Lorena Rodríguez-Alonso

A new rapid quantitative test for fecal calprotectin predicts endoscopic activity in ulcerative colitis.

Background:Fecal calprotectin (FC) determined by the enzyme-linked immunosorbent assay (ELISA) test has been proposed as a promising biomarker of endoscopic activity in ulcerative colitis (UC). However, data on its accuracy in predicting endoscopic activity is scarce. Besides, FC determined by the quantitative-point-of-care test (FC-QPOCT) that provides rapid and individual results could optimize its use in clinical practice. The aims of our study were to evaluate the ability of FC to predict endoscopic activity according to the Mayo score in patients with UC when determined by FC-QPOCT and to compare it with the ELISA test (FC-ELISA). Methods:FC was determined simultaneously by FC-ELISA and FC-QPOCT in patients with UC undergoing colonoscopy. Clinical disease activity and endoscopy were assessed according to the Mayo score. Blood tests were taken to analyze serological biomarkers. Results:A total of 146 colonoscopies were performed on 123 patients with UC. FC-QPOCT correlated more closely with the Mayo endoscopic subscore (Spearman’s correlation coefficient rank r = 0.727, P < 0.001) than clinical activity (r = 0.636, P < 0.001), platelets (r = 0.381, P < 0.001), leucocytes (r = 0.300, P < 0.001), and C-reactive protein (r = 0.291, P = 0.002). The prediction of “endoscopic remission” (Mayo endoscopic subscore ⩽1) with FC-QPOCT (280 µg/g) and FC-ELISA (250 µg/g) presented an area under the curve of 0.906 and 0.924, respectively. The interclass correlation index between both tests was 0.904 (95% confidence interval, 0.864–0.932; P < 0.001). Conclusions:FC determined by QPOCT was an accurate surrogate marker of “endoscopic remission” in UC and presented a good correlation with the FC-ELISA test.

An urgent referral strategy for symptomatic patients with suspected colorectal cancer based on a quantitative immunochemical faecal occult blood test

BACKGROUND European health systems have developed referral guidelines for the selection of patients for the urgent investigation of suspected colorectal cancer. AIM To evaluate whether quantitative faecal immunochemical testing performs better than commonly used high-risk symptoms based strategies for fast-tracking cancer referrals. METHODS We prospectively studied 1054 symptomatic patients referred for a colonoscopy who provided a sample for faecal immunochemical testing. The usefulness of faecal immunochemical testing and two current guidelines for urgent referral were compared for their efficacy in the detection of colorectal cancer and advanced neoplasia. RESULTS The guidelines detected 46.7% and 43.3% of cases of colorectal cancer while faecal haemoglobin concentration ≥15μg Hb/g detected 96.7% of cases. The diagnostic accuracy of both the guidelines and faecal haemoglobin concentration ≥15μg Hb/g for the detection of advanced neoplasia was: sensitivity 38.3%, 36.1%, 57.1% and specificity 71.8%, 69.5%, 86.6%, respectively. Male gender (OR 2.35; p<0.001), age (1.34; p=0.002), and faecal haemoglobin concentration ≥10μg Hb/g (7.81; p<0.001) were independent predictive factors of advanced neoplasia. CONCLUSIONS A faecal immunochemical test based-strategy performs better than current high-risk symptoms based strategies for fast-tracking cancer referrals. A score that combines gender, age and a faecal immunochemical test could accurately estimate the risk of advanced neoplasia.

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.

Intravenous corticosteroids in moderately active ulcerative colitis refractory to oral corticosteroids

BACKGROUND Oral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy. AIM To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not. METHODS All episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids. RESULTS 110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60mg/day [IQR 50-60], median length of course 10days [IQR 7-17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12months (IQR 4-24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the long term (P=0.001). CONCLUSIONS Intravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting.

Síndrome de poliposis serrada

El desarrollo del cáncer colorrectal (CCR) ha sido explicado durante muchos años mediante la secuencia adenomacarcinoma a partir de la vı́a supresora o de inestabilidad cromosómica y la vı́a mutadora o de inestabilidad de microsatélites. En los ú ltimos 20 años, se ha identificado una tercera vı́a de carcinogénesis del CCR. Esta se caracteriza por la hipermetilación aberrante de la región del promotor de determinados genes supresores (CpG island methylator phenotype) permitiendo la silenciación de su función. Se considera que esta vı́a es responsable de un 15-20% del CCR esporádico. Sus lesiones precursoras son las lesiones o pólipos serrados. Actualmente, la Organización Mundial de la Salud (OMS) clasifica los pólipos serrados en 3 tipos: los pólipos hiperplásicos (muy frecuentes, de localización preferentemente distal y, probablemente, sin potencial de malignizar); los pólipos serrados sésiles, con o sin displasia (poco frecuentes, de localización habitualmente proximal, y con potencial maligno, especialmente si presentan displasia) y los adenomas serrados tradicionales (muy infrecuentes, de localización distal y con riesgo de transformación neoplásica). Los criterios clı́nicos que se han relacionado con un mayor riesgo de progresión neoplásica de las lesiones serradas incluyen la multiplicidad, el tamaño (mayor de 10 mm), la localización proximal y la presencia de displasia. Una situación especial es el sı́ndrome de la poliposis serrada (SPS), descrito por primera vez en 1980. Se trata de un sı́ndrome caracterizado por la presencia de numerosos pólipos de extirpe serrada, que pueden ser de gran tamaño, con historia familiar y un riesgo excepcionalmente alto de CCR. La base genética sigue siendo desconocida por lo que, actualmente, la definición sigue siendo fenotı́pica e incluye un grupo muy heterogéneo de pacientes. La OMS ha consensuado los criterios clı́nicos para el diagnóstico clı́nico de SPS, que han sido recientemente actualizados, y se considera que debe cumplir uno de los siguientes criterios: 5 o más pólipos serrados proximales al colon sigmoide, 2 de ellos > 10 mm; cualquier nú mero de pólipos serrados proximales al sigma en un familiar de primer grado con SPS; o más de 20 pólipos serrados repartidos a lo largo de todo el colon. Se trata

