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Background: Individual colorectal polyp risk factors are well characterized; however, insights into their pathway-specific interactions are scarce. We aimed to identify the impact of individual risk factors and their joint effects on adenomatous (AP) and serrated polyp (SP) risk., Methods: We collected information on 363 lifestyle and metabolic parameters from 1597 colonoscopy participants, resulting in over 521,000 data points. We used multivariate statistics and machine-learning approaches to assess associations of single variables and their interactions with AP and SP risk., Results: Individual factors and their interactions showed common and polyp subtype-specific effects. Abdominal obesity, high body mass index (BMI), metabolic syndrome, and red meat consumption globally increased polyp risk. Age, gender, and western diet associated with AP risk, while smoking was associated with SP risk. CRC family history was associated with advanced adenomas and diabetes with sessile serrated lesions. Regarding lifestyle factor interactions, no lifestyle or dietary adjustments mitigated the adverse smoking effect on SP risk, whereas its negative effect was exacerbated by alcohol in the conventional pathway. The adverse effect of red meat on SP risk was not ameliorated by any factor, but was further exacerbated by western diet along the conventional pathway. No modification of any factor reduced the negative impact of metabolic syndrome on AP risk, whereas increased fatless fish or meat substitutes' intake mitigated its effect on SP risk., Conclusions: Individual risk factors and their interactions for polyp formation along the adenomatous and serrated pathways are strongly heterogeneous. Our findings may facilitate tailored lifestyle recommendations and contribute to a better understanding of how risk factor combinations impact colorectal carcinogenesis., (© 2023. The Author(s).)

Aims: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes., Methods and Results: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps., Conclusions: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies., (© 2022 John Wiley & Sons Ltd.)

Backgrounds: MUTYH-associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional MUTYH variants of unknown significance., Methods: Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of MUTYH, as well as other polyposis genes (APC, NTHL1, POLE, POLD1, MSH3, RNF43, and MCM9)., Results: We reclassified 4 out of 10 MUTYH variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the APC gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co-presence of a class 3 MUTYH variant that could be reinterpreted in the next future., Conclusion: Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in Helicobacter pylori infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of H. pylori is hypergastrinemia since H. pylori infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of H. pylori . Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.

Background and Aim: The prevalence of fundic gland polyp (FGP) occurrence has not been clarified in individuals with Helicobacter pylori infection post-eradicated status. This study was performed to examine the relationship between FGP prevalence and H. pylori infection status., Methods: We enrolled 3400 subjects (2185 male subjects and 1215 female subjects; mean age 54.7 ± 9.5 years) with known H. pylori infection status and who underwent an upper gastrointestinal endoscopy examination as part of an annual check-up. Subjects without and with H. pylori infection numbered 1617 and 239, respectively, while 1544 had a post-eradication status. The presence of FGP and degree of gastric mucosal atrophy were determined in each subject using an endoscopic method., Results: Endoscopy findings showed FGPs in 1029 (30.3%) of all subjects. The prevalence ratio of FGP positivity in H. pylori-negative, H. pylori-positive, and post-eradicated subjects was 51.9%, 1.7%, and 12.0%, respectively. Multiple logistic regression analysis revealed that female gender, older age, milder gastric mucosal atrophy, and anti-secretory therapy were significant risk factors for FGP occurrence. As compared with H. pylori-positive subjects, the odds ratios for H. pylori-negative and post-eradication status were 48.3 and 6.6, respectively (P < 0.001). In the post-eradication status subjects, longer duration following bacterial eradication was a significant risk factor for occurrence of FGPs., Conclusion: The risk of FGP occurrence in individuals who have undergone H. pylori eradication treatment is lower as compared with those who have never been infected. However, that risk increases over time following eradication., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Gastric neoplasms (GN), including gastric adenoma and carcinoma, are well known as extracolonic manifestations of familial adenomatous polyposis (FAP). We aimed to investigate the clinicopathological features of GN in FAP patients and to clarify their relationship with the endoscopic status of the background mucosa., Methods: We analyzed the records of 39 patients who were diagnosed with FAP and underwent esophagogastroduodenoscopy between April 2005 and July 2016. Patients were divided into two groups according to atrophic gastritis (AG) status. Endoscopic findings of GN and background mucosa, and histopathological findings, including phenotypic expression of GN and mutation locus of adenomatous polyposis coli (APC) gene, were evaluated., Results: Gastric neoplasms were more predominant in the AG-positive group than in the AG-negative group (6/9, 66.7% vs 7/30, 23.3%; P = 0.039). Of 36 GN detected in 13 patients, six GN in five patients were followed and 30 GN in eight patients were endoscopically resected and analyzed. GN in the AG-negative group frequently showed whitish color, were located in the proximal stomach, and presented the gastric immunophenotype compared to GN in the AG-positive group. All GN were intramucosal lesions and were curatively resected regardless of AG status. APC germline mutations were identified in 32 patients. In patients with GN, a significantly higher number of mutation loci were among exons 10-15 (codons 564-1465)., Conclusion: Clinicopathological characteristics and phenotypic expressions of GN in FAP patients depend on background mucosa status with or without AG. These findings are useful for detecting GN in FAP patients., (© 2019 Japan Gastroenterological Endoscopy Society.)

