Colorectal Hyperplastic Polyps Research Articles

Development and Validation of a Deep Learning-Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions.

The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)-based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models.

Endoscopic features of lymphoid follicles in the colonic mucosa using the image enhanced endoscopy and its association with colorectal adenoma.

Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.

The ability of HALP score to distinguish between malignant and benign colorectal neoplasms and its prognostic importance in colorectal cancers

Systemic inflammation and nutritional status play important roles in the development and progression of various cancers, including colorectal cancer. The prognosis for malignancies can be predicted using the inflammatory marker known as HALP (calculated by hemoglobin, albumin, lymphocytes, and platelets). Furthermore, recent studies have claimed the HALP score to help distinguish between benign and malignant lesions. We aimed to research the diagnostic importance of the HALP score in the differentiation of malignant (colorectal cancer) and benign colorectal neoplasms (colorectal adenomas and hyperplastic polyps) and its prognostic significance in colorectal cancer patients. Patients diagnosed with colorectal cancer, colorectal adenoma, and hyperplastic polyps were evaluated retrospectively between January 2017 and January 2022. The median HALP score in the colorectal cancer group was significantly lower than the other groups (colorectal adenoma and hyperplastic polyps) (p<0.001). There was no statistical difference between the median HALP scores of the colorectal adenoma and hyperplastic groups (p=0.525). ROC analysis found the cut-off value of the HALP score as 41.01 to differentiate colorectal cancer from benign colorectal lesions (sensitivity= 0.73, specitivity=0.62, 95% CI=0.67-0.76, p<0.001). The HALP level below 28.1 was associated with worse overall survival (p=0.046) and was shown to be an independent prognostic factor in the colorectal cancer group. The HALP score can be used to differentiate colorectal cancer from benign colorectal neoplasms and as a prognostic factor in colorectal cancer.

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Background and study aims A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms. Patients and methods We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium. Results In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group ( P < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells. Conclusions This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.

Methylation Status of miR-200b Promoter in Colorectal Polyp and Adenocarcinoma Tissues

Background: Aberrant DNA methylation is a common molecular feature in colorectal cancer (CRC). Hypermethylation of miR-200b promoter, as an epigenetic factor, is involved in CRC tumorigenesis. The methylation status of miR-200b has been examined in CRC and adjacent normal tissues. Objectives: This study aimed to investigate miR-200b methylation in a series of colorectal adenomatous polyps, hyperplastic polyps, and adenocarcinoma tissues as precursors of CRC in the Iranian population for the first time. Materials and Methods: In this cross-sectional study (2017-2018), the methylation status of the miR-200b promoter was investigated using methylation-specific PCR in 131 fresh samples, including 30 adenocarcinoma specimens, 17 tumor-adjacent normal tissues, 78 primary lesions (55 adenomatous polyps and 23 hyperplastic polyps) and 6 healthy individuals. Results: Methylation of miR-200b was detected in adenocarcinoma samples (86%) and adenomatous polyps (85%); however, most of the hyperplastic polyps were unmethylated (69.6%). Neither control individuals nor tumor-adjacent normal tissues exhibited methylation in the miR-200b promoter. Aberrant methylation of miR-200b was significantly more common in tumor tissues and adenomatous polyps than in hyperplastic polyps (P&lt;0.0001) and tumor-adjacent normal samples (P&lt;0.0001). Conclusion: Methylation status of the miR-200b promoter was significantly altered during CRC development and may be identified as an attractive biomarker for the early detection of the disease.

