Diseases of the Esophagus Pt. 2 Flashcards
What kind of epithelium is present in the esophagous? How is this beneficial?
Non-keratinized stratified squamous epithelium - resistant to abrasion from foods but is sensitive to acid
What structures in the proximal and distal esophagous contribute to mucosal protection?
Sub-mucosal glands
What type of epithelium is present in the stomach?
Columnar epithelium
What is the difference between mucosa in the stomach and the esophagus?
- Esophageal mucosa is made for transportation
- Stomach mucosa is for protection against acids
What are some mechanisms of epithelial defense against acidity?
- Intracellular buffering by negatively charged proteins and bicarbonate ion
- H+ extrusion processes for regulation of pH
- Also apical cell membrane and intracellular junctional complex
What is the most important barrier against reflux?
The constant LES tone (prevents reflux of acidic gastric contents which are under positive abdominal pressure)
In addition to acid, _____ ____ reflux may exacerbate mucosal injury
Dudodenal bile
How does inflammation lead to a reduction of LES tone?
- Inflammation induces the production of IL-6 which leads to an increase of H2O2 in the muscle
- H2O2 is the main cause of increase in platelet activating factor and PGE2 which reduce ACh release and LES tone
What is incompetent LES and how does it happen?
- Incompetent is LES is when the gastroesophageal junction barrier is defective
- It may occur through transient LES relaxation (majority), strain (may be caused by exercise/crural diaphram contraction), or a hypotonic LES
Transient LES relaxation is a part of the _____ reflex
Belch
What leads to transient LES relaxation?
The efferent pathway is in the vagus nerve and NO is the postganglionic neurotransmitter
What type of hernia is associated with incompetent LES?
Hiatal hernia - Protrusion of the stomach into the thorax through the gap between the diaphragmatic crura and LES
What are the two types of hiatal hernia and which is more common?
- Sliding and para-esophageal
- Sliding hiatal hernia is more common and asymptomatic (90% of the time)
The morphology of mucosa in acid reflux shows basal zone hyperplasia exceeding __% of total thickeness and also the presence of ____ in the squamous mucosa
20%; eosinophils (followed by neutrophils)
What may be seen in reflux esophagitis endoscopically?
Simply hyperemia (redness) and possible mucosal breaks (erosions)
What are risk factors and symptoms of reflux esophagitis?
- Most common in adults > 40yrs
- Obesity is a risk factor
- Symptoms:
- Heartburn
- Regurgitation
- Dysphagia (less common)
- (May also see atypical chest pain, chronic cough, or hoarseness)
What are three modalities for diagnosis of reflux esophagitis?
- Endoscopy (90% specific in GERD but only 50% sensitivity)
- Ambulatory reflux monitoring (70% sensitivity)
- Radiography
*note: symptoms do not necessarily correlate with degree of mucosal damage
What alarm symtoms indicate the need for an endoscopy in a patient experiencing GERD?
- Dysphagia
- Anemia
- Weight loss
- Abdominal Mass
- Vomiting
What lifestyle modifications can be done to help with GERD?
- Weight loss (for overweight patients)
- Elevation of bed
- Avoiding late meals (patients with nocturnal symptoms)
- Avoiding trigger foods (ETOH, caffeine, chocolate)
What pharmacologic therapies can be used for GERD?
- Anti-secretory drugs (healing esophagitis and symptomatic relief)
- Proton pump inhibitors are more effective than histamine blockers
What operative therapies can be used to manage GERD?
- Fundoplication (surgery)
- Substitution of devices to enforce LES
What are some complications of GERD?
- Esophageal ulcer
- Esophageal stricture
- Bleeding
- Barrett’s esophagus
Stricture is most often due to ______ and ______
inflammation and scarring
What can cause esophageal stricture (3)?
- Chronic gastroesophageal reflux
- Radiation
- Caustic injury
Narrowing with esophageal strictures is generally caused by…
- Fibrous thickening of the submucosa
- Atrophy of the muscularis propria
- Secondary epithelial damage
What is Eosinophilic Esophagitis (EOE)?
Epithelial infiltration by large numbers of eosinophils, particularly superficially
How can you differentiate EOE from GERD?
Abundance of eosinophils and location far from GE junction
What is the clinical presentation of EOE in adults vs. children?
- Adults: predominantly dysphagia
- Children: nausea, burning and food intolerance
What is the general clinical presentation of EOE?
- Failure of the acid suppressive treatment and the absence of acid reflux
- Personal or family history of atopia
EOE involves ______ whicih leads to eosinophil infiltration and activation
T-cell (mediated hypersensitivity)
How does eosinophil infiltration in EOE lead to change in the mechanical properties of the esophagus?
Cascade of cytokine release from esoinophils and deposition of major basic protein and increased expression of IL-5 and IL-13 within the affected esophageal epithelium - leads to tissue remodeling and fibrosis
Histologic confirmation of > __ eosinophils per HPF (high power field) in esophageal mucosa is needed
15
What type of diet is used to treat EOE?
