Colorectal cancer(CRC)is the third most commonly diagnosed cancer in the world.The incidence and mortality show wide geographical variations.Screening is recommended to reduce both incidence and ...mortality.However,there are significant differences among studies in implementation strategies and detection.This review aimed to present the results and strategies of different screening programs worldwide.We reviewed the literature on national and international screening programs published in Pub Med,on web pages,and in clinical guidelines.CRC Screening programs are currently underway in most European countries,Canada,specific regions in North and South America,Asia,and Oceania.The most extensive screening strategies were based on fecal occult blood testing,and more recently,the fecal immunochemical test(FIT).Participation in screening has varied greatly among different programs.The Netherlands showed the highest participation rate(68.2%)and some areas of Canada showed the lowest(16%).Participation rates were highest among women and in programs that used the FIT test.Men exhibited the greatest number of positive results.The FIT test has been the most widely used screening program worldwide.The advent of this test has increased participation rates and the detection of positive results.
Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer ...(CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty‐eight patients showed no neoplastic lesions, whereas 288 patients showed low‐risk adenomas, and 354 patients presented high‐risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log‐additive models, OR: 0.67, 95%CI:0.54–0.83, and OR:0.66, 95%CI:0.54–0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low‐ and high‐risk adenomas in controls, being this effect stronger in low‐risk adenomas (log‐additive models, OR:0.63, 95%CI:0.47–0.84 and OR:0.64, 95%CI:0.47–0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low‐risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06–0.72, and OR:0.08, 95%CI:0.03–0.61) and controls (dominant models, OR:0.50, 95%CI:0.34–0.75, and OR:0.52, 95%CI:0.35–0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.
What's new?
While numerous candidate gene variants have been associated with colorectal cancer, little is known about the relevance of genetic susceptibility or influence of family history in the development of precancerous colorectal adenomas. In the present study, certain genetic variants previously associated with colorectal cancer risk, including two variants in the CASC8 gene and two in the lnc‐RNA LINC00709 gene, were found to be also involved in susceptibility to colorectal adenomas. The associations were modified by family history of colorectal cancer. The results could have implications for colorectal cancer screening and the identification of individuals at increased risk of colorectal adenoma.
Esophageal cancer is one of the most unknown and deadliest cancers worldwide, mainly because of its extremely aggressive nature and poor survival rate. Esophageal cancer is the 6(th) leading cause of ...death from cancer and the 8(th) most common cancer in the world. The 5-year survival is around 15%-25%. There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide. There are areas of high incidence of squamous cell carcinoma (some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas. In Europe and United States the predominant histologic subtype is adenocarcinoma. The role of early diagnosis of adenocarcinoma in Barrett's esophagus remains controversial. The differences in the therapeutic management of early esophageal carcinoma (high-grade dysplasia, T1a, T1b, N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage. In areas where the incidence is high (China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus.
Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f‐Hb), age and sex, may simplify CRC ...diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi‐square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02–1.05), male sex: 1.6 (95% CI: 1.1–2.3) and f‐Hb (0–<20 µg Hb/g feces): 2.0 (95% CI: 0.7–5.5), (20‐<200 µg Hb/g): 16.8 (95% CI: 6.6–42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3–164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85–0.90) in the derivation and 0.91 (95% CI: 0.90–093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value—PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients.
What's new?
Lower gastrointestinal symptoms potentially indicative of colorectal cancer (CRC) are a common reason for physician visits. While the probability that any one of those symptoms is associated with CRC is low, identifying patients for further screening remains a challenge. Here, the possibility of improving CRC diagnostic accuracy and risk stratification was explored using a three‐variable FAST Score based on fecal hemoglobin concentration, age, and sex. Among symptomatic patients referred to colonoscopy, the FAST Score prediction model identified three risk groups, the lowest of which ruled out CRC. Threshold scores were sensitive across variables, including country, age, and sex.
We solve the problem of determining the energy actions whose moduli space of extremals contains the class of Lancret helices with a prescribed slope. We first see that the energy density should be ...linear both in the total bending and in the total twisting, such that the ratio between the weights of them is the prescribed slope. This will give an affirmative answer to the conjecture stated in Barros and Ferrández (J Math Phys 50:103529,
2009
). Then, we normalize to get the best choice for the helical energy. It allows us to show that the energy, for instance of a protein chain, does not depend on the slope and is invariant under homotopic changes of the cross section which determines the cylinder where the helix is lying. In particular, the energy of a helix is not arbitrary, but it is given as natural multiples of some basic quantity of energy.
Faecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating ...in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC).
To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 μg Hb/g faeces) without CRC.
Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion.
We included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT ≥ 10 µgr Hb/gr. During a mean time of 45.5 ± 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age ≥ 70 years (OR 2.7, 95%CI: 1.1-7.0).
Symptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC.
Introduction
Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in ...combination with other demographic and clinical factors.
Methods
In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed.