Objective: We present the case of a 57-year-old man with a history of Roux-en-Y gastric bypass (RYGB) and colonic polyps who presented with an upper gastrointestinal obstruction based on massive stomach polyposis in the pouch., Methods: Two months prior to this acute admission, he had undergone resection of the gastric remnant due to massive refractory intraluminal bleeding from a polypoid mass. Ten years earlier, right colectomy was performed due to hypertrophic polyposis unsuitable for endoscopic polypectomy. Upper gastrointestinal endoscopy showed a polypoid mass in the pouch causing obstruction. Benign biopsies were obtained. A resection of the stomach pouch with esophagojejunostomy was performed. Macroscopic evaluation of the pouch lumen showed massive polyposis with a sharp demarcation near the Z-line and at the gastrojejunostomy. On clinical examination, the presence of atrophic nail changes, alopecia, and palmar hyperpigmentation was noticed., Results: Postoperative course was uneventful and feeding was restarted successfully. Histological analysis revealed hyperplastic polypoid tissue, which resembled the polyps in the stomach remnant and colon. Together with the ectodermal changes, the diagnose of Cronkhite-Canada syndrome was established., Conclusion: Diffuse polyposis in Cronkhite-Canada syndrome is a rare cause for pouch obstruction after RYGB. Clinical examination should focus on dermatologic findings.

Goals: The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications., Background: Smoking is an established risk factor for several cancers, including colorectal cancer. However, the association between lifetime smoking habits including intensity, duration, and cessation, and premalignant colorectal polyps is yet to be established., Study: A case-control study among 828 consecutive subjects aged 40 to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria were: medically treated diabetes, colectomy, and belonging to colorectal cancer high risk group. Polyps were stratified according to histology (serrated or adenomatous polyp) and location. All participants underwent anthropometric measurements and a structured medical and lifestyle interview., Results: Current-smoking was more strongly associated with increased odds for distal rather than proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68 and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively). All levels of smoking intensity (daily cigarettes) were associated with colorectal polyps. A dose-response association was seen between smoking duration and colorectal polyps. Smoking duration of ≥20 years was strongly associated with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential confounders, smoking intensity and years since smoking cessation. All associations were stronger for distal serrated polyps., Conclusions: Smoking duration is associated with colorectal plyps, independently of other potential confounders, smoking intensity, and cessation. The association is stronger with distal rather than proximal polyps, and with serrated polyps rather than adenomas.

Background & Aims: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1), and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in the initiation and progression of colitis-associated cancer (CAC) in mice., Methods: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1 ΔIEC , Mel18 ΔIEC , DKO, and TKO mice). We also disrupted Bmi1 and/or Mel18 specifically in intestinal epithelial cells (IECs) using the villin-CreER T2 -inducible promoter. CAC was induced in cre-negative littermate mice (control) and mice with conditional disruption of Bmi1 and/or Mel18 by intraperitoneal injection of azoxymethane (AOM) followed by addition of dextran sulfate sodium (DSS) to drinking water. Colon tissues were collected from mice and analyzed by histology and immunoblots; IECs were isolated and used in cDNA microarray analyses., Results: Following administration of AOM and DSS, DKO mice developed significantly fewer polyps than control, Bmi1 ΔIEC , Mel18 ΔIEC , Reg3b ΔIEC , or TKO mice. Adenomas in the colons of DKO mice were low-grade dysplasias, whereas adenomas in control, Bmi1 ΔIEC , Mel18 ΔIEC , Reg3b ΔIEC , or TKO mice were high-grade dysplasias with aggressive invasion of the muscularis mucosa. Disruption of Bmi1 and Mel18 (DKO mice) during late stages of carcinogenesis significantly reduced the numbers of large adenomas and the load of total adenomas, reduced proliferation, and increased apoptosis in colon tissues. IECs isolated from DKO mice after AOM and DSS administration had increased expression of Reg3b compared with control, Bmi1 ΔIEC , or Mel18 ΔIEC mice. Expression of REG3B was sufficient to inhibit cytokine-induced activation of STAT3 in IECs. The human REG3β protein, the functional counterpart of mouse REG3B, inhibited STAT3 activity in human 293T cells, and its expression level in colorectal tumors correlated inversely with pSTAT3 level and survival times of patients., Conclusions: BMI1 and MEL18 contribute to the development of CAC in mice by promoting proliferation and reducing apoptosis via suppressing expression of Reg3b. REG3B negatively regulates cytokine-induced activation of STAT3 in colon epithelial cells. This pathway might be targeted in patients with colitis to reduce carcinogenesis., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population., Methods: A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression., Results: There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use., Conclusions: Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps., Methods: A 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., Results: The 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)., Conclusion: NAFLD 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., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest with the paper presented.

A 56-year-old man with gastroesophageal reflux disease (GERD) was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed no evidence of any polypoid lesions in the stomach, and the patient had no history of Helicobacter pylori infection. He received omeprazole (20 mg) once daily for the GERD. EGD was performed at 1 year after the start of omeprazole administration, and this time, gastric hyperplastic polyps (GHPs) were detected. The GHPs increased in size as the omeprazole treatment continued, but they markedly decreased in size following omeprazole discontinuation. Thus, the administration of proton pump inhibitors may be a risk factor for the development of GHP independent of H. pylori infection.

Background: Low folate status is associated with an increased risk of colorectal carcinogenesis. Optimal folate status may be genoprotective by preventing uracil misincorporation into DNA and DNA hypomethylation. Adenomatous polyps have low folate status compared with normal colonic mucosa, and they are surrounded by histologically normal mucosa that also is of low folate status., Objective: In a randomized controlled trial conducted at a single Dublin hospital between April 2002 and March 2004, we assessed the effect of folic acid supplementation on tissue folate, uracil misincorporation into DNA, and global DNA hypomethylation in colonocytes isolated from sites of adenomatous polyps and from histologically normal tissue adjacent and 10-15 cm distal to them., Methods: Twenty patients with adenomatous polyps on initial colonoscopy and polypectomy were randomly assigned to receive either 600 μg folic acid/d [n = 12, 38% men, mean age 64.3 y, and body mass index (BMI, in kg/m(2)) 26.6] or placebo (n = 8, 50% men, mean age 68.4 y, and BMI 27.2) for 6 mo, and then repeat the colonoscopy. Blood and colonocyte tissue folate concentrations were measured with the use of a microbiological assay. Uracil misincorporation and global DNA hypomethylation were measured in colonocytes with the use of modified comet assays., Results: Over time, folic acid supplementation, compared with placebo, increased tissue folate (mean ± SEM) from 15.6 ± 2.62 pg/10(5) cells to 18.1 ± 2.12 pg/10(5) cells (P < 0.001) and decreased the global DNA hypomethylation ratio from 1.7 ± 0.1 to 1.0 ± 0.1 (P < 0.001). The uracil misincorporation ratio decreased by 0.5 ± 0.1 for the site adjacent to the polyp over time (P = 0.05)., Conclusion: A response to folic acid supplementation, which increased colonocyte folate and improved folate-related DNA biomarkers of cancer risk, was seen in the participants studied. Exploratory analysis points toward the area formerly adjacent to polyps as possibly driving the response. That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field's causing the appearance of the polyp., (© 2016 American Society for Nutrition.)

Background and Study Aims: Despite ample research on the dysplasia to carcinoma risk in ulcerative colitis, there are scant data on the prevalence of adenomatous polyps in this population., Methods: The number and histology of all polyps detected at colonoscopies of ulcerative colitis patients aged > 50 during 2006 - 2012 were compared with similarly aged controls undergoing screening colonoscopy., Results: There were 206 patients with ulcerative colitis and 624 controls included in the study (mean age 61.7 ± 8.7 vs. 60.8 ± 6.1, respectively; P = 0.15). Adenomatous polyps were detected in only 13/206 colonoscopies for ulcerative colitis compared with 162 /624 controls (6.3 % vs. 25.9 %, respectively; odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.1 - 0.34; P < 0.0001). When also considering all prior colonoscopies performed over 7.7 ± 4.6 years of follow-up (mean 4.1 ± 2.9 colonoscopies/patient, range 1 - 15, total 832 colonoscopies), the risk of ever finding an adenoma in ulcerative colitis patients was still significantly lower compared with controls (14.1 % vs. 25.9 %, respectively; OR 0.47, 95 %CI 0.3 - 0.72; P = 0.0005). On multivariable analysis, adenomas were positively associated with advanced age (OR 1.07/year, 95 %CI 1.03 - 1.1; P < 0.0001) and with increasing body mass index (BMI; OR 1.06/kg/m(2), 95 %CI 1.01 - 1.1; P = 0.01) and negatively associated with having ulcerative colitis (OR 0.15, 95 %CI 0.09 - 0.44; P = 0.0005). Among 115 Crohn's disease patients aged > 50 years, the rate of ever-adenomas in small-bowel Crohn's disease was similar to the controls (P = 0.8) and not influenced by 5-aminosalicylic acid use, whereas patients with colonic Crohn's disease had a significantly lower rate of adenomas compared with the controls (3.9 % vs. 25.9 %; P = 0.002)., Conclusion: Unlike patients with small-bowel Crohn's disease, patients with ulcerative colitis or with colonic Crohn's disease seldom develop sporadic adenomatous polyps. These data may provide novel clues to a possible role for colonic immune activation in restricting the adenoma to carcinoma sequence while propagating the dysplasia to carcinoma pathway., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Endometrial polyps (EPs) and colorectal polyps (CPs) are common disorders and the incidence of both increase rapidly with aging. CPs are focal lesions and incidence increases with age., Aim: In this study, we aimed to analyze retrospectively the relationship between the EPs and CPs sharing similar clinical and genetic factors in their etiopathogenesis., Materials and Methods: This study was retrospectively performed between 2010 and 2013 and it included patients diagnosed to have eEPs. The study group and the control group consisted of patients who were diagnosed with or without EPs and who underwent colonoscopy at the same period., Results: The study group was formed by 57 patients with diagnosis of EP who underwent colonoscopy during the same period. The control group consisted of 71 patients without EP examined with colonoscopy. Among 128 patients assessed in this study, 24 were diagnosed with CPs, all of which were adenomatous polyps smaller than 1cm. No hyperplastic or inflammatory polyps were diagnosed. While 18 of 57 patients with EPs had CPs, 6 of 71 control subjects had CPs. Hence, the risk of having CP was 5 times greater in patients with EP compared to those without (P < 0.05)., Conclusion: The present study demonstrated that the prevalence of CPs increased significantly in postmenopausal patients with EPs. Recommending colonoscopy to these patients irrespective of age may be beneficial for detecting more CPs and preventing colorectal cancer., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Purpose: BRAF inhibitors (BRAFi) extend survival in BRAF-mutant melanoma but can promote the growth of Ras-mutant neoplasms. This study determined if gastrointestinal polyps found in BRAFi-treated patients harbored Ras mutations., Experimental Design: Colonic and gastric polyps were identified and resected from BRAFi-treated melanoma patients. Next-generation sequencing (NGS) was performed on polyps. The ability of BRAFi to promote polyp formation was functionally characterized in Apc Min(+/-) mice. MAPK and β-catenin pathway activity was assessed by immunohistochemistry in mouse and human polyps., Results: Fourteen patients treated with BRAFi underwent endoscopy to assess for polyps. Seven out of 7 patients >40 years of age and treated for >2 years were found to have colonic tubular adenomas with 4 out of the 7 patients having 5 or more polyps. One patient presented with bleeding from hyperplastic gastric polyps that recurred 6 months after BRAFi rechallenge. NGS performed on polyps found no mutations in MAPK pathway genes, but found APC mutations in all tubular adenomas. A significant increase in the number of polyps was observed in BRAFi-treated compared with control-treated Apc Min(+/-) mice (20.8 ± 9.2 vs 12.8 ± 0.1; P = 0.016). No polyps were observed in BRAFi-treated wild-type mice., Conclusions: BRAFi may increase the risk of developing hyperplastic gastric polyps and colonic adenomatous polyps. Due to the risk of gastrointestinal bleeding and the possibility of malignant transformation, further studies are needed to determine whether or not endoscopic surveillance should be recommended for patients treated with BRAFi., (©2015 American Association for Cancer Research.)

