Publications by authors named "Cecilio Santander"

32 Publications

Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring.

Nutrients 2020 Dec 30;13(1). Epub 2020 Dec 30.

Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain.

A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the "gold standard" method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh-Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients' self-reported gluten consumption was found ( = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.
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http://dx.doi.org/10.3390/nu13010098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824460PMC
December 2020

Giant colon lipoma complicated with intussusception and low digestive hemorragy.

Gastroenterol Hepatol 2021 Feb 26;44(2):126-128. Epub 2020 Sep 26.

Servicio de Aparato Digestivo e Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, España.

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http://dx.doi.org/10.1016/j.gastrohep.2020.05.025DOI Listing
February 2021

Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry.

Aliment Pharmacol Ther 2020 09 17;52(5):798-807. Epub 2020 Jul 17.

Tomelloso, Spain.

Background: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown.

Aims: To assess the effectiveness of PPI therapy for EoE in real-world practice.

Methods: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses.

Results: Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4-9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3-5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype.

Conclusions: Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term.
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http://dx.doi.org/10.1111/apt.15957DOI Listing
September 2020

Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Jan;27(2):268-274

Servicio de Aparato Digestivo, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa & Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.

Background: Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients.

Methods: Eighteen CP and 64 patients with IBD were categorized by diagnoses of Crohn disease (CD) and ulcerative colitis (UC), either endoscopically active (inflamed) or quiescent. Circulating type 1 conventional DC, type 2 conventional DC, plasmacytoid DC, classical monocytes, nonclassical monocytes, and intermediate monocytes were identified by flow cytometry in each individual and characterized for the expression of 18 markers. Association between DC/monocytes and IBD risk was tested by logistic regression. Discriminant canonical analyses were performed to classify the patients in their own endoscopy category considering all markers on each subset.

Results: CCRL1, CCR3, and CCR5 expression on circulating type 1 DC; CCRL1 expression on nonclassical monocytes; and CCR9 and β7 expression on classical monocytes allowed us to discriminate among the different study groups. Indeed, the same markers (excluding β7) were also associated with IBD when all DC and monocyte subsets were considered at the same time.

Conclusions: Monitoring the phenotype of human circulating DC and monocyte subsets may provide novel tools as biomarkers for disease diagnosis (CD/UC) or mucosal status (inflamed/noninflamed) in the absence of an invasive colonoscopy.
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http://dx.doi.org/10.1093/ibd/izaa151DOI Listing
January 2021

Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice.

Clin Gastroenterol Hepatol 2020 Dec 25;18(13):2903-2911.e4. Epub 2020 Jan 25.

Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Instituto de Investigación Sanitaria Princesa, Madrid, Spain; Centro de Investigacion Biomedica en Red Enfermedades Hepáticas y Digestivas, Madrid, Spain. Electronic address:

Background & Aims: Topical steroids, proton pump inhibitors (PPIs), and dietary interventions are recommended first- and second-line therapies for eosinophilic esophagitis (EoE). We investigated differences in their effectiveness in a real-world, clinical practice cohort of patients with EoE.

Methods: We collected data on the efficacy of different therapies for EoE (ability to induce clinical and histologic remission) from the multicenter EoE CONNECT database-a database of patients with a confirmed diagnosis of EoE in Europe that began in 2016. We obtained data from 589 patients, treated at 11 centers, on sex, age, time of diagnosis, starting date of any therapy, response to therapy, treatment end dates, alternative treatments, and findings from endoscopy. The baseline endoscopy was used for diagnosis of EoE; second endoscopy was performed to evaluate response to first-line therapies. After changes in treatment, generally because lack of efficacy, a last endoscopy was performed. The time elapsed between endoscopies depended on the criteria of attending physicians. Clinical remission was defined by a decrease of more than 50% in Dysphagia Symptom Score; improvement in symptoms by less than 50% from baseline was considered as clinical response. Histologic remission was defined as a peak eosinophil count below 5 eosinophils/hpf. A peak eosinophil count between 5 and 14 eosinophils/hpf was considered histologic response. We identified factors associated with therapy selection and effectiveness using χ2 and multinomial logistic regression analyses RESULTS: PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%). Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%). Among the 344 patients who switched to a second-line therapy, dietary interventions were selected for 47.1% of patients, followed by PPIs (for 29.1%) and topical steroids (for 18.6%). Clinical and histologic remission or response was achieved by 80.7% of patients treated with topical steroids, 69.2% of patients given PPIs, and 41.7% of patients on empiric elimination diets. Multivariate analyses found the stricturing phenotype of EoE to be associated with selection of topical steroids over PPIs as the first-line therapy; lack of fibrotic features at initial endoscopy was associated with selection of elimination diets over topical steroids as a second-line therapy. The recruiting center was significantly associated with therapy choice; second-line treatment with topical steroids or PPIs were the only variables associated with clinical and histologic remission.

