Task Specific Project 4

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Esophageal adenocarcinoma is a significant source of morbidity and mortality and its incidence rate has increased over 350% among white males and is now the 7th leading cause of cancer-related deaths97'98 with an annual age adjusted incidence of 2.5 per 100,000." The presence of Barrett's metaplasia, a condition in which the normal esophageal squamous mucosa is replaced by columnar epithelium is however, strongly associated with esophageal adenocarcinoma. Patients with Barrett's metaplasia have an estimated 30-40 fold greater risk.of adenocarcinoma than the general population.100 The malignant potential of this condition is evidenced by the progression of certain cells from Barrett's metaplasia to low-grade dysplasia, high-grade dysplasia, and finally to invasive adenocarcinoma. For this reason, patients with Barrett's metaplasia are enrolled in endoscopic surveillance programs with the intent of detecting high-grade dysplasia or early cancers prior to invasion and metastasis. A major risk factor for the development of Barrett's metaplasia is gastroesophageal reflux disease (GERD) which is often increased in obese individuals and obesity is rapidly increasing in Western countries. In those patients with GERD, Barrett's mucosa is found in up to 10-12% at the time of initial endoscopy.101'102 Familial factors may also be involved in the development of esophageal adenocarcinoma103 and GERD.104 Despite advances in surgical technique and multimodal therapy, the 5-year survival rate for esophageal cancer remains dismal at 5-15%.105'106 The advanced stage of disease at the time of initial diagnosis and the high rates of recurrence of local-regional and distant metastatic disease directly contribute to the low 5-year survival of this cancer. This highlights the importance of developing and refining methods for early cancer detection in patients who have GERD and Barrett's metaplasia.