We present a case of gastritis cystica polyposa (GCP) that developed early after laparoscopy-assisted distal gastrectomy with BillrothⅠreconstruction. GCP is a chronic inflammatory gastric mucosal lesion that emerges at an anastomotic site usually after a long post-gastrectomy period, which is mainly caused by constant chemical stimulation by duodenal juice. In addition, chronic mechanical stimulation caused by reflux or stasis of gastrointestinal contents may also trigger GCP. Surgeons should ensure a functional and physiologically patent anastomosis during surgery. Hypergastrinemia, caused by persistent Helicobacter pylori infection or continuing administration of proton pump inhibitors, may also contribute to the development of GCP, as GCP is a type of hyperplastic polyp. Therefore, appropriate postoperative follow-up, including pylorus eradication and avoidance of unnecessary administration of proton pump inhibitors, seems to be needed in order to prevent the development of GCP. In our case, many factors exhibited the multiplier effect, resulting in early development of GCP. As GCP also attracts much attention as a precancerous lesion, appropriate prevention and prompt treatment are required.

Background/aims: Current epidemiological data suggest that the incidence of gastric polyps (GP) is rare, and its etiology and pathogenesis are still not clear. This study analyzed and compared the occurrence and pathological types of GPs in southeast Chinese patients according to gender and age., Materials and Methods: This was a retrospective study of patients diagnosed with GP (n=2125) in Wenzhou People's Hospital (China) between January 2004 and December 2013. The relationships between the detection rate, the characteristics of GP, and the patients' demographic data were analyzed., Results: The detection rate of GP was 2.3% and 3.9% in males and females, respectively (p<0.01). The detection rate increased with increasing age in both genders. Polyps in the gastric antrum and gastric body were the most prevalent in both genders. Similarly, inflammatory polyps and hyperplastic polyps were the most prevalent in both genders. Hyperplastic polyps were more common in females than in males (28.6% vs. 24.2%, p<0.05), while there was no difference for inflammatory polyps, fundic GP, and adenoma (p>0.05). Age had no impact on the pathology of GP (p>0.05)., Conclusions: The incidence of GPs was associated with gender and age.

Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of β-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA.

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

Aims: Most patients with familial adenomatous polyposis (FAP) develop gastric fundic gland polyps, with many displaying low-grade dysplasia. This study evaluates the natural history and morphological phenotype of dysplasia in FAP-associated fundic gland polyps., Methods and Results: Patients with FAP and dysplastic fundic gland polyps (n = 24) were identified. Twenty-two of 24 FAP-associated dysplastic fundic gland polyps showed a gastric phenotype and two had mixed phenotype. During a mean 6.1-year follow-up (range 0.8-12.6 years) and 5.7 endoscopies (range 2-22), one patient (4%) was diagnosed with a fundic gland polyp with high-grade dysplasia, while 23 patients (96%) in this cohort had either no dysplasia or persistent low-grade dysplasia. Contemporary patients with sporadic fundic gland polyps with low-grade dyplasia had similar morphology and outcomes to the FAP-associated fundic gland polyp cohort. Dysplasia in fundic gland polyps (FAP-associated and sporadic) was associated less frequently with intestinal phenotype, high-grade dysplasia and the finding of concurrent or subsequent carcinoma compared to contemporary patients with sporadic gastric dysplasia not occurring in fundic gland polyps., Conclusions: This cohort of patients with FAP-associated dysplastic fundic gland polyps rarely developed high-grade dysplasia and gastric adenocarcinoma was absent., (© 2014 John Wiley & Sons Ltd.)

Increasing body fatness has been associated with an increased burden from colorectal cancer. An increased susceptibility spanning the entire continuum from precancerous adenomatous polyps to the development of colorectal cancer, poor outcome with treatment, and reduced survival when compared to those with normal body weight has been described. It is unknown which age period and which degree and duration of excess weight are associated with increased colorectal cancer risk. It is uncertain whether weight loss can reverse this risk. If it can, how long will the new lower or normal weight be maintained to effect enduring risk reduction? Furthermore, it is controversial whether the increased burden of colorectal cancer warrants earlier and/or more frequent screening for obese persons. This article reviews the relationship between obesity and colorectal neoplasia, explores the postulated mechanism of carcinogenesis, discusses interventions to reduce the burden of disease, and suggests future directions of research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: While diabetes is considered as a risk factor for colorectal cancer, there are few studies that address the association between glycemic statuses and different colon polyps, ranging from non-neoplastic polyps to advanced adenomatous polyps., Methods: A total of 6,348 participants, consisting of 3,777 men and 2,571 women, with a mean age of 50.5 years, were included for final analysis after excluding subjects with a past history of colorectal cancer, colon polyps/polypectomy, familial adenomatous polyposis, and colorectomy, or missing data. Diabetes and pre-diabetes were defined using the 2011 American Diabetes Association criteria. Subjects were classified into four groups: polyp-free, non-neoplastic polyps, non-advanced and advanced adenomatous polyps., Results: There were significant differences in the prevalence of diabetes and pre-diabetes among groups with different kinds of colon polyps. In addition, significant differences were also noted in age, total cholesterol, body mass index, triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose, and the prevalence of male gender, hypertension, obesity, current smoking and alcohol drinking among groups. In the multinomial logistic regression analyses, diabetes was related to both non-advanced and advanced adenomatous polyps, while pre-diabetes was only related to non-advanced adenomatous polyps. In addition, age ≥65 years and male gender were associated with both non-advanced and advanced adenomatous polyps, while hypertension and current smoking were independently related to advanced and non-advanced adenomatous polyps, respectively., Conclusions: Diabetes, but not pre-diabetes, was associated with a higher risk of advanced adenomatous polyps. In addition, both diabetes and pre-diabetes were important correlates of non-advanced adenomatous polyps.

Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10-expressing T cells to mice with polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APC(Δ468) mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell-specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs.

Low folate status is a risk factor for colon carcinogenesis; mechanisms proposed to account for this relationship include uracil misincorporation into DNA and global DNA hypomethylation. We investigated whether such biomarkers are related to folate status in isolated colonocytes from colonoscopy patients. In cases with adenomatous polyps (n = 40) or hyperplastic polyps (n = 16), colonocytes were isolated from biopsies from the polyp, from a site adjacent to the polyp, and from normal mucosa 10-15 cm distal to the polyp. In polyp-free controls (n = 53), biopsies were taken from ascending, transverse, and descending areas of colon. Within adenoma cases, there was a trend (P-trend < 0.001) of decreasing colonocyte folate (pg/10⁵ cells, mean ± CI) from the site distal to the polyp (16.9 ± 2.4), to the site adjacent to the polyp (14.7 ± 2.3), to the polyp (12.8 ± 2.0). Correspondingly, there were increases in uracil misincorporation (P-trend < 0.001) and global DNA hypomethylation (P-trend = 0.012) across the 3 sites. Colonocyte folate concentrations were significantly correlated with RBC folate concentrations, but only in individuals with generally lower (≤484 μg/L) RBC folate status (r = 0.54; P = 0.006; n = 24), and were also significantly lower in normal mucosa of cases with adenomatous polyps than in controls matched for colonic segment. In conclusion, localized folate deficiency in specific areas of colon might create carcinogenic fields and affect the development of colorectal polyps through uracil misincorporation and DNA hypomethylation; alternatively, the polyp itself might deplete folate in the surrounding tissue. Folate supplementation trials aimed at colon cancer prevention should target individuals with suboptimal folate status.

Background: Current guidelines for colorectal cancer (CRC) screening recommend initial screening at 50 years of age for normal-risk patients. Alcohol and tobacco use can be associated with an earlier onset of CRC and possibly polyps., Methods: We reviewed all colonoscopies performed at our institution from January to December 2007. Patient data were collected on age, sex, tobacco and alcohol history, and the presence of colon lesions., Results: Our data included 663 patients (643 men and 20 women) with a mean age of 60.7 years (range 23-89 years); 68.5% were current/former tobacco users, 53.7% were current/former alcohol users, 37.6% had used both, and 21.7% had used neither. Colonoscopy findings were as follows 64% of patients had no lesions, 30.6% had tubular polyps, 3.5% had villous polyps, and 2% had cancer. The current use of tobacco, alcohol, or both was associated with the early development of colon pathology (ie, 66.9 years, 61.1 years, and 59.2 years [P < .05], respectively). In nonusers, the mean age was 67.7 years., Conclusions: Our work confirms that the use of alcohol and tobacco is associated with an earlier onset of colon pathology. Consideration should be given to modifying screening guidelines to include these habits as "high-risk" factors., (Published by Elsevier Inc.)

Colorectal cancer is one of the most commonly diagnosed neoplasms still associated with relatively high mortality. Viral infections are often mentioned among the neoplasm transformation risk factors. Incidence of human papilloma virus (HPV), associated with high oncogenic risk, in the large intestine and the meaning of its presence in the colorectal carcinogenesis are still not clear. The aim of the study was to show a presence of HPV in specimens of adenomatous polyps and colorectal cancer using the Q-PCR method. Fifty patients (32 M/18W, mean age 62.8 years) were enrolled in the study, for whom tissue samples were obtained. Study material involved paraffin blocks derived from samples collected by flexible sigmoidoscopy from 10 polyps and 10 large intestine adenocarcinomas and 30 paraffin blocks with specimens of surgically removed large intestine adenocarcinomas. Presence of HPV genome was confirmed by quantitative PCR method using commercially available Abbott RealTime High Risk HPV test. The test is able to detect 14 most prevalent high oncogenic risk subtypes of human papilloma virus. Status of HPV DNA was successfully assessed in all 50 samples. No HPV DNA was discovered in any of the tested samples. Presence of high oncogenic risk HPV subtypes in large intestine adenoma and adenocarcinoma seems to be very rare, and its dominating role in the pathogenesis of colorectal cancer, even if possible, is unlikely.

Background: Putrescine, spermidine, and spermine are the polyamines required for human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the development of colorectal adenomas. A database was developed to estimate dietary polyamine exposure and relate exposure to health outcomes., Objective: We hypothesized that high polyamine intake would increase risk of colorectal adenoma and that the allelic variation at ODC G>A +316 would modify the association., Design: Polyamine exposure was estimated in subjects pooled (n = 1164) from the control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n = 579)] by using baseline food-frequency questionnaire data. All subjects had to have a diagnosis of colorectal adenoma to be eligible for the trial., Results: A dietary intake of polyamines above the median amount in the study population was associated with 39% increased risk of colorectal adenoma at follow-up (adjusted OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48, 4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had significantly increased odds of colorectal adenoma if they consumed above-median polyamine amounts., Conclusions: This study showed a role for dietary polyamines in colorectal adenoma risk. Corroboration of these findings would confirm a previously unrecognized, modifiable dietary risk factor for colorectal adenoma.

