Barrett's esophagus BY MINA NABIL DEFINITION

• Barrett's esophagus is a condition in • which there is an abnormal (metaplastic)change in the mucosal cells lining the lower portion of the esophagus, from normal stratified squamous to simple columnar epithelium with interspersed goblet cells that are normally present only in the small intestine, and large intestine. This change is considered to be a premalignant condition because it is associated with a high incidence of further transition to esophageal adenocarcinoma, an often-deadly cancer.[1][2] Other names

• Barrett's oesophagus, • Allison-Johnstone anomaly, columnar epithelium lined lower Oesophagus (CELLO • The main cause of Barrett's esophagus is thought to be an adaptation to chronic acid exposure from reflux esophagitis CLASSIFICATION OF CELLS

• The cells of Barrett's esophagus are classified into four categories: nondysplastic, low-grade dysplasia, high-grade dysplasia, and frank carcinoma. • In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.[1] • The condition is found in 5–15% of patients who seek medical care for heartburn (gastroesophageal reflux disease, or GERD), although a large subgroup of patients with Barrett's esophagus are asymptomatic. Signs and symptoms

• The change from normal to premalignant cells that indicate Barrett's esophagus Signs and symptoms does not cause any particular symptoms. Barrett's esophagus, however, is associated with these symptoms • frequent and longstanding heartburn • trouble swallowing (dysphagia) • vomiting blood (hematemesis) • pain under the sternum where the esophagus meets the stomach • unintentional weight loss because eating is painful (odynophagia RISK FACTOR

• The risk of developing Barrett's esophagus is increased by central obesity The difference in • distribution of fat among men (more central) and women (more peripheral) may explain the increased risk in males. • The principal cause of the chronic inflammation is gastroesophageal reflux disease, GERD • acidic stomach, bile, and small intestine and pancreatic contents cause damage to the cells of the lower esophagus. Recently, bile acids were shown to be able to induce intestinal differentiation, in gastroesophageal junction cells, MECHANISM

• inhibition of the epidermal growth factor (EGFR) and the Akt.[10] This results in the eventual up-regulation of the p50 subunit of protein complex NF-κB (NFKB1), and ultimately activation of the homeobox CDX2, which is responsible for the expression of intestinal such as guanylate 2C.[11] This mechanism also explains the selection of HER2/neu (also called ERBB2) and the overexpressing (lineage-addicted) cancer cells during the process of carcinogenesis, and the efficacy of targeted therapy against the Her-2 receptor with trastuzumab (Herceptin) in the treatment of adenocarcinomas at the gastroesophageal junction. Screening

• Screening endoscopy is recommended among males over the age of 60 who have reflux symptoms that are of long duration and not controllable with treatment.[15] Among those not expected to live more than 5 years screening is not recommended. • The presence of goblet cells, called intestinal metaplasia, is necessary to make a diagnosis of Barrett's esophagus • The metaplasia is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope to determine whether cells are gastric or colonic in nature. • Colonic metaplasia is usually identified by finding goblet cells in the epithelium and is necessary for the true diagnosis. • Many histologic mimics of Barrett's esophagus are known (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar [gastric] type mucin simulates the acid mucin true goblet cells) • TO DIFFERNTIATE :1-Assessment of relationship to submucosal glands and transitional-type epithelium with examination of multiple levels through the tissue may allow the pathologist to reliably distinguish between goblet cells of submucosal gland ducts and true Barrett's esophagus (specialized columnar metaplasia). • Use of the histochemical stain Alcian blue pH 2.5 is also frequently used to distinguish true intestinal-type mucins from their histologic mimics. • Immunohistochemical analysis with antibodies to CDX-2 (specific for mid and hindgut intestinal derivation) has also been used to identify true intestinal-type metaplastic cells • The protein AGR2 is elevated in Barrett's esophagus[16] and can be used as a biomarker for distinguishing Barrett epithelium from normal esophageal epithelium. • The presence of intestinal metaplasia in Barrett's esophagus represents a marker for the progression of metaplasia towards dysplasia and eventually adenocarcinoma.This factor combined with two different immunohistochemical expression of p53, Her2 and p16 leads to two different genetic pathways that likely progress to dysplasia in Barrett's esophagus.[18] Also intestinal metaplastic cells can be positive for CK 7+/CK20-. Epidemiology

• The incidence in the United States among Caucasian men is eight times the rate among Caucasian women and five times greater than African American men. Overall, the male to female ratio of • The relative risk of esophageal adenocarcinoma is approximately 10 in those with Barrett's esophagus, compared to the general population. MANAGEMENT

• Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years • Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direcT Management evidence supports this practice Treatment options

• high-grade dysplasia include surgical removal of the esophaguses (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablatION • Balloon-based radiofrequency ablation, • radiofrequency ablation has an efficacy of 90% or greater with respect to complete clearance of Barrett's esophagus and dysplasia with durability up to five years and a favorable safety • Anti-reflux surgery has not been proven to prevent esophageal cancer. However, the indication is that proton pump inhibitors are effective in limiting the progression • Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. A recent five- year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor Treatment options

• Endoscopic mucosal resection has also been evaluated as a management technique • Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus. • In a variety of studies, nonsteroidal antiinflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in people with Barrett's esophagus. • High-grade dysplasia and early stages of adenocarcinoma may be treated by endoscopic resection or radiofrequency ablation.[4] Later stages of adenocarcinoma may be treated with surgical resection or palliation. Those with • nondysplastic or low-grade dysplasia are managed by annual observation with endoscopy, or treatment with radiofrequency ablation • In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater. • THANK YOU