Family History Of Colorectal Carcinoma Research Articles

Clinicopathological and Immunohistochemical Association of CD55 and CD59 in Colorectal Carcinoma: A Cross-sectional Study

Introduction: Colorectal Carcinoma (CRC) is one of the significant causes of fatality worldwide. High-grade and highstage cancers contribute to this fatality. In most terminal cases, new immunomarkers (CD55 and CD59) are commonly detected as positive. The expression of these immunomarkers and their clinical relevance in CRC has not yet been firmly established. While their upregulation has been demonstrated in some CRC several groups have also reported that they are not highly expressed in CRC tissues. Aim: To study the expression of CD55 and CD59 in CRC. Materials and Methods: This was a cross-sectional study involving 90 patients with colorectal growth, conducted from February 2020 to July 2021 in the Department of Pathology in collaboration with the Department of General Surgery at Nil Ratan Sircar Medical College, Kolkata, West Bengal, India. Histopathological findings were evaluated, and associations of grading, staging, tumour type, tumour location, age, and sex were studied with immunomarkers (CD55 and CD59). Clinical parameters of the patients with CRC diagnosed by colonoscopic biopsy were also studied, including age, sex, clinical pictures, food habits, family history of CRC, and prior chemotherapy. The Chi-square test was used to determine the significance of the study. Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 27.0 (IBM, Illinois, US). A p-value of ≤0.05 was considered statistically significant. Results: A total of 90 CRC patients were included in this study, with the majority being male 56 (62.2%) aged 51-60 years. Most cases 59 (65.6%) were moderately differentiated adenocarcinoma, followed by poorly differentiated adenocarcinoma 18 (20%) and well-differentiated adenocarcinoma 13 (14.4%). About 62 (68.9%) and 28 (31.1%) patients showed strong and weak CD55 expression, respectively. In total, 65 (72.2%) and 25 (27.8%) patients exhibited strong and weak CD59 expression, respectively. The association of CRC grade and stage with CD55 and CD59 was significant (p-value=0.0001, p-value=0.0013, p-value=0.0001, and p-value=0.0001, respectively). Conclusion: There are several variables to consider during the histopathological reporting of CRC, with tumour differentiation, grade, and stage being among the most important. Particularly, high-grade (poorly differentiated) and high-stage adenocarcinomas demonstrate enhanced expression of CD55 and CD59, indicating a poor prognosis. It is essential for pathologists to meticulously perform grossing and reporting of CRC and dispatch the histopathology report after proper clinicopathological correlations. These immunomarkers can also be included in a routine IHC panel for prognostic and therapeutic purposes.

S276 Does Hepatitis C Independently Increase the Risk of Colorectal Adenoma?

Introduction: Hepatitis C virus (HCV) infection has been associated with extrahepatic malignancies, one such is colorectal carcinoma (CRC). The majority of CRC arise from adenomatous polyps, it is not known if HCV infection influences the growth of these precancerous lesions. This study evaluates the prevalence of colorectal adenomas in HCV patients compared to the general population and if HCV is an independent risk factor for the detection of colorectal adenomas. Methods: This case-control study included patients who underwent screening colonoscopy at our hospital. Patients were divided into cases (HCV) and controls (non-HCV). Patients with no biopsy reports, hepatitis B, and inflammatory bowel disease were excluded. Colonoscopy findings were stratified on the biopsy results i.e., hyperplastic, adenomatous, CRC or normal mucosa. Continuous variables were analyzed using Mann Whitney U test and categorical variables using Chi-square and Fisher's exact test with p< 0.05 considered statistically significant. After 1:1 propensity score matching (PSM), a matched cohort of cases and controls was generated. A multivariate regression analysis to compute an odds ratio for colorectal adenoma detection rate was done. Results: 415 patients were screened, of which 109 HCV patients and 97 controls were included. Descriptive analysis showed that age (p = 0.03), BMI (p = 0.001), aspirin (p = 0.01), smoking (p = 0.004), alcohol use (p = 0.01) and adenoma detection (p = 0.006) were significantly different between both groups. After propensity matching, multivariate regression analysis showed patients with HCV had odds ratio (OR) = 2.06 (p = 0.03), and aspirin use had OR = 0.38 (p = 0.01) in having colorectal adenoma. (Table) Conclusion: Our study shows a significantly higher rate of adenomas in chronic HCV patients. On multivariate analysis with and without propensity score matching, HCV infection was found to be an independent risk factor for colorectal adenoma. Current guidelines do not recommend earlier screening for CRC for such patients. Prospective studies would be required to assess if treatment of HCV leads to lower adenoma detection rates. Table 1. - Multivariate logistic regression for colorectal adenoma detection Variables p value Odds ratio Lower Limit of 95% CI Upper Limit of 95% CI Age ( >60, median) 0.0295* 1.043 1.034 2.125 Hepatitis C 0.0314* 2.152 1.125 3.810 Family history of CRC 0.220 1.984 0.665 5.922 Aspirin use 0.0116* 0.387 0.253 0.89 Smoking 0.499 1.229 0.677 2.231 Alcohol use 0.293 1.527 0.694 3.359 Female Gender 0.869 1.050 0.586 1.882 Diabetes Mellitus 0.529 1.244 0.630 2.459 HIV 0.895 1.148 0.150 8.806

