Objective: This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon. Methods: Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays. Results: The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q. Conclusion: This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.

BACKGROUND: MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression. METHODS: Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT -PCR. Messenger RNA c-myc expression was also determined by real-time RT -PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available. RESULTS: From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found. CONCLUSION: Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.

In the course and prognosis of colorectal cancer (CRC), early detection and treatment are essential factors. Fecal immunochemical tests (FITs) are currently the most commonly used non-invasive screening tests for CRC and premalignant (advanced) adenomas, however, with restricted sensitivity. We hypothesized that fecal volatile organic compounds (VOCs) may serve as a diagnostic biomarker of CRC and adenomas. In this proof of concept study, we aimed to assess disease-specific VOC smellprints in fecal gas to distinguish patients with CRC and advanced adenomas from healthy controls. Fecal samples of patients who were scheduled to undergo an elective colonoscopy were collected. An electronic nose (Cyranose 320V R ) was used to measure VOC patterns in fecal gas from patients with histopathologically proven CRC, with advanced adenomas and from controls (no abnormalities seen at colonoscopy). Receiver operator characteristic curves and corresponding sensitivity and specificity for detection of CRC and advanced adenomas were calculated. A total of 157 stool samples (40 patients with CRC, 60 patients with advanced adenomas, and 57 healthy controls) were analyzed by electronic nose. Fecal VOC profiles of patients with CRC differed significantly from controls (area under curve 6 95%CI, p-value, sensitivity, specificity; 0.92 6 0.03, <0.001, 85%, 87%). Also VOC profiles of patients with advanced adenomas could be discriminated from controls (0.79 6 0.04, <0.001, 62%, 86%). The results of this proof of concept study suggest that fecal gas analysis by an electronic nose seems to hold promise as a novel screening tool for the (early) detection of advanced neoplasia and CRC.Colorectal cancer (CRC) is one of the predominant cancers, contributing to a high burden of morbidity and mortality in the United States of America and Europe. 1,2 Early detection and treatment are critical factors in the course and prognosis of CRC, and screening programs have proven to be an important means to reduce both mortality and secondary economic burden. [3][4][5] Colonoscopy is considered the gold standard for CRC and advanced adenoma screening. Fecal immunochemical tests (FIT) are currently the most commonly used non-invasive fecal screening tests. However, sensitivity of FIT for CRC is between 66-88% 6-10 depending on the cut-off values used, whereas sensitivity for advanced adenomas is disturbingly low (27-41%). 6,8,11,12 As CRC prevention programs should primarily focus on early detection of premalignant advanced adenomas, the search for novel, more accurate non-invasive screening methods remains warranted.Analysis of volatile organic compounds (VOCs) in exhaled breath has been reported as a potential non-invasive diagnostic biomarker test for lung cancer, breast cancer, malignant melanomas and CRC. [13][14][15] VOCs are gaseous carbon-based chemicals resulting from biochemical processes in the body, which are discharged by exhaled air, sweat, urine and feces. 16 VOCs in fecal gases are mainly produced by the intestinal microbiota in the colon...

In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging “cancer methylome”. In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-β (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC.

Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions ≤ 30 mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry. Methods Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. Results Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), re-resection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9 %). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4 %) and full-thickness resection in 288 (83.2 %). The median diameter of resected specimens was 23 mm. Overall adverse event rate was 9.3 % (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. Conclusion eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed.

