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PURPOSE - 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.
METHODS - 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.
RESULTS - 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.
CONCLUSION - 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.
BACKGROUND & AIMS - Capsule colonoscopy is a minimally invasive imaging method. We measured the accuracy of this technology in detecting polyps 6 mm or larger in an average-risk screening population.
METHODS - In a prospective study, asymptomatic subjects (n = 884) underwent capsule colonoscopy followed by conventional colonoscopy (the reference) several weeks later, with an endoscopist blinded to capsule results, at 10 centers in the United States and 6 centers in Israel from June 2011 through April 2012. An unblinded colonoscopy was performed on subjects found to have lesions 6 mm or larger by capsule but not conventional colonoscopy.
RESULTS - Among the 884 subjects enrolled, 695 (79%) were included in the analysis of capsule performance for all polyps. There were 77 exclusions (9%) for inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes, 45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI, 91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and 97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%-93) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively, of false-negative findings from capsule analyses.
CONCLUSIONS - In an average-risk screening population, technically adequate capsule colonoscopy identified individuals with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity and 82% specificity. Capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional studies are needed to improve capsule detection of serrated lesions. Clinicaltrials.gov number: NCT01372878.
Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Computer-aided detection (CAD) systems have been shown to improve the diagnostic performance of CT colonography (CTC) in the detection of premalignant colorectal polyps. Despite the improvement, the overall system is not optimal. CAD annotations on true lesions are incorrectly dismissed, and false positives are misinterpreted as true polyps. Here, we conduct an observer performance study utilizing distributed human intelligence in the form of anonymous knowledge workers (KWs) to investigate human performance in classifying polyp candidates under different presentation strategies. We evaluated 600 polyp candidates from 50 patients, each case having at least one polyp ≥6 mm, from a large database of CTC studies. Each polyp candidate was labeled independently as a true or false polyp by 20 KWs and an expert radiologist. We asked each labeler to determine whether the candidate was a true polyp after looking at a single 3D-rendered image of the candidate and after watching a video fly-around of the candidate. We found that distributed human intelligence improved significantly when presented with the additional information in the video fly-around. We noted that performance degraded with increasing interpretation time and increasing difficulty, but distributed human intelligence performed better than our CAD classifier for "easy" and "moderate" polyp candidates. Further, we observed numerous parallels between the expert radiologist and the KWs. Both showed similar improvement in classification moving from single-image to video interpretation. Additionally, difficulty estimates obtained from the KWs using an expectation maximization algorithm correlated well with the difficulty rating assigned by the expert radiologist. Our results suggest that distributed human intelligence is a powerful tool that will aid in the development of CAD for CTC.
Copyright © 2012. Published by Elsevier B.V.
In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods.
Transformation of epithelial cells is associated with loss of cell polarity, which includes alterations in cell morphology as well as changes in the complement of plasma membrane proteins. Rab proteins regulate polarized trafficking to the cell membrane and therefore represent potential regulators of this neoplastic transition. Here we have demonstrated a tumor suppressor function for Rab25 in intestinal neoplasia in both mice and humans. Human colorectal adenocarcinomas exhibited reductions in Rab25 expression independent of stage, with lower Rab25 expression levels correlating with substantially shorter patient survival. In wild-type mice, Rab25 was strongly expressed in cells luminal to the proliferating cells of intestinal crypts. While Rab25-deficient mice did not exhibit gross pathology, ApcMin/+ mice crossed onto a Rab25-deficient background showed a 4-fold increase in intestinal polyps and a 2-fold increase in colonic tumors compared with parental ApcMin/+ mice. Rab25-deficient mice had decreased beta1 integrin staining in the lateral membranes of villus cells, and this pattern was accentuated in Rab25-deficient mice crossed onto the ApcMin/+ background. Additionally, Smad3+/- mice crossed onto a Rab25-deficient background demonstrated a marked increase in colonic tumor formation. Taken together, these results suggest that Rab25 may function as a tumor suppressor in intestinal epithelial cells through regulation of protein trafficking to the cell surface.
