Download Esophagus/cancer physiopathology

Esophageal cancer
SCC
 Adenocarcinoma
 SCC and adenocarcinoma :more than 95
percent of esophageal malignant tumors.
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Epidemiology
AC is largely a disease of Caucasians and males,
who outnumber females by as much as 6-8to 1 .
 incidence of esophageal AC in Caucasian males
was 4.2 per 100,000 per year, double that of
Hispanics and four-fold higher than those of
blacks and Asians .
 SCC incidence rates were highest in blacks (8.8
per 100,000 per year), and Asians (3.9 per
100,000 per year)
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Esophagus/cancer
early/advanced
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Early esophageal cancer may appear
as a superficial plaque or ulceration .
Esophagus/cancer
Esophagus/cancer
Advanced/gross features
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Advanced lesions may appear as a
stricture an ulcerated mass ,a
circumferential mass or a large ulceration.
Esophagus/cancer
Esophagus/cancer
Esophagus/cancer
Esophagus/cancer
SCC/major risk factors
 Smoking
and alcohol are major
predisposing factors for
squamous cell tumors.
Esophagus/cancer
Risk factors
history of smoking,
 alcohol consumption,
 diets low in fruits and vegetables
accounted for almost 90 percent of
esophageal squamous cell carcinoma
in the United States.
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Esophagus/cancer
Adenocarcinoma/risk factors
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Barrett's esophagus with specialized
intestinal metaplasia and possibly GERD
itself are the only known major risk factors
for adenocarcinoma.
Barrett’s esophagus
Esophageal adenocarcinoma with
barrett’s esophagus
Epidemiology
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the incidence of SCC is decreasing in the United
States,
the incidence of adenocarcinoma (AC) is rising
dramatically.
The prognosis for both types of cancer is poor.
Five-year survival is 10 to 13 percent,
patients diagnosed with early stage disease may
be cured by surgery or multimodality therapy.
Esophagus/cancer
Epidemiology
Squamous cell carcinoma
 incidence : varies among geographic regions
 The highest rates : Asia (particularly in China
and Singapore), Africa, and Iran .
 Geographic variation has also been reported
within an individual country. Within China, rates
of esophageal cancer range from 1.4 to 140 per
100,000 in the Hebi and Hunyuan counties,
respectively .
Demographic and socioeconomic
factors/SCC
Wide difference in the rates of SCC have provided
insight into risk factors associated with the disease.
 In high incidence regions, the disease has no gender
specificity.
 SCC is more common in men in low incidence regions.
 The incidence is higher in urban areas (compared to
rural areas) of the United States, particularly among
African-American men.
 Lower socioeconomic status was associated with
esophageal SCC in a large population-based study.
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Risk factors for SCC
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Smoking and alcohol are also risk factors
for head and neck cancers, which are
found in approximately 10 to 15 percent
of patients diagnosed with esophageal
cancer.
Risk factors for SCC
Dietary factors
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Foods containing N-nitroso compounds have long been implicated
Certain types of pickled vegetables and other food-products
consumed in high-risk endemic areas are rich in N-nitroso
compounds
Toxin-producing fungi have also been identified in food sources
within endemic areas and may, in part, exert their mutagenic
potential by reducing nitrates to nitroso compounds.
Betel nut chewing, which is widespread in certain regions of Asia,
has been implicated in the development of esophageal SCC .The
mechanism may involve the release of copper with resulting
induction of collagen synthesis by fibroblasts.
Risk factors for SCC
In other endemic regions, such as Iran, Russia,
and South Africa, ingestion of very hot foods
and beverages (such as tea) has been
associated with esophageal SCC.
 In one epidemiologic study, significantly more
people in high-risk regions within Iran drank
their tea at temperatures greater than 65ºC
compared to low-risk regions (62 versus 19
percent)
 inhabitants of high-risk regions drank
approximately 2.5 times more hot tea than their
low-risk counterparts.
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Protective factors for SCC
Low levels of serum selenium were associated
with the development of squamous cell cancer
of the esophagus and gastric cardia cancer in a
study from Linxian, China .
 selenium supplementation may be associated
with a reduced risk of these cancers
 zinc deficiency and esophageal squamous cell
cancer.
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Protective factors for SCC
potential mechanisms :
 Zinc deficiency enhances the carcinogenic
effects of nitrosamines in rat models of
esophageal carcinogenesis
 zinc appears to reduce overexpression of COX-2,
which is thought to contribute to carcinogenesis
by enhancing cellular proliferation, inhibition of
apoptosis, and increasing metastatic potential
 increased dietary folate :reduced risk of
squamous cell and adenocarcinoma of the
esophagus
Risk factors for SCC
Underlying esophageal disease
 Achalasia : the risk of SCC was increased more
than 16-fold. cancer was detected an average of
14 years after the diagnosis of achalasia
 caustic strictures: SCC developed 41 years
following ingestion.
 Patients who have undergone a partial
gastrectomy also may be at increased risk?
Risk factors for SCC
Human papilloma virus
 Tylosis (hyperkeratosis of the palms of the
hands and soles of the feet, autosomal dominant
to chromosome 17q25.1, which probably
contains a tumor suppressor gene.
 Deletions in this gene have also been implicated
in sporadic forms of esophageal SCC, occurring
in 70 percent of patients with esophageal SCC in
one series).