Proton pump inhibitors reduce the accuracy of faecal immunochemical test for detecting advanced colorectal neoplasia in symptomatic patients

Background The faecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening and for the detection of advanced colorectal neoplasia (AN) in symptomatic patients, but its accuracy could be improved. Our objective was to assess the impact of proton pump inhibitors (PPI) on the accuracy of the FIT in the detection of AN, namely advanced colorectal adenoma and CRC. Methods and findings We performed a prospective study of 1002 individuals referred for a diagnostic colonoscopy at Bellvitge University Hospital from September 2011 through to October 2012. An exhaustive interview was performed by a gastroenterologist, prescription drug dispensing database was reviewed and the patient was given a FIT prior to colonoscopy. The positivity threshold of FIT used was ≥ 20 μg Hb/g feces and the main outcome was AN. AN was detected in 13.2% (133) of patients. The accuracy of FIT for detecting AN in the PPI users and non-PPI users were: sensitivity 43.0% vs 65.6%, P = 0.009; specificity 86.9% vs 92.3%, P = 0.010; and, predictive positive value 34.4% vs 55.5%, P = 0.007, respectively. In multivariate analysis, adjusting for potential confounders, PPIs were associated with false positives in AN detection by FIT (OR 1.63 CI 95% 1.02–2.59, P < 0.037). The ROC curve for the FIT in the detection of AN in the PPI users and non-PPI users was 0.68 (CI 95% 0.61–0.76) and 0.85 (CI 95% 0.79–0.90). Conclusions PPI therapy reduces the accuracy of FIT for detecting AN in symptomatic patients.

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.

External Evaluation Of Population Pharmacokinetic Models Of Infliximab In Inflammatory Bowel Disease Patients

Background: Infliximab (IFX) trough levels vary markedly between patients with inflammatory bowel disease (IBD), which is important for clinical response. The aim of this study was to evaluate the performance of previously developed population pharmacokinetic models in patients with IBD for dose individualization for Crohn disease (CD) and ulcerative colitis in our clinical setting. Methods: The authors collected 370 trough levels prospectively from 100 adult patients with IBD who were undergoing IFX treatment between July 2013 and August 2016. The external evaluation included prediction- and simulation-based diagnostics [prediction-corrected visual predictive check, prediction- and variability-corrected visual predictive check, and normalized prediction distribution error tests]. Results: In prediction-based diagnostics, the authors observed a nonsignificant overall mean relative bias of −6.87% and an acceptable imprecision of 8.45%. Approximately 100% of the prediction error was within ±30%, indicating satisfactory predictability. Simulation-based diagnostics indicated model misspecification; thus, the model may not be appropriate for simulation-based applications. Conclusions: While simulation-based diagnostics provided unsatisfactory results, the prediction-based diagnostics demonstrate that the population pharmacokinetic model developed by Fasanmade et al for CD can be used to predict and design individualized IFX dose regimens that meet the individual needs of patients with CD and ulcerative colitis.

P275 Bile acid malabsorption involvement in Crohn's disease symptoms. Its relationship with ROME III criteria

Results Forty-two patients with CD were included, 66% (28/42) had bowel resection. Seventy-one percent (30/42) of the patients fulfilled ROME III criteria (20/42 IBS-D, 10/42 FD). Ileocolonoscopy identified ileal inflammation (Rutgeerts equal or greater than 2, SES-CD >3) in 7/24 of the patients with bowel resection and in 5/13 of the non surgical group. Seventy percent (28/40) had BAM (23/26 in the surgical group and 5/14 in the non surgical group).

Mo1678 A New Rapid Test for Fecal Calprotectin (FC) Predicts Mucosa Healing (MH) in Ulcerative Colitis (UC) and Crohn's Disease (CD)

L (OR = 10.64, P 12.9 g/dL (OR = 33.52, P 39.2 g/L” had the best diagnostic accuracy for predicting clinical remission with a percentage of 89% of cases correctly classified and an area under the ROC curve of 0.912 (95% CI, 0.843 to 0.958; P 39.2 g/L” reliably predicts clinical remission.