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1.
Clin Transl Gastroenterol ; 11(4): e00151, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32251017

RESUMEN

INTRODUCTION: We aimed to estimate the effects of a family history of colorectal cancer (CRC) or esophageal cancer on the risk of Barrett's esophagus (BE) and identify variants in cancer genes that may explain the association. METHODS: Men scheduled for screening colonoscopy were recruited to undergo upper endoscopy. Cases and noncases were screenees with and without BE, respectively. The effects of family histories on BE were estimated with logistic regression, adjusting for the potential confounders. We additionally recruited men recently diagnosed with BE by clinically indicated endoscopies. Banked germline DNA from cases of BE with ≥2 first-degree relatives (FDRs) with CRC and/or an FDR with esophageal cancer underwent next-generation sequencing using a panel of 275 cancer genes. RESULTS: Of the 822 men screened for CRC who underwent upper endoscopy, 70 were newly diagnosed with BE (8.5%). BE was associated with family histories of esophageal cancer (odds ratio = 2.63; 95% confidence interval = 1.07-6.47) and CRC in ≥2 vs 0 FDRs (odds ratio = 3.73; 95% confidence interval = 0.898-15.4). DNA analysis of subjects with both BE and a family history of cancer identified one or more germline variants of interest in genes associated with cancer predisposition in 10 of 14 subjects, including the same novel variant in EPHA5 in 2 unrelated individuals. DISCUSSION: We found an increased risk for BE associated with a family history of esophageal cancer or CRC. Although analysis of germline DNA yielded no clinically actionable findings, discovery of the same EPHA5 variant of uncertain significance in 2 of 14 cases merits additional investigation.


Asunto(s)
Esófago de Barrett/genética , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Esofágicas/epidemiología , Anamnesis/estadística & datos numéricos , Anciano , Esófago de Barrett/diagnóstico , Esófago de Barrett/epidemiología , Esófago de Barrett/patología , Estudios de Casos y Controles , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Análisis Mutacional de ADN , Neoplasias Esofágicas/genética , Esofagoscopía , Esófago/diagnóstico por imagen , Esófago/patología , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo
2.
Clin Gastroenterol Hepatol ; 16(6): 862-869.e3, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29432922

RESUMEN

BACKGROUND & AIMS: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Guidelines recommend that patients with nondysplastic BE (NDBE) undergo surveillance endoscopy every 3-5 years. We aimed to identify factors associated with surveillance endoscopy of patients with NDBE and identify trends in appropriate surveillance endoscopy of NDBE at a large tertiary care center. METHODS: We performed a retrospective analysis of data from a Barrett's Esophagus Registry, identifying patients with NDBE who underwent endoscopy in 2002 or later. We identified patients with NDBE and collected data on length of BE segment, esophageal lesions, demographic features, medications, histology findings, comorbidities, development of EAC, and dates of follow-up endoscopies. We defined appropriate surveillance as 3-5 years between 2nd and 3rd endoscopies, over-utilizers as patients who had less than 3 years between their 2nd and 3rd endoscopies, under-utilizers as patients who had more than 5 years between their 2nd and 3rd endoscopies; and never-surveilled as patients who never received a 2nd endoscopy. The primary outcomes were effects of patient factors, year, and referring providers on appropriateness of surveillance intervals. RESULTS: We identified 477 patients with NDBE. Only 15.9% had appropriate surveillance; 37.9% were over-utilizers 15.7% were under-utilizers and 30.4% were never surveilled. Patients were less likely to be over-surveilled if their primary care physician referred them for their 3rd endoscopy instead of a gastroenterologist (adjusted odds ratio, 0.51; 95% CI, 0.27-0.95). Male patients or those with an increased number of comorbidities were more likely to be under-surveilled or never-surveilled, whereas patients with long BE segment were more likely to be over-surveilled. CONCLUSIONS: In a retrospective analysis of data from a registry of patients with BE, we found that less than 16% receive appropriate surveillance for NDBE. A primary care provider in the same health system as the endoscopy clinic reduced risk of over-surveillance. This could reflect better coordination of care between specialists and primary care providers.


Asunto(s)
Adenocarcinoma/diagnóstico , Esófago de Barrett/complicaciones , Detección Precoz del Cáncer/estadística & datos numéricos , Endoscopía Gastrointestinal/estadística & datos numéricos , Neoplasias Esofágicas/diagnóstico , Utilización de Instalaciones y Servicios/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria
3.
Gut ; 63(2): 230-5, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23461896

RESUMEN

OBJECTIVE: Abdominal obesity has been associated with erosive oesophagitis (EO) and Barrett's oesophagus (BO). As gluteofemoral obesity protects against diabetes mellitus and cardiovascular disease, we hypothesised that gluteofemoral obesity would be inversely associated with EO and BO. DESIGN: We conducted a cross-sectional study on 822 male colorectal cancer screenees who were recruited to also undergo upper endoscopy. An additional 80 patients with BO clinically detected by upper endoscopy referred for clinical indications were recruited shortly after their diagnoses of BO. Logistic regression was used to estimate the effects of abdominal obesity (waist circumference), gluteofemoral obesity (hip circumference) and waist-to-hip ratio (WHR) on EO and BO (vs neither condition). RESULTS: There were 225 cases of either BO or EO and 675 controls. After adjustment for potential confounders, a positive association was observed between waist circumference and BO and/or EO, which became stronger with further adjustment for hip circumference. In contrast, hip circumference was inversely associated with BO and/or EO. Compared with the lowest quartile of WHR, the adjusted ORs were 1.32 (95% CI 0.747 to 2.33) for the 2nd quartile, 1.54 (95% CI 0.898 to 2.63) for the 3rd quartile, and 2.68 (95% CI 1.57 to 4.55) for the highest quartile. Similar results were obtained for BO and EO treated as separate outcomes. CONCLUSIONS: In a population of older, mostly overweight men, the distribution of obesity is associated with the presence of EO and BO. Abdominal obesity appears to increase the risk of these outcomes, whereas gluteofemoral obesity may be protective.


