Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Follow-up evaluation of patients with liver test abnormalities detected during SARS-CoV2 infection.

Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease.

Evaluating the Potential of Polygenic Risk Score to Improve Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer has high incidence and associated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario. METHODS: We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were genotyped. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated. RESULTS: Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02-1.06; P < 0.0001]. A 2-fold increase in colorectal cancer risk was observed for subjects in the highest decile of risk alleles (≥65), compared with those in the first decile (≤54; OR = 2.22; 95% CI, 1.59-3.12; P < 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62-0.66]. CONCLUSIONS: This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers. IMPACT: PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers.

Prevalence and characteristics of hepatitis C virus-related hepatocellular carcinoma in a Spanish university hospital.

BACKGROUND: Hepatocellular Carcinoma (HCC) arises in chronic liver diseases, particularly caused by hepatitis C virus (HCV) and alcohol in Europe. We aimed at evaluating the characteristics and mortality of patients with HCV-related HCC as compared to other HCC etiologies. METHODS: We retrospectively evaluated data from 887 patients with HCC identified through the Hospital del Mar Cancer Registry (Barcelona, Spain), during the 2001-2020 period. We estimated crude and adjusted hazard ratios (aHR) of dying and its 95% confidence interval (95%CI). RESULTS: Among 887 patients with HCC, 617 (69.6%) were HCV-infected. Underlying cirrhosis was more frequent in HCV-related HCC compared to other etiologies (97% vs. 89%, p < 0.001). The prevalence of HCV-related HCC decreased from 79% in 2001-2005 to 55% in 2015-2020 (p < 0.001). HCV infection did not increase the hazard of death [aHR 0.95 (CI95% 0.81-1.13)]. Mortality was independently related to age > 75 years, advanced BCLC stage at diagnosis, and diagnosis before 2010. CONCLUSION: In our cohort, HCV-related HCC frequently occurred in a cirrhotic background, but showed similar clinical characteristics and mortality as compared to other HCC etiologies.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

xDEEP-MSI: Explainable Bias-Rejecting Microsatellite Instability Deep Learning System in Colorectal Cancer.

The prediction of microsatellite instability (MSI) using deep learning (DL) techniques could have significant benefits, including reducing cost and increasing MSI testing of colorectal cancer (CRC) patients. Nonetheless, batch effects or systematic biases are not well characterized in digital histology models and lead to overoptimistic estimates of model performance. Methods to not only palliate but to directly abrogate biases are needed. We present a multiple bias rejecting DL system based on adversarial networks for the prediction of MSI in CRC from tissue microarrays (TMAs), trained and validated in 1788 patients from EPICOLON and HGUA. The system consists of an end-to-end image preprocessing module that tile samples at multiple magnifications and a tissue classification module linked to the bias-rejecting MSI predictor. We detected three biases associated with the learned representations of a baseline model: the project of origin of samples, the patient's spot and the TMA glass where each spot was placed. The system was trained to directly avoid learning the batch effects of those variables. The learned features from the bias-ablated model achieved maximum discriminative power with respect to the task and minimal statistical mean dependence with the biases. The impact of different magnifications, types of tissues and the model performance at tile vs patient level is analyzed. The AUC at tile level, and including all three selected tissues (tumor epithelium, mucin and lymphocytic regions) and 4 magnifications, was 0.87 ± 0.03 and increased to 0.9 ± 0.03 at patient level. To the best of our knowledge, this is the first work that incorporates a multiple bias ablation technique at the DL architecture in digital pathology, and the first using TMAs for the MSI prediction task.

Predictors of Metachronous Risk Polyps After Index Colonoscopy.