Background and aims There are conflicting data concerning the association between diverticular disease and colorectal carcinoma (CRC). This study was performed to determine the prevalence and association of diverticulosis, diverticulitis, polyps, and CRC. Materials and methods In a cross-sectional, retrospective study, we analyzed the colonoscopy reports of complete colonoscopies and patho-histological results of all patients referred for colonoscopy in a period of 3 months in 18 hospitals in The Netherlands. Diverticulosis was defined as three or more diverticula present and diverticulitis as diverticulosis with inflammation. Polyps were also coded according to localization and size. Advanced neoplastic lesions were defined as polyps ≥10 mm in diameter and/or villous architecture and/or adenomas with high grade dysplasia and/or invasive cancer. Actual and previous described CRC were registered. Results A total of 4,241 patients were included in the study [1,996 (47%) male], mean age of 59 and range 18-95. Diverticula, diverticulitis, and polyps were seen in 1,052 (25%), 75 (2%), and 1,282 (30%) patients, respectively. No association was found between patients with polyps and those with and without diverticulosis (p=0.478). Invasive adenocarcinoma and adenomas ≥10 mm were most frequently observed. CRC was present in 372 (9%) patients. Negative relation between diverticulosis and CRC and invasive adenocarcinoma was observed. No association was found between polyps and CRC and patients with diverticulitis and CRC. In conclusion, there is no relation between patients with diverticulosis and higher incidence of polyps or CRC when using age-stratified analysis. No increased risk for polyps or CRC was found in patients with diverticulitis.

In 4.3 % of the patients, advanced neoplasia was missed by incomplete colonoscopy. Our data therefore suggest that additional imaging is obligatory to visualize the remaining colon adequately.

Our study aimed to evaluate the oral cavity as a reservoir from where Helicobacter pylori may be transmitted. Histology and PCR amplification were performed. Eighty-four percent of the stomach biopsies tested positive; however, H. pylori was not detected in dental samples, indicating the absence of H. pylori within the oral cavity.It has been suggested that the oral cavity may play a role in the transmission of Helicobacter pylori. Increased H. pylori prevalence rates have been reported in Chinese immigrants who use chopsticks and in African infants whose mothers premasticate their food (4, 16). H. pylori has been detected in dental plaque and saliva by culture and PCR methods, with the results obtained ranging from 0 to 100% for culture and 0 to 90% for PCR (1-3, 5, 7, 9, 11, 12, 14, 15, 17, 18, 20, 21). The role of the oral cavity as a permanent reservoir for H. pylori infection in healthy nonhospitalized individuals is still unclear (6, 10).Seventy-nine (25 men and 54 women; mean age, 27 years; range, 5 to 65 years) healthy individuals from a rural community in South Africa were included in this study. We previously showed that this community had a high H. pylori seroprevalence rate (23,24). The ethics committee of the University of Pretoria and the Review Board of Unitas Hospital approved this study.Cumulative dental plaque samples were obtained from the oral cavity, and biopsies were taken from two sites in the stomach (two from the antrum and two from the corpus). One biopsy specimen from each site was placed in 10% formalin, cut, and stained with hematoxylin-eosin and methylene blue. DNA was extracted from the remainder of the samples by using the QIAamp DNA Mini kit (QIAGEN, Hilden, Germany) per the manufacturer's instructions and stored at Ϫ20°C. The quality and concentration of the extracted DNA was assessed by means of a Nanodrop Spectrophotometer (A 260 /A 280 , 1.6 to 2.00).A single-step PCR directed toward the urease AB gene and a heminested PCR directed toward the phosphoglucosamine mutase (glmM) gene of H. pylori were performed on dental plaque and biopsy samples (8). A third nested PCR directed toward the 860-bp DNA region of H. pylori was performed on dental plaque samples (21,22). Negative and positive controls (H. pylori type strain Hp115.90) were included in each batch of amplifications. Amplification was performed on the GeneAmp 9700 thermocycler (Applied Biosystems, Foster City, Calif.). To exclude the possibility of PCR amplifications being negative due to the presence of inhibitors, the single-step PCR amplifying the urease AB gene was repeated for dental plaque samples spiked with DNA isolated from the positive control.The sensitivities, specificities, and percentages of infected individuals are represented in Table 1. Sensitivity and specificity were calculated compared to the gold standard of histology. Dental plaque samples were not collected for five individuals, and biopsy samples were not collected for one individual included in the study. Five samples were excluded due to the fac...