Advanced Colorectal Polyps Research Articles

MO16-5 Identification and evaluation of a serum microRNA panel for screening advanced colorectal polyps

MO16-5 Identification and evaluation of a serum microRNA panel for screening advanced colorectal polyps

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

AB055. SOH23ABS_092. The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis

AB055. SOH23ABS_092. The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis

Immunohistochemical assessment of COX2, P53, and beta-catenin expression to predict metachronous lesion development following polypectomy.

234 Background: Following colorectal polypectomy, 20-50% develop metachronous polyps, and some have increased colorectal cancer (CRC) risk. Surveillance colonoscopy is recommended to high-risk patients, based on index polyp number, histology and size. We aimed to assess if COX2, p53 and beta-catenin expression could predict metachronous polyp/ CRC risk. Methods: Tissue microarrays (TMA’s) were constructed for 339 patients from the INCISE study, a retrospective analysis of all patients undergoing screening polypectomy (Apr’09-Dec’16) followed by surveillance (6months-6years) in Glasgow, UK. Epithelial COX2, p53 and beta-catenin expression were assessed for each patient’s most advanced index polyp using immunohistochemistry, quantified by QuPath software. Kaplan-Meier analysis, log-rank tests and univariate/ multivariate cox regression assessed the association between marker expression and time to metachronous polyp/ CRC detection. Results: Low nuclear p53 expression was associated with shorter time to metachronous polyp/ CRC detection (p=0.024). Low nuclear (p=0.012) and membranous (p=0.046) beta-catenin expression was associated with shorter time to metachronous polyp/ CRC detection. There was no association between cytoplasmic COX2 expression and time to metachronous polyp/ CRC detection overall (p=0.309), but high cytoplasmic COX2 expression was associated with shorter time to detection of advanced metachronous lesions (advanced colorectal polyps/ CRC) (p=0.011). A combined score using the two most powerful biomarkers (nuclear p53 and nuclear beta-catenin – both high/ one low/ both low) was also associated with shorter time to metachronous polyp/ CRC detection (p=0.011). Univariate and multivariate cox regression are shown. Conclusions: Index polyp number and combined nuclear p53/beta-catenin expression independently predicted time to metachronous polyp/ CRC detection. [Table: see text]

S259 Patients With Advanced Colorectal Polyps Have Poor Knowledge of Colorectal Cancer Risk and Screening Recommendations for Their First-Degree Relatives

S259 Patients With Advanced Colorectal Polyps Have Poor Knowledge of Colorectal Cancer Risk and Screening Recommendations for Their First-Degree Relatives

Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA

BackgroundCurrent noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions.MethodsWe evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR.ResultsLINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients.ConclusionsHypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.

Serum Chloride and Admission Status Are Potential Prognostic Markers of High-Risk Polyps: A Prospective Characterization of Colorectal Polyps in a Tertiary Hospital in Saudi Arabia.

Background: Colorectal cancer (CRC) is the most common cancer in men in Saudi Arabia. Other than age and family history, clinical and laboratory prognostic surrogates that may aid in streamlining and prioritization of screening colonoscopies are scarce. Through the examination of the local prevalence of advanced and malignant colorectal polyps, we hypothesized that the presence of certain clinical or laboratory parameters may signify an association with having high-risk polyps.Methods: A prospective study over a period of one year starting on January 21, 2018 and involving all adult patients undergoing colonoscopy at King Saud Medical City, Riyadh. Of the total 1,104 recruited patients, 717 were included. The patients were sub-grouped based on the presence or absence of polyps. Patients with polyps were further sub-grouped into high-risk or low-risk polyps. Comparisons between groups were performed using univariate, relative risks (RRs), and multivariate analyses.Results: Our polyp detection rate was 34.7% and our adenoma detection rate was 21.3%. The prevalence of advanced adenoma was 15.2% and the prevalence of malignant polyps was 6.7%. Several prognostic markers were associated with high-risk polyps such as advanced age (RR = 1.35, 95% confidence interval [CI]: 1.03 to 1.78), male gender (RR = 1.18, 95% CI: 1.06 to 1.31), inpatient status (RR = 1.46, 95% CI: 1.04 to 2.21), and low serum chloride (RR = 1.89, 95% CI: 1.05 to 2.37). With multivariate analysis, the hazard ratios for inpatient status and hypochloremia were 1.67 (95% CI: 1.034 to 2.612) and 1.12 (95% CI: 1.011 to 1.265), respectively.Conclusion: We report the prevalence of malignant colorectal polyps in Saudi Arabia which was not reported before. Two unique prognostic markers for high-risk polyps were identified, namely, inpatient status and hypochloremia.

