[The role of ferments in food sustainability]. / El rol de los fermentos en la sostenibilidad alimentaria.

Introduction: Food fermentation is one of the oldest conservation techniques and has evolved over the centuries. This study contributes to the understanding of the impact of fermentation and consequently of fermented products in the evolution of humanity and its influence on sustainability and food use. The production of fermented dairy products is the second industry after alcoholic beverages; thus, yogurt is one of the main fermented products consumed worldwide. Considering fermentation as a technology, this brings us different benefits such as sustainability, since in Spain each person wastes 77 kilos of food per year in their homes and we know that 9% of food waste in our country corresponds to dairy products. For this reason, we have worked with different ferments to select those that allow us to extend the useful life of the product, making it more flexible in its distribution and conservation. Also considering food safety due to the change in pH and the production of certain substances that will protect against pathogens and undesirable bacteria, guaranteeing the highest quality standards.

Introducción: La fermentación de los alimentos constituye una de las técnicas de conservación más antiguas, que ha ido evolucionando a lo largo de los siglos. Este estudio contribuye a la comprensión del impacto de la fermentación y, en consecuencia, de los productos fermentados en la evolución de la humanidad y su influencia en la sostenibilidad y en el aprovechamiento alimentario. La elaboración de productos lácteos fermentados es la segunda industria después de la de bebidas alcohólicas, así pues, el yogur es uno de los principales productos fermentados consumidos en todo el mundo. Considerando la fermentación como una tecnología, esta nos aporta distintos beneficios como la sostenibilidad, ya que en España cada persona desperdicia 77 kilos de alimentos al año en sus hogares y sabemos que el 9 % del desperdicio alimentario en nuestro país corresponde a los lácteos. Por esta razón, se ha trabajado con diferentes fermentos para seleccionar aquellos que permitan alargar la vida útil del producto y hacerlo más flexible en su distribución y conservación, teniendo en cuenta también la seguridad alimentaria debido al cambio de pH y a la producción de determinadas sustancias que protegen frente a patógenos y bacterias indeseables, garantizando los máximos estándares de calidad.

Memory T Cell Subpopulations as Early Predictors of Remission to Vedolizumab in Ulcerative Colitis.

Background: Vedolizumab is a humanized monoclonal antibody targeting the α4ß7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4+ and CD8+ memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis. Methods: Prospective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin <250 mcg/g or Mayo endoscopic subscore ≤1. Results: At week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α4ß7 + memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α4ß7 + memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction. Conclusion: CD8+ α4ß7 + memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders.

El rol de los fermentos en la sostenibilidad alimentaria / The role of ferments in food sustainability

La fermentación de los alimentos constituye una de las técnicas de conservación más antiguas, que ha ido evolucionando a lo largo de los siglos. Este estudio contribuye a la comprensión del impacto de la fermentación y, en consecuencia, de los productos fermentados en la evolución de la humanidad y su influencia en la sostenibilidad y en el aprovechamiento alimentario.La elaboración de productos lácteos fermentados es la segunda industria después de la de bebidas alcohólicas, así pues, el yogur es uno de los principales productos fermentados consumidos en todo el mundo. Considerando la fermentación como una tecnología, esta nos aporta distintos beneficios como la sostenibilidad, ya que en España cada persona desperdicia 77 kilos de alimentos al año en sus hogares y sabemos que el 9 % del desperdicio alimentario en nuestro país corresponde a los lácteos. Por esta razón, se ha trabajado con diferentes fermentos para seleccionar aquellos que permitan alargar la vida útil del producto y hacerlo más flexible en su distribución y conservación, teniendo en cuenta también la seguridad alimentaria debido al cambio de pH y a la producción de determinadas sustancias que protegen frente a patógenos y bacterias indeseables, garantizando los máximos estándares de calidad. (AU)