Conclusions: In an analysis of data from a large cohort of patients with EoE in Europe, we found topical steroids to be the most effective at inducing clinical and histologic remission, but PPIs to be the most frequently prescribed. Treatment approaches vary with institution and presence of fibrosis or strictures.
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http://dx.doi.org/10.1016/j.cgh.2020.01.024DOI Listing
December 2020

Immunomodulatory Effect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease.

Nutrients 2019 Oct 31;11(11). Epub 2019 Oct 31.

Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain.

Bioactive peptides secreted by probiotic (peptide B7) and opportunistic pathogen (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.
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http://dx.doi.org/10.3390/nu11112605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893616PMC
October 2019

Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms.

Therap Adv Gastroenterol 2019 5;12:1756284819857358. Epub 2019 Aug 5.

Servicio de Aparato Digestivo, Hospital Clínico San Carlos, Universidad Complutense, Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain.

Background: Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population.

Methods: In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 μg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling 'better' or 'much better' the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response.

Results: A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1-19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%).

Conclusions: Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.
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http://dx.doi.org/10.1177/1756284819857358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683318PMC
August 2019

Safety and Oncological Outcomes of Bevacizumab Therapy in Patients With Advanced Colorectal Cancer and Self-expandable Metal Stents.

Clin Colorectal Cancer 2019 09 8;18(3):e287-e293. Epub 2019 Jun 8.

Department of Medical Oncology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.

Background: Malignant bowel obstruction can occur in 18% of cases. Self-expandable metal stents (SEMS) can be an alternative to surgery. Bevacizumab (BV) has been associated with bowel perforation, but data on the safety of SEMS for occlusive colon cancer during BV-containing regimens are lacking.

Material And Methods: This is a retrospective analysis of 78 patients with malignant bowel obstruction who underwent placement of SEMS as a palliative intent for stage IV disease. Chemotherapy and BV-containing regimens, stent-related complications, and outcomes were recorded.

Results: Overall, major stent-related complications were observed in 27 (35%) patients: Re-obstruction occurred in 14 (52%) patients, and there were 7 (26%) perforations, 4 (15%) minor bleeding, and 2 (7%) migrations. Sixteen patients received BV; 2 (12.5%) had a perforation. No differences were observed between chemotherapy alone and BV in overall complications. Univariate analysis did not show that BV was more likely to develop perforations, although the incidence was higher in this subset of patients. Kaplan-Meier analysis showed a significant association with longer overall survival for patients treated with systemic therapy (27 vs. 11 months; P ≤ .00001). Also, there is a significant benefit of BV compared with chemotherapy alone (43 vs. 39 months; P = .02).

Conclusion: Placement of SEMS is effective and relatively safe but with an overall complication rate of 35% in the metastatic setting. The major early risk is perforation, which can increase up to 12% during BV treatment. In patients with obstructing advanced colorectal cancer that would benefit from SEMS, we should consider the risks associated with systemic therapies, taking into account the improvement in survival observed with BV.
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http://dx.doi.org/10.1016/j.clcc.2019.05.009DOI Listing
September 2019

Phase IV noninferiority controlled randomized trial to evaluate the impact on diagnostic thinking and patient management and the test-retest reproducibility of the Gaxilose test for hypolactasia diagnosis.

Medicine (Baltimore) 2018 Nov;97(46):e13136

Venter Pharma S.L. Alcobendas, Madrid.

Background: The diagnostic accuracy of the Gaxilose test (GT) for hypolactasia diagnosis has already been proved. The objectives of this clinical trial were to demonstrate the noninferiority of the GT compared to the hydrogen breath test (HBT) on the impact on diagnostic thinking and patient management, to evaluate the GT reproducibility with urine accumulated from 0 to 4 hours and from 0 to 5 hours and to assess test safety.

