Barrett Esophagus (Clinical)

Epidemiology and Risk Factors

Epidemiology^[3,4,8]

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: approximately 1%–10% in the United States
• Mean age is approximately 55 years.
• Men are more commonly affected.
• More prevalent in white men than in women or other races

Risk Factors^[1,2,8]

• Chronic gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD)) > 5 years
• Age > 50 years
• Tobacco use
• Male sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
• White or European American
• Central obesity Central Obesity Cushing Syndrome
• 1st-degree relative with Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy

Pathophysiology

Mucosal injury^[9]

• Chronic reflux of gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD):
  • Low pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance
  • Duration of exposure
• Compromised protection mechanisms
  • Antireflux barrier:
    • Lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy (LES)
    • Extrinsic compression Compression Blunt Chest Trauma of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy
  • Clearing mechanism:
    • Gravity
    • Bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes secretion Secretion Coagulation Studies from esophageal and salivary glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands: Anatomy
    • Peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility
  • Epithelial defense factors to resist acid entry into intercellular spaces:
    • Thick epithelial layer
    • Tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions
    • Lipid-rich intercellular space

Metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation^[9,11]

• Occurs when 1 type of differentiated tissue replaces another
• Adaptive response to injury
• Mechanism:
  • Erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes of mucosa → inflammatory cell infiltration → epithelial necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Repair of damaged esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy → replacement with columnar cells
    • Transdifferentiation of squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology into columnar epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology
    • Potential migration of progenitor or residual embryonic from gastric cardia or gastroesophageal junction Gastroesophageal junction The area covering the terminal portion of esophagus and the beginning of stomach at the cardiac orifice. Esophagus: Anatomy

Dysplasia^[9]

• Acid and bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy salts → oxidative DNA damage DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a mutation or a block of DNA replication. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (pyrimidine dimers) or interstrand crosslinking. Damage can often be repaired (DNA repair). If the damage is extensive, it can induce apoptosis. DNA Repair Mechanisms in epithelial cells → cell proliferation and abnormal development
• Also a genetic component
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with dysplasia are at increased risk for esophageal adenocarcinoma Esophageal Adenocarcinoma Esophageal Cancer (EAC).

Progression to cancer^[9]

• Traditionally thought to evolve gradually:
  • Stepwise sequence of genetic and epigenetic alterations
  • Eventual dysplasia 
• Now thought that most tumors in Barrett metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation develop through a “genome-doubled pathway”:
  • p53 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations acquired first 
  • Subsequent whole-genome doubling →
    • Genomic instability
    • Oncogene amplification 
    • Malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology
    • Results in cancer faster than the traditional pathway
• Neoplastic progression ( carcinogenesis Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Carcinogenesis) includes alterations in:
  • Tumor Tumor Inflammation suppressor genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure p53 and p16 
  • Cyclin D1 Cyclin D1 Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11; 14) translocation, and is implicated in various neoplasms. Non-Hodgkin Lymphomas proto-oncogene
• Abnormal flow cytometry Flow cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. X-linked Agammaglobulinemia is seen in > 90% of adenocarcinomas; same abnormalities may predict progression from Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy to cancer

Clinical Presentation and Diagnosis

Clinical presentation^[1,8]

• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with symptoms associated with GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) and its complications.
  • Heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD)
  • Regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Odynophagia Odynophagia Epiglottitis
• Physical exam is generally unremarkable.

Diagnosis^{[1–5,11,12]}

Screening Screening Preoperative Care recommendations:

• Screening Screening Preoperative Care for Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy is recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with multiple risk factors for EAC.
  • Chronic GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) (10%–15% risk of Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy)
  • Hiatal hernia Hiatal hernia Stomach herniation located at or near the diaphragmatic opening for the esophagus, the esophageal hiatus. Congenital Diaphragmatic Hernias
  • Long-standing symptoms (> 5 years)
  • Age > 50 years
  • White race
  • Male sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
  • Central obesity Central Obesity Cushing Syndrome
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 
  • 1st-degree relative with EAC
• Screening Screening Preoperative Care of the general public is not recommended.

Procedure of choice is esophagogastroduodenoscopy (EGD):

• Evidence of columnar epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology:
  • Erythematous distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
  • Velvet or “tongue”-like texture Texture Dermatologic Examination
  • Squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology is usually pale and glossy.
• Squamocolumnar junction Squamocolumnar junction Esophagus: Anatomy ( Z-line Z-line Esophagus: Anatomy) is where columnar and squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology meet in the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy:
  • Above the gastroesophageal junction Gastroesophageal junction The area covering the terminal portion of esophagus and the beginning of stomach at the cardiac orifice. Esophagus: Anatomy (GEJ) 
  • Irregular border
• Criteria for Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy:
  • Diagnosis in the United States requires the presence of both of the following:^[2,11]
    • Columnar epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology in ≥ 1 cm of the distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
    • Histology showing intestinal metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation with goblet cells Goblet cells A glandular epithelial cell or a unicellular gland. Goblet cells secrete mucus. They are scattered in the epithelial linings of many organs, especially the small intestine and the respiratory tract. Glandular Epithelium: Histology
  • British Society of Gastroenterology:^[5]
    • Includes the above criteria from the US guidelines
    • In addition to intestinal metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation, presence of cardiac or oxyntocardiac mucosa is also adequate for diagnosis.
• Terms:
  • Long-segment Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy: ≥ 3 cm in length
  • Short-segment Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy: < 3 cm

Management

The management of Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy has been addressed in several society guidelines, and there is considerable disagreement among experts. The information here is based on: 

• American College of Gastroenterology (ACG) 2016 Guideline^[2]  
• American Society of Gastrointestinal Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) 2019 Guideline^[3]
• American Gastroenterological Association (AGA) Expert Review from the Clinical Practice Updates Committee 2016^[4] 
• British Society of Gastroenterology 2014 Guidelines^[6]

General Management

The goal is to treat underlying acid reflux disease and decrease the risk of cancer development.

Proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors (PPIs):^[2,5,6,11]

• Significantly reduce the risk of progression to EAC
• Treatment is lifelong.
• Dosing:
  • Omeprazole Omeprazole A 4-methoxy-3, 5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits an h(+)-k(+)-exchanging ATPase which is found in gastric parietal cells. Gastric Acid Drugs 20 mg daily:
    • Decrease dose to 10 mg daily in Asian patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (increased risk of CYP2C19 poor metabolizer)
    • Give before meals.
  • Pantoprazole Pantoprazole 2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of gastroesophageal reflux and peptic ulcer. Gastric Acid Drugs 40 mg daily for 8 weeks, then 20–40 mg daily
  • Lansoprazole Lansoprazole A 2, 2, 2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits h(+)-k(+)-exchanging ATPase which is found in gastric parietal cells. Lansoprazole is a racemic mixture of (r)- and (s)-isomers. Gastric Acid Drugs 30 mg daily for 8 weeks, then 15 mg daily
  • Rabeprazole Rabeprazole A 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of stomach ulcers and zollinger-ellison syndrome. The drug inhibits h(+)-k(+)-exchanging ATPase which is found in gastric parietal cells. Gastric Acid Drugs 20 mg daily

Lifestyle modifications:^[1,2,5,10]

• Diet modification with avoidance of:
  • Fatty foods
  • Acidic foods and drinks
  • Caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants 
  • Eating prior to bedtime
• Avoidance of NSAIDs NSAIDS Primary vs Secondary Headaches
• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery if overweight or obese

Surveillance Surveillance Developmental Milestones and Normal Growth and dysplasia management^[3,10–12]

The intention of close surveillance Surveillance Developmental Milestones and Normal Growth is to detect dysplasia and EAC early and initiate treatment promptly. This will generally be guided by specialist consultation (e.g., gastroenterology). 

When Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy is diagnosed on endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD):

• If 4-quadrant biopsies every 2 cm were not obtained → repeat endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsies within a year.
• If no dysplasia found on histology → surveillance Surveillance Developmental Milestones and Normal Growth endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsies in 3–5 years
• If histology is indefinite for dysplasia:
  • Optimize antireflux therapy (PPI twice daily)
  • Repeat endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsies in 2–6 months
    • If no dysplasia → surveillance Surveillance Developmental Milestones and Normal Growth endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsies in 3–5 years
    • If indefinite histology again, confirm findings with a second pathologist with expertise in esophageal histopathology
• Low-grade dysplasia (LGD) → either ablation or endoscopic surveillance Surveillance Developmental Milestones and Normal Growth
• If histology show high-grade dysplasia (HGD) or intramucosal carcinoma → endoscopic eradication with 1 of the following:
  • Radiofrequency ablation Radiofrequency ablation Removal of tissue using heat generated from electrodes delivering an alternating electrical current in the frequency of radio waves. Hepatocellular Carcinoma (HCC) and Liver Metastases
  • Photodynamic therapy Photodynamic Therapy Actinic Keratosis
  • Spray cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma
  • Esophagectomy Esophagectomy Excision of part (partial) or all (total) of the esophagus. Esophageal Cancer if endoscopic eradication is not available
• If histology shows EAC → refer to oncology

Cancer risk^[2,3]

• Risk of progression to EAC:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with nondysplastic Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy: approximately 0.2%–0.5% per year
  • LGD: approximately 0.7% per year
  • HGD: approximately 7% per year
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy die of causes other than EAC.

Differential Diagnosis

• Esophageal adenocarcinoma Esophageal Adenocarcinoma Esophageal Cancer: a malignant tumor Tumor Inflammation of the distal esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD), and smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases are risk factors for this malignancy Malignancy Hemothorax. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD), and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is used to diagnose and differentiate cancer from Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Management is based on staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis and the patient’s overall health; it may include surgical resection, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and chemotherapy Chemotherapy Osteosarcoma.
• Esophageal squamous cell carcinoma Esophageal Squamous Cell Carcinoma A carcinoma that originates usually from cells on the surface of the middle and lower third of the esophagus. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in rnf6, lzts1, TGFbr2, dec1, and wwox1 genes are associated with this cancer. Esophageal Cancer: a malignant tumor Tumor Inflammation of the middle esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Risk factors include smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and alcohol. Symptoms are similar to EAC and include dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD), and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. Diagnosis is by endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment depends on staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis and the patient’s overall health, and includes surgical resection, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and chemotherapy Chemotherapy Osteosarcoma.
• Eosinophilic esophagitis Eosinophilic esophagitis Chronic esophagitis characterized by esophageal mucosal eosinophilia. It is diagnosed when an increase in eosinophils are present over the entire esophagus. The reflux symptoms fail to respond to proton pump inhibitors treatment, unlike in gastroesophageal reflux disease. The symptoms are associated with ige-mediated hypersensitivity to food or inhalant allergens. Esophagitis: a chronic, immune-mediated condition that leads to esophageal dysfunction. Symptoms include heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD), chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, and food impaction. Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma will show strictures, stacked circular rings, linear furrows, and eosinophil-predominant inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, differentiating this condition from Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Management includes evaluation for food allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction, PPIs, and topical glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids.
• Gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD)): a condition caused by reflux of gastric contents into the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy leading to irritation and symptoms. GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) can be a precursor to Barrett esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. Symptoms include heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD), dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics. Diagnosis is usually clinical, but those with severe symptoms or risk factors may require EGD for further evaluation. Treatment includes lifestyle modifications and PPIs.