Predictive Value of Genetic Risk Scores in the Development of Colorectal Adenomas.

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.

Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps.

BACKGROUND & AIMS: T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node). METHODS: We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions >10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy. RESULTS: Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P < .001). However, pedunculated morphology (P < .007), ulceration (P = .026), depressed areas (P < .001), or nodular mixed type (P < .001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable. CONCLUSIONS: In an analysis of 2123 colon lesions >10 mm, we found the NICE classification and morphologic features identify those with deep lesions with >96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

Genetic susceptibility in the development of colorectal adenomas according to family history of colorectal cancer.

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.

Short- and long-term clinical outcomes of self-expandable metal stents inserted for colorectal obstruction and efficacy of different insertion techniques.

OBJECTIVES: (1) To evaluate the short- and long-term clinical outcomes of patients after colorectal stent placement and (2) to assess the safety and efficacy of the stents for the resolution of colorectal obstruction according to the insertion technique. METHODS: Retrospective cohort study which included 177 patients with colonic obstruction who underwent insertion of a stent. RESULTS: A total of 196 stents were implanted in 177 patients. Overall, the most common cause of obstruction was colorectal cancer (89.3%). Ninety-two stents (47%) were placed by radiologic technique and 104 (53%) by endoscopy under fluoroscopic guidance. Technical success rates were 95% in both groups. Clinical success rates were 77% in the radiological group and 81% in the endoscopic group (p>0.05). The rate of complications was higher in the radiologic group compared with the endoscopic group (38% vs 20%, respectively; p=0.006). Among patients with colorectal cancer (158), 65 stents were placed for palliation but 30% eventually required surgery. The multivariate analysis identified three factors associated with poorer long-term survival: tumor stage IV, comorbidity and onset of complications. CONCLUSIONS: Stents may be an alternative to emergency surgery in colorectal obstruction, but the clinical outcome depends on the tumor stage, comorbidity and stent complications. The rate of definitive palliative stent placement was high; although surgery was eventually required in 30%. Our study suggests that the endoscopic method of stent placement is safer than the radiologic method.

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14.

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients.

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.

Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: COLONPREDICT is a highly accurate prediction model for CRC detection.

Endoscopic surveillance in patients with multiple (10-100) colorectal polyps.

BACKGROUND AND STUDY AIMS: Endoscopic surveillance in patients with multiple colorectal polyps aims to reduce colorectal cancer (CRC) incidence and mortality, as well as the need for colorectal surgery. The aim of this study was to determine the risk of developing CRC or the need for surgery during endoscopic surveillance in a cohort of patients with multiple (10 - 100) colorectal polyps. PATIENTS AND METHODS: This was a multicentrer, longitudinal, observational study in 15 CRC high risk clinics in Spain, carried out between January 2009 and December 2010. Patients who were included in the EPIPOLIP trial and had at least 1 year of follow-up were included in the study. The primary outcome of interest was the incidence of CRC at least 1 year following the initial colonoscopy. The secondary outcome was the need for colorectal surgery. RESULTS: A total of 265 patients were followed for a median of 3.8 years. Patients underwent a median of 5 colonoscopies, and 17 patients (6.4 %) were diagnosed with CRC. A total of 32 patients (12.1 %) underwent surgery, including 15 (5.7 %) for prophylaxis without a diagnosis of CRC. The corresponding incidence density rates for CRC and colorectal surgery were 1.4 (95 % confidence interval [CI] 0.7 to 2.1) and 2.7 (95 %CI 1.7 to 3.6) per 100 patient-years, respectively. Only the presence of symptoms at first colonoscopy was independently associated with CRC diagnosis (hazard ratio [HR] 7.7, 95 %CI 1.1 to 59.3) and colorectal surgery (HR 4.6, 95 %CI 1.02 to 20.6). CONCLUSIONS: Patients with more than 10 neoplastic polyps required frequent colonoscopies within a short follow-up period. More than 10 % of patients required colorectal surgery within 4 years, more than half for incident CRC.

Incomplete type of intestinal metaplasia has the highest risk to progress to gastric cancer: results of the Spanish follow-up multicenter study.

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.

On the energy density of helical proteins.

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.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.

Endomapper dataset of complete calibrated endoscopy procedures.

Computer-assisted systems are becoming broadly used in medicine. In endoscopy, most research focuses on the automatic detection of polyps or other pathologies, but localization and navigation of the endoscope are completely performed manually by physicians. To broaden this research and bring spatial Artificial Intelligence to endoscopies, data from complete procedures is needed. This paper introduces the Endomapper dataset, the first collection of complete endoscopy sequences acquired during regular medical practice, making secondary use of medical data. Its main purpose is to facilitate the development and evaluation of Visual Simultaneous Localization and Mapping (VSLAM) methods in real endoscopy data. The dataset contains more than 24 hours of video. It is the first endoscopic dataset that includes endoscope calibration as well as the original calibration videos. Meta-data and annotations associated with the dataset vary from the anatomical landmarks, procedure labeling, segmentations, reconstructions, simulated sequences with ground truth and same patient procedures. The software used in this paper is publicly available.