FREQUENCY OF INCREASED PLASMA C-PEPTIDE LEVELS IN COLORECTAL CANCER PATIENTS

Objective: To assess the increased frequency of serum C-peptide levels in patients of colorectal carcinoma.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from Jul 2018 to Jan 2019.&#x0D; Methodology: A total of 100 cases of colorectal carcinoma were enrolled. Blood samples were obtained to assess C-peptide level. The C-peptide serum concentrations were deliberate through the Cobas 6000 by using the electro-chemi-luminescence immunoassay (ECLIA) method. If level of C-peptide was &gt;2 pmol/mL, then it was noted.&#x0D; Results: The mean age of all patients was 58.3 ± 5.4 years. There was a total of 136 (68%) females and 64 (32%) were males. The mean BMI of patients was 28.96 ± 12.31 kg/m2. The family history of colorectal carcinoma was positive in 6 (6%) cases. The mean C-peptide level was 4.55 ± 2.37 pmol/L. There were 33 (33%) patients with raised C-peptide level while 67 (67%) had normal c-peptide level.&#x0D; Conclusion: It is concluded that increased C-peptide level is high in patients with colorectal cancer.

Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study.

The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. The lifetime (0-79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5-1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6-1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1-3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3-2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.

128 Prevalence and Predictors of Adenomas in Young Adults Undergoing Diagnostic Colonoscopy in a Multicenter Midwest U.S. Cohort

INTRODUCTION: Colorectal cancer incidence in population younger than 50 years of age is increasing in the United States. Data on prevalence of colon neoplastic polyps in young adults remains spars, especially in population &lt;40 years of age. We aimed to identify the prevalence of adenoma, sessile serrated polyp and advanced adenoma in young adults undergoing diagnostic colonoscopy stratified by age 20–30, 31–40 and 41–49 years. METHODS: We reviewed diagnostic colonoscopies performed for lower gastrointestinal symptoms in young adult ≤49 years by 18 gastroenterologists at two institutions in the Midwest from October 2016 to April 2019. Patients with strong family history of colorectal carcinoma were excluded. RESULTS: We included 575 patients, mean age 34 (8) years, 220 (38%) were males, and mean BMI 30 (8), Table 1. Colon neoplastic polyps (adenoma and/or sessile serrated polyps) were noted in 116 (20%) patients, adenomas in 110 (19%), SSP/A in 30 (5%) patients and advanced adenoma was in 29 (5%). The prevalence of neoplastic polyps was 5% in patients &lt;30 years of age, 24% in age 30–40, and 37% in age 40–49 years. Similar trend was noted for each of adenomas, SSP/A, and advanced adenomas (Table 2). Mix of adenoma and SSP/A were seen in 25 (4%) patients; with prevalence of 0.5% for age &lt;30, 5.8% for age 30–40, and 7.4% for age 41–49 (Table 2). Males had a significantly higher adenoma prevalence (P &lt; 0.001); no significant gender differences were noted in the prevalence of SSP/A (P = 0.17) (Table 3). CONCLUSION: Patients between 30 to 49 years of age undergoing diagnostic colonoscopy in US Midwest population is significantly higher than previously reported prevalence of neoplastic colon polyps. This is consistent with the reported increase in the incidence of colorectal neoplasia in this population. Therefore, a careful inspection for colon polyps is recommended during diagnostic colonoscopies in this population.