INTRODUCTION: Guidelines for surveillance after polypectomy are lacking in strong evidence. Our aim was to identify some precursors of colorectal cancer lesions at 3 years after polypectomy to improve stratification and surveillance programs. METHODS: We included patients with high-risk lesions (HRLs), defined as advanced adenoma (AA), large serrated polyps (SPs), and multiplicity (≥3 of any adenomas/SPs). Data on age, sex, cardiovascular risk factors, pharmacological treatment, and the histological characteristics in each individual, and mutations in genes involved in the most advanced index polyp, were collected. Parameters independently associated with a metachronous HRL diagnosis were evaluated through univariate and multivariate analyses. The results are reported as odds ratios and 95% confidence intervals along with P values. RESULTS: A total of 537 cases (median age: 60.7 years; 66% male) were included. Dyslipidemia and smoking correlated with metachronous HRLs. Multivariate logistic regression analysis showed that the presence of multiplicity with ≥3 polyps on the index colonoscopy was significantly associated with metachronous HRL, AA, proximal AA, and ≥3 polyps at 3 years. In addition, independent predictors of metachronous proximal AA were increasing age, female sex, and the loss of expression of the MLH1 protein. DISCUSSION: Multiplicity was a strong predictor of HRLs at 3 years, although the inclusion of other clinical variables (age, sex, smoking status, and dyslipidemia) improves surveillance recommendations. Without these risk factors, the surveillance could be extended to 5 years; we propose examining the somatic expression of MHL1 in all patients.

Narrow-band imaging and high-definition white-light endoscopy in patients with serrated lesions not fulfilling criteria for serrated polyposis syndrome: a randomized controlled trial with tandem colonoscopy.

BACKGROUND: It is unknown whether narrow-band imaging (NBI) could be more effective than high-definition white-light endoscopy (HD-WLE) in detecting serrated lesions in patients with prior serrated lesions > 5 mm not completely fulfilling serrated polyposis syndrome (SPS) criteria. METHODS: We conducted a randomized, cross-over trial in consecutive patients with prior detection of at least one serrated polyp ≥10 mm or ≥ 3 serrated polyps larger than 5 mm, both proximal to the sigmoid colon. Five experienced endoscopists performed same-day tandem colonoscopies, with the order being randomized 1:1 to NBI-HD-WLE or HD-WLE-NBI. All tandem colonoscopies were performed by the same endoscopist. RESULTS: We included 41 patients. Baseline characteristics were similar in the two cohorts: NBI-HD-WLE (n = 21) and HD-WLE-NBI (n = 20). No differences were observed in the serrated lesion detection rate of NBI versus HD-WLE: 47.4% versus 51.9% (OR 0.84, 95% CI: 0.37-1.91) for the first and second withdrawal, respectively. Equally, no differences were found in the polyp miss rate of NBI versus HD-WLE: 21.3% versus 26.1% (OR 0.77, 95% CI: 0.43-1.38). Follow-up colonoscopy in nine patients (22%) allowed them to be reclassified as having SPS. CONCLUSIONS: In patients with previous serrated lesions, the serrated lesion detection rate was similar with NBI and HD-WLE. A shorter surveillance colonoscopy interval increases the detection of missed serrated polyps and could change the diagnosis of SPS in approximately one in every five patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02406547, registered on April 2, 2015.

Personalised surveillance for serrated polyposis syndrome: results from a prospective 5-year international cohort study.

BACKGROUND AND AIMS: Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC). International guidelines recommend surveillance intervals of 1-2 years. However, yearly surveillance likely leads to overtreatment for many. We prospectively assessed a surveillance protocol aiming to safely reduce the burden of colonoscopies. METHODS: Between 2013 and 2018, we enrolled SPS patients from nine Dutch and Spanish hospitals. Patients were surveilled using a protocol appointing either a 1-year or 2-year interval after each surveillance colonoscopy, based on polyp burden. Primary endpoint was the 5-year cumulative incidence of CRC and advanced neoplasia (AN) during surveillance. RESULTS: We followed 271 SPS patients for a median of 3.6 years. During surveillance, two patients developed CRC (cumulative 5-year incidence 1.3%[95% CI 0% to 3.2%]). The 5-year AN incidence was 44% (95% CI 37% to 52%), and was lower for patients with SPS type III (26%) than for patients diagnosed with type I (53%) or type I and III (59%, p<0.001). Most patients were recommended a 2-year interval, and those recommended a 2-year interval were not at increased risk of AN: AN incidence after a 2-year recommendation was 15.6% compared with 24.4% after a 1-year recommendation (OR 0.57, p=0.08). CONCLUSION: Risk stratification substantially reduced colonoscopy burden while achieving CRC incidence similar to previous studies. AN incidence is considerable in SPS patients, but extension of surveillance intervals was not associated with increased AN in those identified as low-risk by the protocol. We identified SPS type III patients as low-risk group that might benefit from even less frequent surveillance. TRIAL REGISTRATION NUMBER: The study was registered on http://www.trialregister.nl; trial-ID NTR4609.

