similarly, no other potential risk factors, including age, gender, ethnicity, and duration and extent of UC, were significantly correlated with the detection of SEC ( P >0.05). In conclusion, the development of SEC in UC is not significantly associated with increased histologic inflammation. Given the reported association of SEC with an increased risk of synchronous and/or metachronous colorectal neoplasia, along with the presence of molecular alterations in some cases (such as TP53 mutations and aneuploidy), SEC may represent an early morphologic indicator of segmental or pan-colonic molecular abnormalities that have not advanced enough to result in colorectal neoplasia, as opposed to being a form of dysplasia.

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&amp;lt;0.025) which is similar to that of NLR (r=-0.7;p&amp;lt;0.035). For prostate cancer, breast, colorectal cancer (CRC), leukemia/MDS, there is a direct correlation between survival and FERAD (r=0.99;p&amp;lt;0.002). There is also an inverse relationship between NLR and PDL-1 response rates (r=-0.8;p&amp;lt;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.

Performance of the Asia-Pacific Colorectal Screening score in stratifying the risk of advanced colorectal neoplasia: A meta-analysis and systematic review.

This study systematically reviewed and meta-analyzed the performance of the Asia-Pacific Colorectal Screening (APCS) score and its incorporation with the fecal immunochemical test (FIT) in stratifying the risk of advanced colorectal neoplasia (ACN). We systematically searched for relevant articles in 12 electronic databases and registers on October 20, 2021, and updated the search to September 1, 2023. Random-effect models were used to obtain the pooled performance statistics of the APCS score for ACN risk. From the 101 records screened, 13 eligible studies in the Asia-Pacific region involving 69762 subjects who had undergone colonoscopy were enrolled. The pooled prevalences of ACN in the average-risk (AR) tier (APCS 0-1), moderate-risk (MR) tier (APCS 2-3), and high-risk (HR) tier (APCS≥4) groups were 0.9%, 3.1%, and 8.1%, respectively. Compared with the combined AR-MR group, the HR group was significantly associated with a higher ACN risk (pooled diagnostic odds ratio: 2.84, 95% confidence interval [CI]: 2.35-3.45, P<0.001). The APCS score showed a sensitivity of 0.42 (95% CI: 0.40-0.44) and a specificity of 0.86 (95% CI: 0.85-0.86) for predicting the ACN risk, with a weighted area under the curve of 0.642 (95% CI: 0.610-0.657). The combination of the APCS score and FIT substantially improved ACN risk identification, demonstrating pooled diagnostic odds ratios of 4.02 (95% CI: 2.50-6.49) in the AR-MR groups and 5.44 (95% CI: 1.89-15.63) in the MR-HR groups. The APCS score could effectively stratify the ACN risk in the Asia-Pacific population. Incorporating FIT further improves its performance in identifying high-risk subjects who should be prioritized for colonoscopy screenings.

The Association of Metabolic Risk Factors with Advanced Adenomas in Hispanic Patients.

Obesity and metabolic syndrome (MetS) have been implicated as rising risk factors for the development of colorectal cancers. A rapid increase in the prevalence of obesity and severe obesity among Hispanic patients in the United States may present substantially increased risk for advanced colorectal neoplasia in this population. Currently, there is very little research in this area. We sought to identify metabolic risk factors for advanced adenomas (AA) in Hispanic Americans. We retrospectively reviewed data from the Los Angeles General (LAG) Medical Center of asymptomatic Hispanic patients above 45 years of age who underwent their first colonoscopies following a positive screening FBT. Patient demographics, metabolic characteristics, as well as colon polyp size and histology were recorded. Polyps were classified as adenomas or AA (including both high-risk adenomas and high-risk serrated polyps). Relative risk for AA was assessed by multivariate logistical regression analyses. Of the 672 patients in our study, 41.4% were male, 67% had adenomas, and 16% had AA. The mean BMI was 31.2kg/m2. The mean HDL-C was 49.5mg/dL (1.28 mmol/L) and the mean triglyceride level was 151mg/dL. 44.6% had diabetes and 64.1% had hypertension. When comparing patients with AA to patients with no adenoma, male sex, BMI > 34.9kg/m2, and elevated fasting triglyceride levels were associated with an increased risk of AA. FIB-4 ≥1.45 was also associated with an increased risk of AA in males. There was no significant difference in the risk of AA with diabetes, hypertension, FIB-4 score, LDL-C level, and HDL-C level. Hispanic patients with a positive FBT were observed to have a high incidence of AA. Class II obesity (BMI ≥ 35kg/m2), elevated triglyceride levels were identified as risk factors among males in our study. Early interventions to address these modifiable risk factors in at-risk populations, such as multi-disciplinary weight management programs for the treatment of obesity and related co-morbidities, could potentially lead to risk reduction and CRC prevention.