Objective: The findings from epidemiological studies addressing the association between adiposity and the risk of colorectal adenomatous polyps are inconsistent. We performed a meta-analysis of epidemiological studies including cross-sectional, case-control, and cohort studies., Methods: We searched PubMed and EMBASE in June, 2010. All searched articles were reviewed and selected independently by two evaluators according to pre-determined selection criteria., Results: We included 25 studies (nine cross-sectional studies, eleven case-control studies, and five prospective cohort studies) that comprised a total of 300,671 participants and 20,903 cases in the final analysis. When all studies were pooled, the odds ratio (OR) or relative risk (RR) of adiposity and abdominal adiposity for colorectal adenomatous polyp risk was 1.43 (95% confidence interval (CI) 1.23-1.67; n = 22) and 1.42 (95% CI 1.30-1.56; n = 12), respectively. Similarly, an increased risk of colorectal adenomatous polyps was observed in most of the subgroup meta-analyses., Conclusions: Overall, we found that adiposity and abdominal adiposity significantly increased the risk of colorectal adenomatous polyps in a meta-analysis of epidemiological studies.

Anthropometric factors have been associated with colorectal cancer and adenomas but with conflicting results in women or regarding adenoma characteristics. The authors aimed to explore associations between anthropometric factors (height, weight, body mass index, waist and hip circumferences, and weight changes) and adenoma risk. They analyzed the 17,391 women of the French Etude épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale (E3N)-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort who underwent a colonoscopy during follow-up (1993-2002), including 1,408 who developed a first colorectal adenoma. In Cox multivariate proportional hazard regression models, obesity was associated with an increased colorectal adenoma risk (hazard ratio = 1.53, 95% confidence interval: 1.21, 1.94). This association was restricted to left colon adenomas (P(homogeneity) = 0.05 and 0.01 for colon vs. rectum and right vs. left colon, respectively), with a dose-effect relation observed from 22 kg/m². A high waist circumference was also associated with left colon adenoma risk (hazard ratio = 1.81, 95% confidence interval: 1.36, 2.41). Mean weight gain over 0.5 kg/year was associated with a 23% increased colorectal adenoma risk. Associations did not differ between advanced and nonadvanced adenomas. In conclusion, study findings suggest that obesity and weight gain are associated with early colorectal carcinogenesis in women, and specifically regarding the distal colon.

Objective: It is suggested that patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps. However, the optimum frequency with which colonoscopic screening should be offered remains unclear., Design: To determine the optimum frequency for repeated colonoscopic surveillance of acromegalic patients., Methods: We retrospectively reviewed the case records of all patients with acromegaly seen in our centre since 1992: 254 patients had at least one surveillance colonoscopy, 156 patients had a second surveillance colonoscopy, 60 patients had a third surveillance colonoscopy and 15 patients had a fourth surveillance colonoscopy., Results: The presence of hyperplastic or adenomatous polyps was assessed in all patients, while one cancer was detected at the second surveillance. At the third surveillance, mean (+/-s.d.) serum IGF1 levels (ng/ml) in patients with hyperplastic polyps were significantly higher than those with normal colons (P<0.05). The presence of an adenoma rather than a normal colon at the first colonoscopy was associated with a significantly increased risk of adenoma at the second (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.4) and at the third (OR 8.8, 95% CI 2.9-26.5) screens. Conversely, a normal colon at the first surveillance gave a high chance of normal findings at the second (78%) or third surveillance (78%), and a normal colon at the second colonoscopy was associated with normality at the third colonoscopy (81%)., Conclusions: Repeated colonoscopic screening of patients with acromegaly demonstrated a high prevalence of new adenomatous and hyperplastic colonic polyps, dependent on both the occurrence of previous polyps and elevated IGF1 levels.

Background: There is limited data assessing the relationship between cholecystectomy and colorectal adenomatous polyps (AP). Our aim was to determine if cholecystectomy was associated with an increased prevalence of advanced AP in male veterans., Methods: The relationship of whether prior cholecystectomy modified the natural history of AP was investigated in a retrospective study. The patients were divided into two groups: 1) those with AP and a history of cholecystectomy, and 2) those with AP, but without a history of cholecystectomy. Factors in each group associated with advanced AP were examined by univariate analysis (UA) and stepwise logistic regression analysis to determine independent predictors of aggressive clinical characteristics of polyps. Statistical significance was determined at a P < or = 0.05., Results: We identified a total of 1234 patients with AP (cases = 127, controls = 1107). The mean age of patients was 64.1 +/- 1.9 (standard deviation) years. By UA, those with a prior cholecystectomy had a greater mean number of AP (4.2 vs. 3.5; P = 0.04) and more advanced polyps (P = 0.037) than those without a cholecystectomy. By logistic regression, prior cholecystectomy was associated with more advanced AP (OR = 1.5 [1.0-2.2]; P = 0.04). Patients who had a cholecystectomy were 51% more likely to have advanced AP. There appeared to be a trend towards increased time from cholecystectomy being associated with advanced polyps (9.69 years vs. 8.99 years, P = 0.056)., Conclusions: A prior cholecystectomy was independently associated with an increased risk of developing advanced AP. Also, there appeared to be a trend toward a greater prevalence of advanced lesions as postcholecystectomy time increased.

Lymphedematous fibroepithelial polyps of the penis are lesions that have only recently been described and are frequently associated with condom catheter use. We report an additional case of lymphedematous fibroepithelial polyps of the penis in association with long-term condom catheter use in a 36-year-old man. Local excision showed large polypoid nodules with compact orthohyperkeratosis and mild acanthosis. The stroma was hypercellular with spindled to stellate fibroblasts and occasional multinucleated cells. Proliferation of small linear to slightly arcuate vessels with some superficial dilatation was a prominent feature. Focal expression of smooth muscle actin and desmin was present in the stroma. Lymphedematous fibroepithelial polyps of the penis are rare lesions with only 11 cases previously reported. We present here an additional example of this entity to highlight the differential diagnosis, the association with condom catheter use and to raise awareness for this unusual diagnosis.

