Upper GI - Esophagus

What type of epithelium lines the normal esophagus?

Nonkeratinized stratified squamous epithelium

What are the major layers of the esophageal wall?

Mucosa → submucosa → muscularis propria → adventitia

What layers make up the mucosa of the esophagus?

Nonkeratinized squamous epithelium

Lamina propria

Muscularis mucosae

What are the two layers of the muscularis propria?

Circular

Longitudinal

Where does the esophagus extend to?

Epiglottis → Gastroesophageal junction

What is unusual about the esophagus compared with most of the GI tract?

It does not have a serosa

• It has an adventitia instead

What type of muscle is found predominantly in the upper 2/3 of the esophagus?

Straited skeletal muscle

• Stratified squamous epithelium

What type of muscle is found predominantly in the lower 1/3 of the esophagus?

Smooth muscle

• Columnar epithelium

How does lymphatic drainage differ with the upper esophagus?

Neck and mediastinal lymph nodes

How does lymphatic drainage differ with the lower esophagus?

Gastric and para-aortic lymph nodes

How does innervation differ with the upper esophagus?

Somatic sensation

• Allowing relatively better localization of pathology

How does innervation differ with the lower esophagus?

Visceral innervation

• Resulting in poorer localization of pathology

What type of carcinoma can arise from the upper esophageal epithelium?

Squamous cell carcinoma

What type of carcinoma commonly arises in the lower esophagus?

Adenocarcinoma

What are examples of mechanical obstructions?

Atresia

Fistulas

Duplications

What is an example of a functional obstruction?

Achalasia

What is esophageal atresia?

Thin, noncanalized cord

• A congenital interruption of the esophagus in which a segment is replaced by

Where does esophageal atresia most commonly occur?

At or near the tracheal bifurcation

What congenital abnormality is commonly associated with esophageal atresia?

A tracheoesophageal fistula connecting an esophageal pouch to the trachea or bronchus

What are major complications of esophageal atresia/tracheoesophageal fistula?

Aspiration

Suffocation

Pneumonitis/Pneumonia

Severe fluid/electrolyte abnormalities

How does esophageal atresia typically present?

Shortly after birth

• Commonly with regurgitation during feeding

How is esophageal atresia treated?

Prompt surgical repair

What is an important long-term complication of repaired esophageal atresia?

Increased risk of:

• Esophageal dysmotility

• Aspiration

• Squamous cell carcinoma

Which abnormality is the most common atresia/fistula?

Proximal atresia w/ distal fistula

What is esophageal stenosis?

Narrowing of the esophageal lumen

• 1-99%

Is esophageal stenosis more commonly congenital or acquired?

Acquired

• Strong bases heavily contribute

What causes acquired esophageal stenosis?

Fibrous thickening of the submucosa and atrophy of the muscularis propria

What conditions can cause acquired esophageal stenosis?

Chronic GERD/inflammation and scarring

Radiation

Ingestion of caustic substances

What is the classic progression of dysphagia in esophageal stenosis?

Difficulty swallowing solids first

• Followed by difficulty with liquids

What is achalasia?

Discoordinated contraction or spasm of the muscularis leading to esophageal dysmotility

• Waves of peristaltic contraction

failure of progressive peristalsis

Incomplete relaxation of the lower esophageal sphincter (LES)

What complication is associated with achalasia?

Diverticula

What are the three classic features of achalasia?

1. Incomplete LES relaxation

2. Increased LES tone

3. Esophageal aperistalsis — Muscles are unable to squeeze to move food downward

What is the underlying pathologic process in primary achalasia?

Progressive inflammatory destruction of ganglion cells in the distal esophagus

What happens to the esophagus proximal to the LES in achalasia?

It becomes progressively dilated

What is the classic radiographic appearance of achalasia?

Dilated proximal esophagus with distal narrowing producing a “bird-beak” appearance

What histologic findings can be seen in achalasia?