Epstein Barr virus antibody reactivity and gastric cancer: A population-based case-control study.

BACKGROUND: In contrast to the recognized role of Helicobacter pylori in the etiology of non-cardia gastric cancer (GC), there is still insufficient epidemiological evidence for the involvement of Epstein-Barr virus (EBV) in gastric carcinogenesis. We aimed to evaluate the relation of antibody profile and antibody reactivity intensity against four individual EBV proteins to GC risk. METHODS: We used information from 281 GC cases and 2071 age and sex frequency matched controls recruited in the frame of the MCC-Spain multicase-control study, between 2008 and 2013. Sociodemographic, lifestyle and environmental factors were assessed in face-to-face interviews. Antibody responses to four EBV proteins (EBNA-1, ZEBRA, EA-D, and VCA-p18) were analyzed by multiplex serology. Odds ratios (OR) and 95% confidence intervals were calculated by using logistic regression mixed models to evaluate the association of seropositivity and antibody reactivity against EBV proteins with GC, adjusting for GC risk factors. Stratified analyses by tumor location (cardia vs. non-cardia) and morphology (intestinal vs. diffuse) were done. RESULTS: Among controls, seropositivity for EA-D, ZEBRA, EBNA-1 and VCA-p18 was 85%, 91%, 97% and 99%, respectively. Even though seropositivity for none of the studied proteins was associated with a higher GC risk, increasing antibody reactivity against EBNA-1 and VCA-p18 was associated with higher OR of GC. This association was present for cardia and non-cardia cancer cases, and for intestinal and diffuse types. CONCLUSION: Our results support the hypothesis that EBV may play a role in GC etiology, and highlight the importance of evaluating specific antibodies and the dose-response relations when studying widespread infections.

Randomized Clinical Trial: A Normocaloric Low-Fiber Diet the Day Before Colonoscopy Is the Most Effective Approach to Bowel Preparation in Colorectal Cancer Screening Colonoscopy.

BACKGROUND: Clinical guidelines recommend either a clear-liquid diet or a low-fiber diet for colonoscopy preparation. Participants in a screening program are usually motivated healthy individuals in which a good tolerability is important to improve adherence to potential surveillance colonoscopies. OBJECTIVE: Our aim was to assess whether or not a normocaloric low-fiber diet followed the day before a screening colonoscopy compromises the efficacy of bowel cleansing and may improve the tolerability of bowel preparation. DESIGN: This is a randomized, endoscopist-blinded, noninferiority clinical trial. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: A total of 276 consecutive participants of the Barcelona colorectal cancer screening program were included. INTERVENTION: Participants were randomly assigned to a clear-liquid diet or a normocaloric low-fiber diet the day before the colonoscopy. Both groups received 4 L of polyethylene glycol in a split-dose regimen. MAIN OUTCOME MEASURES: Primary outcome was the adequate bowel preparation rate measured with the Boston bowel preparation scale. Secondary outcomes included tolerability, fluid-intake perception, hunger, side effects, and acceptability. RESULTS: Participants in both groups were similar in baseline characteristics. Adequate bowel preparation was achieved in 89.1% vs 95.7% in clear-liquid diet and low-fiber diet groups, showing not only noninferiority, but also superiority (p = 0.04). Low-fiber diet participants reported less fluid-intake perception (p = 0.04) and less hunger (p = 0.006), with no differences in bloating or nausea. LIMITATIONS: The single-center design of the study could limit the external validity of the results. The present findings may not be comparable to other clinical settings. CONCLUSION: A normocaloric low-fiber diet the day before a screening colonoscopy achieved better results than a clear-liquid diet in terms of adequate colon preparation. Moreover, it also improved the perception of hunger and excessive fluid intake. Registered at clinicaltrials.gov: NCT02401802. See Video Abstract at http://links.lww.com/DCR/A829.