It is becoming increasingly evident that cancer stem cells play a vital role in development and progression of cancers and relapse following chemotherapy. The present study examines the presence of cancer stem-like cells (CSC) in adenomatous polyps and in normal appearing colonic mucosa in humans during aging. The number of polyps was found to increase linearly with advancing age (r(2)=0.92, p<0.02). Immunohistochemical analysis revealed co-localization of CSC markers CD44 and CD166 in colonic polyps. Real-time RT-PCR analysis of normal appearing mucosa from subjects with adenomatous polyps showed an age-related rise in CSC as evidenced by the increased expression of CD44, CD166 and ESA. A similar phenomenon was also observed for EGFR. In addition, the expression each CSC marker was found to be about 2-fold higher in subjects with 3-4 polyps than those with 1-2 polyps. In conclusion, our results show that colon cancer stem-like cells are present in the premalignant adenomatous polyps as well in normal appearing colonic mucosa. Moreover, our observation of the age-related rise in CSC in macroscopically normal colonic mucosa suggests a predisposition of the organ to developing colorectal cancer.

Background and Study Aims: Advanced neoplasia may occur in the remaining colon and distal ileum of familial adenomatous polyposis (FAP) patients who have had a prophylactic colon resection. The role of post operative lower GI endoscopic surveillance and management of advanced neoplasia in FAP patients is not well defined. The aims of this study were to determine the prevalence of post operative neoplasia and to evaluate the safety and effectiveness of lower GI endoscopic surveillance and ablative therapy following prophylactic colon resection., Patients and Methods: A retrospective analysis of 42 FAP patients with prior primary colon cancer preventative surgery undergoing lower GI surveillance and ablative therapy from 1992 to 2006., Results: All patients had adenomatous disease identified upon initial endoscopy with advanced neoplasia identified in 6/42 (14%). Patients had a median of 4 endoscopic procedures of which 2 (range 0-12) were therapeutic, over a 49 month follow-up period (range 0-168) Thermal ablation with argon plasma coagulation, polypectomy and surgical intervention were required in 55%, 7% and 14% of patients. Ablative therapy complications were due to Nd: YAG laser and snare polypectomy (5%). Progression to advanced neoplasia from baseline pathology occurred despite ablative therapy in 3/42 (7%) patients. We propose a lower GI tract endoscopic surveillance program for post surgical FAP patients., Conclusion: Despite prophylactic colon surgery, FAP patients continue to be at risk of neoplasia. The development of advanced neoplasia is infrequent in patients embarking upon endoscopic surveillance. Ablative therapy is effective and safe for the vast majority of FAP patients.

Background: High-glycemic-load diets may increase colorectal cancer risk through hyperinsulinemic effects., Objective: We analyzed data for 191,004 participants in the Multiethnic Cohort Study to determine the risk of colorectal cancer associated with glycemic load (GL), carbohydrate, and sucrose and to ascertain whether this risk was modified by sex and ethnicity., Design: During 8 y of follow-up, 2379 incident cases of colorectal adenocarcinoma occurred. We used baseline quantitative food-frequency questionnaire data to assess usual dietary intake over the preceding year. Using Cox regression, we calculated adjusted relative risks (RRs) and 95% CIs for colorectal cancer associated with quintiles of GL, carbohydrate, and sucrose., Results: For both men and women in this cohort, white rice was the major contributor to GL. In multivariate models, RRs for colorectal cancer decreased significantly with increasing GL in women (RR for the highest quintile versus the lowest: 0.75; 95% CI: 0.57, 0.97; P for trend = 0.02) but not in men (RR: 1.15; 95% CI: 0.89, 1.48; P for trend = 0.19). Results for carbohydrate and sucrose were similar. The inverse association with GL was found in women of all ethnic groups (P for interaction = 0.58). In men, an interaction was found between ethnicity and GL (P < 0.01): white men had a positive association with increasing GL (RR: 1.69; 95% CI: 0.98, 2.92; P for trend < 0.01), but men of other ethnic groups did not., Conclusion: GL and carbohydrate intake appear to protect against colorectal cancer in women in the Multiethnic Cohort, perhaps because a major source of GL is white rice.

The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n = 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for > or =35 years of smoking, odds ratios were 1.9 (95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 (95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 (95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for > or =20 years since quitting, odds ratios were 0.4 (95% CI: 0.3, 0.6) for adenoma only, 0.2 (95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 (95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps.

Unlabelled: Colon carcinogenesis is a multi-steps process in which many growth factors are involved. In some studies the increased risk of colon cancer development was observed in patients with diabetes mellitus type 2 with accompanying hyperinsulinemia. It is also known that insulin-like growth factor I (IGF-I) plays an important role in proliferation, growth, differentiation and inhibiting apoptosis of both epithelial and carcinoma cells. The aim of the study was to evaluate the serum concentration of insulin, C-peptide and IGF-I in patients with colon adenomas and colorectal cancer., Materials and Methods: In 17 patients with colon cancer, 32 patients with colon adenomas and in 12 healthy persons the serum concentration of insulin, C-peptide and IGF-I was determined using ELISA kits., Results: In patients with colon cancer significantly higher serum IGF-I concentration comparing to the control group was observed (85.66 ng/ml vs. 60.96 ng/ml; p < 0.05). Higher IGF-I concentration was also observed in patients with distal tumors comparing to the proximal localisation (95.40 ng/ml vs. 64,65 ng/ml, p < 0.05) and in more differentiated tumors (84.36 ng/ml vs. 75.24 ng/ml). Similarly, higher C-peptide concentrations were observed in distal tumors (635.64 pmol/ I vs. 578.69 pmol/l) and in well-differentiated carcinoma (671.32 pmol/ I vs. 575.66 pmol/l). In patients with colon adenomatous polyps we also observed higher serum IGF-I concentrations I comparing to the control group (82.1 ng/ml vs. 60.96 ng/ml), in high dysplasia adenomas (84.12 ng/ml vs. 79.67 ng/ml) and in smaller adenomas to 1 cm diameter (97.98 ng/ml vs. 73.28 ng/ml), but the differences were not significant. We also observed higher concentration of C-peptide in patients with low grade dysplasia adenomas (665.24 pmol/l vs. 498.13 pmol/l) and with small polyps (611.51 pmol/l vs. 514.89 pmol/l). There were no differences in serum concentration of IGF-I and C-peptide between patients with tubular and villous adenomas. There was no statistical difference observed in insulin serum concentration in all groups of patients., Conclusions: IGF-I is probably involved particularly in the early stage of colon carcinogenesis.