Chronic ganglionitis or aganglionosis

Wallerian degeneration

Hypertrophy of the circular layer of the muscularis propria

What are complications of achalasia?

Regurgitation

Aspiration pneumonia

Diverticula

Markedly increased risk of esophageal squamous cell carcinoma

How much is the risk of esophageal SCC increased in achalasia according to the lecture?

Approximately 33-50x

What infections can cause an achalasia-like disorder?

Chagas disease, caused by Trypanosoma cruzi, through destruction of the myenteric plexus

What is pseudoachalasia?

An achalasia-like syndrome caused by another process

• Such as tumor invasion of the myenteric plexuses

What is an esophageal “inlet patch”?

A focus of ectopic gastric mucosa within the esophagus

• Ectopia

Where is an inlet patch most commonly located?

The upper third of the esophagus

• Mostly asymptomatic

Why can an inlet patch cause symptoms?

Gastric mucosa can secrete acid into the esophagus

What complications can result from an ectopia?

Dysphagia

Esophagitis

Barrett esophagus

Rarely adenocarcinoma

What are esophageal varices?

Engorged, tortuous, dilated veins caused by portal hypertension

• Can cause massive and life-threating bleeding (medical emergency)

  

What is the most common cause of esophageal varices according to the lecture?

Alcoholic liver disease

What other cause of esophageal varices is listed?

Hepatic schistosomiasis

Why do esophageal varices develop in portal hypertension?

Increased portal venous pressure causes blood to be diverted through portosystemic collateral vessels

• Including veins in the distal esophagus

What is the classic clinical presentation of bleeding esophageal varices?

Hematemesis

What is the approximate mortality associated with the first variceal bleeding episode according to the lecture?

~50%

What is the normal venous blood flow for the GI tract>

GI tract venous blood flow → portal vein → liver → inferior vena cava (First-pass effect)

What is a Mallory-Weiss tear?

A mucosal laceration at/near the gastroesophageal junction caused by severe retching or vomiting

What is the most common cause of esophageal laceration?

Mallory-Weiss tear

Where does a Mallory-Weiss tear typically occur?

At the gastroesophageal junction

What is Boerhaave syndrome?

A transmural esophageal rupture/perforation

• Classically following severe vomiting

Which is more severe: Mallory-Weiss tear or Boerhaave syndrome?

Boerhaave syndrome

• It involves full-thickness perforation

In what patient population does infectious esophagitis primarily occur?

Immunocompromised patients

What are the major causes of infectious esophagitis?

Candida (fungal organism)

HSV

CMV

Which organism is the most common cause of infectious esophagitis?

Candida

What is the characteristic gross/endoscopic appearance of esophageal candidiasis?

Adherent gray-white pseudomembranes/plaques covering the mucosa

What is the classic description of Candida plaques?

“Cottage cheese” plaques

What makes up the pseudomembranes in esophageal candidiasis?

Densely matted fungal hyphae and inflammatory cells

What is the characteristic endoscopic appearance of HSV esophagitis?

Punched-out ulcers

Where are HSV inclusions found histologically?

Nuclear viral inclusions within a rim of degenerating epithelial cells at the ulcer edge

What are the classic HSV nuclear changes (Triple M)?

Multinucleation

Margination of chromatin

Molding of nuclei

How does CMV esophagitis typically appear endoscopically?

Relatively shallow ulcerations

• Compared with HSV

Which cells are characteristically infected by CMV in esophageal biopsies?

Endothelial cells

Stromal cells

What type of inclusions are characteristic of CMV?

Both nuclear and cytoplasmic inclusions

What is the classic appearance of the CMV nuclear inclusion?

“Owl-eye” inclusion

Compare the classic findings of the three infectious esophagitis causes

Infection	Classic finding
Candida	Cottage-cheese plaques
HSV	Punched-out ulcers + Triple M
CMV	Shallow ulcers + owl-eye inclusions

What are the three types of chemical esophagitis causes?

Pill esophagitis (bisphosphanates, doxycycline)

Cytotoxic chemotherapy

Radiation therapy

What is the most common cause of esophagitis?