Kudo's pit pattern classification for in vivo optical diagnosis and discrimination of advanced colorectal polyps.

Colonoscopy is currently the basic diagnostic tool for the large intestine. The size of lesions assessed during the investigation is one criterion for assessing the risk of polyps transforming into colorectal cancer. The techno-logical development of endoscopes and the possibility of direct assessment of lesion's surface during the endoscopic examination and to use appropriate treatment. The aim of this study is to analyze the consistency between the histopathological assessment of high-risk lesions in colonoscopy and the determination according to Kudo's pit pattern classification. The analysis included the results of colonoscopies performed over a 2-year period, in which polyps were diagnosed endoscopically and either polypectomies were performed, or sections were taken from these polyps and a pit pattern analysis was done according to Kudo's classification. A total of 1038 patients (age, 67.2 ± 12.7 years) were enrolled in the study. Of the 1981 samples taken in total, polyps larger than 1 cm were found in 96 cases, laterally spreading tumors (LSTs) were found in 48 cases, and macroscopic infiltration or tumors were found in 110 cases. The results of the histopathological examination were obtained in 248 cases. A value of 4 or higher in the Kudo classification turned out to be the best parameter to differentiate malignant lesions from benign ones for lesions larger than 1 cm and laterally spreading tumors, with a sensitivity of 91.2% and a specificity of 70.4%. The assessment of polyps according to Kudo's classification is a useful tool for assessing the malignancy of lesions as part of a routine colonoscopy.

Histology, Size, and Number of Advanced Polyps are Associated With Guideline-Discordant Surveillance Recommendations

Surveillance guidelines following polypectomy promote cost-effective reductions in future colorectal cancer (CRC) risk, but high nonadherence rates1 can have negative consequences on costs and effectiveness. Professional societies recommend a 3-year interval for patients with advanced colorectal polyps (ACPs), although few studies report provider adherence to surveillance intervals.2 This study evaluated rates and predictors of guideline-discordant recommendations for patients with ACPs.

Continuing Medical Education Questions: July 2020

Article Title: Increased Risk of Colorectal Cancer Tied to Advanced Colorectal Polyps; An Untapped Opportunity to Screen First-Degree Relatives and Decrease Cancer Burden.

Increased Risk of Colorectal Cancer Tied to Advanced Colorectal Polyps: An Untapped Opportunity to Screen First-Degree Relatives and Decrease Cancer Burden.

Advanced adenomas represent a subset of colorectal polyps that are known to confer an increased risk of colorectal neoplasia to the affected individual and their first-degree relatives (FDRs). Accordingly, professional guidelines suggest earlier and more intensive screening for FDRs of those with advanced adenomas similar to FDRs of those with colorectal cancer (CRC). Although the risk to family members is less clear among patients with advanced serrated polyps, they are often considered in the same category. Unfortunately, there is a growing concern that patients, endoscopists, and primary care providers are unaware of the familial risk associated with these polyps, leaving a wide gap in screening these high-risk individuals. Herein, we propose a standardized language around advanced colorectal polyps and present a detailed review of the literature on associated familial risk. We outline the challenges to implementing the current screening recommendations and suggest approaches to overcome these limitations, including a proposed new colonoscopy quality metric to capture communication of familial CRC risk. Improving screening in these high-risk groups has the potential to substantially reduce the burden of CRC.