Methods: We conducted a randomized, parallel, noninferiority clinical trial. Patients with clinical symptoms suggestive of lactose intolerance were screened for inclusion and randomly assigned to the GT arm or the HBT arm of the study. The impact on diagnostic thinking and patient management was analyzed with pretest and posttest questionnaires in which the investigators indicated their estimated probability of hypolactasia diagnosis and the intended management before and after the GT or the HBT (noninferiority margin: -10%). The primary outcome of the study was the impact on diagnostic thinking, expressed as the mean of the absolute values of the differences between the pretest and posttest probabilities of hypolactasia diagnosis. Patients randomized to the GT arm performed also the retest to evaluate the reproducibility of the GT.

Results: A total of 147 patients were included in the intend-to-treat (ITT) population. Among them, 74 performed the HBT and 73 performed the GT. The results proved the noninferiority of the GT compared to the HBT on the impact on diagnostic thinking (ImpactGT = 31.74 ± 23.30%; ImpactHBT = 24.28 ± 19.87%; ΔGT-HBT = 7.46%; 95% confidence interval of ΔGT-HBT: 1.55%, infinite) and on patient management. The test-retest reproducibility was better for the GT with urine accumulated from 0 to 5 h: the intraclass correlation coefficient (ICC) was 0.5761, and the Kappa coefficient was 0.7548, indicative of substantial agreement between both tests. No serious adverse events were reported during the study.

Conclusions: The GT has an impact on diagnostic thinking and patient management noninferior to that of the HBT, is reproducible and well tolerated. These results prove the clinical benefit of its use in the clinical practice (ClinicalTrials.gov identifier: NCT02636413).
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http://dx.doi.org/10.1097/MD.0000000000013136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257416PMC
November 2018

Irritable bowel syndrome: How to improve decision making in clinical practice.

Med Clin (Barc) 2018 12 20;151(12):489-497. Epub 2018 Sep 20.

Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, España.

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder, characterised by the presence of recurrent abdominal pain associated with changes in bowel habits. Its physiopathology is complex, its clinical manifestations are diverse, and the therapeutic possibilities are multiple and not well known. In clinical practice, the diagnosis of IBS represents an important challenge; this means that in many cases the patients do not receive the proper diagnosis, which implies an absence of a targeted treatment, and therefore bad symptomatic control. In this article, the fundamental questions posed by the doctor when dealing with a patient with symptoms compatible with IBS are presented chronologically. The main objective is to provide clinical and eminently practical information that facilitates the management of patients with IBS, from both diagnostic and therapeutic points of view.
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http://dx.doi.org/10.1016/j.medcli.2018.06.020DOI Listing
December 2018

Colon lymphomas: an analysis of our experience over the last 23 years.

Rev Esp Enferm Dig 2018 Dec;110(12):762-767

Aparato Digestivo, Hospital Universitario La Princesa, España.

Introduction: colon lymphoma (CL) is an uncommon variety of non-Hodgkin lymphoma (NHL) that represents less than 0.6% of all primary colonic neoplasms. Early diagnosis is challenging as clinical manifestations are non-specific. The goal of this review was to discuss our experience over the last few years regarding the clinical, endoscopic, histological, diagnostic, therapeutic and evolutionary characteristics of CL.

Patients And Methods: a retrospective, descriptive analysis of patients with CL diagnosed from 1994 to 2016 at the Hospital Universitario de La Princesa (Madrid, Spain) was performed.

Results: a total of 29 patients with CL were identified, with a median age of 67 years; 18 were male (62%). The most common clinical manifestations included abdominal pain, constitutional syndrome, diarrhea and a palpable abdominal mass. Eight (27.6%) patients were asymptomatic and six (20.6%) initially presented with surgical complications. A colonoscopy was performed in 24 patients and the most common findings included diffuse infiltration and solid growth. The most common location was the descending and sigmoid colon. The most common histological subtypes included mantle B-cell NHL and diffuse large B-cell lymphoma. Chemotherapy was administered to 28 patients (96.5%), surgery was performed in six (20.7%) and combined chemo-radiotherapy was administered to one patient. Median survival was 156 months. Survival was 100.0% at one year and 55.0% at ten years.

Conclusions: due to the variable aspects of CL on endoscopy, a histological study of all colonic segments is required. Chemotherapy is the treatment of choice and emergency surgery followed by chemotherapy is required for complications. Primary factors associated with poorer survival include age above 65 years, relapsing disease and partial or nil responses.
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http://dx.doi.org/10.17235/reed.2018.5445/2017DOI Listing
December 2018

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study.