Background: It is possible that high-glycemic-load diets, through their hyperinsulinemic effects, can increase the risk of colorectal cancer., Objective: We analyzed data from a cancer screening study to determine whether persons with high-glycemic-load diets would be at an increased risk of distal adenomas., Design: We included subjects with no prior adenoma or cancer from the Prostate, Lung, Colorectal, and Ovarian screening trial and whose results from flexible sigmoidoscopy exams indicated either no lesions (n = 34 817) or >/=1 distal adenoma (n = 3696). We used a 137-item food-frequency questionnaire to assess usual dietary intake over the preceding 12 mo. Using logistic regression analysis, we calculated, separately for men and women, prevalence odds ratios (ORs) and 95% CIs of sigmoidoscopy-detected, distal adenomas for quintiles of energy-adjusted dietary carbohydrate, glycemic index, and glycemic load., Results: ORs decreased with increasing intakes of carbohydrate for both the men and the women in unadjusted models, but these associations were attenuated in multivariate-adjusted models. Among the men, the association remained significant after adjustment (OR: 0.71; 95% CI 0.60, 0.84; P for trend < 0.0001), but in the women it did not (OR: 0.89; 95% CI: 0.73, 1.10; P for trend = 0.30). The results for glycemic index showed no associations in either men or women. Results for glycemic load closely mirrored those for carbohydrate., Conclusion: Despite expectations that increasing glycemic load and glycemic index would increase the risk of adenoma, we observed no association in women and even an inverse association in men.

Objectives: We wanted to evaluate the relationship between obesity and left colonic adenomatous polyps in Korean adult men., Methods: This study was conducted among 575 adults men (aged between 40 and 69), who had colonoscopy done from January to December 2002 during a routine health examination at Health Promotion Center, Ulsan University Hospital. The patients' colons were examined up to splenic flexure by using fiberoptic colonoscopy. A questionnaire survey on behavioral factors and physical measurements were also done. The body mass index (BMI) and waist-hip ratio (WHR) were used as the indices of obesity. The BMI was categorized into three levels: normal (BMI < or = 22.9), overweight (23 < or = BMI < or = 24.9), and obese (BMI > or = 25.0). The WHR was categorized into four levels with cut-off points at the 30th, 60th, and 90th percentile of the control group. Age, education, smoking, alcohol use and exercise were controlled for by performing multiple logistic regression analysis., Results: There were 99 cases of colonic adenomatous polyps. Four hundred seventy six subjects with normal colonoscopy findings served as the control. The BMI and WHR were associated with the adenomatous polyps (odds ratio, 1.81 [95% CI=1.02-3.19] for a BMI > or = 25.0 as compared with a BMI < or = 22.9, odds ratio, 3.94 [95% CI = 1.77-8.77] for a WHR > or = 0.95 as compared with a WHR < or = 0.86). The BMI was not associated with the risk of adenomatous polyps after additional adjustment was made for the WHR, but the association between the WHR and adenomatous polyps was still positive and independent of the BMI (odds ratio, 4.15 [95% CI=1.63-10.59])., Conclusions: The results support that obesity, and particularly abdominal obesity, can be associated with an increased risk of incurring colonic adenomatous polyps.

Background: Transforming growth factor-beta1 (TGFbeta1) is a multifunctional signalling molecule with a wide array of roles. Animal experiments suggest that TGFbeta1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting malignant transformation of those growths that do develop. A polymorphism in the signal peptide sequence of the TGFbeta1 gene (L10P) has been associated with increased levels of plasma TGFbeta1 in individuals with the P allele., Methods: We investigated whether this polymorphism was associated with the risk of colorectal adenomatous or hyperplastic polyps in a case-control study of individuals from Minnesota. Risk of colorectal polyps was evaluated separately for individuals with adenomatous polyps (n = 513) and hyperplastic polyps (n = 191) relative to polyp-free controls (n = 606) using logistic regression analysis., Results: No overall association was seen between the L10P polymorphism and risk of colorectal adenomatous polyps. The age- and sex-adjusted odds ratios (OR) of developing colorectal hyperplastic polyps were 1.0 (95% CI: 0.7, 1.4) and 0.7 (95% CI: 0.4, 1.1) for individuals with the LP and PP genotypes, respectively, compared with individuals with the LL genotype. When stratified by smoking, evidence for a decreased risk of hyperplastic polyps associated with the P allele was seen only among ever smokers (P for trend = 0.05)., Conclusions: Whereas adenoma risk did not vary by TGFbeta1 L10P genotype, these results suggest that the L10P variant allele may have a protective role in the development of colorectal hyperplastic polyps, possibly consistent with its role as an inhibitor of epithelial growths.