Endoscopic surveillance after colonic polyps and colorrectal cancer resection. 2018 update. / Vigilancia tras resección de pólipos de colon y de cáncer colorrectal. Actualización 2018.

There is limited scientific evidence available to stratify the risk of developing metachronous colorectal cancer after resection of colonic polyps and to determine surveillance intervals and is mostly based on observational studies. However, while awaiting further evidence, the criteria of endoscopic follow-up needs to be unified in our setting. Therefore, the Spanish Association of Gastroenterology, the Spanish Society of Family and Community Medicine, the Spanish Society of Digestive Endoscopy, and the Colorectal Cancer Screening Group of the Spanish Society of Epidemiology, have written this consensus document, which is included in chapter 10 of the "Clinical Practice Guideline for Diagnosis and Prevention of Colorectal Cancer. 2018 Update". Important developments will also be presented as regards the previous edition published in 2009. First of all, situations that require and do not require endoscopic surveillance are established, and the need of endoscopic surveillance of individuals who do not present a special risk of metachronous colon cancer is eliminated. Secondly, endoscopic surveillance recommendations are established in individuals with serrated polyps. Finally, unlike the previous edition, endoscopic surveillance recommendations are given in patients operated on for colorectal cancer. At the same time, it represents an advance on the European guideline for quality assurance in colorectal cancer screening, since it eliminates the division between intermediate risk group and high risk group, which means the elimination of a considerable proportion of colonoscopies of early surveillance. Finally, clear recommendations are given on the absence of need for follow-up in the low risk group, for which the European guidelines maintained some ambiguity.

High incidence of advanced colorectal neoplasia during endoscopic surveillance in serrated polyposis syndrome.

BACKGROUND: Serrated polyposis syndrome (SPS) has been associated with an increased risk of colorectal cancer (CRC). Accordingly, intensive surveillance with annual colonoscopy is advised. The aim of this multicenter study was to describe the risk of advanced lesions in SPS patients undergoing surveillance, and to identify risk factors that could guide the prevention strategy. METHODS: From March 2013 to April 2015, 296 patients who fulfilled criteria I and/or III for SPS were retrospectively recruited at 18 centers. We selected patients in whom successful clearing colonoscopy had been performed and who underwent subsequent endoscopic surveillance. Advanced neoplasia was defined as CRC, advanced adenoma, or advanced serrated lesion that were ≥ 10 mm and/or with dysplasia. Cumulative incidence of advanced neoplasia was calculated and independent predictors of advanced neoplasia development were identified. RESULTS: In 152 SPS patients a total of 315 surveillance colonoscopies were performed (median 2, range 1 - 7). The 3-year cumulative incidence of CRC and advanced neoplasia were 3.1 % (95 % confidence interval [CI] 0 - 6.9) and 42.0 % (95 %CI 32.4 - 51.7), respectively. Fulfilling both I + III criteria and the presence of advanced serrated lesions at baseline colonoscopy were independent predictors of advanced neoplasia development (odds ratio [OR] 1.85, 95 %CI 1.03 - 3.33, P  = 0.04 and OR 2.62, 95 %CI 1.18 - 5.81, P  = 0.02, respectively). During follow-up, nine patients (5.9 %) were referred for surgery for invasive CRC (n = 4, 2.6 %) or because of polyp burden (n = 5, 3.3 %). After total colectomy, 17.9 % patients developed advanced neoplasia in the retained rectum. CONCLUSIONS: Patients with SPS have a substantial risk of developing advanced neoplasia under endoscopic surveillance, whereas CRC incidence is low. Personalized endoscopic surveillance based on polyp burden and advanced serrated histology could help to optimize prevention in patients with SPS.

Diminutive Polyps With Advanced Histologic Features Do Not Increase Risk for Metachronous Advanced Colon Neoplasia.