Fas ligand (FasL/CD95L), a member of the tumor necrosis factor family, interacts with a specific receptor Fas, ultimately leading to cell death. Tumor expression of FasL has been proposed to aid in immune evasion through a "Fas counterattack" mechanism but has also been described as a proinflammatory factor. Here, we tested the role of FasL in a mouse model of spontaneous tumor development. We used the Min mouse in which multiple benign polyps develop in the intestine due to a mutation in the Apc tumor suppressor gene. Mutant mice deficient in functional FasL, termed gld/gld, were crossed to Min mice to generate tumor-prone animals lacking functional FasL. Comparison of FasL-deficient versus proficient Min mice revealed a significant increase in polyp number in the gld/gld mice. We next assessed immune cell infiltration into adenomas. There was no difference in the number of either lymphocytes or macrophages; however, the number of tumor-infiltrating neutrophils was 3-fold lower in the gld/gld specimens compared with controls. Neutrophil migration in vitro was stimulated by wild-type but not mutant FasL. In a nontumor-bearing colitis model in vivo, neutrophil recruitment to the intestine was also reduced in gld/gld mice. Although the Fas counterattack hypothesis suggests that the absence of FasL would result in increased immune-mediated tumor elimination, the opposite is true in the Min model with lack of functional FasL associated with reduced neutrophil influx and increased tumor development. Thus, the proinflammatory rather than counterattack role of tumor FasL is more relevant.
Colorectal cancer is a major cause of morbidity and mortality accounting for an estimated 550,000 deaths annually worldwide. Colonic neoplasia develops in a stepwise fashion progressing from normal mucosa to adenomatous polyps to carcinoma, a process that takes years, thereby providing a prime opportunity for intervention. Although early detection by fecal occult blood testing and sigmoidoscopy can decrease the risk of cancer-related death by 20-30%, most persons never undergo appropriate screening. Population-based studies have previously determined that long-term ingestion of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) leads to a 40-50% reduction in mortality. from colorectal cancer. These observational studies fueled subsequent mechanistic investigations that led to the identification of a molecular target, cyclooxygenase-2 (COX-2). COX-2 has tumor-promoting properties. Expression of COX-2 is virtually undetectable in normal intestinal mucosa, but is increased in approximately 50% of colonic adenomas and in 90% of colorectal carcinomas. Experimental studies in mice have revealed that genetic ablation or pharmacologic inhibition of COX-2 attenuates the number and size of intestinal polyps that develop in animals harboring a mutation in Apc, which confers an increased risk for intestinal neoplasia. Recent clinical studies using specific COX-2 inhibitors have shown that these compounds can: (1) reduce intestinal polyp burden in patients with familial adenomatous polyposis; (2) prevent the occurrence and/ or recurrence of colorectal adenomas and cancers; and (3) negatively regulate angiogenesis in colorectal cancer liver metastases. Compared to nonselective NSAIDs, COX-2 specific inhibitors cause substantially fewer gastrointestinal side effects. These findings indicate that a widely used and relatively safe class of drugs may represent a viable and effective anticancer strategy for a disease that causes over a half-million deaths per year.
A 15-year-old boy with Marshall-Smith syndrome presented with increased frequency and urgency of stooling, hematochezia, and rectal pain. A polypoid mass was found at the anorectal junction and excised. Microscopically, the lesion was covered by both squamous and columnar mucosa. It was villiform in configuration with focal ulceration and strands of smooth muscle in the lamina propria. These features are characteristic of an inflammatory cloacogenic polyp, a lesion not previously reported in the pediatric age group. Inflammatory cloacogenic polyp is related to solitary rectal ulcer syndrome and is most likely due to prolapse of the anorectal transition zone. Although rare in this age group, solitary rectal ulcer and its variants should be considered in the differential diagnosis of anorectal and rectal lesions in the pediatric patient.