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Colorectal cancer is a leading cancer worldwide and in Vietnam. Adenomas (adenomatous polyps) is an important precursor of colorectal cancer. There is currently no study to determine the modifiable risk factors for colorectal adenomas, including body mass index (BMI) in Vietnam. We conducted an individually matched case‐control study of 1149 colorectal adenomas and 1145 controls in a large‐scale colorectal screening program involving 103 542 individuals aged 40‐75 years old in Hanoi, Vietnam. Conditional logistic regression was used to evaluate the association between BMI and colorectal adenomas prevalence, after controlling for potential confounders. Overall, comparing to normal weight (ie, 18.5‐22.9 kg/m2), underweight (ie, BMI < 18.5) was associated with a non‐statistically significant increased prevalence of colorectal adenomas (odd ratio [OR] = 1.29 and 95% confident interval [CI]: 0.88‐1.87). This association became significant among male (OR = 1.98, 95% CI: 1.20‐3.27), male who were ever smokers (OR = 2.59, 95% CI: 1.33‐5.03), nonregular exercise (OR = 2.44, 95% CI: 1.26‐4.73) and individuals with cardiometabolic disorders (OR = 3.46, 95% CI: 1.19‐10.00). The association between underweight and colorectal adenomas did not vary by smoking status, drinking status, family history of cancer, adenomas types or cardiometabolic disorders. No association was observed among obese individuals (BMI ≥ 25). In the population with low prevalence of obesity, we found that the association between BMI and colorectal adenomas followed a reversed J‐shape that underweight was associated with increased prevalence. Further studies are, therefore, warranted to replicate our results and to investigate the biologic mechanism the effect of underweight on colorectal adenomas prevalence. What's new? High body mass index (BMI) has been associated with an increased risk of colorectal adenomas in studies including Asian populations. To date, no study has identified modifiable risk factors for colorectal adenomas in Vietnam, a country with a rising colorectal cancer incidence and low obesity prevalence. This case‐control study based on a large‐scale colorectal cancer screening program in Vietnam reports a potential association between underweight and colorectal adenomas prevalence with an inverse J‐shape. The modification of specific factors such as maintaining a normal BMI range, quitting smoking and exercising regularly showed great potential for colorectal cancer prevention and control programs. [ABSTRACT FROM AUTHOR]

Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are increasingly being observed. These may present diagnostic challenges and cause clinical management issues. Paneth cell metaplasia is a more common occurrence, but the incidence rates of squamous metaplasia, clear cell metaplasia, osseous metaplasia, neuroendocrine differentiation and signet‐ring cell‐like lesion are low, and they can be seen in <1% of colorectal adenomas. Their histomorphological characteristics are quite unique; ancillary studies are not very helpful and often not needed. In this review, we give an overview and describe the potential clinical consequences of such incidental and special morphological findings in colorectal adenomas. [ABSTRACT FROM AUTHOR]

Aim: The association between the use of oral contraceptives and hormone replacement therapy (HRT) or other reproductive factors and the risk of colorectal adenoma (CRA) remains controversial. Our study aimed to review the evidence by conducting a dose–response meta‐analysis to investigate this association. Methods: We searched PubMed and Embase databases for relevant studies published until May 2017. Traditional and dose–response meta‐analyses were conducted. Sensitivity analysis was performed to evaluate the robustness of the results. Cumulative meta‐analysis was used to assess the risk of different oral contraceptive formulations or generations. Results: A total of 19 observational studies, with 21 923 CRA cases and 1 030 711 participants, were included in the meta‐analysis. Ever HRT use showed a potential inverse association with CRA risk [relative risk (RR) 0.83, 95% CI 0.70–1.00]. The dose–response meta‐analysis further demonstrated that HRT use could reduce CRA risk. Compared with no HRT use, the predicted RRs were 0.82 (95% CI 0.67–0.99), 0.76 (95% CI 0.59–0.98) and 0.77 (95% CI 0.62–0.96) for 3, 6 and 9 years of HRT use, respectively. All other factors were not statistically significantly associated with CRA risk. Conclusions: This study indicated that only HRT use might reduce the risk of developing CRA. Any advice regarding HRT use to prevent CRA should be tailored to the individual risks and potential benefits. Large, well‐designed prospective studies with long‐term follow‐up are required to further clarify the aetiology of CRA. [ABSTRACT FROM AUTHOR]

Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and nonlinear dose-response meta-analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random-effects model. For total calcium intake, summary RR for each 300 mg/day increase was 0.95 (95% CI = 0.92-0.98; I2 = 45%; eight studies with 11,005 cases; range of intake = 333-2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI = 0.89-0.94) at 1,000 mg/day and 0.87 (95% CI = 0.84-0.90) at 1,450 mg/day ( pnonlinearity < 0.01). Associations were stronger for high-risk adenomas (≥1 cm in diameter, (tubulo)villous histology, dysplasia, or multiplicity): approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.77 (95% CI = 0.74-0.81) at 1,000 mg/day and reduced to 0.69 (95% CI = 0.66-0.73) at 1,450 mg/da ( pnonlinearity < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI = 0.93-0.99; I2 = 0%; three studies with 4,548 cases; range of supplementation = 0-1,366 mg/day). In conclusion, calcium intake may continue to decrease the risk of adenomas, particularly high-risk adenomas, over a wide range of calcium intake. [ABSTRACT FROM AUTHOR]

Incidence of colorectal cancer (CRC) is growing worldwide. Pathogenetic mechanisms responsible for its onset and progression need further clarification. Colorectal adenomatous polyps are precancerous lesions with malignant potential dependent on histological architecture and grade of nuclear dysplasia. One of the factors conditioning CRC development are abnormalities in sphingolipid metabolism. The aim of this study was to assess the levels of sphingolipids in human colorectal adenomas. The control group (C, n = 12) consisted of patients with no colonic polyps. The examined group consisted of patients with prior diagnosed colonic polyps, qualified to endoscopic polypectomy. This group was further divided due to histological architecture into tubular adenomas group (TA, n = 10), tubulovillous adenomas with low-grade dysplasia (LGD-TVA, n = 10), and tubulovillous adenomas group with high-grade dysplasia (HGD-TVA, n = 11). In tissue samples, sphingolipd metabolite contents were measured using high performance liquid chromatography (HPLC). In cases of polypoid lesions with low malignancy potential (tubular adenomas), concentration of ceramide, which is characterized by proapoptotic and anti-proliferative properties, increases compared with control group ( p < 0.05), whereas content of sphingosine-1-phosphate with anti-apoptotic and stimulating cellular proliferation properties is reduced in comparison with control group ( p < 0.05). On the contrary, in cases of more advanced form of adenomatous polyps (tubulovillous adenomas with high-grade dysplasia), the ceramide level decreases compared with control group ( p < 0.05) while sphingosine-1-phosphate concentration is elevated ( p < 0.05). We found that concentrations of pro-apoptotic ceramide are decreased and pro-proliferative S1P levels are increased in polypoid lesions with high malignancy potential, and it was the opposite in those with low malignancy potential. [ABSTRACT FROM AUTHOR]

Polymerases ϵ and δ are the main enzymes that replicate eukaryotic DNA. Accurate replication occurs through Watson-Crick base pairing and also through the action of the polymerases' exonuclease (proofreading) domains. We have recently shown that germline exonuclease domain mutations ( EDMs) of POLE and POLD1 confer a high risk of multiple colorectal adenomas and carcinoma ( CRC). POLD1 mutations also predispose to endometrial cancer ( EC). These mutations are associated with high penetrance and dominant inheritance, although the phenotype can be variable. We have named the condition polymerase proofreading-associated polyposis ( PPAP). Somatic POLE EDMs have also been found in sporadic CRCs and ECs, although very few somatic POLD1 EDMs have been detected. Both the germline and the somatic DNA polymerase EDMs cause an 'ultramutated', apparently microsatellite-stable, type of cancer, sometimes leading to over a million base substitutions per tumour. Here, we present the evidence for POLE and POLD1 as important contributors to the pathogenesis of CRC and EC, and highlight some of the key questions in this emerging field. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to determine whether the use of the narrow band imaging (NBI) system could enhance the accuracy of adenoma detection during an endoscopic examination of the colon and rectum. Methods: MEDLINE, EMBASE, and the Cochrane Library databases were searched along with a hand search of abstracts from relevant conferences up to June 2011. The rates of adenoma and flat adenoma detection, and withdrawal time were analyzed using Review Manager 4.2. Results: A total of 3049 subjects in eight trials were included. Meta-analysis revealed that there was no statistically significant difference in the rates of adenoma detection between the NBI group and the white light colonoscopy group (pooled relative risk [RR]: 1.09, 95% confidence interval [CI]: 1.00-1.19, P = 0.05). However, after exclusion of high-definition television modalities, the rate of adenoma detection by NBI was significantly higher than that by white light, particularly for patients with one adenoma (pooled RR 1.36, 95%CI 1.07-1.71, P = 0.02). Endoscopy with the NBI system significantly increased the rate of flat adenoma detection (pooled RR 1.96, 95%CI 1.09-3.52, P = 0.02). However, endoscopy with NBI had longer withdrawal time than that with white light (pooled weighted mean difference: 0.90, 95%CI: 0.38-1.42, P = 0.0006). Conclusions: Endoscopy with NBI seems to improve the detection of flat adenomas, particularly with high-definition technology, but prolongs the withdrawal time. These results indicate that endoscopy routinely using the NBI system for the surveillance of adenomas may be recommended after the technique is further modified. [ABSTRACT FROM AUTHOR]