A270 RISK FACTORS FOR COLORECTAL NEOPLASIA DEVELOPMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE-CONTROL STUDY

Abstract Background Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients. Aims We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk. Methods This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up. Conclusions The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD. Funding Agencies None

P188 Cumulative inflammatory burden as a risk factor for colorectal neoplasia in inflammatory bowel disease patients with primary sclerosing cholangitis: a multi-center case-control study

Abstract Background Inflammatory bowel disease (IBD) patients with concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN, but it is unknown whether this also applies to PSC-IBD patients. We aimed to assess the impact of chronic mucosal inflammation per colonic segment on CRN risk in PSC-IBD patients. Methods This is a multi-center case-control study including cases with PSC-IBD and CRN and controls with PSC-IBD without CRN. Subjects were included from 8 medical centers in Canada and the Netherlands. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and &amp;lt;2 available colonoscopy reports. Data was collected on demographics, IBD and PSC disease characteristics, CRN lesions, and endoscopy reports between 1977 and 2023. Pan-colonic and segmental (right colon, transverse colon, left colon, rectum) endoscopic cumulative inflammatory burden scores were calculated as the sum of (mean) endoscopic inflammation severity between colonoscopies x length of the surveillance interval until index procedure. The index procedure was the colonoscopy during which CRN was detected (cases) or randomly selected and matched for disease duration (controls). The primary outcome was a CRN diagnosis, secondary outcomes were CRN grade and location, time to CRN (Kaplan-Meier curve), pan-colonic cumulative inflammatory burden, cumulative inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 335 PSC-IBD patients (224 UC, 101 CD) with a median follow-up of 8 years (IQR: 5.0-14.0) and 6 endoscopies (IQR: 4.0-8.0). Median disease duration was 19.5 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-19.0). Advanced neoplasia (HGD or CRC) was found in 35 out of 102 cases (34%). Fifty-six (55%) cases were diagnosed with &amp;gt; 1 lesion, and 43 (42%) had ≥ 1 right-sided lesion. Median time to index CRN was 17 years (IQR: 8.0-24.0). Sixty-six patients underwent (sub)total colectomy or proctocolectomy, including 49 (74%) due to CRN diagnosis. There was no difference in pan-colonic cumulative inflammatory burden scores (mean scores: 4.7 (cases) and 3.7 (controls); P=0.21, 95%-CI: -2.52-.56) and segmental scores (mean scores: 4.9 (cases) and 4.1 (controls); P=0.27, 95%-CI: -2.29-.65) between cases and controls. Mortality was 13% (n=45.) Conclusion In this large multi-center cohort study, the risk for CRN-associated colectomy in PSC-IBD was high, while pan-colonic and segmental cumulative inflammatory burden scores were not associated with CRN risk.

Ulcerative colitis complicated with hypermucinous dysplasia.

Patients with ulcerative colitis are at increased risk for colorectal neoplasia compared to the general population. The risk factors include family history of colorectal cancer, wide extent of colitis, disease duration, cumulative inflammatory burden, and primary sclerosing cholangitis. Here, we report a case of colorectal neoplasia developed in a patient with ulcerative colitis.