RESUMO
Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia (ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [SIM]), from 2 cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019) but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but not for SIM (P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE (P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa.
Assuntos
Esôfago de Barrett/enzimologia , Esôfago/enzimologia , Proteínas Quinases Ativadas por Mitógeno/análise , Adulto , Idoso , Esôfago de Barrett/complicações , Refluxo Biliar/etiologia , Refluxo Biliar/patologia , Western Blotting , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Esôfago/patologia , Feminino , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/complicações , Humanos , Intestinos/patologia , Masculino , Metaplasia/etiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estudos ProspectivosRESUMO
PURPOSE: Incidence of pancreatic exocrine insufficiency in biliary pathology is estimated for about 30%. The objective was to assess pancreatic exocrine function in biliary tract pathology (cholelithiasis, strictures) before and after endoscopic treatment. PATIENTS AND METHODS: Twenty-eight patients with choledocholithiasis and its complications (19F/9M; aging 31-90 years, median: 69 years) were evaluated. Fecal elastase 1 concentration was measured using ELISA, before, early, and 6-8 weeks after endoscopic treatment. The inflammatory response of pancreas to the treatment was also assessed. RESULTS: Initial fecal elastase 1 concentration in patients (median 454 microg/g) was not significantly different as compared to the control (median 357 microg/g). Nine patients (32%) had low fecal elastase 1 concentration (below 250 microg/g) and out of them 6 had the concentration below 200 microg/g, suggesting impairment of exocrine pancreatic function. Endoscopic treatment was successful in 82% of patients. Pancreatic inflammatory response was noted only in one patient. After 6-8 weeks fecal elastase 1 concentration in the whole group of patients did not significantly change in comparison to the initial level. However, out of 9 patients with initially low fecal elastase 1 concentration (median 191 microg/g) at least in 6 pancreatic function improved (median 310 microg/g), P < 0.001. CONCLUSION: One third of the patients with biliary pathology had a low fecal elastase 1 concentrations, suggesting pancreatic dysfunction. In at least 2/3 of these patients successful endoscopic treatment of biliary pathology resulted in the significant increase of fecal elastase 1 concentration. Therefore, an additional positive effect of such treatment in some patients, could be an improvement of the exocrine pancreatic dysfunction.