Mo1701 PREDICTORS OF ADVANCED COLORECTAL ADENOMA: CASE-CONTROL ANALYSIS

Advanced colorectal adenomatous polyps (ACRAP) is a subtype of adenomas that may progress to carcinoma. Early detection and successful removal of advanced adenomas may reduce the incidence of colorectal carcinoma. We performed this single institution case-control study to analyze the clinico-epidemiological characteristics and risk factors of ACRAP. ACRAP has been defined as adenomatous polyps with 10 mm or larger in size, contains a significant villous component, or has high-grade dysplasia. Between 2013 and 2019, 860 patients were referred for screening colonoscopy among whom 158 had ACRAP and 391 had no evidence of colorectal polyps. We reviewed the electronic medical records of all patients (N=549) and retrieved detailed baseline epidemiological and clinical characteristic of all participants at time of colorectal screening. STATA program was used for data management and statistical analyses. Logistic regression was performed to estimate univariate and multivariate Odd ratio (OR) and 95% confidence interval (95% CI) after adjustment for significant confounding factors. Table-1 presents the baseline characteristics of 158 patients ACRAP. Descriptive analysis indicated a significantly high prevalence of cirrhosis and alcohol consumption among patients with ACRAP as compared to non-polyp population, P <.05. In addition, ACRAP was common among whites. The estimated univariate ORs (95% CIs) for cirrhosis, white race, and alcohol consumption were 1.8 (1.2-2.6), 1.8 (1.2-2.6), and 1.7 (1.2-2.5) respectively; p<.05. Multivariate logistic regression analysis showed that the risk for ACRAP development has increased by 50% among cirrhotic patients and by 60% among white population. The estimated multivariate ORs (95% CIs) are 1.5 (1.1-2.2) p=.03 and 1.6 (1.1-2.3) p=.04, for cirrhosis and white race, respectively. The study showed a significant impact of cirrhosis on ACRAP development and higher risk of white race as compared to other races. Future study with a large sample size is warranted to validate our findings.

Lack of Knowledge about Colonoscopy in High Risk Patients: Clinical and Public Health Challenges

In the United States and worldwide, public health officials are publishing guidelines for the management of high risk patients with biopsy proven colorectal polyps [1]. With respect to high risk patients with colorectal polyps , they have 20.6%risk of developing a recurrence in 3 years when compared with those without this diagnosis following an initial colonoscopy Further, such high risk patients who are diagnosed with advanced colorectal polyps have a 3 fold higher subsequent risk of developing colorectal cancer [2, 3]. These alarming increased rates of recurrence of colorectal polyps as well as colorectal cancer pose clinical and public health challenges.

Lack of Knowledge about Colonoscopy in High Risk Patients: Clinical and Public Health Challenges

In the United States and worldwide, public health officials are publishing guidelines for the management of high risk patients with biopsy proven colorectal polyps [1]. With respect to high risk patients with colorectal polyps , they have 20.6%risk of developing a recurrence in 3 years when compared with those without this diagnosis following an initial colonoscopy Further, such high risk patients who are diagnosed with advanced colorectal polyps have a 3 fold higher subsequent risk of developing colorectal cancer [2, 3]. These alarming increased rates of recurrence of colorectal polyps as well as colorectal cancer pose clinical and public health challenges. Clinical challenges are addressed by prescribing numerous possible screening modalities for such high risk patients which include yearly fecal immune testing, multi-targeted stool DNA testing, flexible sigmoidoscopy, and colonoscopy [4].

Poor Knowledge of Personal and Familial Colorectal Cancer Risk and Screening Recommendations Associated with Advanced Colorectal Polyps.

Advanced colorectal polyps (adenoma or sessile serrated polyp ≥ 1cm, adenoma with villous features, adenoma with high-grade dysplasia, or any sessile serrated polyps with dysplasia) are associated with an increased risk of future advanced colorectal neoplasia and confer an increased risk of advanced neoplasia to first-degree family members. Professional societies therefore recommend more intensive surveillance of these polyps and earlier screening for first-degree relatives. The aim of this study was to assess knowledge of personal and familial risk and recommendations among patients with advanced colorectal polyps and identify predictors of knowledge. An online survey was designed to assess the domains of knowledge and risk perception regarding personal and familial colorectal cancer risk and screening recommendations. After expert review and pilot testing, the 37-item survey was electronically sent to all patients diagnosed with an advanced colon or rectal polyp under the age of 60. Patient report of polyp findings was compared to documented findings in the medical record. Univariable and multivariable regressions were performed to evaluate predictors of knowledge. One hundred thirty-seven out of 344 (39.8%) eligible patients responded to the survey. 28.5% of participants reported that the polyp they had removed was precancerous. 54.8% of participants reported that they have a higher risk of CRC, and 65.2% reported that they should be undergoing colonoscopy surveillance in 3years or less. 40.1% reported that their first-degree family members are at increased CRC risk, and 38.0% reported that first-degree family members should get earlier screening. Participants reported their endoscopists as their top source of information about risk and recommendations, though only 7.3% of endoscopists made recommendations for family members. Female gender and higher income were predictors of accurate knowledge, as endoscopist was the main source of knowledge. Patients with advanced colorectal polyps have poor knowledge of personal and familial CRC risk and recommendations. Endoscopists who remove advanced polyps are in an ideal position to educate their patients about their personal risk and the risk and recommendations for first-degree family members.