Gastroesophageal reflux disease (GERD)/reflux esophagitis.

What causes reflux esophagitis?

Reflux of gastric contents into the esophagus → Produce mucosal injury

What mechanisms can promote GERD?

Decreased lower esophageal sphincter tone and/or increased abdominal pressure

In what age group is reflux esophagitis commonly seen according to the lecture?

Patients >40 years old

What are the characteristic histologic findings of reflux esophagitis?

Basal cell hyperplasia >15% of epithelial thickness

Elongation of lamina propria papillae to >2/3 of epithelial thickness

Scattered intraepithelial eosinophils

Neutrophils in more severe disease

What is eosinophilic esophagitis?

An immunologically mediated chronic esophageal disorder

What are the classic symptoms of eosinophilic esophagitis?

Dysphagia and food impaction

What type of patients are commonly associated with eosinophilic esophagitis?

Patients with other allergic/atopic conditions

What is the characteristic endoscopic appearance of eosinophilic esophagitis?

Multiple concentric rings producing “trachealization” or “feline esophagus”

What is the histologic diagnostic feature of eosinophilic esophagitis emphasized in the lecture?

>15 eosinophils/high-power field, particularly superficially

(Notice the eosinophilic abscess)

Where should the eosinophils be located to support eosinophilic esophagitis?

They can be present at sites far from the gastroesophageal junction

What is Barrett esophagus?

Intestinal metaplasia of the esophageal squamous mucosa

• Usually resulting from chronic GERD

What is the major clinical significance of Barrett esophagus?

It increases the risk of esophageal adenocarcinoma

What is the classic endoscopic appearance of Barrett esophagus?

Salmon-colored mucosa

What is seen microscopically in Barrett esophagus?

Metaplastic intestinal-type mucosa containing goblet cells

How is Barrett esophagus diagnosed?

Endoscopic findings PLUS biopsy demonstrating intestinal metaplasia

What is the common progression of adenocarcinoma due to GERD?

Chronic GERD → Barrett metaplasia → dysplasia → adenocarcinoma

What are the two esophageal tumors?

Adenocarcinoma

Squamous cell carcinoma

What are major risk factors for esophageal adenocarcinoma?

Barrett esophagus (Chronic GERD)

Obesity

Alcohol

Radiation therapy

What demographic pattern is associated with esophageal adenocarcinoma?

Much more common in males

• Approximately 7:1 male-to-female predominance

Where does esophageal adenocarcinoma most commonly arise?

Distal third of the esophagus

Why does adenocarcinoma favor the distal esophagus?

Most arise from Barrett esophagus

• Which develops in the distal esophagus in the setting of chronic reflux

How can one reduce the risks of esophageal adenocarcinoma?

Fresh fruits and vegetables

H. pylori → Gastric atrophy → Reduced acid secretion and reflux → Decreased incidence of Barrett esophagus

How can the location of H. pylori affect effects?

H pylori + esophagus → Good

H pylori + stomach → Bad (carcinoma & lymphoma)

What is the metaplasia-dysplasia-carcinoma sequence for esophageal adenocarcinoma?

Normal squamous epithelium → inflammation/hyperplasia (esophagitis) → Barrett intestinal metaplasia → low-grade dysplasia → high-grade dysplasia → adenocarcinoma

(Likelihood of developing into ECA increases with overall sequence)

What are the common symptoms of esophageal adenocarcinoma?

Pain or difficulty swallowing

Progressive weight loss

Hematemesis

Chest pain

Vomiting

What molecular abnormalities increase as Barrett esophagus progresses toward adenocarcinoma according to the lecture?

Abnormal ploidy

Increasing expression of p53 and GLUT-1

What is the prognosis of esophageal adenocarcinoma when diagnosed at an advanced stage?

A 5-year survival of <25%

What is the approximate 5-year survival when adenocarcinoma is limited to the mucosa and submucosa?

~80%