200 Diagnostic Yield of Colonoscopy in Young Adults With Lower Gastrointestinal Symptoms in Multicenter Midwest Cohort

INTRODUCTION: Serious gastrointestinal (GI) pathologies are common in older adults compared to young adults (≤40 years). There is a lack of data on the diagnostic yield of colonoscopy and flexible sigmoidoscopy in young adults with lower GI symptoms. We aimed to evaluate diagnostic yield of colonoscopy and compare overall diagnostic yield of colonoscopy versus flexible sigmoidoscopy in young adults with lower GI symptoms. METHODS: We reviewed diagnostic colonoscopies performed in young adults by 18 gastroenterologists at two different academic institutions between October 2016 to April 2019. Patients with family history of colorectal carcinoma were excluded. Diagnostic yield was calculated based on proportion of abnormal colonoscopy defined as having inflammatory bowel disease (IBD), microscopic colitis, advanced adenoma, or colorectal cancer (CRC). Presence of pathologies in left colon was considered for diagnostic yield of sigmoidoscopy. RESULTS: We included 454 patients with mean (SD) age was 31 (3) years, 162 (36%) were males and mean (SD) BMI was 30 (8.5). BRBPR was the indication for colonoscopy in 194 (43%) patients, 260 (57%) patients had colonoscopy for other lower GI symptoms (abdominal pain, diarrhea, constipation) but without BRBPR (Table 1). The overall diagnostic yield (DY) of colonoscopy in young adults with lower GI symptoms was 16%; IBD was seen in 43 (10%) patients, microscopic colitis 10 (2%), and advanced neoplasia/CRC 20 (4%) (Table 1). Overall DY in patients with BRBPR was significantly higher than patients without BRBPR (22% vs 11%, P = 0.001) (Table 2). The DY for IBD was also higher in young adults with BRBPR vs without BRBPR (15% vs 6%, P = 0.003) (Table 2). The overall DY was higher with colonoscopy compared to the predicted DY with flexible sigmoidoscopy (13.5% vs 9%) (Table 3). CONCLUSION: Significant proportions of young adults with BRBPR have abnormal pathology (22%) justifying endoscopic evaluation. For other lower GI symptoms, necessity of endoscopic evaluation should be determined clinically on a case-to-case basis as diagnostic yield is low. Colonoscopy rather than flexible sigmoidoscopy should be first line endoscopic evaluation in young patients with BRBPR due to the risk of missing IBD and advanced adenomas.

Deficient mismatch repair and RAS mutation in colorectal carcinoma patients: a retrospective study in Eastern China.

ObjectivesTo investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma.MethodsClinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined.ResultsThe overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients <50 years old (p < 0.001) and in the right side of the colon (p < 0.001). Deficient mismatch repair was also associated with mucinous production (p < 0.001), poor differentiation (p < 0.001), early tumor stage (p < 0.05) and bowel wall invasion (p < 0.05). The overall RAS mutation rate was 45.88%, including 42.56% (346/813) KRAS mutation and 3.69% (30/813) NRAS mutation (including three patients with mutations in both). KRAS mutation was significantly associated with mucinous production (p < 0.05), tumor stage (p < 0.05) and was higher in non-smokers (p < 0.05) and patients with a family history of colorectal carcinoma (p < 0.05). Overall, 44.63% (54/121) dMMR tumors harbored KRAS mutation, however, dMMR tumors were less likely to have NRAS mutation. Moreover, dMMR, KRAS and NRAS mutation were not prognostic factors for stage I–III colorectal carcinoma.ConclusionsThis study confirms that the status of molecular markers involving mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.

Colonoscopic surveillance: quality, guidelines and effectiveness.

Colonoscopic surveillance in patients with a personal or family history of colorectal carcinoma or colonic polyps represents a significant workload for endoscopy services. Effective colonoscopic surveillance relies on quality endoscopic examination and appropriate surveillance interval. This review will discuss quality in colonoscopy and review guidelines for surveillance.