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Risk factors for SCC
Upper aerodigestive tract cancer
history of squamous cell cancer of the head and
neck (ie, oral cavity, oropharynx, hypopharynx,
or larynx), lung or esophagus with synchronous
or metachronous squamous cell carcinoma of
the esophagus
 This probably reflects similar risk factors such as
smoking or alcohol.
 the incidence of synchronous or metachronous
esophageal cancer has range from 3 to 14
percent
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Adenocarcinoma
Epidemiology
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In the 1960s, SCC accounted for >90 % of all esophageal tumors in
the United States, whereas AC were considered so uncommon that
some authorities questioned their existence.
For the past three decades, the frequency of AC of the esophagus
and the gastric cardia has increased dramatically in Western
countries.
SCC and AC now occur with almost equal frequency
incidence rates of esophageal AC rose progressively from 1.8 per
100,000 in 1987 to 1991 to 2.5 per 100,000 during 1992 to 1996.
Whites were affected five times more often than blacks, and men
six-eight times more often than women.
A significant increase in the incidence was observed among persons
aged 45 to 65.
Adenocarcinoma
Risk factors
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Gastroesophageal reflux disease
Esophageal adenocarcinoma arises from Barrett's
metaplasia.
The role of chronic reflux as an independent risk factor
has not been well defined since more than 50 % of
cases of AC have no history of symptomatic reflux
disease .
Reflux symptoms were associated with adenocarcinoma
of the esophagus (odds ratio 7.7)
The risk was greatest among patients with long-standing
(>20 years) and severe (as judged by the patient)
symptoms (odds ratio 43.5).
Adenocarcinoma
Risk factors
Smoking : Smoking probably increases the risk
of AC, particularly in patients with Barrett's
esophagus.the risk of AC was 2.4 times greater
in smokers than a control group, and accounted
for 40 percent of the cases of esophageal AC .
 The risk rose with increasing intensity and
duration of smoking, and remained higher than
in nonsmoking controls for 30 years after
smoking cessation.
 Obesity : Obesity has been linked to esophageal
AC.
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Adenocarcinoma
Risk factors
Helicobacter pylori infection.
 Increased esophageal acid exposure .
 Use of drugs that decrease lower
esophageal sphincter pressure.
 Cholecystectomy
 Nitrosative stress
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Adenocarcinoma
Protective factors
Possible protective effect of cereal fiber
and other nutrients
 Possible protective effect of NSAIDs
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Esophagus/cancer
Signs & symptoms
Early symptoms :subtle and nonspecific.
 Transient "sticking" of apples, meat, hard-boiled
eggs, or bread, which can be easily overcome by
the patient with careful chewing, may precede
frank dysphagia.
 retrosternal discomfort or a burning sensation.
 Most early esophageal cancer in the United
States is detected serendipitously or during
screening of Barrett's esophagus.
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Esophagus/cancer
Signs & symptoms
Regurgitation of saliva or food
uncontaminated by gastric secretions
(advanced disease).
 Aspiration pneumonia ( infrequent).
 Hoarseness (recurrent laryngeal nerve).
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Esophagus/cancer
Signs & symptoms
Chronic gastrointestinal blood loss
(common,IDA) .
 melena or blood in regurgitated
food(rare).
 acute upper gastrointestinal bleeding
(rare ,tumor erosion into the aorta
or pulmonary or bronchial arteries).
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Esophagus/cancer
Signs & symptoms
Tracheobronchial fistulas ( late).
 intractable coughing or frequent
pneumonias.
 Life expectancy is less than four weeks
following the development of this
complication.
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Esophagus/cancer
Clinical manifestations
Both AC and SCC have similar clinical
presentations.
 AC arises much more commonly in the distal
esophagus.
 progressive solid food dysphagia( lumen
diameter is less than 13 mm) which indicates
advanced disease.
 weight loss(due to dysphagia, changes in diet,
and tumor anorexia).
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Esophagus/cancer
Diagnostic tests:
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barium studies
endoscopy .
Esophagus/cancer
Staging
CT scan: to evaluate for the presence of
metastatic disease.
 If negative:EUS
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Esophagus/cancer
EUS
Esophagus/cancer
treatment
Surgery
 Chemoradiation
 Palliative
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Esophagus/cancer
Palliative Rx
Endoscopic interventions for palliation of
dysphagia in the following settings:
 Patients for whom definitive management
with radiation or chemoradiotherapy is
planned, but who have severe dysphagia
at presentation, requiring intervention
prior to therapy.
Esophagus/cancer
Palliative Rx
Failure to achieve adequate palliation of
dysphagia with initial therapy.
 Recurrent dysphagia due to locoregional
failure Recurrent.
 dysphagia due to benign strictures in
patients who are successfully treated with
radiation.
 Patients are poor candidates for either
chemotherapy or radiation therapy.
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Esophagus/cancer
Endoscopic approaches
:
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Dilation
Laser therapy
Endoscopic injection therapies
Endoscopic mucosal resection
Photodynamic therapy
Placement of prosthetic tubes (stenting)
Brachytherapy
Examples of self-expandable
esophageal stents
Esophagus/cancer
others tumor
Mesenchymal tumors
commonly found in the mid to distal third
of the esophagus.
 usually small and asymptomatic
 dysphagia.
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Esophagus/ others tumor
leiomyoma
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More common
more common in men
detected incidentally on a barium swallow or
endoscopy performed for other reasons
In endoscopy: rounded submucosal lesions with
intact overlying mucosa, and feel rubbery when
gently palpated with the endoscope.
Ulceration or bleeding (uncommon).
Esophagus/leiomyoma
Esophagus/leiomyoma
Follow-up studies :repeat endoscopy and
EUS at 6 and 12 months.
 Surgical resection: lesions larger than 2
cm or if produce dysphagia.
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