Food fermentation is one of the oldest conservation techniques and has evolved over the centuries. This study contributes to the understanding of the impact of fermentation and consequently of fermented products in the evolution of humanity and its influence on sustainability and food use.The production of fermented dairy products is the second industry after alcoholic beverages; thus, yogurt is one of the main fermented products consumed worldwide. Considering fermentation as a technology, this brings us different benefits such as sustainability, since in Spain each person wastes 77 kilos of food per year in their homes and we know that 9% of food waste in our country corresponds to dairy products. For this reason, we have worked with different ferments to select those that allow us to extend the useful life of the product, making it more flexible in its distribution and conservation. Also considering food safety due to the change in pH and the production of certain substances that will protect against pathogens and undesirable bacteria, guaranteeing the highest quality standards. (AU)

Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis.

BACKGROUND: Previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer remains unexplored. METHODS: We performed histopathological evaluation and immunohistochemical analysis of early colorectal adenomas and carcinoma adenoma from patients at the Hospital del Mar in Barcelona. We then determined the possible correlation between the different parameters analyzed and with patient outcomes. RESULTS: Paneth cells accumulate in a subset of human colorectal adenomas directly associated with Notch and Wnt/ß-catenin activation. Adenoma areas containing Paneth cells display increased vessel density in the lamina propria and higher levels of the stem cell marker EphB2. In an in-house cohort of 200 colorectal adenoma samples, we also observed a significant correlation between the presence of Paneth cells and Wnt activation. Kaplan-Meier analysis indicated that early adenoma patients carrying Paneth cell-positive tumors display reduced disease-free survival compared with patients with Paneth cell-free lesions. CONCLUSIONS: Our results indicate that Paneth cells contribute to the initial steps of cancer progression by providing the stem cell niche to adenoma cells, which could be therapeutically exploited.

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.

Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.

Cribado poblacional de cáncer colorrectal: cánceres de intervalo y relación con el resultado cuantitativo del test inmunológico de sangre oculta en heces / Population-based colorectal cancer screening: Interval cancers and relationship with the quantitative faecal immunological for hemoglobin

Introducción y objetivo: La sensibilidad de los programas de cribado de cáncer colorrectal determina su efectividad y está directamente relacionada con el cáncer de intervalo (CI). Este estudio describe la frecuencia y las características de los CI del Programa de la ciudad de Barcelona y analiza su relación con el valor cuantitativo del test de cribado previo (FIT). Material y métodos: Se incluyen los CI tras FIT negativo de las primeras dos rondas del Programa (2010-2013); periodo de observación hasta julio de 2017. La fuente de información de los CI es su notificación por profesionales y pacientes y el cruce de bases de datos hospitalarias y CMBD. Resultados: La sensibilidad del Programa es del 82%. Los CI se diagnostican más en colon proximal y recto y en estadios avanzados que los cánceres de cribado, y presentan valores FIT más elevados que el conjunto de personas con FIT negativo. Conclusiones: La sensibilidad obtenida es aceptable y comparable a la de otros programas. El valor cuantitativo del FIT en personas con test negativo debería incluirse en las estrategias de personalización del cribado para reducir el riesgo de CI

Introduction and objective: The sensitivity of colorectal cancer screening programmes determines their effectiveness and is directly related to the interval cancer (IC). This study describes the frequency and characteristics of the IC of the Programme of Barcelona, Spain, and analyses its relationship with the quantitative value of the screening test (FIT). Material and methods: ICs after negative FIT of the first two rounds of the Programme (2010-2013) were included, observation period until July 2017. The information source of the ICs was their notification by professionals and patients, hospital databases and CMBD (Spanish Minimum Basic Data Set). Results: The sensitivity of the Programme is 82%. ICs are diagnosed more in proximal and rectal colon and in advanced stages than screening cancers, and have higher FIT values than overall people with negative FIT. Conclusions: The sensitivity is acceptable and comparable to that of other programmes. The quantitative value of FIT in people with negative test should be included in the personalisation strategies of screening to reduce the risk of IC

Population-based colorectal cancer screening: Interval cancers and relationship with the quantitative faecal immunological for hemoglobin. / Cribado poblacional de cáncer colorrectal: cánceres de intervalo y relación con el resultado cuantitativo del test inmunológico de sangre oculta en heces.

