Advances in Fecal Tests for Colorectal Cancer Screening

textabstractColorectal cancer (CRC) forms an important public health problem, especially in developed countries. CRC screening tests can be used to identify asymptomatic individuals with CRC precursors and (early) cancer. Removal of these lesions reduces CRC incidence and prevents CRC-related mortality. There are a range of screening tests available, each with advantages and disadvantages. Stool screening tests can broadly be divided into fecal occult blood tests (FOBTs) and molecular biomarker test, such as DNA/RNA marker tests, protein markers, and fecal microbiome marker tests. Guaiac fecal occult blood tests (gFOBT) have been demonstrated in large randomized screening trials to reduce CRC mortality. Fecal immunochemical tests (FIT) have superior adherence, usability, and accuracy as compared to gFOBT. Advantage of the use of quantitative FITs in CRC screening programs is the cut-off level that can be adjusted. Molecular biomarker DNA tests have shown to detect significantly more cancers than FIT. By combining biomarker DNA tests with FIT, sensitivity for advanced adenomas can be increased significantly. However, it has lower specificity thus demands more colonoscopy resources, is more cumbersome, and costly. The adherence has not been assessed in population screening trials. For these reasons, FIT is therefore at present regarded as the preferred method of non-invasive CRC screening. This chapter will review the current status of fecal test-based CRC screening

Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival.

Background & aimsPathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome-wide microarray based comparative genomic hybridisation (microarray CGH). With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity.MethodsArray CGH was applied to a series of 35 gastric adenocarcinomas using a genome-wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival.ResultsAll thirty-five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1-p23.3, losses of 5q14.1, 18q22.1, 19p13.12-p13.3, 9p21.3-p24.3, 17p13.1-p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21-q22, and 12q14.1-q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007). Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both).ConclusionsMicroarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21-q22 and 12q14.1-q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s) that may determine aggressive tumour behaviour and poor clinical outcome

Predictors of Gastrointestinal Transit Times in Colon Capsule Endoscopy

Optimizing the accuracy of colon capsule endoscopy (CCE) requires high completion rates. To prevent incomplete CCE, we aimed to identify predictors associated with slow CCE transit times. METHODS: In this population-based study, participants received CCE with a split-dose polyethylene glycol bowel preparation and booster regimen (0.5 L oral sulfate solution and 10 mg metoclopramide if capsule remained in stomach for > 1 hour). The following predictors were assessed: age, sex, body mass index (BMI), smoking, coffee and fiber intake, diet quality, physical activity, dyspeptic complaints, stool pattern, history of abdominal surgery, medication use, and CCE findings. Multivariable logistic and linear regressions with backward elimination were performed. RESULTS: We analyzed 451 CCE procedures with a completion rate of 51.9%. The completion rate was higher among older participants (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.04–2.28, P = 0.03) and participants with a changed stool pattern (OR 2.27, 95% CI 1.20–4.30, P = 0.01). Participants with a history of abdominal surgery had a lower completion rate (OR 0.54, 95% CI 0.36–0.80, P = 0.003). Participants with higher BMI had faster stomach, small bowel, and total transit times (β = −0.10, P = 0.01; β = −0.14, P = 0.001; β = −0.12, P = 0.01). A faster small bowel transit was found in participants with a changed stool pattern (β = −0.08, P = 0.049) and the use of metoclopramide (β = −0.14, P = 0.001). Participants with high fiber intake had a slower colonic transit (β = 0.11, P = 0.03). DISCUSSION: Younger age, unchanged stool pattern, history of abdominal surgery, low BMI, and high fiber intake resulted in slower CCE transit times and lower completion rates. In future practice, these factors can be considered to adjust preparation protocols

The minimal incubation period from the onset of Barrett's oesophagus to symptomatic adenocarcinoma

Background:The interval between the onset of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) can be termed the incubation period. However, the unrecorded onset of BO precludes its direct observation.Methods:Determining the range of intervals between BO diagnosis and OAC within the longest observational BO follow-up study. Exclusion criteria were presence of high-grade dysplasia (HGD) or OAC at baseline, death within <2 years of BO diagnosis, oesophagectomy without HGD/OAC and loss to follow-up. A total of 133 patients (M/F 73/60) were taken into account.Results:In 1967 person years of follow-up there were 13 cases of HGD/OAC, (0.66% p.a.; 95% CI 0.58-0.74), 96 patients died without HGD/OAC and 24 survived without HGD/OAC. The mean intervals between BO diagnosis and either HGD/OAC, death or end of follow-up were 10.8, 12.6 and 25.5 years, respectively, and the mean ages at endpoint were 72.5, 80.0 and 68.3 years, respectively. The survivors without HGD/OAC had a lower age at BO diagnosis (mean 42.8 vs 61.2 and 67.4 years, P=0.001). Baseline presence of low-grade dysplasia was associated with progression to HGD/OAC (log rank P=0.001).Conclusion:The Rotterdam BO follow-up cohort revealed a long incubation period between onset of BO and development of HGD/OAC, in patients without HGD/OAC at baseline as illustrated by 24 patients diagnosed with BO at a young age and followed for a mean period of 25.5 years. Their tumour-free survival established a minimum incubation period, suggesting a true incubation period of three decades or more