Hyperplastic polyp or sessile serrated lesion? The contribution of serial sections to reclassification

BackgroundThe histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections.MethodsClinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed.ResultsOf an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5 mm and < 10 mm. After 8 additional serial sections, 11 (10.7%) were reclassified as sessile serrated lesions. They were all less than 5 mm and represented 14.3% of proximal polyps and 10.4% of distal polyps. An average of 3.6 serial sections were required for a change in diagnosis.ConclusionHistopathological distinction between hyperplastic polyps and sessile serrated lesions remains a challenge. This study has uncovered a potential role for the use of additional serial sections in the morphological reappraisal of small hyperplastic polyps, especially when proximally located.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

Investigation of the screening interval for population with negative colonoscopy examinations

Objective: To investigate the colonscopy screening interval among patients with negative colonscopy. Methods: We selected 14 606 participants who completed the baseline and 3-year or 5-year colonoscopy examinations in the American Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset as the target population. Sociodemographic characteristics (i.e., sex, age, marital status, race, and smoking), lifestyle, family history of cancer, and family history of colorectal cancer were collected. Cochran-Armitage trend analysis was used to examine whether the rate of positive cases (colorectal cancer, advanced adenoma, adenoma, and hyperplastic polyp) was increased with the length of screening interval. We compared the differences in number of detected cases, positive rates, and proportions of 3-year and 5-year screening interval strategies using internal standardization method. Results: The age of the population was （61.9±5.2） years and over half of them were males (54.4%) and 46.2% had family cancer history. The mean screening interval between the first and second endoscopies was （1 639.1±320.9） days. A total of 1 716 cases had positive endoscopic findings. With the screening interval extended, rate of the screened positive cases was also increased (P for trend<0.001). After standardized by the internal standardized population (14 606), 17.99 and 11.57 colorectal cancer cases and 177.37 and 240.35 advanced adenoma cases were detected by 3-year and 5-year screening interval strategies, respectively. Conclusion: Based on the initial screening negative population of colonoscopy in the United States, the 3-year screening interval strategy could detect a relatively large number of colorectal cancer cases, but its health and economic evaluation needs to be further explored.

High risk of colorectal polyps in men with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

This meta-analysis aims to explore the risk of colorectal polyps among non-alcoholic fatty liver disease (NAFLD) patients. We searched PubMed, EMBASE, and Cochrane library databases using predefined search term to identify eligible studies (published up to 7 November 2019). Data from selected studies were extracted by using a standardized information collection form, and meta-analyses were performed using random-effects model. The statistical heterogeneity among studies (I2 ), subgroup analyses, meta-regression analyses, and the possibility of publication bias were assessed. Twenty observational (12 cross-sectional, two case-control, and six cohort) studies met the eligibility criteria, involving 142387 asymptomatic adults. In cross-sectional/case-control studies, NAFLD was found to be associated with an increased risk of colorectal polyps (odds ratio [OR]=1.34; 95% confidence interval [CI]=1.23-1.47) (including unclassified colorectal polyps, hyperplastic polyps, adenomas, and cancers) with statistically significant heterogeneity (I2 =67.8%; P<0.001). NAFLD was also associated with a higher risk of incident colorectal polyps (hazard ratio=1.60; 95% CI=1.36-1.87) with low heterogeneity (I2 =21.8%; P=0.263) in longitudinal studies. The severity of NAFLD was associated with a higher risk of colorectal adenomas (OR=1.57; 95% CI=1.30-1.88), but not colorectal cancer (OR=1.37; 95% CI=0.92-2.03). The subgroup analysis according to gender showed that NAFLD was significantly associated with a higher risk of colorectal polyps in the male population without significant heterogeneity (OR=1.47; 95% CI=1.29-1.67, I2 =0%), but not in the female population (OR=0.88; 95% CI=0.60-1.29, I2 =34.2%). NAFLD was associated with an increased risk of colorectal polyps. There was a significant difference of the relationship between genders, which suggested more precise screening colonoscopy recommendation in NAFLD patients according to gender.

Comparative genome-wide analysis of gastric adenocarcinomas with hyperplastic polyp components.

Gastric hyperplastic polyps are common and generally regarded as benign lesions, whereas gastric adenocarcinomas infrequently occur from gastric hyperplastic polyps. Although gastric hyperplastic polyps have received a lot of attention because of their association with malignant transformation, it remains unclear whether gastric hyperplastic polyps are neoplastic lesions that have sporadic genetic changes similar to colorectal hyperplastic polyps. We performed genome-wide analyses of two gastric adenocarcinomas with hyperplastic polyp components. The interface between "adenocarcinoma" and "hyperplastic polyp" components was fairly sharp, and the adenocarcinoma components had copy number alterations and TP53 mutations, whereas the hyperplastic polyp components had only single nucleotide polymorphisms, which were also found in adenocarcinoma components. We did not detect any somatic changes in the hyperplastic polyp components, even in genome-wide analyses, which was in contrast to the adenocarcinoma components. However, due to the small number of cases examined herein, further genetic analyses of more cases are needed.

Strong associations of a healthy lifestyle with all stages of colorectal carcinogenesis: Results from a large cohort of participants of screening colonoscopy.

The risk of developing colorectal cancer (CRC) is associated with a wide range of dietary and lifestyle factors. The individual contribution of single modifiable factors, such as alcohol consumption, physical activity, smoking, body mass index (BMI) or dietary components, to the development of CRC has been investigated extensively, but evidence on their combined effect at various stages of colorectal carcinogenesis is sparse. The aim of our study was to analyze the association of a healthy lifestyle pattern with prevalence of early and advanced colorectal neoplasms. A total of 13,600 participants of screening colonoscopy in Saarland/Germany (mean age 62.9 years) who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 until 2013 were included in this cross-sectional analysis. Dietary and lifestyle data were collected and colonoscopy results were extracted from physicians' reports. The association of an a priori defined healthy lifestyle score-including dietary intake, alcohol consumption, physical activity, smoking and BMI-with early and advanced colorectal neoplasms was assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. Strong inverse dose-response relationships were observed between an overall healthier lifestyle pattern and presence of advanced colorectal neoplasms, nonadvanced adenomas and hyperplastic polyps (p value <0.0001 in all cases), with adjusted odds ratios (95% CI) for the highest compared to the lowest category of the healthy lifestyle score of 0.41 (0.30-0.56), 0.42 (0.33-0.54) and 0.39 (0.29-0.54) respectively. A healthy lifestyle is strongly associated with lower risk of all stages of colorectal neoplasms.

Accurate Classification of Diminutive Colorectal Polyps Using Computer-Aided Analysis

Narrow-band imaging is an image-enhanced form of endoscopy used to observed microstructures and capillaries of the mucosal epithelium which allows for real-time prediction of histologic features of colorectal polyps. However, narrow-band imaging expertise is required to differentiate hyperplastic from neoplastic polyps with high levels of accuracy. We developed and tested a system of computer-aided diagnosis with a deep neural network (DNN-CAD) to analyze narrow-band images of diminutive colorectal polyps. We collected 1476 images of neoplastic polyps and 681 images of hyperplastic polyps, obtained from the picture archiving and communications system database in a tertiary hospital in Taiwan. Histologic findings from the polyps were also collected and used as the reference standard. The images and data were used to train the DNN. A test set of images (96 hyperplastic and 188 neoplastic polyps, smaller than 5 mm), obtained from patients who underwent colonoscopies from March 2017 through August 2017, was then used to test the diagnostic ability of the DNN-CAD vs endoscopists (2 expert and 4 novice), who were asked to classify the images of the test set as neoplastic or hyperplastic. Their classifications were compared with findings from histologic analysis. The primary outcome measures were diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic time. The accuracy, sensitivity, specificity, PPV, NPV, and diagnostic time were compared among DNN-CAD, the novice endoscopists, and the expert endoscopists. The study was designed to detect a difference of 10% in accuracy by a 2-sided McNemar test. In the test set, the DNN-CAD identified neoplastic or hyperplastic polyps with 96.3% sensitivity, 78.1% specificity, a PPV of 89.6%, and a NPV of 91.5%. Fewer than half of the novice endoscopists classified polyps with a NPV of 90% (their NPVs ranged from 73.9% to 84.0%). DNN-CAD classified polyps as neoplastic or hyperplastic in 0.45 ± 0.07 seconds-shorter than the time required by experts (1.54±1.30 seconds) and nonexperts (1.77 ± 1.37 seconds) (both P < .001). DNN-CAD classified polyps with perfect intra-observer agreement (kappa score of 1). There was a low level of intra-observer and inter-observer agreement in classification among endoscopists. We developed a system called DNN-CAD to identify neoplastic or hyperplastic colorectal polyps less than 5 mm. The system classified polyps with a PPV of 89.6%, and a NPV of 91.5%, and in a shorter time than endoscopists. This deep-learning model has potential for not only endoscopic image recognition but for other forms of medical image analysis, including sonography, computed tomography, and magnetic resonance images.

Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps.

AIMTo investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps.METHODSA retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps.RESULTSThe prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05).CONCLUSIONNAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Novel Endoscopic Findings as Visualized by Magnifying Endoscopy with Narrow-Band Imaging: White Opaque Substance Is Present in Colorectal Hyperplastic Polyps

Background: Magnifying endoscopy (ME) with narrow-band imaging (NBI) can visualize a white opaque substance (WOS) in gastric epithelial neoplasms, gastric intestinal metaplasias, and colorectal epithelial neoplasms. Histological examination showed the WOS to be lipid droplets accumulated in the epithelium. The white appearance of colorectal hyperplastic polyps suggests that they may contain WOS, but this has not been investigated as yet. Aims: The purpose of this study was to determine whether WOS is present in colorectal hyperplastic polyps. Methods: We retrospectively evaluated endoscopic images of 26 consecutive lesions investigated by ME with NBI and subsequently endoscopically resected and confirmed to be hyperplastic polyps. Results: WOS was present in 21 of the 26 colorectal hyperplastic polyps (80.8%) based on the findings of ME with NBI. Adipophilin was present in 24 of the 26 colorectal hyperplastic polyps (92.3%). Conclusions: This study is the first to demonstrate that WOS (i.e. lipid droplets) accumulates in the epithelium of colorectal hyperplastic polyps.

Expression and significance of CD24 in colorectal cancer

Objective To determine the expression of CD24 in colorectal carcinoma, and to explore the relationship between CD24 and the clinicopathological features of colorectal carcinoma. Methods The expression of CD24 in 62 cases of colorectal carcinoma, 47 cases of adenomas, 15 cases of colorectal polyps and 30 cases of the adjacent non-cancerous tissues were observed by immunohistochemical assay. The relationship between CD24 and the clinicopathological features was analyzed. Results The positive rates of CD24 in colorectal carcinoma 72.6% and adenomas 63.8% were significantly higher than those in colorectal hyperplastic polyps 13.3%(χ2=17.83, P=0.00; χ2=11.61, P=0.00)and adjacent non-cancerous tissues 6.7%(χ2=35.15, P=0.00; χ2=24.64, P=0.00). The expression of CD24 in colorectal carcinoma had a significant correlation with the tumor diameter (χ2=5.48, P=0.02), tumor differentiation (χ2=8.86, P=0.00), Duke staging (χ2=11.47, P=0.00) and lymph node metastasis (χ2=8.92, P=0.00). Conclusion The expression of CD24 is high in colorectal carcinoma, having a significant correlation with the size of tumor, degree of differentiation, Duke stage and lymph node metastasis. Key words: Colorectal neoplasms; Antigens, CD24; Immunohistochemistry

Aspects of dietary carbohydrate intake are not related to risk of colorectal polyps in the Tennessee Colorectal Polyp Study.