INTRODUCTION AND OBJECTIVE: The sensitivity of colorectal cancer screening programmes determines their effectiveness and is directly related to the interval cancer (IC). This study describes the frequency and characteristics of the IC of the Programme of Barcelona, Spain, and analyses its relationship with the quantitative value of the screening test (FIT). MATERIAL AND METHODS: ICs after negative FIT of the first two rounds of the Programme (2010-2013) were included, observation period until July 2017. The information source of the ICs was their notification by professionals and patients, hospital databases and CMBD (Spanish Minimum Basic Data Set). RESULTS: The sensitivity of the Programme is 82%. ICs are diagnosed more in proximal and rectal colon and in advanced stages than screening cancers, and have higher FIT values than overall people with negative FIT. CONCLUSIONS: The sensitivity is acceptable and comparable to that of other programmes. The quantitative value of FIT in people with negative test should be included in the personalisation strategies of screening to reduce the risk of IC.

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.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy.

OBJECTIVE: The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's response to chemotherapy. DESIGN: This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). RESULTS: Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). CONCLUSION: We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy.

TFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer.

Purpose: A recent study reported that 5-fluorouracil (5-FU)-based chemotherapy is less effective in treating patients with advanced colorectal cancer demonstrating hypermethylation of the TFAP2E gene. The aim of our study was to confirm and validate these findings in large, uniformly treated, well-characterized patient cohorts.Experimental Design: Two cohorts of 783 patients with colorectal cancer: 532 from a population-based, multicenter cohort (EPICOLON I) and 251 patients from a clinic-based trial were used to study the effectiveness of TFAP2E methylation and expression as a predictor of response of colorectal cancer patients to 5-FU-based chemotherapy. DNA methylation status of the TFAP2E gene in patients with colorectal cancer was assessed by quantitative bisulfite pyrosequencing analysis. IHC analysis of the TFAP2E protein expression was also performed.Results: Correlation between TFAP2E methylation status and IHC staining was performed in 607 colorectal cancer samples. Among 357 hypermethylated tumors, only 141 (39.6%) exhibited loss of protein expression. Survival was not affected by TFAP2E hypermethylation in stage IV patients [HR, 1.21; 95% confidence interval (CI), 0.79-1.87; log-rank P = 0.6]. In stage II-III cases, disease-free survival was not influenced by TFAP2E hypermethylation status in 5-FU-treated (HR, 0.91; 95% CI, 0.52-1.59; log-rank P = 0.9) as well as in nontreated patients (HR, 0.88; 95% CI, 0.5-1.54; log-rank P = 0.7).Conclusions:TFAP2E hypermethylation does not correlate with loss of its protein expression. Our large, systematic, and comprehensive study indicates that TFAP2E methylation and expression may not play a major role in predicting response to 5-FU-based chemotherapy in patients with colorectal cancer. Clin Cancer Res; 24(12); 2820-7. ©2018 AACR.

Meat intake, cooking methods and doneness and risk of colorectal tumours in the Spanish multicase-control study (MCC-Spain).