J Allergy Clin Immunol 2018 04 23;141(4):1365-1372. Epub 2017 Oct 23.

Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain; Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain. Electronic address:

Background: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers.

Objective: We sought to assess the effectiveness of a step-up dietary strategy for EoE.

Methods: We performed a prospective study conducted in 14 centers. Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten-containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food-group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy.

Results: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%.

Conclusions: A TFGED diet achieves EoE remission in 43% of children and adults. A step-up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process.
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http://dx.doi.org/10.1016/j.jaci.2017.08.038DOI Listing
April 2018

Prevalence of Malnutrition and Nutritional Characteristics of Patients With Inflammatory Bowel Disease.

J Crohns Colitis 2017 Dec;11(12):1430-1439

Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain.

Background And Aims: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients.

Methods: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance.

Results: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition.

Conclusions: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.
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http://dx.doi.org/10.1093/ecco-jcc/jjx102DOI Listing
December 2017

Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults.

United European Gastroenterol J 2017 Apr 23;5(3):335-358. Epub 2017 Jan 23.

Department of Health Services Research, Durham University, UK.

Introduction: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE.

Methods: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes.

Results: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice.

Conclusion: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.
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http://dx.doi.org/10.1177/2050640616689525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415218PMC
April 2017

Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal dysmotility patients.

Ann N Y Acad Sci 2017 05 31;1395(1):60-66. Epub 2017 Jan 31.

Universitat Autònoma de Barcelona, Hospital de Mataró, Barcelona, Spain.

High-resolution manometry (HRM) is currently the most important diagnostic test for esophageal motility disorders, providing information on the contraction pattern of the circular muscle layer, which helps classify these esophageal motor diseases. However, with the increasing development of ultrasound, other techniques, such as high-frequency intraluminal ultrasound (HFIUS), have gained importance. This technique uses a flexible shaft with a central wire integrated into a standard endoscope, which facilitates real-time sonography. Its main utility is to provide anatomical information on the structure of the esophageal wall, including both the circular and longitudinal layers that constitute the esophageal muscularis propria. Increasing knowledge about these motility disorders has led to the hypothesis that, in addition to an abnormal contraction pattern of the circular muscle, an overall increased muscle thickness and an abnormal longitudinal muscle contraction could be added as pathophysiological factors. The increase in muscle thickness could be an important indicator of the severity of diseases, such as achalasia, distal esophageal spasm, or hypercontractile esophagus. More studies are required before definitive conclusions can be reached, but HFIUS employed simultaneously with HRM could provide a more complete and precise evaluation of these esophageal motor disorders.
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http://dx.doi.org/10.1111/nyas.13313DOI Listing
May 2017

Non-responsive coeliac disease: Coeliac crisis vs. refractory coeliac disease with response to corticosteroids.

Gastroenterol Hepatol 2017 10 17;40(8):529-530. Epub 2016 Aug 17.

Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, España.

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http://dx.doi.org/10.1016/j.gastrohep.2016.07.003DOI Listing
October 2017

Portal hypertensive polyps, a new entity?

Rev Esp Enferm Dig 2016 May;108(5):279-80

Aparato Digestivo, Hospital Universitario de La Princesa, España.

We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP).
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May 2016

Impaired esophageal motor function in eosinophilic esophagitis.

Rev Esp Enferm Dig 2015 Oct;107(10):622-9

Aparato Digestivo, Hospital de La Princesa, España.

Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the esophagus that represents a major cause of digestive morbidity among the pediatric and young adult populations. Despite the fact that key symptoms in adults include dysphagia and food impaction, many patients lack structural changes in the esophagus to account for their complaints, which suggests the presence of underlying motor disorders and esophageal distensibility impairment. In the last few years the esophageal motility of these patients has been studied using various approaches, most particularly high-resolution manometry, ambulatory manometry, and impedance planimetry. This review focuses on the most relevant findings and scientific evidence regarding esophageal motor disorders in eosinophilic esophagitis.
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http://dx.doi.org/10.17235/reed.2015.3801/2015DOI Listing
October 2015

Normal values for water-perfused esophageal high-resolution manometry.

Rev Esp Enferm Dig 2015 Jun;107(6):354-8

Background: Normal values for water-perfused esophageal high-resolution manometry have still not been established in our environment, despite its generalized use and the recommendation to determine reference values for each Motility Unit based on their equipment. Normal values established with solid-state highresolution manometry are currently being used as reference values for water-perfused high-resolution manometry.

Objectives: To obtain normal values for water-perfused esophageal high-resolution manometry, based on the esophageal motility analysis of healthy subjects.

Methods: 16 healthy volunteers without history of digestive complaints or esophageal symptoms were included. 22-channel water-perfused high-resolution manometry was performed.

Results: Normal values were calculated as 5th-95th percentile ranges for the following parameters; upper esophageal sphincter resting pressure (UESRP) (40-195 mmHg); upper esophageal sphincter residual pressure (UESResP) (30-115 mmHg), contractile front velocity (CFV) (2.4-7.1 cm/s), distal contractile integral (DCI) (285-2820 mmHg.s.cm), distal contraction latency (DL) (6.1-10.9 s), intrabolus pressure (IBP) (7-19 mmHg), integrated relaxation pressure (IRP 4s) (2-20 mmHg), lower esophageal sphincter resting pressure(LESRP) (5-54 mmHg), esophageal shortening (Es) (0.3-1.3 cm) and lower esophageal sphincter lift (LESL) (0,1-1,2 cm).

Conclusion: Normal values for the most important parameters (such as IRP 4s, DL and CFV), obtained using a 22-channel waterperfused system resemble previously published data from other perfusion devices. However, there exist small but significant variations compared with values established with solid-state highresolution manometry. Thus, when using water-perfused catheters, caution is required when normative values are used that were established with solid-state catheters.
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June 2015

Hypercontractile esophagus: Clinical context and motors findings in high resolution manometry.

Rev Esp Enferm Dig 2015 May;107(5):274-9

Background: Hypercontractile esophagus (HE) is a primary hypercontractile disorder of the esophageal musculature not frequently seen in the general population. It is characterized by the presence of at least one contraction with a very high amplitude and duration (DCI > 8,000 mmHg/s/cm) in patients with esophageal symptoms. The aim of our study was to assess the clinical context and manometric characteristics in patients with HE using highresolution manometry (HRM).

Methods: We thoroughly reviewed the clinical features and manometric findings of a total of 720 patients with esophageal symptoms that were attended in the Department of Gastroenterology of our hospital between June 2011 and June 2013.

Results: We found seven patients that met criteria for HE according to the Chicago Classification (2012). All of the patients were women (100%). Mean age was 64 years old. Most frequent symptoms were: Chest pain, dysphagia and heartburn.In one patient (14%) the HE was related to a gastroesophageal reflux disease (GERD) and gastroesophageal junction (GEJ) outflow obstruction. Three patients (43%) had more than one hypercontractile contraction in the study. Four patient (57%) hade multipeaked pattern (Jackhammer esophagus) and y two of them were synchronized with respiration. Two patients (29%) were diagnosed with hiatus hernias. Integrated relaxation pressure (IRP) was not higher in hypercontractile contractions than in normal contractions. Only one patient presented a slight alteration of the relaxation (IRP-4s = 15 mmHg) with normal peristalsis, GEJ outflow obstruction and not multipeakeded pattern. One patient presented pathological acid exposure (PAE) in 24-hours pH-metry.

Conclusions: HE is a rare disorder and HRM is essential for its correct diagnosis and characterization. The treatment of HE should achieve the disappearance or at least improvement of the patient´s symptoms and avoid unnecessary diagnostic testing.
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May 2015

Usefulness of applying lidocaine in esophagogastroduodenoscopy performed under sedation with propofol.

World J Gastrointest Endosc 2013 May;5(5):231-9

Felipe de la Morena, Carlos Esteban, Beatriz de Cuenca, Endoscopy Unit, Department of Gastroenterology, Hospital Universitario Infanta Cristina, CP 28981 Parla, Madrid, Spain.

Aim: To determine whether topical lidocaine benefits esophagogastroduoduenoscopy (EGD) by decreasing propofol dose necessary for sedation or procedure-related complications.

Methods: The study was designed as a prospective, single centre, double blind, randomised clinical trial and was conducted in 2012 between January and May (NCT01489891). Consecutive patients undergoing EGD were randomly assigned to receive supplemental topical lidocaine (L; 50 mg in an excipient solution which was applied as a spray to the oropharynx) or placebo (P; taste excipients solution without active substance, similarly delivered) prior to the standard propofol sedation procedure. The propofol was administered as a bolus intravenous (iv) dose, with patients in the L and P groups receiving initial doses based on the patient's American Society of Anaesthesiologists (ASA) classification (ASA I-II: 0.50-0.60 mg/kg; ASA III-IV: 0.25-0.35 mg/kg), followed by 10-20 mg iv dose every 30-60 s at the anaesthetist's discretion. Vital signs, anthropometric measurements, amount of propofol administered, sedation level reached, examination time, and the subjective assessments of the endoscopist's and anaesthetist's satisfaction (based upon a four point Likert scale) were recorded. All statistical tests were performed by the Stata statistical software suite (Release 11, 2009; StataCorp, LP, College Station, TX, United States).

Results: No significant differences were found between the groups treated with lidocaine or placebo in terms of total propofol dose (310.7 ± 139.2 mg/kg per minute vs 280.1 ± 87.7 mg/kg per minute, P = 0.15) or intraprocedural propofol dose (135.3 ± 151.7 mg/kg per minute vs 122.7 ± 96.5 mg/kg per minute, P = 0.58). Only when the L and P groups were analysed with the particular subgroups of female, < 65-year-old, and lower anaesthetic risk level (ASA I-II) was a statistically significant difference found (L: 336.5 ± 141.2 mg/kg per minute vs P: 284.6 ± 91.2 mg/kg per minute, P = 0.03) for greater total propofol requirements). The total incidence of complications was also similar between the two groups, with the L group showing a complication rate of 32.2% (95%CI: 21.6-45.0) and the P group showing a complication rate of 26.7% (95%CI: 17.0-39.0). In addition, the use of lidocaine had no effect on the anaesthetist's or endoscopist's satisfaction with the procedure. Thus, the endoscopist's satisfaction Likert assessments were equally distributed among the L and P groups: unsatisfactory, [L: 6.8% (95%CI: 2.2-15.5) vs P: 0% (95%CI: 0-4.8); neutral, L: 10.1% (95%CI: 4.2-19.9) vs P: 15% (95%CI: 7.6-25.7)]; satisfactory, [L: 25.4% (95%CI: 10-29.6) vs P: 18.3% (95%CI: 15.5-37.6); and very satisfactory, L: 57.6% (95%CI: 54-77.7) vs P: 66.6% (95%CI: 44.8-69.7)]. Likewise, the anaesthetist's satisfaction Likert assessments regarding the ease of maintaining a patient at an optimum sedation level without agitation or modification of the projected sedation protocol were not affected by the application of lidocaine, as evidenced by the lack of significant differences between the scores for the placebo group: unsatisfactory, L: 5.8% (95%CI: 1.3-13.2) vs P: 0% (95%CI: 0-4.8); neutral, L: 16.9% (95%CI: 8.9-28.4) vs P: 16.7% (95%CI: 8.8-27.7); satisfactory, L: 15.2% (95%CI: 7.7-26.1) vs P: 20.3% (95%CI: 11.3-31.6); and very satisfactory, L: 62.7% (95%CI: 49.9-74.3) vs P: 63.3% (95%CI: 50.6-74.7).

Conclusion: Topical pharyngeal anaesthesia is safe in EGD but does not reduce the necessary dose of propofol or improve the anaesthetist's or endoscopist's satisfaction with the procedure.
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http://dx.doi.org/10.4253/wjge.v5.i5.231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653022PMC
May 2013

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

Gastrointest Endosc 2013 Aug 25;78(2):333-341.e1. Epub 2013 Apr 25.

Department of Gastroenterology, Hospital del Mar. Cancer Research Program, IMIM Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona Pompeu Fabra University, Barcelona, Catalonia, Spain.

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.
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http://dx.doi.org/10.1016/j.gie.2013.03.003DOI Listing
August 2013

Pathophysiological bases of eosinophilic esophagitis therapy.

