Niveles séricos de IGF-1 e IGFBP-3 en pacientes con esófago de Barrett y adenocarcinoma de esófago. Estudio longitudinal / Serological levels of IGF-1 and IGFBP-3 in patients with Barrett's esophagus and esophageal adenocarcinoma: Longitudinal study

Antecedentes: El esófago de Barrett (EB) es una entidad con una progresión histológica a malignidad conocida. Los factores de crecimiento insulínico (IGF, de insulin-like growth factor) están involucrados en la carcinogénesis asociada a la obesidad y se han asociado con el riesgo de padecer algunos tipos de cáncer. Objetivos: Evaluar los niveles serológicos de IGF-1 e IGFBP-3 en pacientes con EB y adenocarcinoma de esófago. Pacientes y métodos: Estudio prospectivo de pacientes con EB y adenocarcinoma de esófago explorados con gastroscopia entre septiembre 2012 y diciembre 2015 a los que se realizó una extracción de sangre para la determinación de IGF-1 e IGFBP-3. Se incluyó un grupo control. Resultados: Se incluyeron 116 pacientes: 36 controles, 62 con EB (42 sin displasia y 20 con displasia) y 18 con adenocarcinoma. El IGF-1 y la ratio molar IGF-1/IGFBP-3 presentaron un aumento progresivo en los grupos con EB y adenocarcinoma comparado con los controles (IGF-1: 135,55±66,07ng/ml; 148,33±81,5ng/ml; 108,19±46,69ng/ml, respectivamente; p=0,049) (ratio molar: 0,23±0,91; 0,29±0,11; 0,19±0,06, respectivamente; p=0,001), sin diferencias entre los diferentes grados histológicos. Cincuenta y cuatro de los 65 pacientes con EB fueron seguidos durante una mediana de 58,50 meses (12-113) y 11 de ellos (20,4%) presentaron progresión a displasia de bajo grado (n=8) o displasia de alto grado/adenocarcinoma (n=3), sin encontrar diferencias en el sistema IGF comparado con los que no progresaron. Conclusiones: Los pacientes con EB y adenocarcinoma esofágico presentan cambios en el sistema IGF aunque los niveles de IGF-1 e IGFBP-3 no se correlacionan con la progresión histológica del EB.(AU)

Background: Barrett's esophagus (BE) is an entity with a known histological progression to malignancy. The insulin-like growth factor (IGF) system is involved in the carcinogenesis through obesity-related mechanisms that include IGF and it has been associated with several types of cancer. Objectives: To evaluate the serological levels of IGF-1 and IGFBP-3 in patients with BE and esophageal adenocarcinoma. Patients and methods: Prospective study of patients with BE and esophageal adenocarcinoma who underwent upper endoscopy between September 2012 and December 2015. A baseline determination of IGF-1 and IGFBP-3 was performed. We included a control group of patients without BE. Results: One hundred sixteen patients were included: 36 controls, 62 with BE (42 without dysplasia and 20 with dysplasia) and 18 with adenocarcinoma. IGF-1 and IGF-1/IGFBP-3 molar ratio showed a progression to high levels in BE and adenocarcinoma than in controls (IGF-1: 135.55±66.07ng/ml, 148.33±81.5ng/ml, 108.19±46.69ng/ml, respectively; P=.049) (molar ratio: 0.23±0.91, 0.29±0.11, 0.19±0.06, respectively; P=.001), without differences between the histological types of BE. Fifty-four out of the 65 patients with BE were followed up (median of 58.50 months, range 12–113) and 11 of them (20.4%) presented progression to low-grade dysplasia (n=8) or high-grade dysplasia/adenocarcinoma (n=3), without differences in the IGF system compared with patients without progression. Conclusions: Patients with BE and esophageal adenocarcinoma have changes in the IGF system although the serological levels of IGF-1 and IGFBP-3 do not correlate with histological progression of BE.(AU)

Serological levels of IGF-1 and IGFBP-3 in patients with Barrett's esophagus and esophageal adenocarcinoma: Longitudinal study. / Niveles séricos de IGF-1 e IGFBP-3 en pacientes con esófago de Barrett y adenocarcinoma de esófago. Estudio longitudinal.

