Efficacy of the glucagon-like peptide-1 agonist exenatide in the treatment of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon-like peptide-1 (GLP-1) is a key hormone, produced by L-cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurs, as in SBS, GLP-1 levels may be deficient. In this study, we test whether the use of GLP-1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS. METHODS: Five consecutive patients with SBS based on ≤90 cm of small bowel and clinical evidence of nutritional deprivation were selected. Baseline SBS symptoms, demographic and laboratory data were obtained. Antroduodenal manometry was performed on each subject. Each patient was then started on exenatide and over the following month, the baseline parameters were repeated. KEY RESULTS: The subjects consisted of four males and one female, aged 46-69 years. At baseline, all had severe diarrhea that ranged from 6 to 15 bowel movements per day, often occurring within minutes of eating. After exenatide, all five patients had immediate improvement in bowel frequency and form; bowel movements were no longer meal-related. Total parenteral nutrition was stopped successfully in three patients. Antroduodenal manometry revealed continuous low amplitude gastric contractions during fasting which completely normalized with exenatide. CONCLUSIONS & INFERENCES: Exenatide is a novel and safe treatment option for SBS. It produced substantial improvement in the bowel habits, nutritional status and quality of life of SBS patients. Successful treatment with exenatide may significantly reduce the need for parenteral nutrition and small bowel transplant.

Tobacco and other factors have a negative impact on quality of life in hepatitis C patients.

Hepatitis C virus (HCV) is known to adversely affect general, social, emotional and mental health domains. This study was designed to identify variables that may be associated with these measurable outcomes. We conducted a cross-sectional retrospective review of demographic and clinical data from 800 patients with HCV evaluated between January 1998 and November 2007. Data were collected using a standardized questionnaire filled out by the patients at the first encounter. Variables evaluated included fibrosis stages (i.e. FS0/1/2 vs FS3/4), demographics, comorbid health conditions, tobacco and alcohol use, high-risk social behaviours and laboratory data. Variables assessed were depression, fatigue, problems sleeping and loss of interest in sex. Statistical analysis was performed using univariate and multivariate logistic regression. Depression (29.3%) in our HCV study population was associated with female gender, tobacco use, hyperlipidemia, history of heavy alcohol use and intravenous drug use. Fatigue (44.6%) was associated with end-stage renal disease, past and current tobacco use and current alcohol use. Difficulty sleeping (13.8%) was associated with past and current tobacco use, current alcohol use and diabetes. Loss of interest in sex (7.7%) was associated with current tobacco use, multiple risk factors for HCV and age at time of evaluation. Fibrosis stage (FS) also had a significant positive association with alcohol use (OR 2.61; P = 0.003) and tobacco use (OR 2.00; P = 0.002). Smoking and alcohol use have a significant negative impact on the presence of depression, fatigue, difficulty sleeping and loss of interest in sex in HCV patients. Practitioners should be aware of these associations, particularly tobacco use, which significantly and negatively impacted every variable evaluated.

Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 +/- 2.2/HPF, EoE 19.8 +/- 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 +/- 0.7 and 74.9 +/- 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 +/- 0.16/HPF) and EoE (0.09 +/- 0.04; P = 0.07). Eight of the 39 RE specimens had >or=50 lymphocytes in >or=1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = -0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 +/- 1.3 vs 22.2 +/- 2.3/HPF; P = 0.030) and eosinophils (55.6 +/- 5.2 vs 76.0 +/- 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.

Heterotopic gastric mucosa (inlet patch) in a patient with laryngopharyngeal reflux (LPR) and laryngeal carcinoma: a case report and review of literature.

The inlet patch is an area of heterotopic gastric mucosa most commonly located in the postcricoid portion of the esophagus at, or just below, the level of the upper esophageal sphincter. Esophageal and supraesophageal symptoms are commonly associated with inlet patch, while esophageal adenocarcinoma rarely complicates it. Laryngeal adenocarcinoma associated with inlet patch is not described in the literature. Herein, we present the first reported case of inlet patch associated with laryngeal carcinoma. A 33-year-old female with long-standing asthma and presumed gastroesophageal reflux developed laryngeal cancer at age 22 years that was treated with concomitant radiation and induction chemotherapy. Subsequently, she had refractory heartburn, dysphagia, and cough. These symptoms continued despite two Nissen fundoplications, glottic web division, and optimal medical management. Upper endoscopy at our institution revealed an upper esophageal stricture and a 1 cm inlet patch. Biopsies showed columnar mucosa (predominantly gastric cardiac/fundic type) consistent with inlet patch, with focal intestinal metaplasia. Subsequent endoscopic mucosal resection of the inlet patch resulted in an amelioration of throat and chest pain, cough, and hoarseness. Dysphagia and regurgitation were improved by serial dilatations of the upper esophageal stricture. This case reveals a number of clinical findings associated with inlet patch--chest pain, dysphagia, cough, and hoarseness--as well as a clinical finding that has not been previously associated with inlet patch: laryngeal cancer. Symptoms refractory to optimal medical management and/or surgical intervention should make the clinician and endoscopist more cognizant of the inlet patch.