Inflamm Allergy Drug Targets 2013 Feb;12(1):46-53

Alergología Clínica (Servicio de Medicina Interna), Hospital Rey Juan Carlos I, Móstoles, Madrid, Spain.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of unknown etiology, presenting a dense mucosal infiltration of eosinophils that is not reversible with proton pump inhibitor therapy. Endoscopy has reported EoE commonly polymorphous disease with subtle mucosal changes, accompanied by variations in the caliber of the esophagus. The suggestion of EoE as an allergic disease is still short of evidence and recently, it has only been confirmed that the esophagus mucosal layer infiltrated by eosinophils may determine an association with allergy after exposure to allergens. A comprehensive review of symptoms, risk factors, diagnoses and mechanisms involved in the pathogenesis of EoE was carried out, with an analysis of the different treatment options available for this disease firmly maximizing in incidence and prevalence. The management of EoE is multidisciplinary and can involve gastroenterologists, pathologists, allergists and dietitians, particularly in pediatric patients, because dietary food restrictions appear to be more beneficial in children versus adults. EoE can successfully be treated with topical corticosteroids, which eliminate the clinical manifestations and histological lesions in most cases. Prolonged treatment is advised for EoE because it recurs frequently, particularly on discontinuation of therapy. Experimental treatments using immunotherapy are being investigated, but their safety and efficacy are yet to be defined.
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http://dx.doi.org/10.2174/1871528111312010007DOI Listing
February 2013

Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.

N Engl J Med 2012 Feb;366(8):697-706

Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain.

Background: Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population.

Methods: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations.

Results: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001).

Conclusions: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).
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http://dx.doi.org/10.1056/NEJMoa1108895DOI Listing
February 2012

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry.

J Gastroenterol Hepatol 2011 Sep;26(9):1447-50

Department of Gastroenterology and Hepatology, País Vasco University, Donostia Hospital, San Sebastián, Spain.

Background And Aim: Esophageal motility abnormalities, as measured by conventional manometry (CM), are non-specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high-resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction.

Methods: All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed.

Results: HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan-esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan-esophageal pressurization in controls. Nine of 10 patients with pan-esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings.

Conclusions: The most frequent esophageal motor abnormality measured by HRM was a pan-esophageal pressurization. Bolus impaction in patients with EoE was associated with pan-esophageal pressurization.
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http://dx.doi.org/10.1111/j.1440-1746.2011.06770.xDOI Listing
September 2011

Prospective evaluation of a clinical guideline recommending early patients discharge in bleeding peptic ulcer.

J Gastroenterol Hepatol 2010 Sep;25(9):1525-9

Gastroenterology Unit, La Princesa University Hospital and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.

Background And Aim: To validate an early discharge policy in patients admitted with upper gastrointestinal bleeding (UGIB) due to ulcers.

Methods: Patients with gastroduodenal ulcer or erosive gastritis/duodenitis were included in a previous study aiming to develop a practice guideline for early discharge of patients with UGIB. Variables associated with unfavorable evolution were analyzed in order to identify patients with low-risk of re-bleeding. After that, a one-year prospective analysis of all UGIB episodes was carried out.

Results: A total of 341 patients were identified in the retrospective study. Variables associated with unfavorable evolution were: systolic blood pressure < or = 100 mmHg, heart rate > or = 100 bpm, and a Forrest endoscopic classification of severe. 10% of patients were immediately discharged; however, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 34% of patients. A total of 77 patients were included in the prospective analysis. Although only 19.5% of patients were immediately discharged without complications, 29 patients (37.7%) were theoretically suitable for early discharge.

Conclusions: Patients with UGIB who have clean-based ulcers and are stable on admission can be safely discharged immediately after endoscopy. Implementation of the clinical practice guideline safely reduced hospital admission for those patients.
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http://dx.doi.org/10.1111/j.1440-1746.2010.06374.xDOI Listing
September 2010

[Questions and answers in gastroenterology].

Gastroenterol Hepatol 2008 Jun-Jul;31(6):388-9

Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

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http://dx.doi.org/10.1157/13123606DOI Listing
October 2008

[Upper digestive hemorrhage due to aortoesophageal fistula].

Gastroenterol Hepatol 2006 Jun-Jul;29(6):338-40

Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Madrid, Spain.

We describe the case of a 60-year-old woman who presented with thoracic pain followed by hematemesis. Aortoesophageal fistula was diagnosed. Double aortic and esophageal protheses were placed with good clinical outcome. After 15 days, the patient presented migration of the esophageal prothesis and a further endoscopic examination was performed. A fishbone was visualized in the fistula orifice.
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http://dx.doi.org/10.1157/13089713DOI Listing
September 2006

Factors influencing the rate of fibrosis progression in chronic hepatitis C.

Dig Dis Sci 2004 Nov-Dec;49(11-12):1971-6

Fundación Hospital Alcorcón, Av Budapest 1, 28922 Madrid, Spain.

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.
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http://dx.doi.org/10.1007/s10620-004-9603-2DOI Listing
January 2005