Dome-Type Carcinoma of the Ascending Colon: A Case Report

Background: Dome-type carcinoma (DC) is a rare clinical entity first described by De Petris et al in 1999 followed by Jass et al in 2000. The tumor is described as a focus of adenocarcinoma contained within dense lymphoid stroma associated with dome type epithelium. Herein we report the endoscopic and pathologic findings in an additional case of DC in order to add to the limited number of documented cases. Case Presentation: An asymptomatic 78 year old male with a prior personal history of four tubular adenomas was found to have three broad-based polyps on routine surveillance colonoscopy. Pathology showed prominent lymphoid aggregates with nests of invasive adenocarcinoma that were well to moderately differentiated and contained no goblet cells. The findings were confined to the superficial submucosa. The final pathologic features were consistent with the typical appearance of dome-type carcinoma. The patient subsequently underwent an uncomplicated right hemicolectomy with an uneventful post-operative recovery. Conclusion: DC is a distinct variant of colorectal carcinoma with dense lymphoid component but devoid of microsatellite instability or EBV infection. The tumor is felt to arise from M cells associated with the follicle-associated epithelium of gut-associated lymphoid tissue within the colon. This assumption comes from the lack of goblet cells and the association with lymphoid tissue. Nearly all cases are low grade with excellent prognosis without recurrence. To our knowledge our reported case appears to be the only case found in a patient without abdominal complaints or a family history of colorectal carcinoma, as most patients have one or both findings. Through this case report we hope to bring further attention to this distinct clinical entity while adding another case to the current body of literature.Figure 1Figure 2Figure 3

Comparison of 64-Detector CT Colonography and Conventional Colonoscopy in the Detection of Colorectal Lesions.

Background:Colon cancer is a leading cause of morbidity and mortality in developed countries. The early detection of colorectal cancer using screening programs is important for managing early-stage colorectal cancers and polyps. Modalities that allow examination of the entire colon are conventional colonoscopy, double contrast barium enema examination and multi-detector computed tomography (MDCT) colonography.Objectives:To compare CT colonography and conventional colonoscopy results and to evaluate the accuracy of CT colonography for detecting colorectal lesions.Patients and Methods:In a prospective study performed at Gastroenterology and Radiology Departments of Medical Faculty of Eskisehir Osmangazi University, CT colonography and colonoscopy results of 31 patients with family history of colorectal carcinoma, personal or family history of colorectal polyps, lower gastrointestinal tract bleeding, change in bowel habits, iron deficiency anemia and abdominal pain were compared. Regardless of the size, CT colonography and conventional colonoscopy findings for all the lesions were cross - tabulated and the sensitivity, specificity, and positive and negative predictive values were calculated. To assess the agreement between CT colonography and conventional colonoscopy examinations, the Kappa coefficient of agreementt was used. Statistical analysis was performed by SPSS ver 15.0.Results:Regardless of the size, MDCT colonography showed 83% sensitivity and 95% specificity, with a positive predictive value of 95% and a negative predictive value of 83% for the detection of colorectal polyps and masses. MDCT colonography displayed 92% sensitivity and 95% specificity, with a positive predictive value of 92% and a negative predictive value of 95% for polyps ≥ 10 mm. For polyps between 6mm and 9 mm, MDCT colonography displayed 75% sensitivity and 100% specificity, with a positive predictive value of 100% and a negative predictive value of 90%. For polyps ≤ 5 mm MDCT colonography displayed 88% sensitivity and 100% specificity with a positive predictive value of 100% and a negative predictive value of 95%.Conclusions:CT colonography is a safe and minimally invasive technique, a valuable diagnostic tool for examining the entire colon and a good alternative compared to other colorectal cancer screening tests because of its high sensitivity values in colorectal lesions over 1 cm.

Risk factors for the development of colorectal carcinoma: A case control study from South India.

To study the association of colorectal carcinoma (CRC) with diet, smoking, alcohol, physical activity, body mass index, family history and diabetes. All consecutive patients with CRC confirmed by histopathology diagnosis were included. Age (± 5 years) and gender matched controls were selected among the patients admitted in surgery ward for various conditions without any co-existing malignancy. Food frequency questionnaire (FFQ) was developed and validated after pretesting by investigator trained in data collection techniques. Cases and controls were interviewed ensuring privacy, in similar interview setting, with same duration of time for both cases and controls without any leading question. Biological variables like family history of CRC in first degree relatives, history of diabetes mellitus; behavioral factors like tobacco use both smoking and smokeless form, alcohol consumption and physical activity were recorded. Dietary details were recorded using a FFQ consisting 29 food items with seven categories. Analysis was done using appropriate statistical methods. Ninety-four histopathologically confirmed cases of CRC and equal number of age and gender matched controls treated over a period of two years were studied. Age distribution, mean age, male to female ratio, education level and socioeconomic status were similar in cases and controls. Intake of food items was categorized into tertile due to skewed distribution of subjects as per recommended cut off for consumption of food item. On univariate analysis red meat [OR = 7.4 (2.935-18.732)], egg [OR = 5.1 (2.26-11.36)], fish, fried food and oil consumption were found to be risk factors for CRC. On multivariate analysis red meat consumption of more than 2-3 times a month (OR = 5.4; 95%CI: 1.55-19.05) and egg consumption of more than 2-3 times a week (OR = 3.67; 95%CI: 1.23-9.35) were found to be independent risk factors for the development of CRC. Egg and red meat consumption found to be independent risk factors for CRC. Smoking, alcohol, physical activity and family history were not associated with increased risk.