Most previous studies of the natural history of small colorectal adenomas showed no increase in size, no changes that would have necessitated treatment within a couple of years and that malignant transformation is rare. Using endoscopic follow up for a mean period of 43.1 months we assessed the development and progression of 408 protuberant adenomas that were under 10 mm in diameter. Of the 408 lesions, 22 (5.4%) underwent morphological changes. There were 12 lesions (2.9%) whose final tumor diameter had reached 10 mm or more. There were three lesions (0.7%) that developed and progressed into intramucosal cancer. We concluded from the literature and from our own results that small colorectal protuberant adenomas do not grow to advanced adenomas within 5 years. [ABSTRACT FROM AUTHOR]

Background and Aim: In 1999, a group of Western and Asian pathologists gathered in Vienna reached consensus regarding the classification of gastrointestinal epithelial neoplasia. In this study, that classification is applied to colorectal adenomas. Methods: Colorectal adenomas from 1552 patients were histologically classified according to the categories listed in Vienna: category 3, low-grade dysplasia; 4.1, high-grade dysplasia; 4.2, carcinoma in situ; 4.3, suspicious of intramucosal carcinoma; 5.1, intramucosal carcinoma; and 5.2, submucosal carcinoma. The criteria used to diagnose these lesions are described in detail. Adenomas with dysplasia (categories 3 and 4.1) or with carcinoma (categories 4.2, 4.3, 5.1 and 5.2) were analyzed separately. On basis of their configuration, adenomas were classified into tubular, tubulovillous, villous, serrated, microtubular and combined phenotypes (i.e. other than tubulovillous). Results: The highest percentage of adenomas with carcinoma was found amongst villous adenomas (29.6%), followed by combined adenomas (27.8%). Villous adenoma with carcinoma was the most frequent neoplasia at all ages; combined adenomas with carcinoma were more frequent among younger patients. In elderly patients (≥60 years of age) the highest percentage of adenomas with carcinoma was recorded in villous adenomas (28.1%), followed by serrated adenomas (19.2%). Villous adenomas and combined adenomas with carcinoma were more frequent in males. Conclusion: The Vienna classification of colorectal adenomas seems to be influenced by parameters inherent to the patient such as age and sex and by the histological phenotype of the adenoma. With the recent improvement in medical technology it is possible to laser-microdisect a defined group of neoplastic glands (such as with carcinoma in situ or with intramucosal carcinoma) for specific molecular analysis. This modern technology will permit in future the translation of histological structures into molecular terms. [ABSTRACT FROM AUTHOR]

To detect and analyse ki-ras point mutations in colorectal adenomas and carcinomas in patients from Greece, where mortality rate from colorectal cancer is lower than that in other European countries and the USA.As a method we used PCR-RFLP technique, to examine ki-ras codons 12 and 13 mutations in 450 paraffin embedded tissues, consisting of 141 normal mucosas, 165 adenomas and 144 sporadic colorectal cancers taken from 141 patients.Frequency of ki-ras mutations was 3.2% (3/93) in small adenomas, 5.2% (3/57) in greater than 1 cm adenomas, 20% (3/15) in tissues where adenoma and cancer coexisted and 39.5% (57/144) in colorectal cancer.These data showed that the frequency of ki-ras mutations was low in all sizes of polyps and high in carcinomas in a sample of a population, characterized by a low mortality rate from colorectal cancer. Ki-ras mutations were not an early event of colon carcinogenesis in these patients and the low frequency of ki-ras mutations in adenomas may probably have some relevance to the low mortality rate. Our findings could be explained, not by the dietary habits of this population, but by the presence of other hitherto unknown environmental factors. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second‐leading cause of cancer‐related mortality worldwide, which may be effectively reduced by early screening. Colon cancer secreted protein‐2 (CCSP‐2) is a promising blood marker for CRC. An electric‐field effect colorectal sensor (E‐FECS), an ion‐sensitive field‐effect transistor under dual gate operation with nanostructure is developed, to quantify CCSP‐2 directly from patient blood samples. The sensing performance of the E‐FECS is verified in 7 controls and 7 CRC samples, and it is clinically validated on 30 controls, 30 advanced adenomas, and 81 CRC cases. The concentration of CCSP‐2 is significantly higher in plasma samples from CRC and advanced adenoma compared with controls (both P < 0.001). Sensitivity and specificity for CRC versus controls are 44.4% and 86.7%, respectively (AUC of 0.67), and 43.3% and 86.7%, respectively, for advanced adenomas (AUC of 0.67). CCSP‐2 detects a greater number of CRC cases than carcinoembryonic antigen does (45.6% vs 24.1%), and the combination of the two markers detects an even greater number of cases (53.2%). The E‐FECS system successfully detects CCSP‐2 in a wide range of samples including early stage cancers and advanced adenoma. CCSP‐2 has potential for use as a blood‐based biomarker for CRC. [ABSTRACT FROM AUTHOR]