44772672 lect 2 diseases of esophagus

8/3/2019 44772672 Lect 2 Diseases of Esophagus

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1

Esophagus

Upper 1/3 is skeletalmuscle

Lower 1/3 is smooth

muscle middle is combo of both

Contains two sphincters

Lined by squamousepithelium

< 3 cm below diaphragm



BARRETT ESOPHAGUS Barrett esophagus is a complication of long-standing

gastroesophageal reflux, occurring in up to 10% of patients

with persistent symptomatic reflux disease, as well as in somepatients with asymptomatic reflux.

Barrett esophagus is defined as the replacement of the normal

distal stratified squamous mucosa by metaplastic columnar

epithelium containing goblet cells. Prolonged and recurrent gastroesophageal reflux is thought to

produce inflammation and eventually ulceration of the

squamous epithelial lining.

Healing occurs by in growth of stem cells and re-epithelialization.

In the microenvironment of an abnormally low pH in the distal

esophagus caused by acid reflux, the cells differentiate into

columnar epithelium.



MORPHOLOGY

Barrett esophagus is apparent as a

salmon-pink, velvety mucosa

between the smooth, pale pink

esophageal squamous mucosa and

the more lush light brown gastric

mucosa.

Microscopically, the esophageal

squamous epithelium is replaced

by metaplastic columnar

epithelium. Critical to the pathologic evaluation

of patients with Barrett mucosa is the

recognition of dysplastic changes in

the mucosa that may be precursors

of cancer.



1/11/2012 4

Barrett esophagus. A, Endoscopic view showing

red velvety gastrointestinal-type mucosa

extending from the gastroesophageal orifice.

Note paler squamous esophageal mucosa.

B, Microscopic view showin

g mixed

gastric- and

intestine-type columnar epithelial cells in

glandular mucosa.



Barrett esophagus affects males more often than females (ratio of 4:1) and ismuch more common in whites than in other races. Genetic factors aresuggested by clustering in families.

Ulcer and stricture may develop as a complication of Barrett esophagus.However, the chief clinical significance of Barrett esophagus relates to thedevelopment of adenocarcinoma. Patients with Barrett esophagus have a 30-to 40-fold greater risk of developing esophageal adenocarcinoma comparedwith normal populations.



ESOPHAGEAL CARCINOMA

Benign tumors may arise in the esophagus from both the

squamous mucosa and underlying mesenchyme. However, theseare overshadowed by cancer of the esophagus, of which thereare two types: squamous cell carcinomas andadenocarcinomas.

Worldwide, squamous cell carcinomas constitute 90% of

esophageal cancers.

Adenocarcinoma arising in Barrett esophagus is more common inwhites than in blacks. By contrast, squamous cell carcinomas aremore common in blacks worldwide.

There are striking and puzzling differences in the geographicincidence of esophageal carcinoma. In the United States, thereare about 6 new cases per 100,000 population per year.

In regions of Asia extending from the northern provinces of Chinato Iran, the prevalence is well over 100 per 100,000.



Etiology and Pathogenesis

The environmental and dietary factorsassociated with squamous cell carcinoma.

An important contributing factor is retardedpassage of food through the esophagus,prolonging mucosal exposure to potentialcarcinogens such as those contained intobacco and alcoholic beverages.

There is a well-defined predisposing role for chronic esophagitis, itself associated withalcohol and tobacco.

The role of genetic predisposition is extremely

ill defined, but the rare genetic syndrome of tylosis, characterized by excess keratinformation in the skin of the palm and soles,carries an almost certain probability of thedevelopment of esophageal cancer.



RISK FACTORS FOR SQUAMOUS CELL CARCINOMA OF THE

ESOPHAGUS

Esophageal Disorders

Long-standing esophagitis

Achalasia

Plummer-Vinson syndrome (esophageal webs, microcytichypochromic anemia, atrophic glossitis)

Alcohol consumption Tobacco abuse

Deficiency of vitamins (A, C, riboflavin, thiamine,pyridoxine)

Deficiency of trace metals (zinc, molybdenum)

Fungal contamination of foodstuffs High content of nitrites/nitrosamines

Genetic Predisposition

Tylosis (hyperkeratosis of palms and soles)



MORPHOLOGY

Squamous cell carcinomas are usually preceded

by a long prodrome of mucosal epithelial dysplasia

followed by carcinoma in situ and, ultimately, by theemergence of invasive cancer.

Early overt lesions appear as small, gray-white,

plaque like thickenings or elevations of the mucosa.

In months to years, these lesions become tumorous,taking one of three forms:

(1) polypoid exophytic masses that protrude into the

lumen;

(2) necrotizing cancerous ulcerations that extend

deeply and sometimes erode into the respiratory tree,aorta, or elsewhere; and

(3) diffuse infiltrative neoplasms that impart

thickening and rigidity to the wall and narrowing of

the lumen.Whichever the pattern, about 20% arise in

the cervical and upper thoracic esophagus, 50% in

the middle third, and 30% in the lower third.

Large

ulcerated

squamous

cellcarcinoma of

the

esophagus

Ex ophytic

growing outward



Adenocarcinomas appear to arise fromdysplastic mucosa in the setting of Barrettesophagus.

Unlike squamous cell carcinomas, they areusually in the distal one third of theesophagus and may invade the subjacentgastric cardia.

Initially appearing as flat or raised patches

on an otherwise intact mucosa, they maydevelop into large nodular masses or exhibitdeeply ulcerative or diffusely infiltrativefeatures.

Microscopically, most tumors are mucin-producing glandular tumors exhibiting

intestinal-type features, in keeping with themorphology of the preexisting metaplasticmucosa.

The occasional development of tumors of other alimentary cell types supports theconcept that Barrett epithelium arises frommultipotential cells.



1/11/2012 copyright (your organization) 2003 11



Clinical Features

Esophageal carcinoma is insidious in onset and producesdysphagia and obstruction gradually and late.

Weight loss, anorexia, fatigue, and weakness appear, followed bypain, usually related to swallowing. Diagnosis is usually made byimaging techniques and endoscopic biopsy.

Because these cancers extensively invade the rich esophageallymphatic network and adjacent structures, surgical excision rarelyis curative.

Thus, there is emphasis on routine screening procedures,particularly for those with manifestations of chronic esophagitis or known Barrett esophagus.

Esophageal cancer detected when confined to the mucosa or submucosa is amenable to surgical treatment.



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44772672 lect 2 diseases of esophagus

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