Advanced Colorectal Polyps on Colonoscopy: A Trigger for Earlier Screening of Family Members.

Advanced Colorectal Polyps on Colonoscopy: A Trigger for Earlier Screening of Family Members.

Prevalence and Spectrum of Cancer Susceptibility Among Patients With Advanced Colorectal Polyps

Prevalence and Spectrum of Cancer Susceptibility Among Patients With Advanced Colorectal Polyps

2843 Lack of Knowledge About Follow-Up Colonoscopy in Patients With Biopsy Proven Advanced Colorectal Polyps: A Major Clinical and Medicolegal Challenge

INTRODUCTION: The most recent guidelines from the American College of Gastroenterology recommend that patients with biopsy proven advanced colorectal polyps undergo repeat surveillance colonoscopy at a minimum of three years following resection. The rationale is based on rates of recurrence and progression to colorectal cancer. In this report we quantitate the knowledge of patients with biopsy proven advanced colorectal polyps about if, and when, they need a repeat colonoscopy. METHODS: Methods: Written informed consents were obtained and brief telephone interviews conducted by trained interviewers among 84 patients with biopsy proven advanced colorectal polyps. In semi-structured questionnaires that included eleven questions the patients provided self-reports about their awareness of the need to have a repeat colonoscopy as well as the proper surveillance interval. RESULTS: Among the 84 patients, who ranged in age from 41-91 years, 24 (28.6%) were unaware of either the need for a repeat colonoscopy or the proper surveillance interval. These included 10 (12.0%) who were not even aware that they required a follow up colonoscopy and 14 (16.6%) who were unaware of the proper three year interval. CONCLUSION: Discussion: These data pose medical and legal challenges to clinicians to educate patients with biopsy proven advanced colorectal polyps about their need for repeat colonoscopy as well as the proper surveillance interval to reduce their risks of colorectal cancer. Specifically, without proper knowledge of the advanced colorectal polyp three year surveillance protocol, 28.6% of these high risk patients would have forgone or delayed the colonoscopy. With advances in technology and digitized medical records, clinicians may need to rely on a more objective and reproducible centralized database of past colonoscopy findings rather than self-reports. These clinical and medicolegal challenges may also be addressed, at least in part, by automated recalls that ensure there is a safety net to remind patients of their subsequent colonoscopy appointment. The success of these strategies will depend on meticulous attention by the clinician to ensure accurate data pertaining to guideline based appropriate surveillance intervals for colonoscopy. These strategies may also reduce any overutilization of colonoscopies. Of far greater import, the achievement of this goal may reduce morbidity and mortality from colorectal cancer in high risk patients with advanced colorectal polyps.

Sa1003 – Poor Knowledge of Personal and Familial Cancer Risk and Guideline-Based Screening Recommendations in Patients with Advanced Colorectal Polyps

Sa1003 – Poor Knowledge of Personal and Familial Cancer Risk and Guideline-Based Screening Recommendations in Patients with Advanced Colorectal Polyps

Mo1630 – Histology, Total Number of Polyps, and Size of the Largest Polyp are Associated with Inaccurate Surveillance Interval Recommendation in Patients with Advanced Colorectal Polyps

Mo1630 – Histology, Total Number of Polyps, and Size of the Largest Polyp are Associated with Inaccurate Surveillance Interval Recommendation in Patients with Advanced Colorectal Polyps