P0180Stage-specific proteomic profiles of primary colorectal adenocarcinomas in Malaysian patients

Background We aimed to characterise stage-specific colorectal carcinoma tumour-specific proteomic profiles in Malaysian patients with colorectal carcinoma as a starting point for the development of local screening, diagnostic, or treatment scheme. Methods Stringent criteria were applied for patients’ selection—i.e., newly-diagnosed cases without personal history of cancer or family history of colorectal carcinoma, with no known hereditary colorectal carcinoma syndrome, and not receiving any neoadjuvant chemo- or radiotherapy. Ten stage II, five stage III, and five stage IV colorectal carcinoma patients were recruited for our comparative protein expression analysis via a combination of 2-D DIGE and LC-MS/MS. Findings Twenty protein spots of interest were reported in the stage II colorectal carcinoma group (p 0.05). Interpretation Our failure to identify aberrantly regulated proteins in advanced stage colorectal adenocarcinomas warrants further investigation. One of the possibilities is that, the adjacent histologically normal colonic mucosa might experience certain molecular changes to create a permissive microenvironment for tumour invasion and metastasis. If this is confirmed, the use of adjacent macroscopically normal colonic mucosa as a normal control in pair-wise analyses of colorectal carcinomas needs to be re-evaluated.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas

BackgroundThe objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. Patients and methodsWe conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. ResultsNinety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17–3.96), renal cell carcinoma (6.00; CI 95% 2.74–11.39) and thyroid carcinoma (5.56; CI 95% 1.80–12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. ConclusionWe report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Abstract 4855: Poor performance of published clinical screening criteria for the population-based identification of endometrial cancer patients with Lynch Syndrome.

Abstract Objective: Clinically based risk assessment tools, targeting those with young age of cancer onset and family history of specific cancers, have been used to identify individuals with Lynch Syndrome (LS). Women with LS are equally likely to develop endometrial carcinoma (EC) as they are colorectal carcinoma (CRC). To identify women presenting with EC at risk for LS, the Society of Gynecologic Oncology (SGO) published recommendations in 2007 regarding which patients would benefit from further genetic evaluation for LS. These criteria are comparable to the Revised Bethesda Guidelines. The primary objective of this study was to evaluate SGO criteria's ability to predict women at risk for LS in the EC population and to ascertain if alternative criteria exist that can better identify high-risk patients. Methods: 408 sequential EC cases were evaluated for immunohistochemical expression of four DNA mismatch repair (MMR) proteins. Tumors with loss of MSH2, MSH6 or PMS2 were designated as probable Lynch Syndrome (PLS). Tumors with loss of MLH1 and absence of MLH1 promoter methylation were also designated PLS. Clinical and pathologic data were collected from the electronic medical record. Results: Of the 408 EC cases, 43 (10.5%) of the patients were defined as probable Lynch Syndrome (PLS). 97/408 (23.7%) of EC cases met SGO criteria, but only 14 of these 97 cases (14.4%) were PLS. Of the 43 PLS cases, 29/43 (67.4%) did not meet SGO criteria. Comparison of clinical and pathologic characteristics, including age of cancer diagnosis and family history of EC and/or CRC, revealed no statistically significant differences between sporadic and PLS tumors with the exception of tumors arising from the lower uterine segment. Tumors with this sight of origin are more likely to be associated with PLS. The sensitivity and specificity of SGO criteria was 32.6% and 77.2%, respectively. Conclusions: Existing clinical guidelines for detecting endometrial carcinoma patients at elevated risk for having Lynch Syndrome perform poorly in an unselected patient population. With the exception of tumors arising from the lower uterine segment, there are no statistically significant clinical or pathological differences between sporadic tumors and PLS tumors. Lower uterine segment EC occurs in only 3% of all EC cases and is not a useful screening tool. SGO clinical criteria correctly identified 32.6% of women with PLS, which results in missed CRC screening opportunities for 67% of women with increased risk profiles. These results suggest that the SGO guidelines are inadequate for identifying LS. Given the lack of effective clinical or pathological screening tools, MMR IHC and MLH1 methylation testing of all endometrial cancer patients may be the best way to identify women at risk for having Lynch Syndrome. Citation Format: Amanda S. Bruegl, Bojana Djordjevic, Bryan M. Fellman, Diana L. Urbauer, Raja Luthra, Karen H. Lu. Poor performance of published clinical screening criteria for the population-based identification of endometrial cancer patients with Lynch Syndrome. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4855. doi:10.1158/1538-7445.AM2013-4855