BACKGROUND & AIMS: With advances in endoscopic imaging, it is possible to differentiate adenomatous from hyperplastic diminutive (1-5 mm) polyps during endoscopy. With the optical Resect-and-Discard strategy, these polyps are then removed and discarded without histopathology assessment. However, failure to recognize adenomas (vs hyperplastic polyps), or discarding a polyp with advanced histologic features, could result in a patient being considered at low risk for metachronous advanced neoplasia, resulting in an inappropriately long surveillance interval. We collected data from international cohorts of patients undergoing colonoscopy to determine what proportion of patients are high risk because of diminutive polyps advanced histologic features and their risk for metachronous advanced neoplasia. METHODS: We collected data from 12 cohorts (in the United States or Europe) of patients undergoing colonoscopy after a positive result from a fecal immunochemical test (FIT cohort, n = 34,221) or undergoing colonoscopies for screening, surveillance, or evaluation of symptoms (colonoscopy cohort, n = 30,123). Patients at high risk for metachronous advanced neoplasia were defined as patients with polyps that had advanced histologic features (cancer, high-grade dysplasia, ≥25% villous features), 3 or more diminutive or small (6-9 mm) nonadvanced adenomas, or an adenoma or sessile serrated lesion ≥10 mm. Using an inverse variance random effects model, we calculated the proportion of diminutive polyps with advanced histologic features; the proportion of patients classified as high risk because their diminutive polyps had advanced histologic features; and the risk of these patients for metachronous advanced neoplasia. RESULTS: In 51,510 diminutive polyps, advanced histologic features were observed in 7.1% of polyps from the FIT cohort and 1.5% polyps from the colonoscopy cohort (P = .044); however, this difference in prevalence did not produce a significant difference in the proportions of patients assigned to high-risk status (0.8% of patients in the FIT cohort and 0.4% of patients in the colonoscopy cohort) (P = .25). The proportions of high-risk patients because of diminutive polyps with advanced histologic features who were found to have metachronous advanced neoplasia (17.6%) did not differ significantly from the proportion of low-risk patients with metachronous advanced neoplasia (14.6%) (relative risk for high-risk categorization, 1.13; 95% confidence interval 0.79-1.61). CONCLUSION: In a pooled analysis of data from 12 international cohorts of patients undergoing colonoscopy for screening, surveillance, or evaluation of symptoms, we found that diminutive polyps with advanced histologic features do not increase risk for metachronous advanced neoplasia.

Association study of dietary non-enzymatic antioxidant capacity (NEAC) and colorectal cancer risk in the Spanish Multicase-Control Cancer (MCC-Spain) study.

PURPOSE: Studies attempting to link dietary non-enzymatic antioxidant activity (NEAC) and colorectal cancer (CRC) risk have reported mixed results. We examined this association in the Spanish Multicase-Control Study considering the likely influence of coffee and other dietary factors. METHODS: 1718 CRC cases and 3312 matched-controls provided information about diet through a validated 140-item food frequency questionnaire. Dietary NEAC was estimated for three methods [total radical-trapping antioxidant parameters (TRAP), ferric reducing/antioxidant power (FRAP) and TEAC-ABTS] using published values of NEAC content in food, with and without coffee's NEAC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through unconditional logistic regression models adjusted for lifestyle and dietary factors. RESULTS: Overall dietary intake of NEAC was significantly lower in cases compared to controls and associated with a significantly reduced CRC risk, in both men (ORQ5vsQ1 = 0.67, 95% CI 0.47-0.96 for FRAP) and women (ORQ5vsQ1 = 0.53, 95% CI 0.32-085 for FRAP), in multivariate models with and without the antioxidant contribution from coffee. The effect was similar for all the NEAC methods evaluated and for both colon and rectum. The association between dietary NEAC and CRC risk became non-significant when adjusting for fiber intake. However, intakes of NEAC and fiber were correlated. CONCLUSION: This study indicates that intake of an antioxidant-rich plant-based diet, both with and without NEAC from coffee, is associated with decreased CRC risk.

Helicobacter pylori seroprevalence in Spain: influence of adult and childhood sociodemographic factors.

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.

Changes in FIT values below the threshold of positivity and short-term risk of advanced colorectal neoplasia: Results from a population-based cancer screening program.