Asunto(s)
Esófago de Barrett/prevención & control , Nalgas/fisiología , Esofagitis/prevención & control , Cabeza Femoral/fisiología , Obesidad/fisiopatología , Anciano , Esófago de Barrett/etiología , Esófago de Barrett/fisiopatología , Estudios Transversales , Esofagitis/etiología , Esofagitis/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/fisiopatología , Medición de Riesgo , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-Cadera
4.
Clin Gastroenterol Hepatol ; 12(2): 239-45, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23988686

RESUMEN

BACKGROUND & AIMS: Infection with Helicobacter pylori, particularly the cytotoxin-associated gene A (cagA)+ strain, is believed to protect against Barrett's esophagus, but it is not clear if it protects against gastroesophageal reflux disease (GERD). We aimed to determine whether H pylori infection is associated with GERD symptoms, erosive esophagitis, and Barrett's esophagus within the same cohort. METHODS: We analyzed data from a case-control study of 533 men (ages, 50-79 y) who underwent colorectal cancer screening at 2 tertiary medical centers in Michigan between 2008 and 2011 and who also were recruited to undergo upper endoscopy. We assessed 80 additional men found to have Barrett's esophagus during clinically indicated upper-endoscopy examinations. Logistic regression was used to estimate the associations between serum antibodies against H pylori or cagA and GERD symptoms, esophagitis, and Barrett's esophagus, compared with randomly selected men undergoing colorectal cancer screens (n = 177). RESULTS: H pylori infection was associated inversely with Barrett's esophagus (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.97), particularly the cagA+ strain (OR, 0.36; 95% CI, 0.14-0.90). There was a trend toward an inverse association with erosive esophagitis (H pylori OR, 0.63; 95% CI, 0.37-1.08; and cagA+ OR, 0.47; 95% CI, 0.21-1.03). However, GERD symptoms were not associated with H pylori infection (OR, 0.948; 95% CI, 0.548-1.64; and cagA+ OR, 0.967; 95% CI, 0.461-2.03). CONCLUSIONS: Based on a case-control study, infection with H pylori, particularly the cagA+ strain, is associated inversely with Barrett's esophagus. We observed a trend toward an inverse association with esophagitis, but not with GERD symptoms.


Asunto(s)
Esófago de Barrett/complicaciones , Esofagitis/complicaciones , Reflujo Gastroesofágico/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Anciano , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Esófago de Barrett/microbiología , Estudios de Casos y Controles , Reflujo Gastroesofágico/microbiología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad
5.
Gastroenterology ; 145(6): 1237-44.e1-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23999171

RESUMEN

BACKGROUND & AIMS: Insulin and leptin have proliferative and anti-apoptotic effects. Ghrelin promotes gastric emptying and secretion of growth hormone and inhibits inflammation. We assessed whether diabetes mellitus and serum levels of insulin, leptin, and ghrelin are associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus. METHODS: We conducted a case-control study in 822 men undergoing colorectal cancer screening who were recruited to also undergo upper endoscopy. We identified 70 with Barrett's esophagus; 80 additional men with Barrett's esophagus were recruited shortly after their clinical diagnoses. Serum levels of insulin, leptin, and ghrelin were assayed in all 104 fasting men with Barrett's esophagus without diabetes and 271 without diabetes or Barrett's esophagus. Logistic regression was used to estimate the effects of diabetes and levels of insulin, leptin, and ghrelin on GERD and Barrett's esophagus. RESULTS: Among men with GERD, diabetes was inversely associated with Barrett's esophagus (adjusted odds ratio [OR] = 0.383; 95% confidence interval [CI]: 0.179-0.821). Among nondiabetics, hyperinsulinemia was positively associated with Barrett's esophagus, but the association was attenuated by adjustment for leptin and ghrelin. Leptin was positively associated with Barrett's esophagus, adjusting for obesity, GERD, and levels of insulin and ghrelin (OR for 3(rd) vs 1(st) tertile = 3.25; 95% CI: 1.29-8.17); this association was stronger in men with GERD (P = .01 for OR heterogeneity). Ghrelin was positively associated with Barrett's esophagus (OR for an increment of 400 pg/mL = 1.39; 95% CI: 1.09-1.76), but inversely associated with GERD (OR for 3(rd) vs 1(st) tertile = 0.364; 95% CI: 0.195-0.680). CONCLUSIONS: Based on a case-control study, leptin was associated with Barrett's esophagus, particularly in men with GERD. Serum insulin level was associated with Barrett's esophagus, but might be mediated by leptin. Serum ghrelin was inversely associated with GERD, as hypothesized, but positively associated with Barrett's esophagus, contrary to our hypothesis. Additional studies are needed in men and women to replicate these findings.


Asunto(s)
Esófago de Barrett/epidemiología , Complicaciones de la Diabetes/complicaciones , Reflujo Gastroesofágico/epidemiología , Ghrelina/sangre , Insulina/sangre , Leptina/sangre , Anciano , Esófago de Barrett/sangre , Esófago de Barrett/diagnóstico , Estudios de Casos y Controles , Complicaciones de la Diabetes/sangre , Endoscopía Gastrointestinal , Reflujo Gastroesofágico/sangre , Reflujo Gastroesofágico/diagnóstico , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo
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