BACKGROUND: Barrett's esophagus (BE) is an entity with a known histological progression to malignancy. The insulin-like growth factor (IGF) system is involved in the carcinogenesis through obesity-related mechanisms that include IGF and it has been associated with several types of cancer. OBJECTIVES: To evaluate the serological levels of IGF-1 and IGFBP-3 in patients with BE and esophageal adenocarcinoma. PATIENTS AND METHODS: Prospective study of patients with BE and esophageal adenocarcinoma who underwent upper endoscopy between September 2012 and December 2015. A baseline determination of IGF-1 and IGFBP-3 was performed. We included a control group of patients without BE. RESULTS: One hundred sixteen patients were included: 36 controls, 62 with BE (42 without dysplasia and 20 with dysplasia) and 18 with adenocarcinoma. IGF-1 and IGF-1/IGFBP-3 molar ratio showed a progression to high levels in BE and adenocarcinoma than in controls (IGF-1: 135.55±66.07ng/ml, 148.33±81.5ng/ml, 108.19±46.69ng/ml, respectively; P=.049) (molar ratio: 0.23±0.91, 0.29±0.11, 0.19±0.06, respectively; P=.001), without differences between the histological types of BE. Fifty-four out of the 65 patients with BE were followed up (median of 58.50 months, range 12-113) and 11 of them (20.4%) presented progression to low-grade dysplasia (n=8) or high-grade dysplasia/adenocarcinoma (n=3), without differences in the IGF system compared with patients without progression. CONCLUSIONS: Patients with BE and esophageal adenocarcinoma have changes in the IGF system although the serological levels of IGF-1 and IGFBP-3 do not correlate with histological progression of BE.

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

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

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

BACKGROUND AND AIM: In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence. METHODS: A follow-up study was carried-out including 649 patients, diagnosed with PL between 1995-2004 in 9 participating hospitals from Spain, and who repeated the biopsy during 2011-2013. Medical information and habits were collected through a questionnaire. Based on morphology, IM was sub-classified as complete (small intestinal type, CIM) and incomplete (colonic type, IIM). Analyses were done using Cox (HR) models. RESULTS: At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34% IIM, and 4% dysplasia. Mean follow-up was 12 years. 24 patients (3.7%) developed a gastric adenocarcinoma during follow-up. The incidence rate of GC was 2.76 and 5.76 per 1,000 person-years for those with CIM and IIM, respectively. The HR of progression to CG was 2.75 (95% CI 1.06-6.26) for those with IIM compared with those with CIM at baseline, after adjusting for sex, age, smoking, family history of GC and use of NSAIDs. CONCLUSIONS: IIM is the PL with highest risk to progress to GC. Sub-typing of IM is a valid procedure for the identification of high risk patients that require more intensive surveillance.

Prevalencia y características epidemiológicas del esófago de Barrett en la provincia de Barcelona / Prevalence and epidemiology of Barrett's esophagus in the province of Barcelona

INTRODUCCIÓN: La prevalencia del esófago de Barrett (EB) es del 0,45-2,2% en los pacientes que se realizan una endoscopia digestiva alta y superior al 12% si la indicación es por síntomas de reflujo, habiéndose descrito un aumento progresivo en los últimos años. Sin embargo, se desconoce cuál es la prevalencia de esta entidad en la provincia de Barcelona. OBJETIVOS: Determinar la prevalencia del EB y sus características epidemiológicas en nuestro medio. PACIENTES Y MÉTODOS: Se evaluaron de forma prospectiva pacientes que acudieron a las Unidades de Endoscopia del Hospital Clínic y Hospital General de Catalunya para la realización de una endoscopia digestiva alta. Se excluyeron pacientes con EB conocido, endoscopia digestiva alta previa, cirugía esófagogástrica o negativa de participar en el estudio. Se registraron datos demográficos, consumo de alcohol y tabaco, infección por Helicobacter pylori (H. pylori) y consumo de antisecretores, entre otros. Los participantes completaron un cuestionario estandarizado para valorar la presencia de síntomas de reflujo gastroesofágico (RGE) y su severidad. RESULTADOS: Entre julio 2010 y julio 2012 se incluyeron 200 pacientes (100 en cada centro). La media de edad fue de 48,9 ± 15,6 y la mayoría eran mujeres (n = 120, 60%). Cuarenta y seis pacientes (23%) tenían síntomas de RGE y 31 (15,5%) presentaron algún grado de esofagitis. La infección por H. Pylori estaba presente en 29,7%. En 14 (7%) pacientes hubo sospecha endoscópica de EB, con confirmación histológica en 8 (4%). La única variable que se correlacionó con el hallazgo de EB fue el género masculino. CONCLUSIÓN: La prevalencia de EB en nuestro medio es similar a la descrita en los países occidentales. La ausencia de síntomas de reflujo no descarta la posibilidad de EB