Results
Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3–2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63–0.69). The GRS showed a different behavior depending on sex and age.
Conclusion
Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.
A
bstract
We exhibit a surprising phenomenon that happens in the conformal Lorentz Minkowski three space, which has no counterpart in a Riemannian setting. Whenever a curve, no matter its causal ...character, propagates transversely through a conformal geodesic null vector field, it is generating the worldsheet of an extrinsic Polyakov string solution. Furthermore, the Polyakov extrinsic energy of these solutions only depend on the world-sheet topology and it can be computed not only intrinsically, but also holographically by measuring the hyperbolic angles in the boundary corners. This geometric approach, to provide extrinsic string solutions, can be considered as an alternative to the Pohlmeyer reduced mechanism. Then, we describe how to translate these solutions to the language of Pohlmeyer theory. We will also show that any curve in the conformal boundary of the anti de Sitter 3-space can be viewed as a piece of the generalized Wilson loops associated with an extrinsic string solution obtained by this geometric mechanism.
Risk prediction models for colorectal cancer (CRC) detection in symptomatic patients based on available biomarkers may improve CRC diagnosis. Our aim was to develop, compare with the NICE referral ...criteria and externally validate a CRC prediction model, COLONPREDICT, based on clinical and laboratory variables.
This prospective cross-sectional study included consecutive patients with gastrointestinal symptoms referred for colonoscopy between March 2012 and September 2013 in a derivation cohort and between March 2014 and March 2015 in a validation cohort. In the derivation cohort, we assessed symptoms and the NICE referral criteria, and determined levels of faecal haemoglobin and calprotectin, blood haemoglobin, and serum carcinoembryonic antigen before performing an anorectal examination and a colonoscopy. A multivariate logistic regression analysis was used to develop the model with diagnostic accuracy with CRC detection as the main outcome.
We included 1572 patients in the derivation cohort and 1481 in the validation cohorts, with a 13.6 % and 9.1 % CRC prevalence respectively. The final prediction model included 11 variables: age (years) (odds ratio OR 1.04, 95 % confidence interval CI 1.02-1.06), male gender (OR 2.2, 95 % CI 1.5-3.4), faecal haemoglobin ≥20 μg/g (OR 17.0, 95 % CI 10.0-28.6), blood haemoglobin <10 g/dL (OR 4.8, 95 % CI 2.2-10.3), blood haemoglobin 10-12 g/dL (OR 1.8, 95 % CI 1.1-3.0), carcinoembryonic antigen ≥3 ng/mL (OR 4.5, 95 % CI 3.0-6.8), acetylsalicylic acid treatment (OR 0.4, 95 % CI 0.2-0.7), previous colonoscopy (OR 0.1, 95 % CI 0.06-0.2), rectal mass (OR 14.8, 95 % CI 5.3-41.0), benign anorectal lesion (OR 0.3, 95 % CI 0.2-0.4), rectal bleeding (OR 2.2, 95 % CI 1.4-3.4) and change in bowel habit (OR 1.7, 95 % CI 1.1-2.5). The area under the curve (AUC) was 0.92 (95 % CI 0.91-0.94), higher than the NICE referral criteria (AUC 0.59, 95 % CI 0.55-0.63; p < 0.001). On the basis of the thresholds with 90 % (5.6) and 99 % (3.5) sensitivity, we divided the derivation cohort into three risk groups for CRC detection: high (30.9 % of the cohort, positive predictive value PPV 40.7 %, 95 % CI 36.7-45.9 %), intermediate (29.5 %, PPV 4.4 %, 95 % CI 2.8-6.8 %) and low (39.5 %, PPV 0.2 %, 95 % CI 0.0-1.1 %). The discriminatory ability was equivalent in the validation cohort (AUC 0.92, 95 % CI 0.90-0.94; p = 0.7).
COLONPREDICT is a highly accurate prediction model for CRC detection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aim
In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective ...strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence.
Methods
A follow‐up study was carried‐out including 649 patients, diagnosed with PL between 1995–2004 in 9 participating hospitals from Spain, and who repeated the biopsy during 2011–2013. Medical information and habits were collected through a questionnaire. Based on morphology, IM was sub‐classified as complete (small intestinal type, CIM) and incomplete (colonic type, IIM). Analyses were done using Cox (HR) models.
Results
At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34% IIM, and 4% dysplasia. Mean follow‐up was 12 years. 24 patients (3.7%) developed a gastric adenocarcinoma during follow‐up. The incidence rate of GC was 2.76 and 5.76 per 1,000 person‐years for those with CIM and IIM, respectively. The HR of progression to CG was 2.75 (95% CI 1.06‐6.26) for those with IIM compared with those with CIM at baseline, after adjusting for sex, age, smoking, family history of GC and use of NSAIDs.
Conclusions
IIM is the PL with highest risk to progress to GC. Sub‐typing of IM is a valid procedure for the identification of high risk patients that require more intensive surveillance.
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