PURPOSE: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study. METHODS: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses. Odds ratios (OR) and confidence intervals (CI) were estimated by logistic regression models adjusted for known confounders. RESULTS: Total meat intake was associated with increased risk of CRC (OR T3-T1 1.41; 95% CI 1.19-1.67; p trend < 0.001), and similar associations were found for white, red and processed/cured/organ meat. Rare-cooked meat preference was associated with low risk of CRC in red meat (ORrare vs. medium 0.66; 95% CI 0.51-0.85) and total meat (ORrare vs. medium 0.56; 95% CI 0.37-0.86) consumers, these associations being stronger in women than in men. Griddle-grilled/barbecued meat was associated with an increased CRC risk (total meat: OR 1.45; 95% CI 1.13-1.87). Stewing (OR 1.25; 95% CI 1.04-1.51) and oven-baking (OR 1.18; 95% CI 1.00-1.40) were associated with increased CRC risk of white, but not red, meat. CONCLUSIONS: Our study supports an association of white, red, processed/cured/organ and total meat intake with an increased risk of CRC. Moreover, our study showed that cooking practices can modulate such risk.

Accuracy of Colon Capsule Endoscopy in Detecting Colorectal Polyps in Individuals with Familial Colorectal Cancer: Could We Avoid Colonoscopies?

Background. Individuals with a family history of colorectal cancer (CRC) have an increased risk of CRC. We evaluated the diagnostic yield of CCE in the detection of lesions and also two different colon preparations. Methods. A prospective multicenter study was designed to assess CCE diagnostic yield in a cohort of asymptomatic individuals with a family history of CRC. CCE and colonoscopy were performed on the same day by 2 endoscopists who were blinded to the results of the other procedure. Results. Fifty-three participants were enrolled. The sensitivity, specificity, PPV, and NPV of CCE for detecting advanced adenomas were 100%, 98%, 67%, and 100%. Sensitivity, specificity, PPV, and NPV of CCE for the diagnosis of individuals with polyps were 87%, 97%, 93%, and 88%, respectively. CCE identify 100% of individuals with significant or advanced lesions. Overall cleanliness was adequate by 60.7% of them. The PEG-ascorbic boost seems to improve colon cleanliness, with similar colonic transit time. Conclusion. CCE is a promising tool, but it has to be considered as an alternative technique in this population in order to reduce the number of colonoscopies performed. More studies are needed to understand appropriate screening follow-up intervals and optimize the bowel preparation regimen.

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs.

BACKGROUND: The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. METHODS: Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. RESULTS: The median ADR was 31% (range, 14%-51%) in the colonoscopy group and 55% (range, 21%-83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson's coefficient 0.716; p < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p = 0.009); sex, 0.09 (p = 0.09); age, 0.3 (p = 0.5); and region 0.00 (p = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%-56%). CONCLUSIONS: ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated.

Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.

Long-Term Prediction of the Demand of Colonoscopies Generated by a Population-Based Colorectal Cancer Screening Program.

OBJECTIVE: To estimate the long-term need for colonoscopies after a positive fecal immunochemical test (FIT) and post-polypectomy surveillance in the context of a population-based colorectal cancer (CRC) screening program. METHODS: A discrete-event simulation model was built to reproduce the process of CRC screening and post-polypectomy surveillance following European guidelines in a population of 100,000 men and women aged 50-69 years over a 20-year period. Screening consisted of biennial FIT and colonoscopy in participants with positive results. The model was mainly fed using data from the first and second rounds of a Spanish program (2010-2013). Data on post-polypectomy surveillance results were obtained from the literature. A probabilistic multivariate sensitivity analysis was performed on the effect of participation, FIT positivity, and adherence to surveillance colonoscopies. The main outcome variables were the number of colonoscopies after a positive FIT, surveillance colonoscopies, and the overall number of colonoscopies. RESULTS: An average yearly number of 1,200 colonoscopies after a positive FIT were predicted per 100,000 inhabitants with a slight increase to 1,400 at the end of the 20-year period. Surveillance colonoscopies increased to an average of 1,000 per 100,000 inhabitants in the long-term, showing certain stabilization in the last years of the 20-year simulation horizon. The results were highly sensitive to FIT positivity. CONCLUSIONS: Implementing a population-based CRC screening program will increase the demand for colonoscopies, which is expected to double in 20 years, mainly due to an increase in surveillance colonoscopies.