INTRODUCTION: The prevalence of Barrett's esophagus (BE) varies from 0.45% to 2.2% in patients who undergo upper endoscopy and is >12% when the indication is for reflux symptoms. The prevalence has progressively increased in recent years but is unknown in the population of the province of Barcelona. OBJECTIVES: To determine the prevalence of BE and its epidemiological characteristics in our population. PATIENTS AND METHODS: We prospectively evaluated patients referred to the Endoscopy Unit of Hospital Clinic and Hospital General de Catalunya for an upper endoscopy. We excluded patients with known BE, prior upper endoscopy, esophagogastric surgery or refusal to participate in the study. Demographic data, alcohol intake, Helicobacter pylori infection and consumption of antisecretory agents were recorded, among other information. Participants completed a standardized questionnaire to assess the presence of gastroesophageal reflux disease (GERD) symptoms and their severity. RESULTS: Between July 2010 and July 2012, we included 200 patients (100 in each center). The mean age was 48.9±15.6 years and the majority were women (n=120, 60%). Symptoms of GERD were present in 46 patients (23%) and some degree of esophagitis was present in 31 (15.5%). Infection by H. pylori was present in 29.7%. BE was found endoscopically in 14 (7%) patients, but was histologically confirmed in only 8 (4%). The only variable that correlated with the finding of BE was male sex. CONCLUSION: The prevalence of BE in our environment is similar to that reported in Western countries. The absence of reflux symptoms does not rule out the possibility of BE

[Prevalence and epidemiology of Barrett's esophagus in the province of Barcelona]. / Prevalencia y características epidemiológicas del esófago de Barrett en la provincia de Barcelona.

INTRODUCTION: The prevalence of Barrett's esophagus (BE) varies from 0.45% to 2.2% in patients who undergo upper endoscopy and is >12% when the indication is for reflux symptoms. The prevalence has progressively increased in recent years but is unknown in the population of the province of Barcelona. OBJECTIVES: To determine the prevalence of BE and its epidemiological characteristics in our population. PATIENTS AND METHODS: We prospectively evaluated patients referred to the Endoscopy Unit of Hospital Clinic and Hospital General de Catalunya for an upper endoscopy. We excluded patients with known BE, prior upper endoscopy, esophagogastric surgery or refusal to participate in the study. Demographic data, alcohol intake, Helicobacter pylori infection and consumption of antisecretory agents were recorded, among other information. Participants completed a standardized questionnaire to assess the presence of gastroesophageal reflux disease (GERD) symptoms and their severity. RESULTS: Between July 2010 and July 2012, we included 200 patients (100 in each center). The mean age was 48.9 ± 15.6 years and the majority were women (n=120, 60%). Symptoms of GERD were present in 46 patients (23%) and some degree of esophagitis was present in 31 (15.5%). Infection by H. pylori was present in 29.7%. BE was found endoscopically in 14 (7%) patients, but was histologically confirmed in only 8 (4%). The only variable that correlated with the finding of BE was male sex. CONCLUSION: The prevalence of BE in our environment is similar to that reported in Western countries. The absence of reflux symptoms does not rule out the possibility of BE.

Bolivian migrants with Chagas disease in Barcelona, Spain: a qualitative study of dietary changes and digestive problems.

Due to international migration, Chagas disease, endemic in Latin America, has become more common in non-endemic areas. Chronic Chagas disease can cause damage to the digestive system leading to constipation. However, a range of factors influences constipation and a better understanding of the role of non-Chagas related factors is required to improve management of Chagas-related digestive problems. This study explores perceptions of constipation and changes in food and exercise habits amongst Bolivians in Barcelona, Spain. Bolivian migrants attending the Tropical Medicine Unit (Hospital Clínic, Barcelona) were interviewed about their food habits in Spain and Bolivia, migratory experience, work and leisure activities. Chagas seropositive participants also received radiological examinations. Bolivian migrants experienced dietary changes, influenced by work-related factors, which included reductions in quantities of food and liquid consumed. Almost half the participants reported changes in digestive rhythm since arriving in Spain. Constipation, which was common, in some cases was only recounted during interviews. Bolivian migrants' constipation may be associated with chronic Chagas disease or migration-related dietary changes. Careful questioning using the Rome III criteria is however required to ensure its diagnosis. Radiological studies are also required to confirm the role of Chagas disease and identify potentially serious intestinal damage.