Elimination diet - avoid seafood, wheat, soy, nuts, milk, and eggs
Aside from diet, how else is EOE treated?
- Topical steroids
- Systemic steroids
- Endoscopic dilation
What other types of esophagitis (aside from EOE) exist?
- Chemical
- Infectious
- Iatrogenic
- Skin Disorder associated
What types of irritants can cause chemical esophagitis?
- Corrosive acid
- Corrosive alkali
- Alcohol
- Excessively hot fluids
- Heavy smoking
- Medicinal pills (may lodge and dissolve in esophagus)
What symptoms are associated with chemical esophagitis?
- Generally causes only self-limited pain
- Odynophagia - pain with swallowing
- Hemorrhage, stricture, or perforation may occur
Infectious esophagitis is most frequent in those who are ___________
immunosuppressed
Viral Esophagitis is often due to which types of viruses? What appearance is associated with each?
- Herpes simplex virus: punched-out ulcers
- Cytomegalovirus: shallow ulcerations
What type of fungi are associated with fungal esophagitis?
- Most common: Candida
- May also be mucormycosis and aspergillosis
Bacterial esophagitis accounts for about __% of infectious esophagitis cases
10
What are some morphologic changes associated with Iatrogenic Esophagitis?
Non-specific with ulceration and accumulation of neutrophils
What are some causes of Iatrogenic Esophagitis?
- Cytotoxic chemotherapy
- GvH disease
- Radiation
What skin diseases are associated with esophagitis?
- Desquamative skin disease
- Lichen planus
- Chron’s disease
What characterizes Barrett’s Esophagus (BE)?
Normal esophageal squamous epithelium is replaced by metaplastic columnar mucosa (intestinal metaplasia)
What types of cells define intestinal metaplasia and how are they identified?
Goblet cells; identified by distinct mucous vacuoles
What percentage of GERD patients have BE? What percentage of BE patients develop epithelial dysplasia?
10%; 0.2-1.0%
Which gene probably plays a role in BE? What abnormalities may lead to the development of dysplasia and later carcinogenesis?
- Cdx is expressed in 100% of Barrett specimens but not normal esohagus or stomach
- Abnormalities in P53 and cyclin D1 expression have been associated with dysplasia and later carcinogenesis
What characterizes adenocarcinoma (intramucosal carcinoma)?
Characterized by invasion of neoplastic epithelial cells into the lamina propria (associated with BE)
How does BE appear morphologically?
- Tongues or patches of red, velvety mucosa extending upward from the GE junction
- BE metaplastic mucosa alternates with residual smooth, pale squamous mucosa proximally
What evidence is required for BE diagnosis?
BOTH endoscopic evidence of abnormal mucosa above the GE junction AND histologically documented metaplasia
What is the clinical presentation of BE?
- Typically white adult male (40-60yrs) with long term reflux symptoms
- Often is completely asymptomatic (silent disease)
- BE usually doesn’t lead to esophageal cancer
Esophageal Adenocarcinoma has a higher incidence in…?
- Developed western countries
- White middle aged males
What are some well known risk factors for esophageal adenocarcinoma?
- Dysplasia in BE
- Tobacco use
- Obesity
- Radiation therapy
T or F: Progression of BE to adenocarcinoma occurs quickly and through a single acquisition of genetic change
False!
BE to adenocarcinoma occurs over time through the stepwise acquisition of genetic and epigenetic changes
What types of genetic mutations are associated with BE to adenocarcinoma change?
- P53 mutations
- Amplifications of c-ERB-B2, cyclin D1 and cycline E genes
- Increased expression of TNF and NF-kB dependent genes
Esophageal adenocarcinoma usually occurs where in the esophagus?
The distal third of the esophagus (and may invade the adjacent gastric cardia)
In microscopic examination of esophageal carcinoma, tumors typically produce _____ and form _____
mucin; glands
Squamous cell carcinoma (SCC) typically occurs in what demographic?
African-American male adults older than 45 years of age
What are some risk factors associated with SCC?
- Alcohol and tobacco use (majority in developed world)
- Poverty
- History of caustic esophageal injury
- Achalasia and Plummer Vinson syndrome
- Frequent consumption of very hot beverages
- Previous radiation therapy
Half of SCCs occur in the ____ part of the esophagus
middle
Early lesions of SCC appear as…?
Gray-white plaque like thickenings (can grow into tumor masses that protrude into and obstruct the lumen)
Symptoms of esophageal SCC?
- Dysphagia
- Odynophagia
- Obstruction
- Patients may adjust by altering their diet (solid to liquid foods)
What are the 5 year survival rates for patients with superficial esophageal carcionma? What is the overall 5 year survival rate?
75%; 9%
What lymph nodes are associated with the different parts of the esophagus?
- Upper third: cervical
- Middle third: mediastinal, paratracheal, and tracheobronchial
- Lower third: gastric and celiac nodes
Esophageal carcinoma:
- What is the 5 year survival rate for superficial adenocarcinoma?
- Overall 5 year survival rate?
80%; 25%