Familial Colorectal Cancer and Genetic Susceptibility: Colorectal Risk Variants in First-Degree Relatives of Patients With Colorectal Cancer.

INTRODUCTION: Epidemiological studies estimate that having a first-degree relative (FDR) with colorectal cancer (CRC) increases 2-fold to 3-fold the risk of developing the disease. Because FDRs of CRC patients are more likely to co-inherit CRC risk variants, we aimed to evaluate potential differences in genotype distribution of single nucleotide polymorphisms (SNPs) related to CRC risk between FDRs of patients with nonsyndromic CRC (cases) and individuals with no family history of CRC (controls). METHODS: We designed a case-control study comprising 750 cases and 750 Spanish Caucasian controls matched by sex, age, and histological findings after colonoscopy. Genomic DNA from all participants was genotyped for 88 SNPs associated with CRC risk using the MassArray (Sequenom) platform. RESULTS: Ten of the 88 SNPs analyzed revealed significant associations (P < 0.05) with a family history of CRC in our population. The most robust associations were found for the rs17094983G>A SNP in the long noncoding RNA LINC01500 (odds ratio = 0.72; 95% confidence interval: 0.58-0.88, log-additive model), and the rs11255841T>A SNP in the long noncoding RNA LINC00709 (odds ratio = 2.04; 95% confidence interval: 1.19-3.51, dominant model). Of interest, the observed associations were in the same direction than those reported for CRC risk. DISCUSSION: FDRs of CRC patients show significant differences in genotype distribution of SNPs related to CRC risk as compared to individuals with no family history of CRC. Genotyping of CRC risk variants in FDRs of CRC patients may help to identify subjects at risk that would benefit from stricter surveillance and CRC screening programs.

Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions.

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.

Compound Endoscopic Morphological Features for Identifying Non-Pedunculated Lesions ≥20 mm with Intramucosal Neoplasia.

BACKGROUND: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. OBJECTIVE: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. DESIGN: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions' endoscopic characteristics. RESULT: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions' characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3-52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6-81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2-90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5-97.8%; p < 0.001). CONCLUSION: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/- therapeutic endoscopic submucosal dissection should be considered.

Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort.

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3-3.1), CRC (HR 4.4, 95% CI 1.1-17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0-2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3-5.8), rectal bleeding (OR 0.3, 95% CI 0.1-0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7-7.1). However, CEA was increased only in 31.8% (95% CI, 16.4-52.7%) and 50% (95% CI, 25.4-74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.

Factors associated with mortality in patients with infected pancreatic necrosis: the "surgery effect".

Severe acute pancreatitis complicated by infection is associated with high mortality. Invasive treatment is indicated in the presence of infected (suspected) pancreatic and/or peripancreatic necrosis (IPN) in the absence of response to intensive medical support. Step-up approach (SUA) has been demonstrated to lower complication rate compared to upfront open surgery. However, this approach has not been associated with lower mortality, and no factors have been studied that could help to identify the high risk patients. In this study, we aimed to analyse those factors associated with mortality following the invasive treatment of IPN, focusing on the role of surgical necrosectomy. A retrospective and observational study based on a multicentre prospective database was conducted. The database was coordinated by the Hospital General Universitario de Alicante, Spain and the Spanish Association of Pancreatology. Demographics, clinical data, and laboratory and imaging findings were collected. Atlanta 2012 criteria were considered to classify acute necrotizing pancreatitis and for the definition of IPN. Step-up approach was used in all centres with the intention of avoiding surgery whenever possible. Surgical necrosectomy was performed by open approach. From January 2013 to October 2014, a total of 1655 patients with the diagnosis of acute pancreatitis were included in our database. 1081 were recruited for the final analysis. Out of them, 205 (19%) were classified into acute necrotizing pancreatitis. 77 (8.3%) patients underwent invasive treatment of INP and were included in our study. Overall mortality was 29.9%. Upfront endoscopic or percutaneous drainage was performed in 60 (77.9%) patients and mortality was 26.6%. Out of 60, 22 (36.6%) patients subsequently received rescue surgery; mortality in rescue surgery group was 18.3%. Upfront surgery was carried out in 17 (22.1%) patients; mortality in this group was 41%. At univariate analysis, surgical necrosectomy, extrapancreatic infection, immunosuppression and de-novo haemodialysis were associated with mortality. At multivariate analysis, only surgical necrosectomy was significantly associated with mortality (p = 0.002 OR 3.89). Surgical approach for IPN is associated with high mortality rate. However, these data should be interpreted with caution, since we are not able to assess whether this occurs due to the need of surgery as the only resort when the other approaches are not feasible or fail.

Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test.

BACKGROUND: 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). AIM: To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 µg Hb/g faeces) without CRC. METHODS: 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. RESULTS: 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). CONCLUSION: 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.