Clinical and Molecular Assessment of Men With High Risk for Esophageal Disorders
Clinical and Molecular Assessment of Men With High Risk for Esophageal Disorders
In this study,the investigators will evaluate participants that have clinical features
 associated with an increased risk of esophageal disorders.The investigators will also see if
 there is a positive association of esophageal disorders in men,40-60 with or without
 abdominal obesity in the diagnosis of the following diseases; Gastroesophageal reflux
 disease, Barrett Esophagus and Esophageal Adenocarcinoma. The investigators hypothesize that
 most obese patients referred for Esophagogastroduodenoscopy will exhibit esophageal
 disorders. Since currently the rates of obesity and adenocarcinoma of the esophagus have
 increased significantly over the past 15 years, the investigators hope to find biochemical
 markers (i.e. pro-inflammatory mediators) in the esophagus. The investigators hope these
 samples will lead us to a differential expression of molecular markers and inflammatory
 mediators in the varying degrees of esophageal disorder
Patients with elevated central adiposity have an increased risk of esophageal disorders; we
 will correlate central adiposity with advanced esophageal pathologies (BE and EAC). This will
 be done by comparing body mass and fat distribution to tissue abnormalities found by
 pathology review of EGD biopsy. It is anticipated that the group of men in this study will
 have an increased likelihood of histopathologic alteration, which we will fit into our scale
 (0-no inflammation, 1-inflammation or BE, 2-BE with dysplasia, and 3-carcinoma) according to
 the referral pattern at UAB's outpatient gastroenterology clinic.

 At the molecular level, there is also a relationship between pro-inflammatory cytokines and
 obesity, which may contribute to esophageal disorder [28]. Metabolically active fat cells
 secrete cytokines exclusive to adipose tissue (adipokines, leptin/adiponectin) as well as the
 more classic signaling molecules, tumor necrosis factor alpha (TNF-α); interleukins (IL)-1,
 IL-6, IL-8, and IL-10; monocyte chemoattractant protein 1 (MCP-1); and macrophage
 inflammatory protein 1 (MIP 1) [29-33]. Obesity-triggered pro-inflammatory molecules may
 promote tissue injury, leading to metaplasia and dysplasia in BE and, subsequently, to
 carcinoma.

 Thus, by measuring these pro-inflammatory markers in our prospective patient population, it
 will be determined if patients with elevated levels exhibit pathologic disorders in the
 esophagus and if the differential expression of these molecular markers correlates with
 degree of esophageal disorder. We will analyze samples collected from men for adipocytokines
 and for inflammatory mediators that are released with tissue injury. Additionally, we will
 examine molecular markers that correlate with more advanced esophageal disorders (BE with
 high grade dysplasia and EAC).

 Persistent stimulation is needed to cause stepwise progression from the early stages of
 esophageal injury, to BE, to carcinoma. Since the molecular events that lead to this
 transformation are not known, our goal is to profile biopsy tissues collected from the
 prospective cohort of 60 men, analyzed by IHC for p53, Ki67, cyclin D1, IL-6, IL-8, Cox-2,
 DKK-1, CD44, leptin, and adiponectin. These molecules are known to be involved in
 transformation of normal esophageal epithelium to EACs via progression from metaplasia and BE
 to low-grade dysplasia and high-grade dysplasia. [34]. The clinical outcome measurements will
 be correlated with the levels of these molecules, determined by IHC, with metaplasia, degree
 of dysplasia in BE, and stage of EAC. For BE tissues, there is a correlation between the
 extent of p53 staining and aggressive clinical features. Our preliminary findings on six BEs,
 selected from the patient population at UAB, indicate that a high proportion of p53 staining
 directly correlates with high-grade lesions
Inclusion Criteria:

 1. Men only who are referred for upper endoscopy for the first time.Or who have had
 normal upper endoscopy in the last 10 years

 2. Age criteria: 25-75 years in age

 3. Patients undergoing EGD and willing to also consent to tissue biopsy, blood work and
 CT scan.

 4. ECOG PFS 0-1

 Exclusion Criteria:

 1. Unstable medical condition, such as uncontrolled diabetes mellitus or hypertension or
 active infections requiring systemic therapy

 2. Clinical evidence of cardiac or pulmonary dysfunction including, but not limited to,
 unstable congestive heart failure, uncontrolled arrhythmias, unstable coagulation
 disorders, or recent myocardial infarction (within 6 months)

 3. Documented history of erosive esophagitis or non-erosive esophageal luminal. No prior
 history of Barrett's esophagus.