High digestible carbohydrate intakes can induce hyperglycemia and hyperinsulinemia and collectively have been implicated in colorectal tumor development. Our aim was to explore the association between aspects of dietary carbohydrate intake and risk of colorectal adenomas and hyperplastic polyps in a large case-control study. Colorectal polyp cases (n=1,315 adenomas only, n=566 hyperplastic polyps only and n=394 both) and controls (n=3,184) undergoing colonoscopy were recruited between 2003 and 2010 in Nashville, Tennessee, USA. Dietary intakes were estimated by a 108-item food frequency questionnaire. Unconditional logistic regression analysis was applied to determine odds ratios (OR) and corresponding 95% confidence intervals (CI) for colorectal polyps according to dietary carbohydrate intakes, after adjustment for potential confounders. No significant associations were detected for risk of colorectal adenomas when comparing the highest versus lowest quartiles of intake for total sugars (OR 1.03; 95% CI 0.84-1.26), starch (OR 1.01; 95% CI 0.81-1.26), total or available carbohydrate intakes. Similar null associations were observed between dietary carbohydrate intakes and risk of hyperplastic polyps, or concurrent adenomas and hyperplastic polyps. In this US population, digestible carbohydrate intakes were not associated with risk of colorectal polyps, suggesting that dietary carbohydrate does not have an etiological role in the early stages of colorectal carcinogenesis.

Expression and significance of c-myc and CD24 in colorectal cancer

Objective To determine the expression of c-myc and CD24 in colorectal carcinoma, colo-rectal polyp and normal mucosa, and to explore the role and correlation of them in the carcinogenesis of colorectal carcinoma. Methods The expression of c-myc and CD24 in colorectal carcinoma (n=60), colorectal adenomatous polyp (n=45), colorectal hyperplastic polyp (n=15) and the adjacent non-cancerous tissue (n=30) was observed by immunohistochemical assay. Results The positive rate of c-myc in colorectal carcinoma were 73.3%, significantly higher than that in colorectal adenomatous polyp 44.4% (χ2=9.016 8, P<0.01), colorectal hyperplastic polyp 13.3% (χ2=18.215 9, P<0.01) and adjacent non-cancerous tissue 6.7% (χ2=25.133 0, P<0.01); the positive rate of CD24 in colorectal carcinoma was 76.7%, significantly higher than that in colorectal hyperplastic polyp 6.7% (χ2=25.133 0, P<0.01) and adjacent non-cancerous tissue 3.3% (χ2=43.107 4, P<0.01). c-myc expression in colon cancer was significantly correlated with cancer site (χ2=8.352 3, P<0.01), lymph node metastasis (χ2=4.275 1, P<0.05), differentiation (χ2=4.115 3, P<0.05) and TNM stage (χ2=5.739 9, P<0.05). CD24 expression in colon cancer was significantly correlated with cancer size (χ2=9.333 6, P<0.01), lymph node metastasis (χ2=7.693 0, P<0.01), differentiation (χ2=5.870 0, P<0.05) and TNM stage (χ2=4.498 7, P<0.05). There was a positive correlation relationship between CD24 and c-myc in colorectal carcinoma tissue (χ2=10.824 9, r=0.39, P<0.05). Conclusion The expression of c-myc and CD24 are high in colorectal cancer, having a significant correlation with some of the clinicaopathological features. c-myc is likely to act as a downstream target gene of CD24 signaling pathway, whose expression is probably regulated by CD24 in colorectal carcinoma tissue. Key words: Colorectal neoplasms; Immunohistochemistry; Genes, myc; CD24

Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma.

Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5-year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non-neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL.

Abstract 2132: Personalized prevention of colorectal rectal trial (PPCCT)