INTRODUCTION: Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program. METHODS: FIT results were categorised into non-detectable nFIT (0-3.8 µg haemoglobin/g feces), low nFIT (3.9-9.9) and high nFIT (10.0-19.9). Multivariable adjusted logistic regression was used to estimate the odds ratios (OR) of advanced neoplasia and IC with the nFIT results in the first two screens. RESULTS: More than 90% of the 42,524 persons had non-detectable nFIT in the first and second screen; 4.5% and 5.8% had a low nFIT, respectively, and 2.2% and 2.9% had a high nFIT. The probability of testing positive and being diagnosed of advanced neoplasia or IC rose with increasing values of nFIT. Compared with those with two non-detectable nFIT results, the highest OR were found among those who had two high nFIT results (OR 21.75; 95% confidence interval: 12.44, 38.04) and those with one low nFIT and one high nFIT (ORs around 20). CONCLUSIONS: Participants with nFIT results above the detection limit of the test had an increased risk of advanced neoplasia and IC in subsequent participations. This information could be used in the design of personalised screening strategies.

Detection of serrated lesions in proximal colon by simulated sigmoidoscopy vs faecal immunochemical testing in a multicentre, pragmatic, randomised controlled trial.

BACKGROUND: The diagnostic yield of the faecal immunochemical test and sigmoidoscopy in detecting proximal serrated polyps in a colorectal cancer screening programme has not been fully assessed. AIM: We determined the detection rate of proximal serrated polyps by simulated sigmoidoscopy and faecal immunochemical test compared with total colonoscopy in a population-based, multicentre, nationwide, randomised controlled trial (ColonPrev study). METHODS: Sigmoidoscopy yield was simulated based on the UK-Flexible Sigmoidoscopy Trial for total colonoscopy referral. Definitions were: proximal serrated polyp (proximal serrated polyp): sessile serrated polyp or hyperplastic polyp of any size and proximal at-risk serrated polyp (at-risk proximal serrated polyp): sessile serrated polyp of any size or hyperplastic polyp ≥ 10 mm, both located proximally to the splenic flexure. RESULTS: A total of 10,611 individuals underwent faecal immunochemical test and 5059 underwent total colonoscopy and were evaluated by simulated sigmoidoscopy. Sigmoidoscopy and faecal immunochemical test were less accurate in detecting proximal serrated polyps (odds ratio: 0.13; 95% confidence interval: 0.10-0.18 and 0.13; 0.09-0.18, p < 0.0001, respectively). Both tests were inferior to colonoscopy in detecting at-risk proximal serrated polyps, and sigmoidoscopy was inferior to faecal immunochemical test in detecting these lesions (odds ratio: 0.17; 95% confidence interval: 0.10-0.30 and 0.25; 0.17-0.37, p < 0.0001, respectively). CONCLUSION: Sigmoidoscopy and faecal immunochemical test are less accurate in detecting proximal serrated polyps than colonoscopy, particularly in women.

Narrow band imaging and white light endoscopy in the characterization of a polypectomy scar: A single-blind observational study.

AIM: To assess the incremental benefit of narrow band imaging (NBI) and white light endoscopy (WLE), randomizing the initial technique for the detection of residual neoplasia at the polypectomy scar after an endoscopic piecemeal mucosal resection (EPMR). METHODS: We conducted an observational study in an academic center to assess the incremental benefit of NBI and WLE randomly applied 1:1 (NBI-WLE or WLE-NBI) in the follow-up of a post-EPMR scar by the same endoscopist. RESULTS: A total of 112 EPMR scars were included. The median baseline polyp size was 20 mm (interquartile range: 14-30). At first review, NBI and WLE showed good sensitivity (85.0% vs 78.9%), specificity (77.1% vs 84.2%) and overall accuracy (80.0% vs 82.5%). NBI after WLE (WLE-NBI group) improved accuracy, but this difference was not statistically significant [area under the curve (AUC): 86.8% vs 81.6%, P = 0.15]. WLE after NBI (NBI-WLE group) did not improve accuracy (AUC: 81.4% vs 81.1%, P = 0.9). Overall, recurrence was found in 39/112 (34.8%) lesions. CONCLUSION: Although no statistically significant differences were found between the two techniques at the first post-EPMR assessment, the use of NBI after WLE may improve residual neoplasia detection. Nevertheless, biopsy is still required in the first scar review.