Sessile Serrated Adenomas in the Proximal Colon are Likely to be Flat, Large and Occur in Smokers

Purpose: Sessile serrated adenomas (SSA) have been implicated in the alternative pathway for colorectal carcinoma (CRC) and might account for interval CRC given the fact that these are often flat and difficult to detect. Most of the studies have focused on the relatively common left-sided serrated polyps and little is known about the proximal SSA. Our goal was to examine the epidemiology and morphology of proximal SSA. Methods: We conducted a retrospective study to identify patients with SSA using a pathology database query from 01/2007-04/2011. Data collected included: age, gender, ethnicity, BMI, diabetes, smoking, family history of CRC, aspirin, and statin use. We collected data on morphology of SSA including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). SPSS software was used for all statistical analysis. P value <0.05 was considered significant. Results: 120 patients with SSA were identified: 61% were distal and 39% were proximal SSA. 78% of the distal SSA were flat compared to the proximal SSA which were all flat (p=0.0001). Proximal SSA were more likely to occur in smokers compared to distal (OR: 2.63; 95% CI: 1.17-5.90; p=0.02; Table 1). Similarly, smokers were more likely to have proximal (p=0.02) and flat (p=0.01) SSA compared to non-smokers. Proximal SSA were also more likely to occur in patients with family history of CRC (OR: 4.72; 95% CI: 1.43-15.55; p=0.01; Table 1). Proximal SSA were more likely to be ≥6 mm in size (OR: 2.94; 95% CI: 1.37-6.31; p=0.008), and also more likely to be large (≥1 cm) SSA (OR: 4.55; 95% CI: 1.92-10.77; p=0.0005) compared to the distal lesions as shown in Table 2.Table 1: No Caption available.Table: [1996] Table 2Conclusion: Proximal SSA which accounted for two-fifths of all SSA were more likely to present as flat lesions, larger SSA, and were more likely to occur in smokers and in patients with family history of CRC. Our study is the first to our knowledge examining morphology of SSAs specifically, and its association with smoking. Given the potential for malignancy of SSAs as well as their proclivity to a flat morphology, these lesions may explain the lack of protection of colonoscopy in the proximal colon. Our data has implications for CRC screening.

Predictors of Lymph Node Count in Colorectal Cancer Resections

To identify factors that influence the total and negative lymph node counts in colorectal cancer resection specimens independent of pathologists and surgeons. We used multivariate negative binomial regression. Covariates included age, sex, body mass index, family history of colorectal carcinoma, year of diagnosis, hospital setting, tumor location, resected colorectal length (specimen length), tumor size, circumferential growth, TNM stage, lymphocytic reactions and other pathological features, and tumor molecular features (microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element 1 [LINE-1] methylation, and BRAF, KRAS, and PIK3CA mutations). Two US nationwide prospective cohort studies. Patients with rectal and colon cancer (N=918). The negative and total node counts (continuous). Specimen length, tumor size, ascending colon location, T3N0M0 stage, and year of diagnosis were positively associated with the negative node count (all P.002). Mutation of KRAS might also be positively associated with the negative node count (P=.03; borderline significance considering multiple hypothesis testing). Among node-negative (stages I and II) cases, specimen length, tumor size, and ascending colon location remained significantly associated with the node count (all P.002), and PIK3CA and KRAS mutations might also be positively associated (P=.03 and P=.049, respectively, with borderline significance). This molecular pathological epidemiology study shows that specimen length, tumor size, tumor location, TNM stage, and year of diagnosis are operator-independent predictors of the lymph node count. These crucial variables should be examined in any future evaluation of the adequacy of lymph node harvest and nodal staging when devising individualized treatment plans for patients with colorectal cancer.

Prevalence of any size adenomas and advanced adenomas in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history of colorectal carcinoma in a first-degree relative

Per current guidelines, patients with a first-degree relative (FDR) with colorectal cancer (CRC) should get screened at least at age 40. Data about the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking. To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy for family history of CRC. Retrospective chart review. Asymptomatic patients 40 to 49 years of age undergoing their first screening colonoscopy at the University of Michigan during the period 1999 to 2009 because of an FDR with CRC. Prevalence of adenomas (any size), AAs, and risk factors associated with adenomas. Among 640 study patients, the prevalence of adenomas (any size) was 15.4% and 3.3% for AAs. Adenoma prevalence was lower if the FDR with CRC was younger than 60 years of age versus an FDR with CRC older than 60 years of age (12.4% vs 19%, P = .034). Male sex (odds ratio 2.6; 95% CI, 1.06-4.4) and advancing age (odds ratio 1.16; 95% CI, 1.03-1.31) were associated with adenomas. Limited data on risk factor exposure and insufficient sample size to assess risk factors for AAs. Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with CRC, the prevalence of adenomas and AAs is low. Further research should determine whether these individuals have a higher prevalence of adenomas compared with average-risk individuals.

Do indication and demographics for colonoscopy affect completion? A large national database evaluation

Indication for colonoscopy has not been examined as a predictor of colonoscopy completion. We hypothesized that colonoscopy conducted for colorectal cancer screening might have higher in completion rates than colonoscopy conducted for other indications. The study design was a retrospective cohort. Colonoscopies recorded within the Clinical Outcomes Research Initiative database conducted between 1 January 2002 and 30 June 2003 were analyzed. Indication included: average-risk screening; surveillance; nonspecific abdominal symptoms; bleeding symptoms; or family history of colorectal carcinoma. Demographic factors and indication for colonoscopy were evaluated for the outcome of incomplete colonoscopy using logistic regression analysis. 129 549 Colonoscopy procedures were analyzed. Average risk screening seemed to be protective for completion (relative risk: 0.69; 95% confidence interval: 0.63-0.75). Bleeding and nonspecific symptoms had higher risk of incomplete procedure compared to other indications. Males had higher completion rates compared to females (relative risk: 0.62; 95% confidence interval: 0.58-0.66). Community setting had higher completion rates compared to academic or Veteran's administration sites. Increasing age was associated with higher rate of incomplete colonoscopy. Colonoscopy conducted for screening indication has comparable completion rates when compared with other indications. An overall completion rate of around 95% was noted in this study. This is the largest study to date verifying that completion rates are meeting recommended multisociety guidelines in the USA. Nonspecific abdominal symptoms in Caucasian population, female sex, advanced age, clinical setting, and ethnic groups African-American and Hispanic were found to have increased risk of incomplete procedure.

Does One Pill a Day Keep the Colonoscopist Away?

Does One Pill a Day Keep the Colonoscopist Away?

P53 codon 72 polymorphism in patients affected with ulcerative colitis

The p53 tumor suppressor protein plays a fundamental role in maintaining genomic integrity through its ability to arrest the cell cycle in G1 and induce apoptosis. The proapoptotic activity of p53 seems to be strictly related to proline-rich regions, homologous to the SH3 binding domain. In the literature, reported data suggest a role for polymorphism at codon 72 of p53 in the predisposition to neoplastic transformation, although the results are still controversial. In this study, we investigated Arg72Pro polymorphism of p53 and related this polymorphism to clinical parameters in patients affected with ulcerative colitis (UC). We studied 243 consecutive outpatients affected with well-established UC. The control group comprised 142 healthy blood donors, with age and sex comparable to those of the patients. p53 Pro/Pro was significantly related to the clinical course and duration of disease (odds ratio, 55.8 and 8.8, respectively). Nineteen of 24 patients with Pro homozygosity had a duration of disease >7 years. In contrast, 87 of 123 patients with Arg/Arg had short-standing UC (< or =7 yrs) and 66 of 96 with Arg/Pro had short-standing UC (chi-squared, 22.86; P < 0.0001). Thirty-four of 243 patients affected with UC had a positive family history for colorectal carcinoma (CRC). In those patients p53, Pro/Pro was significantly related to a family history of CRC (odds ratio, 38.1). These preliminary data suggest that polymorphism at codon 72 of the p53 gene influences the clinical course of UC, with continuous disease associated with p53 Pro homozygosity.