Abstract We previously reported from the Tennessee Colorectal Polyp Study that high total intakes of calcium or magnesium may only be related to a reduced risk of colorectal adenoma or hyperplastic polyp when the calcium/magnesium intake ratio was below 2.8. Furthermore, we found that calcium/magnesium intake ratio significantly interacted with the common Thr1482Ile polymorphism (rs8042919, GA) in the TRPM7 gene, in relation to both adenomas and hyperplastic polyps. The TRPM7 gene is involved in magnesium and calcium re(absorption) and homeostasis. Compared to those with the GG genotype, we found that people who carry A allele(s) were at 60% and 85% increased risks of adenoma and hyperplastic polyp, respectively, if they also consumed diets with calcium/magnesium intake ratio &amp;gt;2.8; and the corresponding risks increased by 345% and 1500% among those with the AA genotype. The risk was not increased among those who carried the A allele(s) if they consumed diets low in calcium/magnesium ratio (&amp;lt;2.8). In a recent report from the Calcium Polyp Prevention Study, a large-scale randomized clinical trial of calcium supplementation, it was found that calcium treatment only significantly reduced colorectal adenoma recurrence risk when the baseline dietary calcium/magnesium intake ratio was under 2.6 and this effect modification by the calcium/magnesium ratio cannot solely be attributed to the baseline dietary intake in calcium or magnesium. It is possible for those with a high calcium/magnesium ratio, reducing the calcium/magnesium intake ratio may be helpful. We are funded by NCI (R01CA149633) to conduct a personalized intervention trial clinical trial among 240 colorectal polyp patients with a high calcium/magnesium intake ratio. We are testing 1) if reducing the calcium/magnesium through magnesium supplementation affects biomarkers related to colorectal carcinogenesis in rectal tissues; and 2) if the effects differ by TRPM7 genotype. As of November 16, 2013, we have enrolled at least 160 participants and we plan to complete the trial by the end of January, 2015. Thus the uniqueness of the trial includes 1) only target colorectal polyp patients with a high calcium/magnesium ratio through nutritional screening using multiple 24-hour dietary recalls; 2) personalized doses are based on and used to reduce the current calcium/magnesium intake ratios; and finally, 3) the participants are also randomized by the TRPM7 genotype. We have conducted immunohistochemical assays to measure expressions of carcinogenesis biomarkers, including apoptosis, cell proliferation, COX2 and TRPM7, in normal rectal tissues collected at baseline and the end of the intervention for 40 participants who first completed the trial. We have also measured lipid profile and blood pressure. We have obtained very promising preliminary findings. We will report updated findings in the presentation. The results from our study may ultimately help to develop personalized strategies to prevent the colorectal cancer. Citation Format: Qi Dai, Martha J. Shrubsole, Xinqing Deng, Xiangzhu Zhu, Eugene Shubin, Tiffany McCray, Wei Zheng, Harvey Murff, Douglas Seidner, Reid M. Ness, Chang Yu. Personalized prevention of colorectal rectal trial (PPCCT). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2132. doi:10.1158/1538-7445.AM2014-2132

Genetic variants in apoptosis-related genes associated with colorectal hyperplasia.

Deregulation of apoptosis is a frequent alteration in early benign lesions of the colon mucosa and is thought to be a major contributor to tumor progression and cancer. Single nucleotide polymorphisms (SNPs) within apoptosis-related genes could affect apoptotic responses and their identification might provide a basis to assess individual risk for development of early lesions. To investigate a possible association between genetic polymorphisms and the occurrence of hyperplastic polyps (HP), we developed a custom DNA chip assay for 1,536 SNPs in the coding and flanking regions of 826 genes with known functional roles in apoptosis or apoptosis-associated (e.g., stress-related) pathways. During a first round of screening, genotypes were determined for 272 endoscopy patients harboring hyperplastic colorectal polyps and for 512 sex and aged-matched controls. A set of 14 candidate SNPs associated with HP (P < 0.01) was then evaluated in an independent cohort of patients (n = 38) and controls (n = 38). Following meta-analysis of Stages I and II, a false discovery rate approach was applied. Among the 14 candidate SNPs, eight showed significant association (combined P < 0.01) with the occurrence of HP. The SNPs rs4709583 (PARK2) and rs10476823 (HDAC3) were analyzed for potential functional effects on RNA splicing and RNA half-life. Despite its location near a splice site, alternative splicing was not detected for rs4709583 (PARK3). By contrast, cDNA analysis revealed use of a cryptic polyadenylation signal in the 3'UTR of HDAC3 mRNA and a longer mRNA half-life in a cell line heterozygous for rs10476823.