Twenty-Four Hour Tonometry in Patients Suspected of Chronic Gastrointestinal Ischemia

Background and aims: Gastrointestinal tonometry is currently the only clinical diagnostic test that enables identification of symptomatic chronic gastrointestinal ischemia. Gastric exercise tonometry has proven its value for detection of ischemia in this patients group, but has its disadvantages. Earlier studies with postprandial tonometry gave unreliable results. In this study we challenged (again) the use of postprandial tonometry in patients suspected of gastrointestinal ischemia. Methods: Patients suspected for chronic gastrointestinal ischemia had standard diagnostic work up, including gastric exercise tonometry and 24-h tonometry using standard meals. Results: Thirty-three patients were enrolled in the study. Chronic gastrointestinal ischemia was diagnosed in 17 (52%) patients. The 24-h tonometry correctly predicted the presence of ischemia in 13/17 patients, and absence of ischemia in 15/16 patients. Conclusions: The use of 24-h tonometry after meals in patients suspected of gastrointestinal ischemia seems feasible, with promising accuracy for the detection of ischemia

Transcriptional profiling of Helicobacter pylori Fur- and iron-regulated gene expression

Intracellular iron homeostasis is a necessity for almost all living organisms, since both iron restriction and iron overload can result in cell death. The ferric uptake regulator protein, Fur, controls iron homeostasis in most Gram-negative bacteria. In the human gastric pathogen Helicobacter pylori, Fur is thought to have acquired extra functions to compensate for the relative paucity of regulatory genes. To identify H. pylori genes regulated by iron and Fur, we used DNA array-based transcriptional profiling with RNA isolated from H. pylori 26695 wild-type and fur mutant cells grown in iron-restricted and iron-replete conditions. Sixteen genes encoding proteins involved in metal metabolism, nitrogen metabolism, motility, cell wall synthesis and cofactor synthesis displayed iron-dependent Fur-repressed expression. Conversely, 16 genes encoding proteins involved in iron storage, respiration, energy metabolism, chemotaxis, and oxygen scavenging displayed iron-induced Fur-dependent expression. Several Fur-regulated genes have been previously shown to be essential for acid resistance or gastric colonization in animal models, such as those encoding the hydrogenase and superoxide dismutase enzymes. Overall, there was a partial overlap between the sets of genes regulated by Fur and those previously identified as growth-phase, iron or acid regulated. Regulatory patterns were confirmed for five selected genes using Northern hybridization. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization. These findings further delineate the central role of Fur in regulating the unique capacity of H. pylori to colonize the human stomach

Face-to-face vs telephone pre-colonoscopy consultation in colorectal cancer screening; A randomised trial

Background: A pre-colonoscopy consultation in colorectal cancer (CRC) screening is necessary to assess a screenees general health status and to explain benefits and risks of screening. The first option allows for personal attention, whereas a telephone consultation does not require travelling. We hypothesised that a telephone consultation would lead to higher response and participation in CRC screening compared with a face-to-face consultation. Methods:A total of 6600 persons (50-75 years) were 1: 1 randomised for primary colonoscopy screening with a pre-colonoscopy consultation either face-to-face or by telephone. In both arms, we counted the number of invitees who attended a pre-colonoscopy consultation (response) and the number of those who subsequently attended colonoscopy (participation), relative to the number invited for screening. A questionnaire regarding satisfaction with the consultation and expected burden of the colonoscopy (scored on five-point rating scales) was sent to invitees. Besides, a questionnaire to assess the perceived burden of colonoscopy was sent to participants, 14 days after the procedure.Results:In all, 3302 invitees were allocated to the telephone group and 3298 to the face-to-face group, of which 794 (24%) attended a telephone consultation and 822 (25%) a face-to-face consultation (P=0.41). Subsequently, 674 (20%) participants in the telephone group and 752 (23%) in the face-to-face group attended colonoscopy (P=0.018). Invitees and responders in the telephone group expected the bowel preparation to be more painful than those in the face-to-face group while perceived burden scores for the full screening procedure were comparable. More subjects in the face-to-face group than in the telephone group were satisfied by the consultation in general: (99.8% vs 98.5%, P=0.014).Conclusion:Using a telephone rather than a face-to-face consultation in a population-based CRC colonoscopy screening progr

Leadership training to improve adenoma detection rate in screening colonoscopy: A randomised trial

Objective Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared t